c-peptide and Diabetes--Gestational

Women's metabolism during pregnancy undergoes numerous changes that can lead to gestational diabetes mellitus (GDM). The cause and pathogenesis of GDM, a heterogeneous disease, are not completely clear, but GDM is increasing in prevalence and is associated with the modern lifestyle. Most diagnoses of GDM are made

Topics: Biomarkers; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Humans; Insulin; Insulin Resistance; Pregnancy

Gestational diabetes mellitus (GDM) is linked to the dysregulation of inflammatory markers in women with GDM compared to women without. It is unclear whether the intensity of glycemic control influences these biomarkers. We aimed to assess whether different glycemic targets for women with GDM and compliance influence maternal and infant biomarkers.. Maternity hospitals caring for women with GDM were randomized in the TARGET Trial to tight or less tight glycemic targets. Maternal blood was collected at study entry, 36 weeks' gestation, and 6 months postpartum, and cord plasma after birth. We assessed compliance to targets and concentrations of maternal serum and infant biomarkers.. Eighty-two women and infants were included in the study. Concentrations of maternal and infant biomarkers did not differ between women assigned to tighter and less tight glycemic targets; however, concentrations were altered in maternal serum leptin and CRP and infant cord C-peptide, leptin, and IGF in women who complied with tighter targets.. Use of tighter glycemic targets in women with GDM does not change the concentrations of maternal and infant biomarkers compared to less tight targets. However, when compliance is achieved to tighter targets, maternal and infant biomarkers are altered.. The use of tighter glycemic targets in gestational diabetes does not result in changes to maternal or cord plasma biomarkers. However, for women who complied with tighter targets, maternal serum leptin and CRP and infant cord C-peptide, leptin and IGF were altered compared with women who complied with the use of the less tight targets. This article adds to the current evidence base regarding the impact of gestational diabetes on maternal and infant biomarkers. This article highlights the need for further research to assess enablers to meet the tighter target recommendations and to assess the impact on relevant biomarkers.

Topics: Biomarkers; C-Peptide; Diabetes, Gestational; Female; Glycemic Control; Humans; Infant; Leptin; Pregnancy

Nutrition therapy for gestational diabetes mellitus (GDM) has conventionally focused on carbohydrate restriction. In a randomized controlled trial (RCT), we tested the hypothesis that a diet (all meals provided) with liberalized complex carbohydrate (60%) and lower fat (25%) (CHOICE diet) could improve maternal insulin resistance and 24-h glycemia, resulting in reduced newborn adiposity (NB%fat; powered outcome) versus a conventional lower-carbohydrate (40%) and higher-fat (45%) (LC/CONV) diet.. After diagnosis (at ∼28-30 weeks' gestation), 59 women with diet-controlled GDM (mean ± SEM; BMI 32 ± 1 kg/m2) were randomized to a provided LC/CONV or CHOICE diet (BMI-matched calories) through delivery. At 30-31 and 36-37 weeks of gestation, a 2-h, 75-g oral glucose tolerance test (OGTT) was performed and a continuous glucose monitor (CGM) was worn for 72 h. Cord blood samples were collected at delivery. NB%fat was measured by air displacement plethysmography (13.4 ± 0.4 days).. There were 23 women per group (LC/CONV [214 g/day carbohydrate] and CHOICE [316 g/day carbohydrate]). For LC/CONV and CHOICE, respectively (mean ± SEM), NB%fat (10.1 ± 1 vs. 10.5 ± 1), birth weight (3,303 ± 98 vs. 3,293 ± 81 g), and cord C-peptide levels were not different. Weight gain, physical activity, and gestational age at delivery were similar. At 36-37 weeks of gestation, CGM fasting (86 ± 3 vs. 90 ± 3 mg/dL), 1-h postprandial (119 ± 3 vs. 117 ± 3 mg/dL), 2-h postprandial (106 ± 3 vs. 108 ± 3 mg/dL), percent time in range (%TIR; 92 ± 1 vs. 91 ± 1), and 24-h glucose area under the curve values were similar between diets. The %time >120 mg/dL was statistically higher (8%) in CHOICE, as was the nocturnal glucose AUC; however, nocturnal %TIR (63-100 mg/dL) was not different. There were no between-group differences in OGTT glucose and insulin levels at 36-37 weeks of gestation.. A ∼100 g/day difference in carbohydrate intake did not result in between-group differences in NB%fat, cord C-peptide level, maternal 24-h glycemia, %TIR, or insulin resistance indices in diet-controlled GDM.

Topics: Adiposity; Blood Glucose; C-Peptide; Diabetes, Gestational; Diet, Fat-Restricted; Female; Glucose; Humans; Infant, Newborn; Insulin Resistance; Obesity; Pregnancy; Random Allocation

C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration.. For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration.. In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 - 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 - 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 - 0.42, p < 0.001; and Coef.= 0.34, 95% CI: 0.06 - 0.63, p = 0.02, respectively).. UC blood concentration of C-peptide is significantly associated with the incidence of maternal GDM and neonatal macrosomia. Using stratification for maternal BMI and gestational weight gain (GWG) and investigating molecular markers like Leptin and IGF-1 in the future might lay the ground to better understand the link between metabolic disturbances of pregnancy and UC blood C-peptide concentration.

Topics: Birth Weight; Body Mass Index; C-Peptide; Cesarean Section; Child; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Iran; Leptin; Pregnancy; Pregnancy Outcome; Weight Gain

The aim of this study was to evaluate the effect of an acute bout of cycling immediately after oral glucose intake on glucose metabolism in pregnant women at risk for gestational diabetes mellitus (GDM). Fifteen pregnant women with BMI ≥ 27 kg/m

Topics: Adult; Bicycling; Blood Glucose; C-Peptide; Cross-Over Studies; Denmark; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin; Pregnancy

Treating women with gestational diabetes mellitus in the third trimester improves perinatal outcomes. It is unknown whether treating women with mild glucose intolerance earlier in pregnancy would be beneficial in the reduction of maternal and neonatal morbidities.. In women with hyperglycemia (hemoglobin A1c ≥5.7% and/or fasting glucose ≥92 mg/dL) in early pregnancy, we sought to determine whether immediate treatment improved maternal and neonatal outcomes.. This unblinded randomized controlled trial enrolled women with hyperglycemia at ≤15+0 weeks gestation between 2013 and 2015. Participants were assigned randomly to early pregnancy or third-trimester treatment of hyperglycemia that included nutrition counseling, glucose monitoring, and medications as needed. Participants underwent a blinded 2-hour glucose tolerance test at 24-28 weeks gestation. Exclusion criteria were pregestational diabetes mellitus and multiple gestations. The primary outcome was the proportion of infants with neonatal umbilical cord C-peptide >1.77 nmoL (90th percentile). Secondary outcomes were neonatal fat mass, infant World Health Organization weight-for-length percentile at birth, maternal gestational weight gain, and diagnosis of gestational diabetes mellitus on glucose tolerance test. Mann-Whitney-Wilcoxon test and Fisher's exact test were used, as appropriate.. A total of 202 women were assigned randomly; 45 women dropped out before delivery, which left cases 157 for analysis (82 with early pregnancy and 75 with third-trimester treatment). The trial was terminated early because of low enrollment. Baseline characteristics were similar between groups. There was no difference in C-peptide >90th percentile between groups (1 [1.5%] vs 4 [6.7%]; P=.19) in the early pregnancy and third-trimester groups, respectively). There was also no difference in fat mass (0.37±0.16 vs 0.36±0.17 kg; P=.91), weight-for-length percentile at birth (25% vs 25%; P=.46), or macrosomia (1.5 vs 5.0%; P=.84). Maternal gestational weight gain was 22.6±12.9 lb and 23.9±11.2 lb in the early pregnancy and third-trimester groups, respectively (P=.88). Gestational diabetes mellitus was diagnosed in 19.0% of the cohort and did not differ between groups (14.2% vs 25.8%; P=.17).. In this population of women with hyperglycemia, treatment in early pregnancy did not appear to improve maternal or neonatal outcomes significantly. Given comparable results in both groups, caution should be used in the initiation of an intensive diabetes mellitus treatment protocol for women with the diagnosis of hyperglycemia in early gestation.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; C-Peptide; Diabetes, Gestational; Female; Humans; Hyperglycemia; Infant, Newborn; Pregnancy

In type 2 diabetic patients, a casein-based protein hydrolysate has been shown to increase plasma insulin and to lower plasma glucose. In the present study, we examined the acute and prolonged effects of protein hydrolysate on postprandial glucose, insulin and C-peptide responses after a standardised breakfast and the effect on daily glucose control in patients with gestational diabetes.. In a single-centre randomised double blind placebo controlled design, patients with mild gestational diabetes (no use of insulin or oral antidiabetic agents; n = 26/group) were allocated to receive a protein hydrolysate drink, 8.5 g before breakfast and 8.5 g before dinner or a placebo drink which was identical to the protein hydrolysate drink in appearance and taste, yet lacked carbohydrate, fat or protein, for 8 days.. Baseline characteristics including fasting levels of glucose, insulin, C-peptide and insulin-glucose ratio were similar between the groups. Compared to the placebo drink, neither the first dose of the protein hydrolysate drink nor the final dose had effects on 4-h area under the curve for plasma levels of insulin and C-peptide, or the insulin-to-glucose ratio; however, plasma glucose was moderately lower between t = 45, 60 and 75 min. In addition, mean daily capillary glucose levels were lower in the protein hydrolysate group. Two patients in the PH drink group had to be withdrawn because of vomiting after the first dose.. In patients with gestational diabetes, a twice-daily dose of 8.5 g of protein hydrolysate of casein had no insulinotropic effects, but did moderately reduce plasma glucose levels, suggesting an increase in insulin sensitivity.

Topics: Adult; Blood Glucose; C-Peptide; Caseins; Diabetes, Gestational; Double-Blind Method; Fasting; Female; Gestational Age; Humans; Insulin; Placebos; Pregnancy; Protein Hydrolysates

Children whose parents have diabetes are at increased risk for developing type 2 diabetes. This report assessed relationships between parental diabetes status and baseline demographics, anthropometrics, metabolic measurements, insulin sensitivity, and β-cell function in children recently diagnosed with type 2 diabetes.. The sample included 632 youth (aged 10-17 years) diagnosed with type 2 diabetes for <2 years who participated in the TODAY clinical trial. Medical history data were collected at baseline by self-report from parents and family members. Youth baseline measurements included an oral glucose tolerance test and other measures collected by trained study staff.. Youth exposed to maternal diabetes during pregnancy (whether the mother was diagnosed with diabetes prior to pregnancy or had gestational diabetes mellitus) were diagnosed at younger ages (by 0.6 years on average), had greater dysglycemia at baseline (HbA1c increased by 0.3% [3.4 mmol/mol]), and had reduced β-cell function compared with those not exposed (C-peptide index 0.063 vs. 0.092). The effect of maternal diabetes on β-cell function was observed in non-Hispanic blacks and Hispanics but not whites. Relationships with paternal diabetes status were minimal.. Maternal diabetes prior to or during pregnancy was associated with poorer glycemic control and β-cell function overall but particularly in non-Hispanic black and Hispanic youth, supporting the hypothesis that fetal exposure to aberrant metabolism may have long-term effects. More targeted research is needed to understand whether the impact of maternal diabetes is modified by racial/ethnic factors or whether the pathway to youth-onset type 2 diabetes differs by race/ethnicity.

Topics: Adolescent; Black or African American; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 2; Diabetes, Gestational; Ethnicity; Family Health; Female; Glucose Tolerance Test; Hispanic or Latino; Humans; Hyperglycemia; Insulin Resistance; Insulin-Secreting Cells; Linear Models; Male; Parents; Pregnancy; Risk Factors; White People

The aim of the article is to determine whether maternal body mass index (BMI) influences the beneficial effects of diabetes treatment in women with gestational diabetes mellitus (GDM).. Secondary analysis of a multicenter randomized treatment trial of women with GDM. Outcomes of interest were elevated umbilical cord c-peptide levels (> 90th percentile 1.77 ng/mL), large for gestational age (LGA) birth weight (> 90th percentile), and neonatal fat mass (g). Women were grouped into five BMI categories adapted from the World Health Organization International Classification of normal, overweight, and obese adults. Outcomes were analyzed according to treatment group assignment.. A total of 958 women were enrolled (485 treated and 473 controls). Maternal BMI at enrollment was not related to umbilical cord c-peptide levels. However, treatment of women in the overweight, Class I, and Class II obese categories was associated with a reduction in both LGA birth weight and neonatal fat mass. Neither measure of excess fetal growth was reduced with treatment in normal weight (BMI < 25 kg/m(2)) or Class III (BMI ≥ 40 kg/m(2)) obese women.. There was a beneficial effect of treatment on fetal growth in women with mild GDM who were overweight or Class I and Class II obese. These effects were not apparent for normal weight and very obese women.

Topics: Adipose Tissue; Adult; Blood Glucose Self-Monitoring; Body Mass Index; C-Peptide; Diabetes, Gestational; Diet Therapy; Female; Fetal Blood; Fetal Macrosomia; Humans; Hypoglycemic Agents; Insulin; Obesity; Overweight; Pregnancy; Pregnancy Complications; Severity of Illness Index; Treatment Outcome; Young Adult

Probiotics are live microorganisms that may confer health benefits on the host. Recent trials of probiotic use among healthy pregnant women demonstrate potential for improved glycemic control. The aim of this study was to investigate the effects of a probiotic capsule intervention on maternal metabolic parameters and pregnancy outcome among women with gestational diabetes.. This double-blind placebo-controlled randomized trial recruited pregnant women with a new diagnosis of gestational diabetes or impaired glucose tolerance following a 3-hour 100-g glucose tolerance test. Women were randomized to a daily probiotic (Lactobacillus salivarius UCC118) or placebo capsule from diagnosis until delivery. Fasting blood samples were collected at baseline and 4-6 weeks after capsule commencement for analysis of glucose, insulin, c-peptide, and lipids. The primary outcome was difference in fasting glucose postintervention, first analyzed on an intention-to-treat basis and followed by per-protocol analysis that excluded women commenced on pharmacological therapy (insulin or metformin). Secondary outcomes were changes in insulin, c-peptide, homeostasis model assessment and lipids, requirement for pharmacological therapy, and neonatal anthropometry.. Of 149 women recruited and randomized, there were no differences between the probiotic and placebo groups in postintervention fasting glucose (4.65 ± 0.49 vs 4.65 ± 0.53 mmol/L; P = 373), requirement for pharmacological therapy (17% vs 14%; P = .643), or birthweight (3.57 ± 0.64 vs 3.60 ± 0.57 kg; P = .845). Among 100 women managed with diet and exercise alone, fasting plasma glucose decreased significantly within both the probiotic (4.76 ± 0.45 to 4.57 ± 0.42 mmol/L; P < .001) and placebo (4.85 ± 0.58 to 4.58 ± 0.45 mmol/L; P < .001) groups, but the levels between groups did not differ (P = .316). The late gestation-related rise in total and low-density lipoprotein (LDL) cholesterol was attenuated in the probiotic vs the placebo group (+0.27 ± 0.48 vs +0.50 ± 0.52 mmol/L total cholesterol, P = .031; +0.08 ± 0.51 vs +0.31 ± 0.45 mmol/L LDL cholesterol, P = .011). No differences were noted between groups in other metabolic parameters or pregnancy outcome.. A probiotic capsule intervention among women with abnormal glucose tolerance had no impact on glycemic control. The observed attenuation of the normal pregnancy-induced rise in total and LDL cholesterol following probiotic treatment requires further investigation, particularly in this obstetric group at risk of future metabolic syndrome.

Topics: Adult; Biomarkers; Blood Glucose; C-Peptide; Cholesterol; Diabetes, Gestational; Double-Blind Method; Female; Humans; Infant, Newborn; Insulin; Intention to Treat Analysis; Lactobacillus; Pregnancy; Pregnancy Outcome; Probiotics; Treatment Outcome

Gestational Diabetes Mellitus (GDM) and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75 g Oral Glucose Tolerance Test (OGTT) and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76%) women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001) and increased fasting insulin (+20% vs 18%, p = 0.034). The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol) reduction in HbA1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.

Topics: Adult; Asian People; Biomarkers; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Humans; Insulin; Metabolic Syndrome; Pregnancy; Vitamin D; Vitamin D Deficiency; Vitamins

To evaluate the value of third trimester ultrasound (estimated fetal weight, cheek-to-cheek diameter, sectional Wharton's jelly area, sectional areas and fractional volumes in extremities) to predict birth weight and cord biochemical markers at birth (leptin, insulin, c-peptide, IGF1, erythropoietin and ferritin) in diabetic pregnancies.. Prospective study in 49 patients with gestational diabetes. An ultrasound was performed between 32 and 34 weeks. Clinical data were collected, and a blood sample was obtained from cord after birth. ROC curve models were evaluated for 75(th) and 90(th) birth weight percentile. Univariate and multivariate models were used to assess the association between ultrasound and neonatal outcomes.. Sectional areas and fractional volumes showed significant differences and highest AUC values for predicting birth weight. A significant association was found for extremities measurements with total birth weight and its percentile. The only marker which showed a significant association to estimated fetal weight was erythropoietin. Sectional areas and fractional volumes related to cord leptin, erythropoietin, insulin and c-peptide.. Sectional areas and fractional volumes improve the predictive value of estimated fetal weight in diabetic pregnancies. They also show a predictive association to biochemical changes in cord (leptin, insulin and erythropoietin) related to increased adiposity and risk of fetal hypoxia. © 2015 John Wiley & Sons, Ltd.

Topics: Adult; Birth Weight; Body Fat Distribution; C-Peptide; Diabetes, Gestational; Erythropoietin; Female; Fetal Blood; Humans; Insulin; Leptin; Pregnancy; Prospective Studies; Ultrasonography, Prenatal

This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated with metformin or insulin and in cord plasma of their offspring and to examine how these markers relate to infant size at birth.. Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial. Fasting maternal plasma glucose, lipids, and CRP were measured at randomization, 36 weeks' gestation, and 6-8 weeks postpartum as well as in cord plasma. Women with available cord blood samples (metformin n = 236, insulin n = 242) were included.. Maternal plasma triglycerides increased more from randomization to 36 weeks' gestation in women treated with metformin (21.93%) versus insulin (9.69%, P < 0.001). Maternal and cord plasma lipids, CRP, and neonatal anthropometry did not differ between treatments. In logistic regression analyses adjusted for confounders, the strongest associations with birth weight >90th centile were maternal triglycerides and measures of glucose control at 36 weeks.. There were few differences in circulating maternal and neonatal markers of metabolic status and no differences in measures of anthropometry between the offspring of women treated with metformin and the offspring of women treated with insulin. There may be subtle effects of metformin on maternal lipid function, but the findings suggest that treating gestational diabetes mellitus with metformin does not adversely affect lipids or CRP in cord plasma or neonatal anthropometric measures.

Topics: Adult; Blood Glucose; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Diabetes, Gestational; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Leptin; Metformin; Pregnancy; Risk Factors; Triglycerides

To compare the safety and tolerability of metformin to insulin for glycemic control among women with preexisting type 2 and early A2 gestational diabetes.. Women with preexisting type 2 diabetes and those diagnosed with gestational diabetes who required medical management prior to 20 weeks were randomly assigned to metformin or insulin. Glycemic control, defined as >50% capillary blood glucose within target range, was compared between groups. Other outcomes included patient tolerance, neonatal and obstetric complications, maternal weight gain, neonatal cord blood C-peptide, and patient satisfaction with therapy.. Twenty-eight women completed the study, with 14 in each group. Of the 15 women assigned to metformin, 100% continued to receive metformin until delivery, although 43% required supplemental insulin to achieve glycemic control. Glucose measures did not differ between the groups, and the proportion who met fasting and postprandial glycemic target values did not differ between the groups. Women treated with metformin had significantly fewer subjective episodes of hypoglycemia compared with those using insulin (0% versus 36%; p = 0.04) as well as reported glucose values < 60 mg/dL (7.1% versus 50%; p = 0.03).. Metformin should be considered for treatment of overt diabetes and early A2 gestational diabetes in pregnancy.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fetal Blood; Humans; Hypoglycemic Agents; Insulin; Metformin; Patient Satisfaction; Pregnancy; Pregnancy in Diabetics

To compare the ability of customized versus normalized population fetal growth norms in identifying neonates at risk for adverse perinatal outcomes (APOs) associated with fetal overgrowth and gestational diabetes (GDM).. Secondary analysis of a multicenter treatment trial of mild GDM. The primary outcome was a composite of neonatal outcomes associated with fetal overgrowth and GDM. Birth weight percentiles were calculated using ethnicity- and gender-specific population and customized norms (Gardosi).. Two hundred three (9.8%) and 288 (13.8%) neonates were large for gestational age by population (LGApop) and customized (LGAcust) norms, respectively. Both LGApop and LGAcust were associated with the primary outcome and neonatal hyperinsulinemia, but neither was associated with hypoglycemia or hyperbilirubinemia. The ability of customized and population birth weight percentiles for predicting APOs were poor (area under the receiver operating characteristic curve < 0.6 for six of eight APOs).. Neither customized nor normalized population norms better identify neonates at risk of APOs related to fetal overgrowth and GDM.

Topics: Adult; Area Under Curve; Birth Weight; Blood Glucose; C-Peptide; Confidence Intervals; Diabetes, Gestational; Female; Fetal Macrosomia; Gestational Age; Humans; Hyperbilirubinemia, Neonatal; Hyperinsulinism; Hypoglycemia; Infant, Newborn; Odds Ratio; Pregnancy; Pregnancy Outcome; Reference Values; ROC Curve; Young Adult

This study was performed to determine the effect of a single, large, intramuscular injection of vitamin D post-partum on glucose tolerance and insulin resistance in women with gestational diabetes.. Forty-five participants in a randomized controlled trial on gestational diabetes mellitus were divided into an intervention group and a control group. Only subjects in the intervention group received one intramuscular injection of 300,000 IU of vitamin D3. HbA(1c), serum 25-hydroxyvitamin D3, fasting insulin and blood glucose, C-peptide, homeostasis model assessment insulin resistance index (HOMA-IR), β-cell function, insulin sensitivity and the Quantitative Insulin Sensitivity Check Index (QUICKI) were measured at baseline and after 3 months of intervention.. Approximately 80% of the mothers had a degree of vitamin D deficiency. Post-intervention, this was found in 4.2 and 71.4% in the intervention and control groups, respectively. The medians of HOMA-IR indices before and after intervention were 0.6 and 0.5 (P = 0.7), respectively, in subjects in the intervention group, and 0.5 and 0.9 (P = 0.01) in subjects in the control group. The mean of the QUICKI fell only in the control group (P = 0.008). In the control group, β-cell function increased by ~8% (P = 0.01) and insulin sensitivity decreased after 3 months (P = 0.002). Post-intervention, the median C-peptide decreased in the intervention group and increased in the control group, but the change was significant only in the control group (P = 0.03).. A single injection of 300,000 IU of vitamin D3 achieves a 3-month serum 25-hydroxyvitamin D range of 50-80 nmol/l and is an efficient, effective and safe procedure for improving the vitamin status and indices of insulin resistance in mothers with gestational diabetes after delivery.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Fasting; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Injections, Intramuscular; Insulin Resistance; Postpartum Period; Pregnancy; Treatment Outcome; Vitamin D

To estimate the association between fasting and 2-hour postprandial blood glucose levels and neonatal outcomes in women treated for mild gestational diabetes.. In this secondary analysis of a multicenter randomized treatment trial of mild gestational diabetes, the median fasting and 2-hour postprandial glucose levels were analyzed in 2-week intervals and change over time (slope) was calculated for women with gestational diabetes (abnormal oral glucose tolerance test) and a fasting glucose less than 95 mg/dL who received nutritional management with self blood glucose monitoring and insulin as needed. Regression analyses were performed to estimate the relationship between median fasting and postprandial glucose and neonatal fat mass, cord blood C-peptide, birth weight, large-for-gestational-age neonates, macrosomia (greater than 4,000 g), and neonatal hypoglycemia.. Among 460 women with gestational diabetes, median fasting (P<.001), postprandial breakfast (P<.001), and postprandial lunch (P<.001) glucose values declined over the treatment period, whereas postprandial dinner values remained stable (P=.83). Higher median fasting glucose during the first 2 weeks of treatment was significantly associated with increased odds ratios for neonatal fat mass (1.35; 95% CI 1.09-1.66; P=.006) and elevated C-peptide (1.29; CI 1.09-1.52; P=.003). Higher median fasting glucose during the last 2 weeks before delivery was associated with higher rates of large-for-gestational-age neonates (1.27; CI 1.05-1.53; P=.01), macrosomia (1.32; CI 1.04-1.65; P = .02), and elevated C-peptide (1.19; CI 1.03-1.38; P=.02).. In women treated for mild gestational diabetes, higher fasting glucose during initiation of diet therapy was associated with increased neonatal fat mass and elevated C-peptide and during the last 2 weeks before delivery with macrosomia, large-for-gestational age, and elevated C-peptide.. II.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Fasting; Female; Gestational Age; Glucose Tolerance Test; Glycemic Index; Humans; Hypoglycemic Agents; Insulin; Odds Ratio; Postprandial Period; Pregnancy; Pregnancy Outcome; Regression Analysis; Risk Assessment; Severity of Illness Index; Young Adult

OBJECTIVE To determine if glucose and C-peptide values obtained as part of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study could be used to estimate insulin sensitivity during late pregnancy. RESEARCH DESIGN AND METHODS A total of 78 women enrolled in the HAPO study were recruited for this ancillary study. Venous plasma samples were drawn after an 8- to 10-h fast (time 0) and at 30, 60, 90, and 120 min after a 75-g glucose challenge, which was performed at 24-32 weeks' gestation. Samples were analyzed for plasma glucose, insulin, and C-peptide. Insulin sensitivity was estimated using the established Matsuda and DeFronzo insulin sensitivity index for oral glucose tolerance tests (IS(OGTT)). Insulin sensitivity was also calculated from two other commonly used indexes of insulin sensitivity (that for homeostasis model assessment [IS(HOMA)] and that for quantitative insulin sensitivity check index [IS(QUICKI)]). A new insulin sensitivity index was calculated using the glucose and C-peptide concentrations at 0 and 60 min to derive IS(HOMA C-pep), IS(QUICKI C-pep), and IS(OGTT C-pep). These indexes were then correlated with insulin sensitivity estimated from the IS(OGTT). RESULTS The strongest correlation with the IS(OGTT) was obtained for IS(OGTT C-pep) (r = 0.792, P < 0.001). Further, the correlations of IS(HOMA) (C-pep) and IS(QUICKI C-pep) with IS(OGTT) were also significant (r = 0.676, P < 0.001 and r = 0.707, P < 0.001, respectively). CONCLUSIONS These data suggest that calculated IS(OGTT C-pep) is an excellent predictor of insulin sensitivity in pregnancy and can be used to estimate insulin sensitivity in over 25,000 women participating in the HAPO study.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Glucose Tolerance Test; Health Status Indicators; Humans; Hyperglycemia; Insulin; Insulin Resistance; Pregnancy; Pregnancy Outcome; Young Adult

Recent work showing that caffeine impairs glucose tolerance may be of particular concern in pregnancy because of a possible negative effect on fetal outcome. The current study sought to assess the effect of acute caffeine ingestion on glucose tolerance in women with or without gestational diabetes mellitus (GDM).. Nineteen women whose routine GDM test was negative (control) and eight women with an initial positive GDM screen completed two trials one week apart in a double-blind randomized crossover study. Following an overnight fast, subjects ingested caffeine (3 mg/kg pre-pregnancy body weight) or an identical-appearing placebo (gelatin) capsule and one hour later began a 75 g 2-hour oral glucose tolerance test.. In the control group, caffeine did not significantly affect blood glucose, insulin, or C-peptide. In the GDM group, glucose area under the curve (AUC) was greater (P < 0.01), C-peptide AUC was greater (P < 0.05), and insulin sensitivity index was lower (18%, P < 0.05) after caffeine than after placebo.. Caffeine impaired insulin sensitivity in women with GDM. Additional research regarding more specific dietary caffeine recommendations for women with GDM is warranted.

Topics: Adult; Blood Glucose; C-Peptide; Caffeine; Central Nervous System Stimulants; Cross-Over Studies; Diabetes, Gestational; Double-Blind Method; Female; Glucose Tolerance Test; Humans; Insulin; Pregnancy

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study is a trial on a high evidence level that included 25,000 women recruited in 15 centers all over the world who underwent a 75-gram oral glucose tolerance test (oGTT) at 24-32 weeks of gestation. Data remained blinded if the fasting plasma glucose level was below 105 mg/dl (5.8 mmol/l) and the 2-hour plasma glucose level was below 200 mg/dl (11.1 mmol/l). The aim of the study was to clarify whether maternal hyperglycemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes. The results indicate a continuous association of maternal glucose levels below those diagnostic of diabetes with an adverse outcome, with the strongest risk for increased birth weight and cord blood serum C peptide levels indicating fetal hyperinsulinism. Additionally an increased risk for maternal complications like preeclampsia was seen. Like in many biological processes, there were no obvious thresholds at which risks increased. An international expert committee proposed how to transfer the HAPO data into criteria for the oGTT in pregnancy for the future diagnosis of gestational diabetes mellitus (GDM) which will be based on acute pregnancy problems in contrast to the recent Carpenter and Coustan criteria. The availability of uniform, internationally accepted and applied GDM criteria will provide more clinical and legal security for the caregivers which will be a big advantage also in Germany where a wide diversity of GDM criteria is used. Beside the threshold discussion, the HAPO data are of enormous relevance for Germany. The HAPO data will significantly influence the decision of the German Health Authorities whether to finally establish a general screening for GDM as obligatory part of prenatal care. A report from the German Institute for Quality and Efficiency in Health Care (IQWiG) which was ordered from the German Health Authorities describes--mainly based on the HAPO Study--an indirect benefit of blood glucose screening for GDM for all pregnant women.

Topics: Birth Weight; C-Peptide; Diabetes, Gestational; Double-Blind Method; Female; Fetal Blood; Fetal Death; Fetal Macrosomia; Germany; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Mass Screening; National Health Programs; Obstetric Labor Complications; Pregnancy; Pregnancy Outcome; Quality Assurance, Health Care; Reference Values; Risk Factors

Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance.. A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT.. Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4.2 +/- 0.3 vs. 5.4 +/- 0.4 10(-4) min(-1) (microU/ml)(-1); OGTT: 440 +/- 7 vs. 472 +/- 9 ml min(-1) m(-2)). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 +/- 5 vs. 124 +/- 7 pmol min(-1) m(-2) mm(-1), P = 0.0407) and insulin secretion at 5 mm glucose (168 +/- 9 vs. 206 +/- 10 pmol min(-1) m(-2), P = 0.003).. Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Pregnancy; Prognosis; Recovery of Function; Sensitivity and Specificity

The aim of our study was to compare the secretion of amylin, as well as glucose, insulin and C-peptide at baseline and in response to glucagon stimulation in 26 lean women with gestational diabetes mellitus (GDM) and in 19 age- and BMI-matched pregnant women with normal glucose tolerance (NGT). Intravenous 1-mg glucagon stimulation test was performed 6 weeks after delivery. Fasting and stimulated glucose levels were significantly higher in GDM patients than in subjects with NGT ( p<0.01 at 0 and 6 min; glucose area under the curve (AUC), 604.8+/-41.8 mg/6 min vs. 572.4+/-52.4 mg/6 min, p<0.05). Insulin AUC was also markedly higher in GDM subjects than in healthy controls (373.9+/-144.2 micro IU/6 min vs. 283.7+/-139.1 micro IU/6 min, p<0.05). There was no difference in fasting C-peptide levels between the groups studied, but stimulated concentrations, as well as C-peptide AUC were significantly higher in patients with GDM ( p<0.01 at 1 min and p<0.005 at 6 min; AUC, 27.4+/-11.3 pmol/6 min vs. 18.4+/-6.9 pmol/6 min, p<0.01). Amylin levels were higher in GDM group in comparison to healthy subjects ( p<0.005 at 1 and 6 min; amylin AUC, 113.3+/-51.2 pg/6 min vs. 72.5+/-15.7 pg/6 min; p=0.14), but in contrast to the other hormones, did not rise in response to glucagon injection. In conclusion, our results provide evidence that in patients with GDM in the post-partum period, the levels of amylin, as well as the secretion of insulin and C-peptide remain elevated, when compared to women with NTG. Further investigations are needed to clarify the significance of this elevation as a predictive factor for the development of late maternal type 2 diabetes.

Topics: Adult; Amyloid; Blood Glucose; Body Mass Index; C-Peptide; Diabetes, Gestational; Female; Glycated Hemoglobin; Humans; Insulin; Islet Amyloid Polypeptide; Postpartum Period; Pregnancy; Thinness

To assess the short-term efficacy of insulin aspart in comparison with regular human insulin in women with gestational diabetes mellitus (GDM) during standardized meal tests.. The study included 15 women with GDM who had inadequate diabetes control with diet alone. On 3 consecutive days, breakfast meal tests were performed-the first with no exogenous insulin and the other two after the injection of either regular insulin or insulin aspart.. The peak insulin concentration was higher and the peak glucose and C-peptide concentrations were lower with both insulin preparations than with no exogenous insulin. Glucose areas under the curve above baseline were significantly lower with insulin aspart (180-min area, 7.1 mg. h. dl(-1); P = 0.018), but not with regular insulin (30.2 mg. h. dl(-1); P = 0.997), than with no insulin (29.4 mg. h. dl(-1)).. This study demonstrates that effective postprandial glycemic control in women with GDM who required insulin was brought about by insulin aspart through higher insulin peak and lower demand on endogenous insulin secretion.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Eating; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Middle Aged; Pregnancy

Hormonal parameters during the last trimester of pregnancy contribute to a natural increase of insulin resistance. It is not known whether any of these are further involved in the manifestation of gestational diabetes mellitus (GDM) in affected individuals. Basal levels of adrenocorticotropic hormone, cortisol, growth hormone, insulin-like growth factor-I, prolactin, glucagon, estradiol, progesterone, human placental lactogen and human chorionic gonadotropin were investigated in 15 nonobese women with GDM and 26 matched normal pregnant women (N). A linear discriminant analysis was performed to further compare the predictive value of the basal hormone levels. Plasma glucagon levels were significantly higher in the GDM group (p = 0.014); this difference was even higher (p = 0.007) when the number of women was increased (GDM = 33, N = 62). No significant differences were found in the levels of any of the other hormones. It is not clear whether elevated glucagon levels have any involvement in the pathogenesis of GDM or simply reflect the relative insulin deficiency of these women.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Glucagon; Hormones; Humans; Insulin; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, Third; Reference Values; Sensitivity and Specificity; Statistics, Nonparametric

Replacement of the two-step, 100 gm, 3-hour National Diabetes Data Group procedure by the one-step, 75 gm, 2-hour World Health Organization oral glucose tolerance test has been hindered by a paucity of data comparing the two tests during pregnancy. The current series compared 100 gm and 75 gm glucose loads and glucose measurements in venous plasma or capillary blood.. After a 75 gm oral glucose tolerance test 30 gestational diabetics and 30 metabolically healthy pregnant women were randomly assigned to a second 75 or 100 gm test within 3+/-1.3 (mean+/-SD) days. Glucose levels at both tests was measured in capillary blood and venous plasma, as were insulin and C peptide.. In controls 1-hour maternal glucose levels (112 vs 128 mg/dl) and 2-hour levels (104 vs 113 mg/dl) differed significantly after a 75 or 100 gm load (paired t test). In gestational diabetes mellitus, however, there was no difference (176 vs 178 mg/dl) but a low insulin/glucose quotient at 1 hour. Only 2-hour levels differed significantly (133 vs 149 mg/dl). In controls glucose measurement in capillary blood and venous plasma differed significantly at 1 hour (126 vs 115 mg/dl) and 2 hours (111 vs 104 mg/dl) independently of the glucose load. In gestational diabetes mellitus, however, glucose measurement in capillary blood and venous plasma differed neither in 1-hour levels (179 vs 174 mg/dl) nor in 2-hour levels (142 vs 139 mg/dl).. In metabolically healthy women both different loading and different blood fractions lead to statistically different blood glucose levels at 1 and 2 hours. In gestational diabetes mellitus, however, 1-hour glucose levels do not differ after a 75 or 100 gm load or after glucose measurement in capillary blood or venous plasma. This is due to elevated insulin resistance shown by a low insulin/glucose quotient at 1 hour. For comparison of tests in gestational diabetes mellitus only, 2-hour values must be adjusted by 16 mg/dl after different loading.

Topics: Adult; Blood Glucose; C-Peptide; Capillaries; Diabetes, Gestational; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Pregnancy; Reproducibility of Results; Veins

Gestational diabetes is a disease appearing in many forms. Up till now the etiopathogenesis was not clearly defined. It has been suggested that counterregulatory of pregnancy or diminished B-cells could the major contributory factors. The aim of the present study was to retrospective verify the diagnoses of gestational diabetes. The investigation was carried out in 42 women aged 25-39 yrs, mean age 30 +/- 6 yrs. Diabetes was diagnosed in the 2nd, and 3rd, trimesters of pregnancy, 30 women were treated by diet only, 25 kcal/kg b.w. depending on weight, and 12 patients had intensified insulin therapy of mean daily dose 18 +/- 8 U. Three to nine months after delivery a glucose tolerance test as well as estimation of C-peptide and insulin concentration by RIA in basic conditions and after administration of 1 mg of glucagon were performed. In the group of women treated by diet only, normal values of glycaemia in glucose tolerance test were observed. C-peptide concentration measured before administration of glucagon was 1.15 +/- 0.49 ng/ml and after administration of 1 mg of glucagon was 3.14 +/- 1.44 ng/ml. In the majority of patients treated during pregnancy with insulin the results of oral glucose tolerance test were pathological. The concentrations of C-peptide in the test with glucagon were significantly lower (0.33 +/- 0.16 and 0.38 +/- 0.32 ng/ml). The concentrations of insulin were much lower in comparison to women treated with diet and healthy controls, these results suggest that, if gestational diabetes could be controlled by diet only, disturbances of carbohydrate metabolism would disappear, however, if insulin therapy was necessary during pregnancy, disturbances of the carbohydrate metabolism would be prolonged.

Topics: Adult; Biomarkers; C-Peptide; Diabetes, Gestational; Female; Glucagon; Glucose Tolerance Test; Humans; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Radioimmunoassay; Retrospective Studies

Women with a history of gestational diabetes mellitus (GDM) tend to be insulin-resistant and hyperinsulinemic and are predisposed to the subsequent development of non-insulin-dependent diabetes mellitus (NIDDM). In the evolution of glucose intolerance, the first clinically detectable abnormality has not been defined and the relative importance of contributions of abnormal insulin secretion and insulin resistance is controversial. The present study was performed to evaluate the insulin secretory responses to oral and intravenous glucose and to mixed meals in women with a history of GDM, and to determine if the hyperinsulinemia present in these subjects is appropriate for the degree of insulin resistance. To address these questions, we studied the insulin secretory responses to oral glucose over a 3-hour period and to three mixed meals over a 24-hour period, and quantified the acute insulin response to glucose (AIRglucose) and insulin sensitivity (SI) during frequently sampled intravenous glucose tolerance tests (FSIVGTTs). Studies were performed in seven subjects with a history of GDM and in seven matched controls. Insulin secretion rates (ISRs) were derived by deconvolution of peripheral C-peptide values using a two-compartment model and standard C-peptide kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Blood Glucose; C-Peptide; Causality; Diabetes Mellitus, Type 2; Diabetes, Gestational; Eating; Female; Glucose; Glucose Tolerance Test; Humans; Hyperinsulinism; Injections, Intravenous; Insulin; Insulin Resistance; Insulin Secretion; Pregnancy; Proinsulin; Time Factors

To examine the effect of prior meal ingestion on the glucose, insulin, and C-peptide response to a 50-g glucose challenge test in the third trimester of pregnancy.. Ten pregnant women with gestational diabetes mellitus and 12 nondiabetic pregnant control subjects matched for age and weight underwent a 50-g glucose challenge test on three occasions within a 2-wk period, in random order. On one occasion the test was administered in the fasting state (fasting glucose challenge test), on a second occasion the test was administered 1 h after ingestion of a standard mixed meal (1-h postprandial study), and on a third occasion the test was administered 2 h after ingestion of a standard mixed meal (2-h postprandial study).. In the control subjects, the plasma glucose level 1 h after ingestion of 50 g of glucose was higher in the fasting study (7.8 +/- 0.4 mM, 7 of 12 subjects with glucose > or = 7.8 mM) than in the 1-h postprandial study (6.7 +/- 0.3 mM, 3 of 12 subjects with glucose > or = 7.8 mM) and the 2-h postprandial study of (6.3 +/- 0.4 mM, 3 of 12 with glucose > or = 7.8 mM) (P < 0.01). In the postprandial studies of control subjects, insulin and C-peptide levels were higher at the time of ingestion of the 50 g of glucose, but the early (1 h) insulin secretory response was less than in the fasting study. In the diabetic patients, glucose levels 1 h after 50-g glucose ingestion were similar in the fasting study (10.5 +/- 0.4 mM, no subjects with glucose value < 7.8 mM) and the 1-h postprandial study (11.0 +/- 0.6 mM, 1 subject with glucose < 7.8 mM), but was lower in the 2-h postprandial study (9.3 +/- 0.3 mM, 1 subject with glucose < 7.8 mM) (P < 0.03). In contrast to the control subjects, the insulin secretory response to 50 g of oral glucose was greater in the two postprandial studies than in the fasting study.. We have reached the following conclusions. 1) In nondiabetic gravidas, plasma glucose concentrations 1 h after ingestion of a 50-g oral glucose load are higher if administered in the fasting state compared with the postprandial state. 2) During normal pregnancy the Staub-Traugott Effect, i.e., improved glucose disposal after successive glucose load administrations, occurs and appears to be caused by mechanisms other than enhanced insulin secretion with successive glucose loads. 3) The effect of the prandial state on plasma glucose response to the 50-g glucose challenge test used to screen for gestational diabetes mellitus may be of sufficient magnitude to significantly alter the operating characteristics, i.e., sensitivity and specificity, of this test.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes, Gestational; Eating; Female; Glucose Tolerance Test; Humans; Inulin; Obesity; Pregnancy; Pregnancy Trimester, Third; Reference Values

Nutritional therapy remains a key tool for prevention and management of gestational diabetes (GDM). Carbohydrate type and absorption rate rather than the carbohydrate amount have more impact on postprandial glucose (PPG) levels in GDM. The effect of refined white bread and whole grain sourdough bread on glycemic indexes were compared in GDM patients.. A total of 43 patients with GDM and 38 healthy pregnant women were included. A similar breakfast menu was given to both groups of patients at two different times in consecutive weeks; however, different types of bread with the same weight were used for both breakfasts; 1) white wheat (WW) bread, 2) sourdough whole grain wheat (SWGW) bread. Blood glucose, insulin and C‑peptide levels were compared before and after breakfast.. Fasting glucose, insulin and c‑peptide levels were similar between groups (p > 0.05). While the second hour glucose levels were similar between the groups, the first hour results of glucose, insulin and C‑peptide levels were lower in the SWGW group (p < 0.05). In the control patients, first hour glucose, insulin and C‑peptide levels were also lower in the SWGW group (p < 0.05).. The WW bread, which is more preferred in daily life routine, causes 45.5% more insulin secretion and 9.6% more first hour postprandial blood glucose compared to SWGW bread both in GDM patients and healthy pregnant women. According to the results of this study, we recommend that sourdough whole grain bread should be preferred in order to increase the success in the management of GDM.

Topics: Blood Glucose; Bread; C-Peptide; Diabetes, Gestational; Female; Glucose; Humans; Insulin; Pregnancy; Triticum; Whole Grains

Previous gestational diabetes mellitus (GDM) entails increased risk of future diabetes. We describe the characteristics of women with previous GDM and compare with no previous GDM from the cohort Diabetes in Kalmar and Kronoberg (DKK) of 1248 adults, 40% women, with new diabetes, and factors affecting age and C-peptide levels at diagnosis of diabetes.. Age-at-diagnosis of diabetes, BMI, hypertension, hyperlipidemia, smoking, physical activity, and pre-existing myocardial infarction, stroke, or peripheral arterial insufficiency were registered at ordinary care visits close to diagnosis of diabetes, for the 43 women (9.4% of 456 from DKK with complete data for this analysis) with self-reported previous GDM (yes/no) and 86 controls without it, matched for date of diagnosis of diabetes. Blood samples were centrally analyzed for GADA and C-peptide for classification of diabetes.. Women with previous GDM had lower mean age-at-diagnosis of diabetes, 53.4 vs 65.0 years, lower systolic blood pressure (SBP), 131.2 vs 137.5 mmHg, and fewer had pre-existing hypertension than without previous GDM (p < 0.001-0.05). Among antibody negative women with previous GDM, BMI (p = 0.024), hypertension (p = 0.023) and hyperlipidemia (p < 0.001) were associated with higher levels of C-peptide, while physical activity was inversely associated (p = 0.035), and SBP (p = 0.02) and hypertension (p = 0.016) were associated with age-at-diagnosis of diabetes.. Women with previous GDM were a decade younger and had lower prevalence of hypertension at diagnosis of diabetes; C-peptide levels were associated with BMI, hypertension, and hyperlipidemia and showed a tendency to be lower, possibly indicating a phenotype with higher risk of overt cardiovascular disease later in life.

Topics: Blood Pressure; C-Peptide; Diabetes, Gestational; Female; Humans; Hypertension; Male; Pregnancy; Risk Factors

We aimed to evaluated if fetuses of subjects with one elevated value on the 3-h GTT had a measurable physiologic difference in fetal C-peptide levels as compared to those with no elevated values on the GTT.. We performed a prospective cohort study to evaluate insulin levels in singleton non-anomalous fetuses of subjects with one elevated value on the GTT as compared to subjects with no elevated values on their GTT. Fetal insulin levels were measured by fetal C-peptide in cord blood. Distribution of data was assessed and outliers representing values > the 99th and < the 1st percentiles were excluded. Data were log transformed to achieve normal distribution and univariable analyses were performed to compare fetal C-peptide levels, baseline maternal characteristics and perinatal outcomes in subjects with one elevated value as compared those with no elevated values.. Our analysis included 99 subjects, with 49 subjects in the one elevated value group and 50 subjects in the no elevated values group. Fetal C-peptide levels (picomoles per liters, pmol/L), were significantly higher in the elevated value group as compared to the no elevated value group (mean ± SD; 4.6 ± 0.8 vs. 4.3 ± 0.7, P = 0.046, respectively). In univariable analysis, there was no significant difference in maternal characteristics or adverse composite perinatal outcomes.. Fetuses of subjects who had one elevated value on their GTT had a measurable physiologic difference in C-peptide levels as compared to fetuses of subjects with no elevated values on the GTT.

Topics: C-Peptide; Diabetes, Gestational; Female; Fetus; Glucose; Glucose Tolerance Test; Humans; Pregnancy; Prospective Studies

This study investigates the impact of evidence-based care on glucose levels and pregnancy outcomes in patients with gestational diabetes mellitus.. We employed a prospective cohort study design. We selected 120 patients with gestational diabetes admitted to our institution from May 2019 to May 2021. Using a computerized blind selection method, we divided these patients into two groups, each consisting of 60 patients. The control group received conventional care, while the observation group underwent evidence-based care in addition to conventional care. We compared changes in various glucose-related indices, pregnancy outcomes, and patient satisfaction before and after implementing evidence-based care in both groups.. Before care, no statistically significant differences were observed in fasting C-peptide levels, HOMA-IR, and HbA1c between the two groups (P > .05). However, after care, the observation group exhibited significantly lower levels of HOMA-IR and HbA1c compared to the control group, with significantly higher fasting C-peptide levels (P < .05). Furthermore, the observation group experienced a lower incidence of various adverse pregnancy outcomes for both mothers and infants when compared to the control group. Patient satisfaction with care was notably higher in the observation group (88.33%) compared to the control group (55.0%), and this difference was statistically significant (P < .05).. Evidence-based nursing interventions can effectively enhance daily care for patients with gestational diabetes. These interventions lead to improved blood glucose control, increased patient compliance, reduced incidence of adverse pregnancy outcomes, and ensured the safety of pregnant women and newborns. These outcomes are achieved through disseminating knowledge, structured dietary and exercise plans, and psychological guidance.

Topics: Blood Glucose; C-Peptide; Diabetes, Gestational; Evidence-Based Medicine; Female; Glycated Hemoglobin; Glycemic Control; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Outcome; Prospective Studies

(1) Background: Pregnancy presents a challenge to maternal glucose homeostasis; suboptimal adaptations can lead to gestational diabetes mellitus (GDM). Human milk oligosaccharides (HMOs) circulate in maternal blood in pregnancy and are altered with GDM, suggesting influence of glucose homeostasis on HMOs. We thus assessed the HMO response to glucose load during an oral glucose tolerance test (OGTT) and investigated HMO associations with glucose tolerance/insulin sensitivity in healthy pregnant women. (2) Methods: Serum of 99 women, collected at 0 h, 1 h and 2 h during a 75 g OGTT at 24-28 gestational weeks was analyzed for HMOs (2'FL, 3'SLN, LDFT, 3'SL) by HPLC; plasma glucose, insulin and C-peptide were analyzed by standard biochemistry methods. (3) Results: Serum 3'SL concentrations significantly increased from fasting to 1 h after glucose load, while concentrations of the other HMOs were unaltered. Higher 3'SL at all OGTT time points was associated with a generally more diabetogenic profile, with higher hepatic insulin resistance (HOMA-IR), lower insulin sensitivity (Matsuda index) and higher insulin secretion (C-peptide index 1). (4) Conclusions: Rapid increase in serum 3'SL post-oral glucose load (fasted-fed transition) indicates utilization of plasma glucose, potentially for sialylation of lactose. Associations of sialylated HMOs with a more diabetogenic profile suggest sustained adaptations to impaired glucose homeostasis in pregnancy. Underlying mechanisms or potential consequences of observed HMO changes remain to be elucidated.

Topics: Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Glucose; Humans; Insulin; Insulin Resistance; Milk, Human; Oligosaccharides; Pregnancy

Gestational diabetes mellitus and antenatal depression are common comorbidities. However, the combined effects of antenatal depression and diabetes mellitus during pregnancy on fetal β-cell function are unknown.. This study aimed to test whether the association of maternal gestational diabetes mellitus and glucose metabolism with cord blood C-peptide levels varies with antenatal depression.. Data on mother-child pairs (N=5734) from the Maternal and Infant Health Cohort Study in Hefei were analyzed. Gestational diabetes mellitus was diagnosed using the 75-g oral glucose tolerance test at 24 to 28 weeks of gestation. Antenatal depression was measured using the Edinburgh Postnatal Depression Scale during midpregnancy and late pregnancy. Cord blood samples were collected at delivery and tested for C-peptide levels.. A total of 1054 mothers (18.38%) were diagnosed with gestational diabetes mellitus. Gestational diabetes mellitus was associated with a 5.57 (95% confidence interval, 3.65-7.50) percentile higher cord blood C-peptide level. This association varied with depression severity: the differences in cord blood C-peptide percentile for gestational diabetes mellitus vs no gestational diabetes mellitus were 5.12 (95% confidence interval, 2.81-9.75) for nonantenatal depression, 7.36 (95% confidence interval, 2.85-13.38) for moderate antenatal depression, and 10.06 (95% confidence interval, 4.69-14.8) for severe antenatal depression in midpregnancy. Similar associations stratified by antenatal depression in late pregnancy were observed. Antenatal depression was significantly positively correlated with fetal hyperinsulinism in participants with gestational diabetes mellitus but not in participants without gestational diabetes mellitus.. Antenatal depression, which is related to maternal hyperglycemia, can aggravate the risk of fetal hyperinsulinism in early life.

Topics: C-Peptide; Cohort Studies; Depression; Diabetes, Gestational; Female; Humans; Hyperinsulinism; Pregnancy

Interactions between polymorphisms of the melatonin receptor 1B (MTNR1B) gene and lifestyle intervention for gestational diabetes have been described. Whether these are specific for physical activity or the healthy eating intervention is unknown.. The aim was to assess the interaction between MTNR1B rs10830962 and rs10830963 polymorphisms and lifestyle interventions during pregnancy.. Women with a BMI (in kg/m2) of ≥29 (n = 436) received counseling on healthy eating (HE), physical activity (PA), or both. The control group received usual care. This secondary analysis had a factorial design with comparison of HE compared with no HE and PA compared with no PA. Maternal outcomes at 24-28 wk were gestational weight gain (GWG), maternal fasting glucose, insulin, insulin resistance (HOMA-IR), disposition index, and development of GDM. Neonatal outcomes were cord blood leptin and C-peptide and estimated neonatal fat percentage. The interaction between receiving either the HE or PA intervention and genotypes of both rs10830962 and rs10830963 was assessed using multilevel regression analysis.. GDM risk was increased in women homozygous for the G allele of rs10830962 (OR: 2.60; 95% CI: 1.34, 5.06) or rs10830963 (OR: 2.83; 95% CI: 1.24, 6.47). Significant interactions between rs10830962 and interventions were found: in women homozygous for the G allele but not in the other genotypes, the PA intervention reduced maternal fasting insulin (β: -0.16; 95% CI: -0.33, 0.02; P = 0.08) and HOMA-IR (β: -0.17; 95% CI: -0.35, 0.01; P = 0.06), and reduced cord blood leptin (β: -0.84; 95% CI: -1.42, -0.25; P = 0.01) and C-peptide (β: -0.62; 95% CI: -1.07, -0.17; P = 0.01). In heterozygous women, the HE intervention had no effect, whereas in women homozygous for the C allele, HE intervention reduced GWG (β: -1.6 kg; 95% CI: -2.4, -0.8 kg). No interactions were found.. In women homozygous for the risk allele of MTNR1B rs10830962, GDM risk was increased and PA intervention might be more beneficial than HE intervention for reducing maternal insulin resistance, cord blood C-peptide, and cord blood leptin.

Topics: Adult; Alleles; Blood Glucose; C-Peptide; Diabetes, Gestational; Diet, Healthy; Exercise; Female; Fetal Blood; Genotype; Gestational Weight Gain; Humans; Infant, Newborn; Insulin; Insulin Resistance; Leptin; Life Style; Polymorphism, Genetic; Pregnancy; Pregnancy Outcome; Prenatal Care; Receptor, Melatonin, MT2

Topics: Adipokines; Adiposity; Bone Density; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Leptin; Obesity; Pregnancy; Prospective Studies; Vascular Endothelial Growth Factor A

Fulminant type 1 diabetes mellitus (FT1DM) is recognised as a novel subtype of type 1 diabetes mellitus characterised by the abrupt onset of insulin-deficient hyperglycaemia and ketoacidosis. Fulminant type 1 diabetes mellitus is known to be associated with pregnancy and had been associated with high fetal mortality. We report a case of a gestational diabetes mellitus (GDM) mother complicated with FT1DM immediately post-delivery. A 29-year-old Malay lady who was diagnosed with GDM at 19 weeks of pregnancy, underwent emergency lower segment caesarean section (EMLSCS) due to fetal distress at 36 weeks of gestation; 18 h post-EMLSCS, she developed abrupt onset Diabetic ketoacidosis (DKA) (blood glucose 33.5 mmol/L, pH 6.99, bicarbonate 3.6 mmol/L, ketone 4.4 mmol/L and HbA1c 6.1%). She received standard DKA treatment and discharged well. Her plasma C-peptide level 3 weeks later showed that she has no insulin reserve (C-peptide <33 pmol/L, fasting blood glucose (FBS) 28 mmol/L). Her pancreatic autoantibodies were negative. This case highlights that FT1DM not only can occur in pregnancy with normal glucose tolerance but can also complicate mother with GDM.

Topics: Adult; Autoantibodies; Bicarbonates; Blood Glucose; C-Peptide; Cesarean Section; Diabetes Mellitus, Type 1; Diabetes, Gestational; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Insulin; Ketones; Mothers; Pregnancy

Females with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes mellitus (T2D) later in life.. This study prospectively examined whether greater habitual coffee consumption was related to a lower risk of T2D among females with a history of GDM.. We followed 4522 participants with a history of GDM in the NHS II for incident T2D between 1991 and 2017. Demographic, lifestyle factors including diet, and disease outcomes were updated every 2-4 y. Participants reported consumption of caffeinated and decaffeinated coffee on validated FFQs. Fasting blood samples were collected in 2012-2014 from a subset of participants free of diabetes to measure glucose metabolism biomarkers (HbA1c, insulin, C-peptide; n = 518). We used multivariable Cox regression models to calculate adjusted HRs and 95% CIs for the risk of T2D. We estimated the least squares mean of glucose metabolic biomarkers according to coffee consumption.. A total of 979 participants developed T2D. Caffeinated coffee consumption was inversely associated with the risk of T2D. Adjusted HR (95% CI) for ≤1 (nonzero), 2-3, and 4+ cups/d compared with 0 cup/d (reference) was 0.91 (0.78, 1.06), 0.83 (0.69, 1.01), and 0.46 (0.28, 0.76), respectively (P-trend = 0.004). Replacement of 1 serving/d of sugar-sweetened beverage and artificially sweetened beverage with 1 cup/d of caffeinated coffee was associated with a 17% (risk ratio [RR] = 0.83, 95% CI: 0.75, 0.93) and 9% (RR = 0.91, 95% CI: 0.84, 0.99) lower risk of T2D, respectively. Greater caffeinated coffee consumption was associated with lower fasting insulin and C-peptide concentrations (all P-trend <0.05). Decaffeinated coffee intake was not significantly related to T2D but was inversely associated with C-peptide concentrations (P-trend = 0.003).. Among predominantly Caucasian females with a history of GDM, greater consumption of caffeinated coffee was associated with a lower risk of T2D and a more favorable metabolic profile.

Topics: Biomarkers; C-Peptide; Coffee; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Pregnancy; Prospective Studies; Risk Factors; Sweetening Agents

Fibroblast growth factor 19 (FGF19) has been implicated in glucose homeostasis. Gestational diabetes mellitus (GDM) enhances fetal insulin secretion and fetal growth. Girls weigh less and are more insulin resistant than boys at birth. We sought to assess whether FGF19 is associated with GDM and fetal growth and explore potential sex dimorphic associations. This was a nested case-control study in the Shanghai Birth Cohort, including 153 pairs of newborns of GDM versus euglycemic mothers matched by infant's sex and gestational age at birth. Cord plasma FGF19, insulin, C-peptide, proinsulin, IGF-I and IGF-II concentrations were measured. Cord plasma FGF19 concentrations were similar in GDM versus euglycemic pregnancies (mean ± SD: 43.5 ± 28.2 versus 44.5 ± 30.2 pg/mL, P=0.38). FGF19 was not correlated with IGF-I or IGF-II. FGF19 concentrations were positively correlated with birth weight (r=0.23, P=0.01) and length (r=0.21, P=0.02) z scores, C-peptide (r=0.27, P=0.002) and proinsulin (r=0.27, P=0.002) concentrations in females. Each SD increment in cord plasma FGF19 was associated with a 0.25 (0.07-0.43) increase in birth weight z score in females. In contrast, FGF19 was not correlated with birth weight or length in males. These sex dimorphic associations remained after adjusting for maternal and neonatal characteristics. The study is the first to demonstrate that GDM does not matter for cord blood FGF19 concentrations. The female specific positive correlation between FGF19 and birth weight is suggestive of a sex-dimorphic role of FGF19 in fetal growth. The observations call for more studies to validate the novel findings and elucidate the underlying mechanisms.

Topics: Birth Weight; C-Peptide; Case-Control Studies; Diabetes, Gestational; Female; Fetal Blood; Fetal Development; Fibroblast Growth Factors; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Pregnancy; Proinsulin

We report on the transition in blood glucose levels before and after the onset of fulminant type 1 diabetes mellitus in a perinatal woman. In week 38 of pregnancy, before which the patient had normal glucose tolerance, idiopathic acute pancreatitis was diagnosed. Five days thereafter, she became hypoglycemic, so we closely monitored her blood glucose levels. A total of 13 days later, she was hyperglycemic with a blood glucose level >16.0 mmol/L and glycated hemoglobin of 6.4%. Her fasting serum C-peptide reactivity level was 3.6 ng/mL on the 5th day, and 0.2 ng/mL on the 18th day. Multiple insulin injection therapy was administered since the 18th day; after that, ketoacidosis did not occur. The patient was diagnosed with fulminant type 1 diabetes mellitus based on hyperglycemia without high glycated hemoglobin levels and sudden onset insulin-dependent diabetes. Monitoring glucose levels in the case of idiopathic acute pancreatitis during pregnancy and prompt initiation of insulin therapy are important.

Topics: Acute Disease; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Pancreatitis; Pregnancy; Pregnancy Complications

To determine predictors of neonatal adiposity and differences in associations by fetal sex in women with gestational diabetes mellitus (GDM), normal-weight and overweight (BMI ≥ 25 kg/m. Skinfold thickness was measured in 576 newborns, and cord blood leptin, c-peptide and lipids in 327 newborns in a multi-centric prospective cohort study.. Compared to neonates of normal-weight NGT women (327), neonates of women with GDM (97) were more often large-for-gestational age (LGA) (16.5% vs 8.6%, p = 0.024) ,but the macrosomia rate (8.2% vs 5.8%, p = 0.388), sum of skinfolds (13.9 mm ± 2.9 vs 13.3 mm ± 2.6, p = 0.067), neonatal fat mass (1333.0 g ± 166.8 vs 1307.3 g ± 160.9, p = 0.356), and cord blood biomarkers were not significantly different. Compared to neonates of normal-weight NGT women, neonates of overweight NGT women (152) had higher rates of macrosomia (12.5% vs 5.8%, p = 0.012), LGA (17.1% vs 8.6%, p = 0.006), higher sum of skinfolds (14.3 mm ± 2.6 vs 13.2 mm ± 2.6, p < 0.001), neonatal fat mass (1386.0 g ± 168.6 vs 1307.3 g ± 160.9, p < 0.001), % neonatal fat mass > 90th percentile (15.2% vs 7.1%, p < 0.001), without significant differences in cord blood biomarkers. Maternal BMI, fasting glycemia, triglycerides, gestational weight gain, cord blood leptin ,and cord blood triglycerides were independent predictors for neonatal adiposity. Gestational weight gain was positively associated with adiposity in boys only.. Compared to neonates of normal-weight NGT women, neonates of GDM women have higher LGA rates but similar adiposity, while neonates of overweight NGT women have increased adiposity. Limiting gestational weight gain might be especially important in the male fetus to reduce neonatal adiposity.

Topics: Adiposity; Adolescent; Adult; Belgium; Birth Weight; C-Peptide; Cohort Studies; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Fetus; Humans; Infant, Newborn; Leptin; Lipids; Male; Middle Aged; Pregnancy; Pregnancy Outcome; Prognosis; Prospective Studies; Sex Characteristics; Skinfold Thickness; Young Adult

Until now, diabetes during pregnancy has been associated with a high risk of maternal, fetal, and neonatal morbidities and mortalities. The main aim of this study was to evaluate the risk factors of hypoglycemia in infants of diabetic mothers (IDMs) and to study the relationship between umbilical cord (UC) C peptide levels and the risk of developing hypoglycemia.. UC blood C-peptide and serial serum blood glucose measurements were done for all included singleton newborns born to diabetic mothers during the study period. Maternal and neonatal data such as gestational age, maternal age, maternal weight, types of diabetics and its control, maternal glycated hemoglobin (HbA1C), birth weight, Apgar score, and neonatal complete blood picture were collected.. In total, 83 IDMs met the inclusion criteria. Fifty-four (65.06%) developed hypoglycemia and 29 (34.94%) remained normoglycemic. However, there were no significant differences between hypoglycemic and normoglycemic IDMs in terms of types of maternal diabetics (P value = 0.41), its duration (P value = 0.43). The hypoglycemia peak occurred within the first 3 h of life, with 33.11 ± 8.84 mg/dl for the hypoglycemia group and 54.10 ± 6.66 mg/dl for the normoglycemic group (P value < 0.0001). Most of the babies had no hypoglycemic manifestation (96.30%). Neonates with hypoglycemia their mothers had poor diabetes control in the last trimester (HbA1C 7.09 ± 0.96%) compared to normoglycemic babies (HbA1C 6.11 ± 0.38%), (P-value < 0.0001). The mean (SD) of UC C-peptide level in hypoglycemic neonates increased to 1.73 ± 1.07 ng/ml compared to normoglycemic ones with 1.08 ± 0.81 ng/ml (P value = 0.005).. Poor diabetes control, especially in the last trimester, is associated with neonatal hypoglycemia. Increased UC C-peptide levels could be used as an early indicator for the risk of developing neonatal hypoglycemia and a predictor for babies need neonatal admission.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes, Gestational; Female; Humans; Hypoglycemia; Infant; Infant, Newborn; Mothers; Pregnancy; Pregnancy in Diabetics; Umbilical Cord

We aimed to examine prospective associations between circulating fatty acids in early pregnancy and incident gestational diabetes mellitus (GDM) among Chinese pregnant women.. Analyses were based on two prospective nested case-control studies conducted in western China (336 GDM cases and 672 matched controls) and central China (305 cases and 305 matched controls). Fasting plasma fatty acids in early pregnancy (gestational age at enrollment: 10.4 weeks(s.d., 2.0)) and 13.2 weeks (1.0), respectively) were determined by gas chromatography-mass spectrometry, and GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Groups criteria during 24-28 weeks of gestation. Multiple metabolic biomarkers (HOMA-IR (homeostatic model assessment for insulin resistance), HbA1c, c-peptide, high-sensitivity C-reactive protein, adiponectin, leptin, and blood lipids) were additionally measured among 672 non-GDM controls at enrollment.. Higher levels of saturated fatty acids (SFAs) 14:0 (pooled odds ratio, 1.41 for each 1-s.d. increase; 95% CI: 1.25, 1.59) and 16:0 (1.19; 1.05, 1.35) were associated with higher odds of GDM. Higher levels of n-6 polyunsaturated fatty acid (PUFA) 18:2n-6 were strongly associated with lower odds of GDM (0.69; 0.60, 0.80). In non-GDM pregnant women, higher SFAs 14:0 and 16:0 but lower n-6 PUFA 18:2n-6 were generally correlated with unfavorable metabolic profiles.. We documented adverse associations of 14:0 and 16:0 but a protective association of 18:2n-6 with GDM among Chinese pregnant women. Our findings highlight the distinct roles of specific fatty acids in the onset of GDM.

Topics: Adiponectin; Adult; Blood Glucose; C-Peptide; C-Reactive Protein; Case-Control Studies; China; Diabetes, Gestational; Fasting; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Leptin; Pregnancy; Prospective Studies; Risk Factors; Young Adult

Background Fibroblast growth factors (FGFs); FGF-21 and FGF-23, have been proposed to be associated with metabolic syndrome. However, data on the role of these peptides in gestational diabetes mellitus (GDM) are limited. Therefore, this study was designed to assess the association of serum FGF-21 and FGF-23 with the risk of GDM. Furthermore, we evaluated the circulation of these peptides in pregnancy and post-puerperium. Materials and methods Fifty-three pregnant subjects with GDM and 43 normal glucose tolerance (NGT) pregnant women participated in this study. Serum FGF-21 and FGF-23 were measured during pregnancy and post-puerperium. Results FGF-21 and FGF-23 were low in GDM compared to NGT during pregnancy. There were no significant differences in the level of these peptides post-puerperium. Using logistic regression, FGF-23 [odds ratio (OR) 0.70 (95% confidence interval [CI]: 0.50-0.96)] was inversely associated with GDM, so a 1-μg/mL decrease in FGF-23 levels was associated with a 1.4-fold increased risk of developing GDM and this remained statistically significant after adjustment for confounders [adjusted OR (aOR) 0.70 (95% CI: 0.50-0.98)]. There was no association of FGF-21 with the development of GDM risk. Conclusions Lower FGF-23 concentrations could be involved in the pathophysiology of GDM. FGF-21, even though associated with metabolic risk factors in pregnancy, may not be a fundamental factor in GDM.

Topics: Adiponectin; Adolescent; Adult; C-Peptide; Case-Control Studies; Diabetes, Gestational; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Follow-Up Studies; Humans; Insulin; Lipids; Middle Aged; Postpartum Period; Pregnancy; Risk; Young Adult

This study is aimed at assessing the association of previously developed indices of glucose homeostasis derived from principal component analysis (PCA) with parameters of insulin action, secretion, and beta cell function during pregnancy.. In this prospective longitudinal study, an oral glucose tolerance test was performed in sixty-seven pregnant women at two prepartum (12+0 to 22+6 and 24+0 to 28+6) and one postpartum (2 to 11 months) visits. Three principal component scores (PCS) were calculated based on measurements of glucose, insulin, C-peptide, age, and BMI to assess their association with fasting and dynamic indices of insulin action, secretion, and. PCS1 was positively associated with fasting and dynamic parameters of insulin sensitivity (Matsuda index:. PCS1 to 3 behaved similarly as compared to previous observations in nonpregnant women and were furthermore associated with the development of GDM. These findings support our hypothesis that PCS1 to 3 could be used as novel indices of glucose disposal during pregnancy.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Resistance; Insulin Secretion; Pregnancy; Principal Component Analysis; Prospective Studies; Young Adult

Previous studies that investigated the relationship between biomarkers and gestational diabetes mellitus (GDM) generally focused on individual biomarkers with significant heterogeneity in terms of the screening methodologies, diagnostic criteria for GDM and sample handling of glucose within these studies. This prospective study used an established panel of ten biomarkers to determine if they could predict the diagnosis of GDM.. Women with risk factors for GDM were recruited at their first antenatal visit. They attended for an oral glucose tolerance test at 26-28 weeks' gestation with strict preanalytical handling of glucose samples to minimise glycolysis. A fasting plasma sample taken simultaneously was stored at -80 °C and analysed in bulk for 10 biomarkers (insulin, c-peptide, glucagon, ghrelin, gastric inhibitory polypeptide (GIP), glucagon like peptide-1 (GLP-1), leptin, visfatin, resistin and plasminogen activator inhibitor-1 (PAI-1)) using the Bio-plex-pro Human Diabetes Assay.. Insulin and C-peptide levels in the third tertile were associated with the development of GDM (adjusted odds ratio (aOR) 2.6, 95 % CI 1.3-5.0, p = 0.005 and aOR 3.7, 95 % CI 1.8-7.4, p < 0.001 respectively, adjusted for maternal obesity). Elevated levels of ghrelin were associated with a lower odds of developing GDM, after adjustment for maternal obesity. However, approximately half of the women with GDM who were in the obesity category did not have insulin or c-peptide levels in the third tertile.. While three of the ten biomarkers were statistically associated with an increased risk of GDM, the large overlap in values between those with normal and abnormal glucose tolerance meant that the biomarkers (alone or in combination) were not useful clinically.

Topics: Biomarkers; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Humans; Pregnancy; Pregnancy Trimester, Second; Prospective Studies

Children and adolescents with a family history of diabetes are at increased risk of overweight, but little is known about the potentially beneficial effects of physical activity on these children. The objective of this study was to investigate the association between moderate to vigorous physical activity (MVPA) and metabolic and inflammatory risks in children and adolescents with a family background of Type 1 diabetes or gestational diabetes.. Valid MVPA measurements, made with accelerometers, were available from 234 participants (median age, 10.2 years) who had a first-degree relative with either Type 1 or gestational diabetes. Anthropometric and metabolic measurements were made and cytokines measured, and were correlated with MVPA measurements, with stepwise adjustment for confounding factors, in a cross-sectional analysis.. MVPA was negatively associated with insulin and C-peptide during challenge with an oral glucose tolerance test. MVPA was also significantly positively associated with the insulin sensitivity index, whereas no consistently significant associations were found between MVPA and BMI, blood pressure or cytokine levels.. Our findings indicate that physical activity may have beneficial effects on insulin and C-peptide metabolism in children and adolescents with a family background of diabetes, but show no evidence of a protective association with other health-related outcomes.

Topics: Adolescent; C-Peptide; Child; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes, Gestational; Exercise; Female; Germany; Glucose; Glucose Tolerance Test; Humans; Insulin; Male; Medical History Taking; Pregnancy; Risk Factors

Explore the maternal body mass index (BMI) relationship with peripheral deiodinase activity further. Examine associations between deiodinase activity, glucose, and C-peptide. Consider findings in the historical context of related existing literature.. Identify fasting plasma samples and selected demographic, biophysical, and biochemical data from a subset of 600 randomly selected non-Hispanic white women recruited in the Hyperglycemia Adverse Pregnancy Outcomes (HAPO) study, all with glucose tolerance testing [545 samples sufficient to measure TSH, free T4 (fT4), and T3]. Exclude highest and lowest 1% TSH values (535 available for analysis). Assess deiodinase activity by using T3/fT4 ratios. Among women with and without gestational diabetes mellitus (GDM), compare thyroid measurements, C-peptide, and other selected data. Examine relationships independent of GDM status between BMI and thyroid hormones and between thyroid hormones and glucose and C-peptide.. Levels of BMI, T3/fT4 ratio, and T3 were significantly higher among women with GDM (P = 0.01, 0.005, and 0.001, respectively). Irrespective of GDM status, maternal BMI was associated directly with both T3/fT4 ratio (r = 0.40, P < 0.001) and T3 (r = 0.34, P < 0.001) but inversely with fT4 (r = -0.21, P < 0.001). In turn, fasting thyroid hormone levels (most notably T3/fT4 ratio) were directly associated with maternal glucose [z score sum (fasting, 1, 2 hours); r = 0.24, P < 0.001] and with C-peptide [z score sum (fasting, 1 hour); r = 0.27, P < 0.001].. Higher BMI was associated with increased deiodinase activity, consistent with reports from elsewhere. Increased deiodinase activity, in turn, was associated with higher glucose. Deiodinase activity accounts for a small percentage of z score sum glucose.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes, Gestational; Fasting; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Iodide Peroxidase; Pregnancy; Pregnancy Outcome; Retrospective Studies; White People; Young Adult

An early identification of the risk groups might be beneficial in reducing morbidities in patients with gestational diabetes mellitus (GDM). Therefore, this study aimed to assess the biochemical predictors of glycemic conditions, in addition to fasting indices of glucose disposal, to predict the development of GDM in later stage and the need of glucose-lowering medication.. A total of 574 pregnant females (103 with GDM and 471 with normal glucose tolerance [NGT]) were included. A metabolic characterization was performed before 15⁺⁶ weeks of gestation by assessing fasting plasma glucose (FPG), fasting insulin (FI), fasting C-peptide (FCP), and glycosylated hemoglobin (HbA1c). Thereafter, the patients were followed-up until the delivery.. Females with NGT had lower levels of FPG, FI, FCP, or HbA1c at the early stage of pregnancy, and therefore, showed an improved insulin action as compared to that in females who developed GDM. Higher fasting levels of FPG and FCP were associated with a higher risk of developing GDM. Moreover, the predictive accuracy of this metabolic profiling was also good to distinguish the patients who required glucose-lowering medications. Indices of glucose disposal based on C-peptide improved the predictive accuracy compared to that based on insulin. A modified quantitative insulin sensitivity check index (QUICKIc) showed the best differentiation in terms of predicting GDM (area under the receiver operating characteristics curve [ROC-AUC], 72.1%) or need for pharmacotherapy (ROC-AUC, 83.7%).. Fasting measurements of glucose and C-peptide as well as the surrogate indices of glycemic condition could be used for stratifying pregnant females with higher risk of GDM at the beginning of pregnancy.

Topics: Adult; Age Factors; Area Under Curve; Blood Glucose; C-Peptide; Diabetes, Gestational; Fasting; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Pregnancy; Prognosis; Prospective Studies; Risk Factors; ROC Curve

To investigate the cord blood levels of adipokine and to assess their association with the fetal insulin resistance and fetal outcomes in newborns of gestational diabetic women (GDM). Methods: This cross-sectional study was performed in 40 GDM women and 40 healthy pregnant women (HPW) in the Department of Obstetrics and Gynecology at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) hospital in Puducherry, India, during the period from May 2016 to December 2017. Cord blood samples were collected at delivery from GDM and HPW groups. Cord plasma biochemical parameters such as insulin, C-peptide, adiponectin, leptin, resistin, and visfatin concentrations were measured. Leptin/adiponectin ratio (L/A), homeostasis model assessment of insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-%S) and beta cell function (HOMA2-%B) were calculated. The pregnancy outcomes such as birth weight (BW), Ponderal index and Apgar scores of the baby were measured. Results: The BW and Ponderal index of the baby were found to be significantly higher in GDM newborns compared to HPW newborns. Cord plasma insulin, C-peptide, HOMA2 -IR, visfatin, leptin, and L/A ratio were significantly higher whereas adiponectin level was lower in GDM compared to HPW. A significant positive correlation was observed between L/A ratio and fetal HOMA2-IR. Conclusion: Altered adipokine levels with increased L/A ratio was observed among the new-borns of Indian gestational diabetic mothers. There was an association between increased L/A ratio, insulin resistance and increased Ponderal index among the new-borns.

Topics: Adipokines; Apgar Score; Biomarkers; Birth Weight; C-Peptide; Cross-Sectional Studies; Diabetes, Gestational; Female; Fetal Blood; Humans; India; Infant, Newborn; Insulin; Insulin Resistance; Leptin; Nicotinamide Phosphoribosyltransferase; Pregnancy; Pregnancy Outcome; Resistin

Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (birth weight ≥90th centile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% for those with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry (

Topics: Adult; Birth Weight; Black People; Blood Glucose; C-Peptide; Caribbean Region; Diabetes, Gestational; Female; Fetal Blood; Fetal Development; Fetal Macrosomia; Genome-Wide Association Study; Genotype; Humans; Infant, Newborn; Insulin; Male; Mexican Americans; Pregnancy; White People

To measure total 25-hydroxyvitamin D levels in women in mid-pregnancy who participated in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) observational study, and to investigate the associations between levels of 25-hydroxyvitamin D and markers of gestational diabetes mellitus and lipid biomarkers.. A total of 1585 pregnant women had serum samples available for measurement. Participants were recruited from the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, at 24-32 weeks' gestation, as part of the HAPO study. 25-hydroxyvitamin D concentrations were measured using liquid chromatography tandem mass spectrometry. Glucose, C-peptide and lipid levels were previously analysed in a central laboratory. Statistical analysis was performed.. The median (interquartile range) 25-hydroxyvitamin D concentration during pregnancy was 38.6 (24.1-60.7) nmol/l, with 65.8% of women being vitamin D-deficient (≤50 nmol/l). In regression analysis, the association between maternal 25-hydroxyvitamin D and fasting plasma glucose levels approached significance [regression coefficient -0.017 (95% CI -0.034 to 0.001); P=0.06], and a significant positive association was observed between maternal 25-hydroxyvitamin D and β-cell function [1.013 (95% CI 1.001 to 1.024); P=0.031]. Maternal 25-hydroxyvitamin D level was positively associated with HDL [0.047 (95% CI 0.021 to 0.073) P≤ 0.001] and total cholesterol [0.085 (95% CI 0.002 to 0.167); P=0.044] in regression analysis.. These results indicate a high prevalence of vitamin D deficiency during pregnancy, which requires identification and treatment; however, only weak associations were observed between 25-hydroxyvitamin D level and markers of glucose and insulin metabolism. This would suggest that these are of doubtful clinical significance.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Blood Glucose; C-Peptide; Calcifediol; Cholesterol; Chromatography, Liquid; Diabetes, Gestational; Diet; Female; Humans; Northern Ireland; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Tandem Mass Spectrometry; Vitamin D; Vitamin D Deficiency; White People; Young Adult

To assess urinary C peptide creatinine ratio (UCPCR) used in a modified Matsuda equation to measure insulin sensitivity (IS) in pregnancy.. In this cross-sectional study, two IS measurements were calculated in 73 pregnant women at ~28 weeks of gestation by two separate methods using modified Matsuda equations. The first using the 0 and 120 min serum C peptide concentration during a 75 g oral glucose tolerance test (OGTT) and the second using the 0 and 120 min UCPCR values. The calculated IS measurements from the two methodologies were evaluated using Person's test and linear regression analysis. The relationship between IS. The IS measured using serum C peptide (IS. The UCPCR provides a practical methodology to assess IS and β-cell function in pregnancy.

Topics: Adult; Blood Glucose; C-Peptide; Creatinine; Cross-Sectional Studies; Diabetes, Gestational; Female; Gestational Age; Glucose Tolerance Test; Humans; Insulin Resistance; Predictive Value of Tests; Pregnancy; Prospective Studies; Regression Analysis

Many common genetic polymorphisms are associated with glycemic traits and type 2 diabetes (T2D), but knowledge about genetic determinants of glycemic traits in pregnancy is limited. We tested genetic variants known to be associated with glycemic traits and T2D in the general population for associations with glycemic traits in pregnancy and gestational diabetes mellitus (GDM). Participants in two cohorts (Genetics of Glucose regulation in Gestation and Growth [Gen3G] and Hyperglycemia and Adverse Pregnancy Outcome [HAPO]) underwent oral glucose tolerance testing at 24-32 weeks' gestation. We built genetic risk scores (GRSs) for elevated fasting glucose and insulin, reduced insulin secretion and sensitivity, and T2D, using variants discovered in studies of nonpregnant individuals. We tested for associations between these GRSs, glycemic traits in pregnancy, and GDM. In both cohorts, the fasting glucose GRS was strongly associated with fasting glucose. The insulin secretion and sensitivity GRSs were also significantly associated with these traits in Gen3G, where insulin measurements were available. The fasting insulin GRS was weakly associated with fasting insulin (Gen3G) or C-peptide (HAPO). In HAPO (207 GDM case subjects), all five GRSs (T2D, fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity) were significantly associated with GDM. In Gen3G (43 GDM case subjects), both the T2D and insulin secretion GRSs were associated with GDM; effect sizes for the other GRSs were similar to those in HAPO. Thus, despite the profound changes in glycemic physiology during pregnancy, genetic determinants of fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity discovered outside of pregnancy influence GDM risk.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Genetic Predisposition to Disease; Genotype; Glucose Tolerance Test; Humans; Insulin Resistance; Polymorphism, Single Nucleotide; Pregnancy; Risk Factors; Young Adult

Fetal hyperinsulinemia in gestational diabetes mellitus (GDM) not only is important during intrauterine life, a time when it can result in macrosomia, but also at delivery, since it can result in neonatal hypoglycemia and hyperbilirubinemia. The question is, how long before delivery does maternal glycemic control contribute to newborn insulinemia in GDM?. In 72 women with GDM, we calculated Spearman's rank (r. At an early visit (32.95 ± 1.8 weeks), r. To further reduce the risk of hypoglycemia and hyperbilirubinemia in infants born to women with GDM, besides applying a strict in-patient glucose control protocol at delivery, it is necessary to improve even more the quality of maternal glucose control during the last 2 weeks prior to delivery.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Fetal Diseases; Glycated Hemoglobin; Humans; Hyperinsulinism; Hypoglycemia; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Longitudinal Studies; Pregnancy; Prospective Studies

Topics: Adiponectin; Adult; Age Factors; Body Mass Index; C-Peptide; Diabetes, Gestational; Female; Humans; Pregnancy; Relaxin

To examine the association of connecting peptide (C-peptide) and the risks of postpartum diabetes and pre-diabetes among women with prior gestational diabetes.. A cross-sectional study of 1263 women with prior gestational diabetes was carried out at 1-5years after delivery in Tianjin, China. Logistic regression was used to assess the associations of C-peptide and the risks of diabetes and pre-diabetes.. The multivariable-adjusted odds ratios based on different levels of C-peptide (0-33%, 34-66%, 67-90%, and >90% as C-peptide cutpoints) were 1.00, 1.93 (95% confidence interval [CI] 0.85-4.39), 2.49 (95% CI 1.06-5.87), and 3.88 (95% CI 1.35-11.1) for diabetes (P for trend <0.0001), and 1.00, 1.66 (95% CI 1.18-2.36), 2.38 (95% CI 1.56-3.62) and 2.35 (95% CI 1.27-4.37) for pre-diabetes (P for trend <0.0001), respectively. Restricted cubic splines models showed a positive linear association of C-peptide as a continuous variable with the risks of type 2 diabetes and pre-diabetes. The positive association was significant when stratified by healthy weight and overweight participants.. We found a positive association between serum C-peptide levels and the risks of diabetes and pre-diabetes among Chinese women with prior gestational diabetes. Our finding suggested that elevated C-peptide levels may be a predictor of diabetes and pre-diabetes.

Topics: Adult; Biomarkers; C-Peptide; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Disease Susceptibility; Female; Glucose Intolerance; Health Surveys; Humans; Incidence; Prediabetic State; Pregnancy; Prevalence; Risk; Up-Regulation

Topics: Birth Weight; Body Mass Index; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Humans; Incidence; Infant, Newborn; Metabolic Syndrome; Overweight; Pregnancy; Pregnancy Complications; Weight Gain

Some women with gestational diabetes (GDM) present with autoantibodies associated with type 1 diabetes. These are usually directed against glutamic acid decarboxylase (GADA) and suggested to predict development of type 1 diabetes. The primary aim of this study was to investigate if GADA IgG subclasses at onset of GDM could assist in predicting postpartum development. Of 1225 women diagnosed with first-time GDM only 51 were GADA-positive. Total GADA was determined using ELISA. GADA subclasses were determined with radioimmunoassay. Approximately 25% of GADA-positive women developed type 1 diabetes postpartum. Titers of total GADA were higher in women that developed type 1 diabetes (142.1 vs 74.2u/mL; p=0.04) and they also had lower titers of GADA IgG4 (index=0.01 vs 0.04; p=0.03). In conclusion we found that that women with high titers of total GADA but low titers of GADA IgG4 were more prone to develop type 1 diabetes postpartum.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Glutamate Decarboxylase; Humans; Immunoglobulin G; Pregnancy; Risk Factors

The objective was to determine the value of clinical and analytical maternal factors to predict birth weight and umbilical cord biochemical markers of diabetic fetopathy.. Prospective evaluation of gestational diabetes pregnancies (n = 50). Maternal weight-related clinical and analytical factors were collected during pregnancy. After birth, an umbilical cord sample was taken.. Univariate linear regression analysis showed relationship between maternal weight, glycated hemoglobin (HbA1c) and insulin-like growth factor 1 (IGF1) with birth weight percentile. A significant association was found between maternal weight and cord insulin and C-peptide. Maternal HbA1c, leptin and insulin during pregnancy showed a positive linear association to cord leptin, insulin and C-peptide. In multivariate analysis models, final maternal BMI showed an independent positive association with cord C-peptide.. Maternal weight-related and analytical parameters show diagnostic value to birth weight and cord markers.

Topics: Adult; Birth Weight; Body Weight; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Fetal Diseases; Glycated Hemoglobin; Humans; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Leptin; Pregnancy

The objective of this study is to evaluate third-trimester fetal liver biometry, to predict birth weight and cord markers at birth in diabetic pregnancies.. Fetal liver biometry (liver diameters, area and volume) was obtained between 32 and 34 weeks. A blood sample was obtained from cord after birth. Receiver operating characteristic (ROC) curve models were evaluated for 75th and 90th birth weight percentile. Univariate and multivariate models were used.. All the hepatic diameters, area and sectional volume demonstrated significant differences in both birth weight percentile ⩾75 and ⩾90. All ROC curves showed significant values. A significant association was observed for all measurements with birth weight. In multivariate model, liver area volume gave significant values for predicting birth weight. Cord leptin, c-peptide and ferritin were related to fetal hepatic size.. The hepatic changes in gestational diabetes were valid to predict birth weight and metabolic changes at birth.

Topics: Adult; Biomarkers; Biometry; Birth Weight; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Fetal Weight; Fetus; Humans; Leptin; Linear Models; Liver; Multivariate Analysis; Organ Size; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Third; Prospective Studies; ROC Curve; Spain; Ultrasonography, Prenatal

Women with previous gestational diabetes mellitus (pGDM) are at increased risk of developing type 2 diabetes later in life. The aim of this study was to determine if circulating levels of metabolic hormones 12 weeks following a GDM pregnancy are associated with an increased risk of type 2 diabetes 8-10 years later.. Fasting plasma concentrations of glucose, insulin, C-peptide, ghrelin, GIP, GLP-1, glucagon, leptin, PAI-1, resistin and visfatin were measured in 98 normal glucose tolerant women, 12 weeks following an index GDM pregnancy. Women were assessed every 2 years for up to 10 years for development of overt type 2 diabetes.. After a median follow-up period of 8.7 years, 22.5% of women with a pGDM pregnancy developed type 2 diabetes. Significant risk factors for the development of type 2 diabetes were fasting plasma glucose levels >5 mmol/L during pregnancy and at 12 weeks post-pregnancy. In addition, higher C-peptide levels and lower ghrelin levels at 12 weeks post-pregnancy were also significant risk factors for the development of type 2 diabetes.. Fasting plasma glucose during pregnancy and post-partum, and post-partum C-peptide and ghrelin levels were significant risk factors for the development of type 2 diabetes in women with pGDM. This is the first report that identifies C-peptide and ghrelin as potential biomarkers for the prediction of type 2 diabetes in women with a history of GDM.

Topics: C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Ghrelin; Humans; Pregnancy

To measure the impact of a "Preventive Letter" designed to encourage the return of gestational diabetes mellitus (GDM) mothers to follow up visit after delivery, in the context of a worldwide concern about low return rates after delivery of these patients. Mothers with GDM require medical evaluation and an oral glucose tolerance test (OGTT) 6 weeks after delivery, in order to: [a] confirm remission of GDM and [b] provide advice on the prevention of type 2 diabetes. In the year 2003 we developed a "Preventive Letter", containing three aspects: [a] current treatment, [b] suggested management during labor, and [c] a stapled laboratory order for OGTT to be performed 6 weeks after delivery. The return rate after delivery was assessed in two groups of GDM mothers: [a] "Without Preventive Letter" (n = 253), and "With Preventive Letter" (n = 215). Both groups, similar with respect to age (33.0 ± 5.4 and 32.3 ± 4.9 years respectively, p = 0.166) and education time (14.9 ± 1.8 and 15.0 ± 1.8 years respectively, p = 0.494), showed a significant difference in the 1-year return rate after delivery, as assessed by the Kaplan-Meier test: 32.0 % for the group "Without Preventive Letter", and 76.0 % for the group "With Preventive Letter" (p < 0.001). The 1-year return rate after delivery of GDM mothers was 2.4 times higher in the group "With Preventive Letter" than in the group without it. We believe that this low-cost approach could be useful in other institutions caring for pregnant women with diabetes.

Topics: Adult; Amino Acids; C-Peptide; Chile; Chromium; Correspondence as Topic; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Health Promotion; Humans; Kaplan-Meier Estimate; Nicotinic Acids; Patient Compliance; Postnatal Care; Pregnancy; Schools, Medical

Early reexamination of carbohydrate metabolism via an oral glucose tolerance test (OGTT) is recommended after pregnancy with gestational diabetes (GDM). In this report, we aimed to assess the dominant patterns of dynamic OGTT measurements and subsequently explain them by meanings of the underlying pathophysiological processes. Principal components analysis (PCA), a statistical procedure that aims to reduce the dimensionality of multiple interrelated measures to a set of linearly uncorrelated variables (the principal components) was performed on OGTT data of glucose, insulin and C-peptide in addition to age and body mass index (BMI) of 151 women (n = 110 females after GDM and n = 41 controls) at 3-6 mo after delivery. These components were explained by frequently sampled intravenous glucose tolerance test (FSIGT) parameters. Moreover, their relation with the later development of overt diabetes was studied. Three principal components (PC) were identified, which explained 71.5% of the variation of the original 17 variables. PC1 (explained 47.1%) was closely related to postprandial OGTT levels and FSIGT-derived insulin sensitivity (r = 0.68), indicating that it mirrors insulin sensitivity in the skeletal muscle. PC2 (explained 17.3%) and PC3 (explained 7.1%) were shown to be associated with β-cell failure and fasting (i.e., hepatic) insulin resistance, respectively. All three components were related with diabetes progression (occurred in n = 25 females after GDM) and showed significant changes in long-term trajectories. A high amount of the postpartum OGTT data is explained by principal components, representing pathophysiological mechanisms on the pathway of impaired carbohydrate metabolism. Our results improve our understanding of the underlying biological processes to provide an accurate postgestational risk stratification.

Topics: Age Factors; Austria; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Disease Progression; Female; Glucose Tolerance Test; Humans; Incidence; Insulin; Insulin Resistance; Insulin-Secreting Cells; Linear Models; Muscle, Skeletal; Predictive Value of Tests; Pregnancy; Principal Component Analysis; Prognosis; Proportional Hazards Models; Risk Factors; Time Factors

We investigated whether obese pregnant women negative for gestational diabetes (GDM) still experience dysglycemia, as indicated by high glycated hemoglobin (Hb A1c) at delivery, and whether this impacts offspring and long-term maternal outcomes.. Data of 462 mother-child pairs of our prospective Programming of Enhanced Adiposity Risk in Childhood - Early Screening (PEACHES) cohort study were analyzed. Of 885 obese and normal-weight pregnancies prospectively enrolled after GDM testing according to the International Association of Diabetes and Pregnancy Study Groups criteria, 462 GDM-negative mothers and their offspring were investigated. We assessed associations of maternal Hb A1c at delivery with large-for-gestational-age (LGA) birth weights, cord-blood C-peptide, and biomarkers of glucose metabolism and inflammation in obese mothers followed for 2.9 years (median) postpartum (n = 42).. Cumulative distribution analysis in GDM-negative normal-weight women (n = 155) revealed that 12% had Hb A1c ≥5.7% at delivery (high Hb A1c). Among obese GDM-negative women (n = 307), 31.9% (95% CI, 26.7%-37.4%) equaled or exceeded this cutoff. In obese GDM-negative women with Hb A1c ≥5.7% (n = 98) vs <5.7% (n = 209) at delivery, newborns were more likely to be born LGA [adjusted odds ratio 3.56 (95% CI, 1.64-8.02)], and mean cordblood serum C-peptide was increased by 0.09 ng/mL (95% CI, 0.01-0.17 ng/mL). In the mothers at follow-up, mean postpartum Hb A1c, fasting glucose, high-sensitivity C-reactive protein, and fibrinogen concentrations were higher by 0.3% (95% CI, 0.1%-0.5%), 6.0 mg/dL (95% CI, 2.4-9.5 mg/dL), 6.8 mg/L (95% CI, 1.4-12.3 mg/L), and 74.9 mg/dL (95% CI, 13.6-136.2 mg/dL), respectively.. Increased Hb A1c in obese GDM-negative women at delivery indicates gestational dysglycemia, potentially conferring offspring and long-term maternal health risks. These findings should raise awareness as to careful monitoring of obese pregnancies. Measurement of Hb A1c at delivery could help select women who may need closer postpartum health checks.

Topics: Birth Weight; Blood Glucose; C-Peptide; Child, Preschool; Delivery, Obstetric; Diabetes, Gestational; Female; Fetal Blood; Glycated Hemoglobin; Humans; Infant; Infant, Newborn; Male; Obesity; Postpartum Period; Pregnancy; Pregnancy Complications; Prospective Studies

The study was undertaken to assess the selected carbohydrate parameters in children exposed to gestational diabetes in utero.. 50 children exposed to gestational diabetes were compared with 46 control subjects. Anthropometric parameters of a newborn were obtained from the medical records. In all participants height, body mass, waist and hip circumferences were measured; BMI, WHR and WHtR were calculated. Values of fasting glucose, insulin, C-peptide and HbA1c were measured and HOMA2-IR, HOMA2-S, HOMA2-B were calculated. In obese children (BMI ≥95th percentile) OGTT was performed.. The prevalence of overweight/obesity in the study group was 38%, in the control group 41% (p=0.19). Higher fasting glucose level (p=0.02) and HbA1c (p=0.00004) were found in the study group comparing to the control. In children exposed to GDM in utero a positive correlation of fasting insulin and WHR (Rs=0.31, p=0.028) as well as significantly lower HOMA2-B (p=0.03) were observed. In the study group higher HOMA2-IR (p=0.0002) and HOMA2-B (p=0.0000039) and also lower HOMA2-S (p=0.0002) were observed among participants with overweight/obesity comparing to children with normal body weight. In the study group a correlation of HOMA2-IR and SD of the birth weight was found (Rs=0.28, p=0.049).. Children exposed to gestational diabetes in utero, in spite of similar prevalence of overweight/obesity comparing to their non-exposed peers, could have higher risk of glucose intolerance and diabetes mellitus in future. Towards observed decreased insulin sensitivity and compensatory increase in insulin secretion, prevention of overweight and obesity in this group seems to be essential.

Topics: Adolescent; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Case-Control Studies; Child; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Obesity; Overweight; Pregnancy; Prenatal Exposure Delayed Effects; Prevalence; Waist-Height Ratio; Waist-Hip Ratio

Gestational diabetes mellitus (GDM) occurs in 3-5% of all pregnancies. GDM increases both maternal and fetal risks, causes fetal macrosomia, and hence increases the rates of caesarean sections and delivery complications such as shoulder dystocia. An early predictive marker and consequent early treatment could be beneficial, so amniotic fluid insulin and C-peptide have been examined in several studies. Increased amniotic fluid insulin in early amniocentesis between the 14th and 20th gestational week predicted a later GDM. A potential direct association with fetal macrosomia remains to be determined.. This retrospective study investigated amniotic fluid insulin/C-peptide from amniocenteses between 14 and 20 weeks of gestation in correlation with fetal birth weight, type of delivery, and complications. To focus on effects of fetal hyperinsulinism apart from therapeutic confounders, we included patients who did not participate in GDM screening. Insulin and C-peptide were measured in 144 samples of frozen amniotic fluid. Birth weight, type of delivery, complications, and birth injuries were noted.. Birth weights ranged from 760 g to 4410 g with a mean weight of 3424 g at an average of 40 weeks gestation. The mean amniotic fluid insulin was 4.36 U/ml and the mean C-peptide concentration was 0.076 ng/ml. There was no correlation between amniotic fluid insulin or C peptide and birth weight, type of delivery, complications, and birth injuries.. Amniotic fluid insulin and C-peptide are unsuitable as predictive marker for fetal macrosomia, type of delivery, complications, or birth injuries.

Topics: Amniocentesis; Amniotic Fluid; Biomarkers; Birth Injuries; Birth Weight; C-Peptide; Diabetes Complications; Diabetes, Gestational; Female; Fetal Macrosomia; Humans; Insulin; Iodine Radioisotopes; Obstetric Labor Complications; Pregnancy; Retrospective Studies

The objective of this feasibility study is to predict the metabolic condition in women with a history of gestational diabetes mellitus (GDM) from the shape of oral glucose tolerance test (OGTT) data. The rationale for this approach is that the evolution to a metabolic condition could be traceable in the shape of OGTT curves. 3-h OGTT data of 136 women with follow up, for a total of 401 OGTTs were analyzed. Subjects were classified as having normal (NGT) or non-normal glucose tolerance (NON-NGT), according to the American Diabetes Association criteria. The measured glucose, insulin, C-peptide data and combination of them were used to build up NGT and NON-NGT reference curves. Similarity between reference and individual OGTT-based curves was calculated using the Kullback-Leibler divergence. Our findings suggest that the shape of OGTT curves (1) contains information on the evolution to disease and (2) could be a reliable indicator to predict with high sensitivity (75%) and high specificity (69%) the metabolic condition of women with a history of GDM. In the future, the proposed shape-based prediction could be easily translated to the clinical practice, because it does not require the intervention of an operator specifically trained, thus facilitating its application in a clinical setting and ultimately empowering risk estimation, by improving/complementing the information which is currently adopted for risk stratification after pregnancy with GDM.

Topics: Blood Glucose; C-Peptide; Diabetes, Gestational; Feasibility Studies; Female; Glucose Tolerance Test; Humans; Insulin; Models, Biological; Pregnancy

We investigated postprandial glucagon-like peptide-1 (GLP-1) responses in pregnant women with and without gestational diabetes mellitus (GDM) and again following delivery when normal glucose tolerance (NGT) was re-established.. Eleven women with GDM [plasma glucose (PG) concentration at 120 min after a 75-g oral glucose tolerance test (OGTT): 10.0 ± 0.9 mM (mean ± SD); age: 31 ± 6 years; body mass index (BMI): 31.6 ± 6.4 kg/m(2) ; haemoglobin A1c (HbA1c): 5.6 ± 0.5%] and eight pregnant women with NGT (PG(120 min), OGTT : 5.7 ± 0.7 mM; age: 28 ± 3 years; BMI: 29.7 ± 5.4 kg/m(2) ; HbA1c: 5.4 ± 0.3%) were investigated with a 4-h liquid meal test during third trimester (TT) and 3-4 months postpartum (PP). All patients with GDM re-established NGT following delivery.. Pregnancy was associated with low postprandial GLP-1 responses. Patients with GDM exhibited reduced postprandial GLP-1 responses compared to their PP levels [area under curve (AUC): 5.5 ± 1.3 vs. 8.4 ± 3.2 nM × min, p=0.005], but the difference among NGT women (7.3 ± 2.8 vs. 8.8 ± 2.0 nM × min, p=0.066) was not statistically significant. Pregnancy did not influence postprandial responses of the other incretin hormone glucose-dependent insulinotropic polypeptide (GIP) in any of the groups, but GDM patients were characterized by greater postprandial GIP responses during both TT and PP compared to NGT subjects.. Pregnancy is associated with reduced postprandial GLP-1 responses (most pronounced in patients with GDM) that normalize after delivery. In contrast, postprandial GIP responses seem unaffected by pregnancy but is increased in GDM patients.

Topics: Adult; Area Under Curve; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Diabetes, Gestational; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Insulin Resistance; Insulin Secretion; Postpartum Period; Postprandial Period; Pregnancy

Abstract We explored the influence of exposure to maternal diabetes in utero on β cell decline measured by fasting C-peptide (FCP) among 1079 youth <20 years with diabetes, including 941 with type 1 and 138 with type 2 diabetes. Youths exposed to maternal diabetes had FCP levels that were 17% lower among youth with type 2 diabetes [95% confidence interval (CI): -34%, +6%] and 15% higher among youth with type 1 diabetes (95%CI: -14%, +55%) than their unexposed counterparts, although differences were not statistically significant (p=0.13 and p=0.35, respectively). Exposure to maternal diabetes was not associated with FCP decline in youth with type 2 (p=0.16) or type 1 diabetes (p=0.90); nor was the effect of in utero exposure on FCP modified by diabetes type. Findings suggest that exposure to maternal diabetes in utero may not be an important determinant of short-term β-cell function decline in youth with type 1 or type 2 diabetes.

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Insulin-Secreting Cells; Male; Pregnancy

Despite widespread use of glyburide to treat pregnancy-related hyperglycemia, the dosing regimen is based in large part on pharmacokinetic and pharmacodynamic studies in men and nonpregnant women. Like many medications used by pregnant women, adequate pharmacokinetic and pharmacodynamic data in pregnancy have been sorely lacking. This lack of information can lead to both overdosing with excessive side effects and underdosing with an inadequate therapeutic response. Both of these problems may apply to glyburide use in pregnancy. This commentary provides a pharmacologic basis for altering the glyburide administration regimen. Taking glyburide 1 hour before a meal may improve efficacy in patients with pregnancy-related hyperglycemia.

Topics: Administration, Oral; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Glyburide; Humans; Hypoglycemic Agents; Insulin; Placenta; Pregnancy

The potential reversibility of a reduced incretin effect is unclear. We investigated the incretin effect during third trimester and 3 to 4months postpartum in women with and without gestational diabetes mellitus (GDM). Ten women with GDM (plasma glucose (PG) concentration at 120min after 75g-oral glucose tolerance test (OGTT) (PG120min): 10.1±0.6mmol/l (mean±SEM)) and eight women with normal glucose tolerance (NGT; PG120min: 7.0±0.1mmol/l) were investigated on four occasions: 4h 50g-OGTT and isoglycaemic intravenous glucose infusion during third trimester and 3 to 4months postpartum. In women with GDM, the incretin effect increased significantly postpartum (31±6 vs. 56±6%, p=0.02), whereas the increment in women with NGT was insignificant (35±12 vs. 56±9%, p=0.08). Similarly, the gastrointestinal-mediated glucose disposal (GIGD=100%×(glucoseOGTT-glucoseIIGI)/glucoseOGTT) was reduced to diabetic levels in women with GDM (37±3%), but increased (p=0.030) to normal levels post partum (58±6%). GIGD did not change significantly in NGT women (48±3 vs. 57±6%, p=0.94). Women with GDM exhibit a reduced incretin effect which is fully reversible alongside the restoration of normal glucose homeostasis, whereas the reduction in incretin effect during pregnancy in women with NGT was insignificant. Our results suggest that decreased incretin effect in women with GDM is a fully reversible phenomenon.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes, Gestational; Female; Humans; Incretins; Insulin; Postpartum Period; Pregnancy; Pregnancy Trimester, Third

Large for gestational age (LAG) neonates who had been exposed to an intrauterine environment of either diabetes or maternal obesity are at increased risk of developing the metabolic syndrome. This can be explained by exposure to high glucose and insulin levels in utero which alter fetal adaptation and programming.. The aim of the study was to evaluate the onset of preclinical atherosclerosis in utero.. We measured umbilical artery wall thickness (ruWT) in the third trimester by obstetric ultrasound and umbilical artery intima-media thickness (uIMT) in pathologic specimens of umbilical cords obtained shortly after delivery and investigated the relation between these measurements and serum insulin level and C-peptide level in cord blood and assessed insulin resistance with the homeostasis model assessment of insulin resistance (HOMA-IR) in infants of diabetic mothers (IDMs), i.e. the study group, which was divided into a large for gestational age group (LGA)-IDM group and an appropriate for gestational age group (AGA)-IDM group and compared with a control group.. The LGA-IDM group had significantly higher insulin (p < 0.001), C-peptide (p = 0.018) and HOMA-IR levels (p < 0.001) compared with the AGA-IDM and control groups. The LGA-IDM group had significantly larger ruWT (p = 0.013) and uIMT (p < 0.001) compared with the AGA-IDM and the control groups. The LGA-IDM group had increased uIMT and ruWT that correlated with the severity of maternal hyperglycemia.. Measurement of ruWT in the third trimester is feasible, reproducible and strongly correlated with pathological serum insulin, C-peptide in cord blood and HOMA-IR levels.

Topics: Adult; Atherosclerosis; C-Peptide; Case-Control Studies; Chi-Square Distribution; Diabetes, Gestational; Diabetic Angiopathies; Female; Fetal Blood; Gestational Age; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Third; Prospective Studies; Tunica Intima; Tunica Media; Turkey; Ultrasonography; Umbilical Arteries

Gestational diabetes mellitus affects approximately 7% of all pregnant women. Some of these women develop autoantibodies that are generally characteristic of Type 1 diabetes. Autoantibodies targeting glutamic acid decarboxylase and tyrosine phosphatase-like protein are the most frequently reported. A recently identified autoantigen in Type 1 diabetes is zinc transporter 8. Some reports suggest that the frequency of zinc transporter 8 antibodies is as high as glutamic acid decarboxylase antibodies in Type 1 diabetes and thus a good diagnostic marker for autoimmune diabetes. There are currently no reports of zinc transporter 8 antibodies in gestational diabetes. The aim of this pilot study was to investigate the frequency of zinc transporter 8 antibodies in patients at clinical onset of gestational diabetes mellitus..   Subjects included in this pilot study were all diagnosed with gestational diabetes at Skåne University Hospital, Lund, Sweden, 2009-2010 (n = 193). Sera samples were analysed for antibodies using a commercial enzyme-linked immunosorbent assay according to the manufacturers' instructions.. We found that 19/193 patients with gestational diabetes, diagnosed in 2009-2010, were positive for at least one autoantibody. Glutamic acid decarboxylase was the most common single autoantibody (52.6%; 10/19), followed by zinc transporter 8 (21.1%; 4/19) and tyrosine phosphatase-like protein (15.8%; 3/19). Combinations of two or more antibodies were rare (10.5%; 2/19).. In this study, we found that zinc transporter 8 added 2.1% (4/193) of autoantibody positivity in women with gestational diabetes who were negative for glutamic acid decarboxylase and tyrosine phosphatase-like protein antibodies. Glutamic acid decarboxylase was still the most prevalent autoantibody in gestational diabetes, but, as zinc transporter 8 was present even in the absence of glutamic acid decarboxylase, this autoantibody could be an important independent marker of autoimmunity in gestational diabetes.

Topics: Adult; Autoantibodies; C-Peptide; Cation Transport Proteins; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Glucose Tolerance Test; Glutamate Decarboxylase; Humans; Incidence; Insulin-Secreting Cells; Pilot Projects; Pregnancy; Sweden; Zinc Transporter 8

Plasma C-peptide reflects the insulin-secretory activity of pancreatic β-cells which modulates fetal growth. Cord blood C-peptide levels were measured in women with gestational diabetes mellitus (GDM) and in women with normal glucose tolerance (NGT). Forty-one women underwent a 75-g oral glucose tolerance test (18 GDM, 23 NGT). Cord blood C-peptide (p = 0.09) and glucose levels (p = 0.08) from newborns of GDM women tended to be higher than those from NGT women. In the entire group, cord blood C-peptide correlated with maternal insulin, fasting C-peptide, insulin sensitivity, interleukin-6, weight and body mass index measured at screening (ρ from 0.34 to 0.48, all p < 0.05) and tended to correlate with offspring weight (ρ = 0.28, p = 0.08). Newborns of GDM women tended to have elevated cord blood C-peptide which correlated with maternal insulin, insulin sensitivity and anthropometric measures at diagnosis and with offspring characteristics. This suggests that insulin-secretory activity of the newborn is related to maternal metabolic parameters.

Topics: Adult; Body Mass Index; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Glucose Tolerance Test; Humans; Insulin Resistance; Interleukin-6; Metabolome; Pregnancy; Pregnancy Outcome; Quebec; Regression Analysis

To investigate the relationship between insulin resistance (IR) and subsequent gestational hypertension (GH) or preeclampsia (PE) in normoglycemic and in gestational diabetic pregnant women. Furthermore, we tested whether this association was independent of the prepregnancy body mass index (BMI).. Each participant underwent a 75-gram oral glucose tolerance test (OGTT) according to World Health Organization recommendation criteria with determination of serum glucose and C-peptide concentrations. IR was determined as a C-peptide-to-glucose ratio at the fasting (FCGR) state and at 2 h (2CGR) after load.. A total of 2,954 women were included with a singleton pregnancy, delivery at term, no chronic hypertension, and data on both glucose and C-peptide. Of these women, 183 (6.2%) developed GH and 49 (1.7%) PE. Gestational diabetes mellitus (GDM) was diagnosed in 6.0% of the participants. The FCGR and 2CGR were significantly higher in all women with GH, irrespective of their BMI, compared to the normotensive group; however, the PE and the normotensive groups had similar FCGR and 2CGR values.. The present study suggests that IR at the OGTT is associated with the later development of GH; on the other hand, it is not associated with PE. These relationships are independent of the maternal BMI.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes, Gestational; Fasting; Female; Glucose Tolerance Test; Humans; Hypertension, Pregnancy-Induced; Insulin Resistance; Pre-Eclampsia; Pregnancy

We aimed to analyze the shape of the glucose, insulin, and C-peptide curves during a 3-h oral glucose tolerance test (OGTT). Another aim was defining an index of shape taking into account the whole OGTT pattern. Five-hundred ninety-two OGTT curves were analyzed, mainly from women with former gestational diabetes, with glycemic concentrations characterized by normal glucose tolerance (n = 411), impaired glucose metabolism (n = 134), and Type 2 diabetes (n = 47). Glucose curves were classified according to their shape (monophasic, biphasic, triphasic, and 4/5-phases), and the metabolic condition of the subjects, divided according to the glucose shape stratification, was analyzed. Indices of shape based on the discrete second-order derivative of the curve patterns were also defined. We found that the majority of the glucose curves were monophasic (n = 262). Complex shapes were less frequent but not rare (n = 37 for the 4/5-phases shape, i.e., three peaks). There was a tendency toward the amelioration of the metabolic condition for increasing complexity of the shape, as indicated by lower glucose concentrations, improved insulin sensitivity and β-cell function. The shape index computed on C-peptide, WHOSH(CP) (WHole-Ogtt-SHape-index-C-peptide), showed a progressive increase [monophasic: 0.93 ± 0.04 (dimensionless); 4/5-phases: 1.35 ± 0.14], and it showed properties typical of β-cell function indices. We also found that the type of glucose shape is often associated to similar insulin and C-peptide shape. In conclusion, OGTT curves can be characterized by high variability, and complex OGTT shape is associated with better glucose tolerance. WHOSH(CP) (WHole-Ogtt-SHape-index) may be a powerful index of β-cell function much simpler than model-based indices.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin-Secreting Cells; Pregnancy; Time Factors

Improved glycaemic control during pregnancy in mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) has resulted in a marked reduction of perinatal mortality and morbidity, but the prevalence of macrosomia is usually high.. We used non-invasive anthropometric methods to estimate the body composition and the thickness of the interventricular heart septum in 18 infants of mothers with well-controlled T1DM, 10 infants of mothers with GDM and 28 infants of healthy control mothers matched for gestational age and mode of delivery.. Skinfold measurements were obtained with a Harpenden calliper within 48 h after delivery. Echocardiography was also performed to measure the thickness of the interventricular septum. Cord blood was sampled for assays of C-peptide, leptin and IGF-I.. The rates of macrosomia (gestational age-adjusted birth weight >2 standard deviation score, SDS) were 56 and 30% in infants of mothers with T1DM and GDM, respectively, compared to 10% in control infants. The body fat content was 40% (0.2 kg) higher and the interventricular heart septum thickness was increased by 20% in both groups of infants of diabetic mothers. We found no associations between maternal levels of HbA1c during pregnancy and body composition or interventricular heart septum thickness. Cord levels of C-peptide and leptin were significantly higher in infants of T1DM mothers than in control infants. Cord leptin level was associated with birth weight SDS and percent body fat in infants of T1DM mothers. IGF-I was associated with percent body fat in infants of GDM mothers and control mothers. A multiple-regression analysis showed that 50% of the variation in body weight SDS could be determined, with IGF-I, leptin and C-peptide as independent variables.. Both fat mass and cardiac septal thickness are increased in newborn infants of women with T1DM and GDM in spite of efforts to achieve good glycaemic control during pregnancy.

Topics: Adipose Tissue; Adult; Blood Glucose; Body Composition; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fetal Macrosomia; Glycated Hemoglobin; Heart Septum; Humans; Hypertrophy; Infant, Newborn; Insulin-Like Growth Factor I; Leptin; Pregnancy; Prevalence; Regression Analysis

Gestational diabetes mellitus (GDM) predisposes women to future development of Type 2 diabetes mellitus (DM2) and the two conditions share similar metabolic alterations. Recent observations suggest that a defective glucose stimulated insulin secretion by glucagon-like peptide-1 (GLP- 1) plays a role in the pathogenesis of DM2. Whether such a defect is impaired in GDM remains to be ascertained.. We have determined GLP-1 secretion in response to oral glucose tolerance test (OGTT) in GDM and normal glucose tolerance (NGT) during and after pregnancy.. 100-g-3h OGTT was performed in 12 GDM and 16 NGT women at 27.3 ± 4.1 weeks of gestation, for determination of plasma GLP-1, glucose, insulin, and C-peptide. Insulin sensitivity (ISI) and insulin secretion (first and second phase); as well as ISI-secretion index (ISSI) were also derived.. NGT and GDM women were comparable for age pre-pregnancy body mass index (BMI) and weight gain. GDM had higher glucose area under the curve (AUC): 27,575.5 ± 3448 vs 20,685.88 ± 2715 mg/dl min (p<0.01), but lower first-phase insulin secretion (993.12±367 vs 1376.61 ± 423, p<0.05) and ISSI compared to controls (3873.23 ± 1185 vs 6232.13 ± 1734, p<0.001). When we examined GLP-1 mean levels in relation to mean glycemic values, GLP-1 secretion was inappropriately low with respect to mean glycemic values in GDM compared to NGT. At follow-up, AUCGLP-1 was significantly lower in post-partum GDM compared to post-partum NGT women (2542 ± 273 vs 10,092 ± 7367 pmol·l-1·min-1, p<0.05, respectively).. Our study suggests that GLP-1 secretion in GDM women is inadequate for the prevailing glycemic levels both in pregnancy and post partum. Moreover, we cannot exclude that other important aspects of the incretin effect may be involved in GDM development.

Topics: Adult; Area Under Curve; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Middle Aged; Pregnancy; Pregnancy Complications

To understand the relationships between maternal glycemia during pregnancy and prenatal and early postnatal growth by evaluating cord C-peptide and IGF-I as mediating biomarkers in boys and girls separately.. We evaluated 342 neonates within the EDEN mother-child cohort study born to mothers without diabetes diagnosis before pregnancy. We measured maternal glycemia at 24-28 weeks of gestation and neonates' cord blood C-peptide (used as a proxy for fetal insulin) and IGF-I at birth. Reported maternal prepregnancy BMI and all measured infant weights and lengths in the 1st year were recorded. Growth modeling was used to obtain an individual growth curve for each infant in the 1st year. Path models, a type of structural equation modeling, were used for statistical analysis. Path analysis is a multivariate method associated with a graphical display that allows evaluation of mediating factors and distinguishes direct, indirect, and total effects.. Cord C-peptide at birth was positively correlated with maternal prepregnancy BMI and maternal glycemia and was higher in girls. In a path model that represented prenatal growth, there was no significant direct effect of maternal glycemia on birth weight, but the effect of maternal glycemia on birth weight was mediated by fetal insulin and IGF-I in both girls and boys. However, in girls only, higher concentrations of cord C-peptide (but not cord IGF-I or maternal glucose) were associated with slower weight growth in the first 3 months of life.. Our study underlines the role of the fetal insulin-IGF-I axis in the relationship between maternal glycemia during pregnancy and birth weight. We also show for the first time that high insulin concentration in female fetuses is associated with slower early postnatal growth. This slow, early growth pattern may be programmed by fetal hyperinsulinemia, and girls may be more susceptible than boys to its consequences.

Topics: Birth Weight; Blood Glucose; Body Height; C-Peptide; Child Development; Cohort Studies; Diabetes, Gestational; Female; Fetal Blood; Growth; Humans; Infant; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Male; Mothers; Pregnancy; Pregnancy Complications; Sex Factors

To report 12 cases of pregnancy-associated fulminant type 1 diabetes mellitus (PF) found in China from 2003 to 2010. The clinical and biochemical characteristics of these cases with PF were compared with a group of cases of child-bearing age with fulminant type 1 diabetes that was not associated with pregnancy (NPF). The clinical and biochemical characteristics of 12 PF cases were analyzed retrospectively and then compared with those characteristics of 20 NPF cases in China. The difference between Chinese and Japanese PF cases was investigated. The mean values of the characteristics from PF and NPF cases in China, including postprandial serum C-peptide concentration, plasma glucose concentration, and serum chloride were different. Compared to the 22 PF cases in Japan, the mean age of these 12 PF cases was much younger. The mean fasting and postprandial serum C-peptide concentration level were lower, and the mean HbA1c levels was higher in 12 PF cases in China. Eight of 12 PF cases in China developed the disease during pregnancy. Other four PF case developed the disease within 2 weeks after delivery. 12 PF cases in China showed more severe beta-cell destruction, the prognosis of their fetuses was extremely poor.

Topics: Acidosis; Adolescent; Adult; Age of Onset; Blood Glucose; C-Peptide; China; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Middle Aged; Pregnancy; Retrospective Studies; Young Adult

There is growing evidence that osteocalcin, an osteoblast-derived protein locally acting on bone formation, can increase insulin secretion as well as insulin sensitivity and thus prevent the development of obesity and diabetes in experimental animals. In humans, osteocalcin has been reported to be decreased in patients with type 2 diabetes. Because gestational diabetes mellitus (GDM) can serve as a model of pre-type 2 diabetes, the aim of this study was to investigate osteocalcin in GDM.. Osteocalcin measurement and an oral glucose tolerance test were performed in 78 pregnant women (26 women had GDM and 52 women had normal glucose tolerance [NGT] during pregnancy; women were matched for age and BMI) and in 34 women postpartum.. During pregnancy osteocalcin was significantly higher in the women with GDM than in the women with NGT (15.6 +/- 6.4 vs. 12.6 +/- 4.0 ng/ml; P < 0.015), whereas no difference was observed between the two groups at 12 weeks postpartum (36.2 +/- 10.2 vs. 36.2 +/- 13.0 ng/ml), when osteocalcin was found to be increased compared with the level in the pregnant state in all women (+145 +/- 102% in GDM vs. +187 +/- 119% in NGT; P < 0.0001). Moreover, osteocalcin showed a significant correlation with basal and total insulin secretion in the whole study group (R = 0.3, P < 0.01).. In GDM osteocalcin was higher and thus less restrained than in women with NGT during pregnancy and furthermore correlated with insulin secretion parameters. Therefore, it could be hypothesized that osteocalcin can enhance insulin secretion in insulin-resistant states; alternatively an effect of hyperinsulinemia on osteocalcin secretion cannot be excluded.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Immunoassay; Insulin; Insulin Secretion; Osteocalcin; Pregnancy

Studies in adipose tissue and skeletal muscle suggest that impaired insulin action is due to defects in the insulin signaling pathway and may play a role in the pathophysiology of insulin resistance associated with gestational diabetes mellitus (GDM) and obesity. The present study tested the hypothesis that endogenous expression levels in the human term placenta of insulin signaling components are altered in placental tissue from GDM women in comparison with normal controls and maternal obesity.. Placental tissue was collected from normal, diet-controlled GDM, and insulin-controlled GDM in both non-obese and obese women (n=6-7 per group). Western blotting and quantitative RT-PCR was performed to determine the level of expression in the insulin signaling pathway.. There was a significant increase in insulin receptor (IR) substrate (IRS)-1 protein expression with a concurrent decrease in IRS-2 protein expression in non-obese women with insulin-controlled GDM compared with diet-controlled GDM and normal controls. Furthermore, a decrease in both protein and mRNA expression of phosphatidyl-inositol-3-kinase (PI3-K) p85alpha and glucose transporter (GLUT)-4 was observed in non-obese and obese women with insulin controlled GDM compared with normal controls. When comparing non-obese to obese patients, significant decreases in mRNA expression of IR-beta, PI3K p85alpha and GLUT-4 was found in obese patients.. Our results suggest that post receptor defects are present in the insulin signaling pathway in placenta of women with pregnancies complicated by diabetes and obesity. In addition, expression studies demonstrate post receptor alterations in insulin signaling possibly under selective maternal regulation and not fetal regulation.

Topics: Adult; Blotting, Western; C-Peptide; Cell Membrane; Cohort Studies; Diabetes, Gestational; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; Glucose; Glucose Transporter Type 4; Humans; Immunohistochemistry; Indicators and Reagents; Insulin; Obesity; Phosphatidylinositol 3-Kinases; Placenta; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction

Topics: Biomarkers; Birth Weight; C-Peptide; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Infant, Newborn; Length of Stay; Pregnancy; Pregnancy Outcome

To study fasting biologically active serum ghrelin (RIA) and resistin (ELISA) levels in different trimesters of pregnancy (HP, n=45, 15 in each) and in gestational diabetes mellitus (GDM, n=30) compared to non-pregnant healthy women (NP, n=40) in correlation with TNF-alpha, soluble (s)TNF-receptor (R)-1, -2, leptin (ELISA), C-peptide (Cp, RIA) and Cp/blood glucose ratio (bg).. Cross-sectional case control study.. Acylated ghrelin levels were significantly increased (p<0.0001) in the 2nd (377+/-38pg/ml, X+/-S.D.) and decreased in the 3rd trimester (252+/-36) and in GDM (226+/-21) compared to NP controls (309+/-20) and HP women in the 1st trimester (314+/-41). Serum resistin levels were higher in the 1st (8.5+/-2.6ng/ml), 2nd (10.2+/-2.1) and 3rd (13.1+/-3.6) trimesters of pregnancy and in GDM (15.7+/-3.5) than in NP controls (6.5+/-2.3). Significant (p<0.01) negative linear correlations were found among fasting serum ghrelin and body mass index (BMI), the fasting C-peptide (Cp) level, C-peptide/blood glucose (Cp/bg) ratio, TNF-alpha, soluble (s)TNFR-2, leptin and resistin concentrations in both, HP and GDM groups. Significant positive correlations were observed between serum acylated ghrelin and adiponectin, and between BMI and fasting Cp, Cp/bg, TNF-alpha, sTNFR-1, -2 and leptin levels in both pregnant groups.. Increased fasting serum acylated ghrelin concentrations in the 2nd trimester may associate with weight gain during pregnancy. Hyperresistinemia may also be associated with the pregnancy-induced insulin resistance. A negative regulatory feed-back mechanism between resistin, TNF-alpha and ghrelin may be hypothesized.

Topics: Blood Glucose; C-Peptide; Case-Control Studies; Cross-Sectional Studies; Diabetes, Gestational; Female; Ghrelin; Humans; Insulin Resistance; Leptin; Multivariate Analysis; Peptide Hormones; Pregnancy; Pregnancy Trimesters; Receptors, Tumor Necrosis Factor; Resistin; Tumor Necrosis Factor-alpha

Obesity and type 2 diabetes are worldwide health issues. The present paper investigates prenatal and postnatal pathways to obesity, identifying different metabolic outcomes with different effects on insulin sensitivity and different underlying mechanisms involving key components of insulin receptor signaling pathways. Pregnant Wistar rats either were fed chow ad libitum or were undernourished throughout pregnancy, generating either control or intrauterine growth restricted (IUGR) offspring. Male offspring were fed either standard chow or a high-fat diet from weaning. At 260 d of age, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and other metabolic parameters were measured. As expected, high-fat feeding caused diet-induced obesity (DIO) and insulin resistance. Importantly, the insulin sensitivity of IUGR offspring was similar to that of control offspring, despite fasting insulin hypersecretion and increased adiposity, irrespective of postnatal nutrition. Real-time PCR and Western blot analyses of key markers of insulin sensitivity and metabolic regulation showed that IUGR offspring had increased hepatic levels of atypical protein kinase C zeta (PKC zeta) and increased expression of fatty acid synthase mRNA. In contrast, DIO led to decreased expression of fatty acid synthase mRNA and hepatic steatosis. The decrease in hepatic PKC zeta with DIO may explain, at least in part, the insulin resistance. Our data suggest that the mechanisms of obesity induced by prenatal events are fundamentally different from those of obesity induced by postnatal high-fat nutrition. The origin of insulin hypersecretion in IUGR offspring may be independent of the mechanistic events that trigger the insulin resistance commonly observed in DIO.

Topics: Animal Feed; Animals; Blood Glucose; C-Peptide; Caloric Restriction; Diabetes, Gestational; Dietary Fats; Female; Fetal Growth Retardation; Fetal Nutrition Disorders; Glucose Clamp Technique; Glycogen; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Lipid Metabolism; Liver; Male; Muscle, Skeletal; Obesity; Phosphoenolpyruvate Carboxykinase (GTP); Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar

We examined the pathogenesis of gestational diabetes mellitus (GDM) in a large Dutch multiethnic cohort.. We used a 2-step testing procedure to stratify 2031 consecutive pregnant women into 4 groups according to American Diabetes Association criteria: (a) normal glucose tolerance (NGT), (b) mild gestational hyperglycemia (MGH), (c) GDM without early postpartum diabetes within 6 months of delivery (GDM1), and (d) GDM with early postpartum diabetes (GDM2). Antepartum and postpartum clinical characteristics and measures of glucose tolerance were documented.. Overall, 1627 women had NGT, 237 had MGH, 156 had GDM1, and 11 had GDM2. Prepregnancy body mass index values progressively increased from NGT to MGH to GDM1. The fasting plasma glucose concentration, the 100-g oral glucose tolerance test (OGTT) area under the curve, and the mean glucose concentration during the OGTT all increased progressively among the 4 groups. The fasting C-peptide concentration displayed an inverted-U pattern, with a maximum at a mean plasma glucose concentration during the OGTT of 9.6 mmol/L in the transition from GDM1 to GDM2. The fasting C-peptide/glucose concentration ratio decreased by 42% in GDM patients compared with NGT patients, whereas the ratios in MGH and NGT women were similar.. Progressive metabolic derangement of glucose tolerance 1st detected during pregnancy mimics the pathogenesis of type 2 diabetes. In addition, our results imply an impaired basal glucose effectiveness in the early prediabetic state. To explain the parallel in both metabolic derangements, we postulate that GDM, like type 2 diabetes, is attributable to the same inherited mitochondrial dysfunction.

Topics: Adult; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Mitochondria; Netherlands; Pregnancy

Former gestational diabetes (fGDM) constitutes a risk condition for the development of Type 2 diabetes. Former gestational diabetes is often characterized by obesity and hyperglycaemia, which may be concomitant and independent risk factors.. To assess insulin sensitivity and beta-cell function in fGDM uncomplicated by obesity and hyperglycaemia, we studied 24 lean fGDM women and 23 control women matched for age (30.7 +/- 0.7 years, whole cohort), body mass index (22.2 +/- 0.3 kg m(-2)), and indistinguishable for plasma glucose both at fasting and at 120 min. Several insulin sensitivity and beta-cell function indices were computed: homeostasis model assessment insulin resistance index (HOMA-R), insulin sensitivity index derived from an oral glucose tolerance test (OGIS), insulinogenic index, other empirical indices of insulin secretion and beta-cell function, and indices obtained using a beta-cell model.. Though the majority of indices, and in particular insulin sensitivity (HOMA-R: 1.35 +/- 0.13 vs. 1.65 +/- 0.14; OGIS: 492.7 +/- 6.3 vs. 496.4 +/- 9.4 mL min(-1) m(-2)), were not significantly different in the two groups, the beta-cell glucose sensitivity obtained by modelling analysis was lower in fGDM (108 +/- 14 vs. 165 +/- 22 pmol min(-1) m(-2) mM(-1), P = 0.031).. Impairment of beta-cell glucose sensitivity may be an intrinsic risk factor in fGDM independently of obesity and hyperglycaemia. Furthermore, we have shown that modelling analysis, in contrast to the empirical parameters, may be able to detect early beta-cell alterations in fGDM women.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Dose-Response Relationship, Drug; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Models, Biological; Pregnancy; Thinness

To compare the degree of insulin resistance in women with gestational diabetes mellitus (GDM) who do and do not develop preeclampsia.. We conducted a prospective cohort study of initially normotensive women with GDM who underwent oral glucose tolerance tests (OGTTs), intravenous glucose tolerance tests (IVGTTs), and glucose clamp studies in the early third trimester (n = 150) and 15 months postpartum (n = 89). After delivery, the women were categorized as nonpreeclamptic or preeclamptic (systolic blood pressure [SBP] > or = 140 mmHg, diastolic blood pressure [DBP] > or = 90 mmHg, and at least >1+ proteinuria or >300 mg/24 h). Metabolic parameters between the groups were compared by chi2 or Fisher's exact tests and ANOVA with P < 0.05 as significant.. A total of 29 women (19%) developed preeclampsia, which was mild in 21 and severe in 8 women. At entry, there were no differences in age, weight indexes, and glycemic measures between the nonpreeclamptic and preeclamptic groups. Those with preeclampsia were significantly taller (61.5 +/- 2.4 vs. 60.1 +/- 2.3 in, P = 0.003), were more often nulliparous (38 vs. 16%, P = 0.01), and had higher entry SBP (112 +/- 10 vs. 103 +/- 6.9 mmHg, P < 0.0001) and DBP (64 +/- 9 vs. 59 +/- 5 mmHg, P = 0.002). No significant differences between the groups were found in any measures of the OGTT glucose levels, insulin sensitivity index, glucose effectiveness, acute response to glucose, or disposition index, nor were there any differences found in the euglycemic clamp measures of basal or steady-state levels of glucose, insulin, free fatty acid, hepatic glucose output, peripheral glucose clearance, C-peptide, or glucagon. At 15 months postpartum, blood pressure levels remained significantly higher in the preeclamptic group (n = 19) compared with the nonpreeclamptic group (n = 70). No differences in any glycemic or insulin resistance measures were found.. Women with GDM were uniformly insulin resistant. Those who developed preeclampsia, when compared with those who remained nonpreeclamptic, were not more insulin resistant in either the third trimester or 15 months postpartum. However, women who developed preeclampsia had blood pressure levels that were significantly higher, although still in the normal range, than those of women who remained nonpreeclamptic.

Topics: Adult; Blood Glucose; C-Peptide; Cohort Studies; Diabetes, Gestational; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Longitudinal Studies; Parity; Postpartum Period; Pre-Eclampsia; Pregnancy

Excessive secretion of the insulin precursor proinsulin, as manifested by an increased serum proinsulin-to-insulin ratio, has been associated with beta-cell dysfunction. In women with gestational diabetes mellitus (GDM), previous studies of the proinsulin-to-insulin ratio have yielded conflicting results, despite the presence of beta-cell dysfunction. The interpretation of the proinsulin-to-insulin ratio, however, may be confounded by the variable effects of hepatic insulin extraction. Thus, we sought to determine whether GDM is characterized by relative hyperproinsulinemia as measured by the proinsulin-to-C-peptide ratio, an alternate measure of proinsulin secretion that is not affected by hepatic insulin extraction.. Serum proinsulin, C-peptide, and insulin were measured in a cross-sectional study of 180 women undergoing oral glucose tolerance tests (OGTTs) in the late second or early third trimester. Based on the OGTT, participants were stratified into three groups: 1) normal glucose tolerance (NGT; n = 93), 2) impaired glucose tolerance (IGT; n = 39), and 3) GDM (n = 48). Insulin sensitivity (IS) was measured using the IS(OGTT) index of Matsuda and DeFronzo, which has been previously validated in pregnant women.. There were no significant differences in mean fasting proinsulin-to-C-peptide ratio between the three glucose tolerance groups (NGT, 0.024; IGT, 0.022; GDM, 0.019; P = 0.4). Furthermore, adjustment for age, weeks' gestation, prepregnancy BMI, ethnicity, previous GDM, and family history of diabetes did not reveal any association between the proinsulin-to-C-peptide ratio and glucose tolerance status. Using Spearman univariate correlation analysis, fasting proinsulin-to-C-peptide ratio was significantly correlated with IS(OGTT) (r = 0.29, P < 0.0001) and inversely related to the homeostasis model assessment of insulin resistance (r = -0.36, P < 0.0001) and prepregnancy BMI (r = -0.23, P < 0.005). On multiple linear regression analysis, IS(OGTT) emerged as the strongest independent correlate of the dependent variable proinsulin-to-C-peptide ratio. Furthermore, after adjustment for potential covariates, a stepwise decrease in proinsulin-to-C-peptide ratio was observed per decreasing tertile of IS(OGTT) (trend P = 0.0019), consistent with enhanced efficiency of proinsulin processing (i.e., reduced proinsulin-to-C-peptide ratio) as insulin resistance increases.. GDM is not independently associated with hyperproinsulinemia as measured by the proinsulin-to-C-peptide ratio. Instead, in pregnant women, increased insulin resistance is associated with decreased proinsulin-to-C-peptide ratio, independently of glucose tolerance status. These data suggest that relative proinsulin secretion in late pregnancy is primarily related to insulin resistance and does not necessarily reflect beta-cell function.

Topics: Adult; Area Under Curve; Blood Glucose; C-Peptide; Cross-Sectional Studies; Diabetes, Gestational; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Proinsulin

Insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-1) may be important determinants of glucose homeostasis. We examined the association between circulating concentrations of IGF-1, IGFBP-1 in early pregnancy and development of gestational diabetes mellitus (GDM).. Maternal plasma (collected at 13 weeks) IGF-1, IGFBP-1, and C-peptide were measured using immunoassay. Relative risks (RR) and 95% CIs were calculated.. The percentage of the cohort that developed GDM was 5.8% (n = 804). Free IGF-1 and IGFBP-1 were inversely associated with GDM risk, while C-peptide was positively associated with GDM risk (P for trend test < .05). Women with free IGF-1 > or = 1.08 ng/mL experienced a 69% reduced risk of GDM (CI 0.12-0.75) compared with women having concentrations < 0.80 ng/mL. There was a 57% reduced risk of GDM among women with IGFBP-1 > or = 68.64 ng/mL (RR = 0.43, CI 0.18-1.05). Women with C-peptide > or = 3.00 ng/mL experienced a 2.28-fold increased risk of GDM (CI 1.00-5.19) compared with women who had concentrations < 1.45 ng/mL.. These associations may help to further elucidate the pathologic process of GDM.

Topics: Adult; C-Peptide; Diabetes, Gestational; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Pregnancy; Risk; Risk Factors

The Trp64Arg polymorphism of beta(3)-adrenergic receptor (ADRB3) has been reported to be associated with insulin resistance and gestational diabetes mellitus (GDM). The objective of this study is to investigate whether the ADRB3 Arg variant confers susceptibility to GDM in a Taiwanese population. A total of 299 pregnant women (mean +/- SD, 31.1 +/- 4.2 years) was recruited. Two-hour, 75-g oral glucose tolerance tests (OGTT) were conducted at 24 to 31 weeks gestation (28.3 +/- 1.6 weeks). Forty-one GDM subjects and 258 controls with normal glucose tolerance (NGT) level were genotyped for the ADRB3 Trp64Arg polymorphism. The genotype distribution and allele frequency of ADRB3 did not significantly differ between GDM and NGT subjects (9.8% v 14.5%). Body weight gain during pregnancy was not different between ADRB3 genotypes. However, the GDM subjects with the Arg64 variant had higher fasting (P =.04) and postload 120 minutes (P =.03) insulin levels as compared with the GDM subjects with the Trp64Trp allele. In all subjects, the women with the Arg64 allele (n = 76) had significantly higher level of insulin secretion (the ratio of Deltainsulin(60)/Deltaglucose(60)) during OGTT than those without (n = 223) (P =.03) despite similar plasma levels of glucose and insulin in both genotypes. Our results indicated that the ADRB3 Trp64Arg variant is not related to the development of GDM and has no effect on obesity during pregnancy in a Taiwanese population. However, ADRB3 polymorphism might be a possible determinant of insulin resistance.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes, Gestational; DNA; Female; Gene Frequency; Genotype; Glucose Tolerance Test; Humans; Insulin; Polymorphism, Genetic; Pregnancy; Receptors, Adrenergic, beta-3; Taiwan

In pregnancies complicated by gestational diabetes mellitus (GDM) an increased demand for insulin is not met due to beta-cell dysfunction. An Ala/Val polymorphism at codon 98 of the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene has been associated with decreased serum insulin and C-peptide responses during an oral glucose tolerance test (OGTT) in glucose-tolerant subjects. The aims of the present study were to evaluate the influence of the polymorphism on the serum insulin and C-peptide responses to an OGTT in glucose-tolerant women with and without previous GDM and to investigate if this polymorphism is associated with GDM.. The Ala/Val98 polymorphism was measured in 376 women of Danish origin with previous GDM, and in 724 age-matched and 310 middle-aged glucose tolerant women using polymerase chain reaction-restriction fragment length polymorphism.. The allelic frequency of the Ala/Val98 polymorphism was 0.043 [95% confidence interval (CI) 0.028, 0.057] in women with previous GDM vs. 0.037 (95% CI 0.028, 0.047) in age-matched and 0.039 (95% CI 0.024, 0.054) in middle-age women. Among 117 glucose-tolerant women with previous GDM, 10 carriers of the Ala/Val98 polymorphism had a non-significant 27% and 22% reduction in serum C-peptide and insulin levels, respectively, at 30 min during an OGTT. Seventy-eight control subjects carrying the Ala/Val98 polymorphism had a 10% (P = 0.001) and 16% (P = 0.004) reduction in serum C-peptide and insulin levels, respectively, compared with 956 Ala/Ala control subjects.. The Ala/Val polymorphism at codon98 of HNF-1alpha is not associated with GDM in Danish women. However, the codon 98 variant is associated with a significant impairment of serum insulin and C-peptide responses during an OGTT in glucose-tolerant women without previous GDM.

Topics: Adult; C-Peptide; Case-Control Studies; Diabetes, Gestational; DNA-Binding Proteins; Female; Glucose Tolerance Test; Hepatocyte Nuclear Factor 1; Hepatocyte Nuclear Factor 1-alpha; Humans; Insulin; Islets of Langerhans; Nuclear Proteins; Polymorphism, Genetic; Pregnancy; Statistics, Nonparametric; Transcription Factors

To investigate serum concentration of tumor necrosis factor (TNF)-alpha and its correlation with insulin resistance in pregnant women with gestational diabetes mellitus (GDM).. Enzyme-linked immunosorbent assay was used to measure the fasting serum TNF-alpha levels of 42 women with GDM (28 approximately 39 gestational weeks), and 40 cases of normal pregnant women in the third trimester. Fasting plasma glucose, insulin, C-peptide and glycosylated hemoglobin (HbA1c) were also measured at the same time. Insulin sensitive index (ISI) was calculated.. (1) Significantly elevated serum TNF-alpha was found in the women with GDM (5.2 +/- 1.6) ng/L as compared with the healthy pregnant women in third trimester (4.5 +/- 0.5) ng/L (P < 0.01); ISI between the two groups was significantly different, (-4.3 +/- 0.5) and (...3.8 +/- 0.3) (P < 0.01). (2) fasting plasma glucose, insulin, C-peptide, HbA1c in GDM group were (5.5 +/- 0.7) mmol/L, (13.4 +/- 3.8) mU/L, (1.6 +/- 0.4) nmol/L, (5.6 +/- 0.5)%, being significantly higher than those in the normal pregnant women (P < 0.01 or P < 0.05). (3) Significant negative linear correlation was revealed between TNF-alpha and ISI (r = -0.703, P < 0.01), and positive linear correlations between TNF-alpha and plasma glucose, C-peptide, and HbA1c were found (r = 0.512, 0.629, 0.386); but no correlation between TNF-alpha and insulin was found in GDM group. In normal group the correlation between ISI and TNF-alpha was also found (r = -0.390, P < 0.05), but less significant than that in the GDM group.. Fasting plasma TNF-alpha levels in pregnant women with GDM is significantly higher than in normal pregnant women. A negative relationship between TNF-alpha and insulin sensitivity index is found in GDM, suggesting increased TNF-alpha may contribute to insulin resistance in pregnant women with gestational diabetes.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Fasting; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Pregnancy; Tumor Necrosis Factor-alpha

To investigate the influence of obstetric factors and indices of maternal metabolic control on perinatal morbidity and mortality, 88 diabetic pregnant Sudanese women (type 1, n=38; type 2, n=31; gestational diabetes, n=19) and 50 non-diabetic pregnant control women were studied. The mean fasting blood glucose was 11.1+/-2.8 mmol/l and the mean HbA(1c) at booking interview was 8.8+/-2.1% in the diabetic women. Pregnancy complications such as Caesarean sections, urinary tract infections, pregnancy-induced hypertension and intrauterine foetal death were higher among diabetic compared with control women (P<0.0001) and varied with the type of diabetes. Infants of diabetic mothers had a higher incidence of neonatal complications than those of non-diabetic women (54.4% vs. 20.0%; P<0.0001). Infants without complications and who were born to diabetic mothers had better Apgar scores at 5 min (9.8+/-0.5 vs. 8.9+/-1.6; P<0.01) and lower cord C-peptide when compared to infants with complications (P<0.05). In conclusion, the prevalence of maternal and neonatal complications among Sudanese diabetic women and their infants is high. Maternal hyperglycaemia is an important factor affecting maternal wellbeing and neonatal morbidity and mortality.

Topics: Adult; Blood Glucose; C-Peptide; Demography; Diabetes, Gestational; Female; Gestational Age; Glycated Hemoglobin; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Pregnancy in Diabetics; Sudan; Surveys and Questionnaires

Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes.. One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study.. Serum AHSG was determined by radial immunodiffusion.. We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns.. AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

Topics: alpha-2-HS-Glycoprotein; Blood Glucose; Blood Proteins; Body Height; Body Weight; C-Peptide; Cephalometry; Diabetes, Gestational; Female; Gestational Age; Humans; Infant, Newborn; Insulin Resistance; Leptin; Pregnancy; Tumor Necrosis Factor-alpha

The contribution of the tumor necrosis factor (TNF) system and leptin was studied in insulin resistance and neonatal development during the course of normal pregnancy and gestational diabetes mellitus (GDM). Thirty patients with GDM and their neonates (n = 30), 35 healthy pregnant women (15 in the first, nine in the second and 11 in the third trimester) and their neonates (n = 20), and 25 healthy matched non-pregnant women participated in the study. Significantly elevated levels of maternal TNF-alpha, sTNF receptor (R)-1 and R-2, leptin (detected by enzyme-linked immunosorbent assay) and fasting C-peptide (measured by radioimmunossay and raised body mass index (BMI) were found in GDM patients and in the third trimester of normal pregnancies. TNF-alpha, sTNFR-2, C-peptide, leptin concentrations and BMI positively correlated with each other in GDM. An inverse relationship between the body length, head circumference and body weight of the newborns, and maternal TNF-alpha, leptin and C-peptide concentrations was shown in GDM. In healthy pregnancies the maternal serum leptin level was in a negative linear correlation with the head circumference of the newborns. In conclusion, increased TNF-alpha and leptin levels may contribute to insulin resistance in GDM and in the third trimester of normal pregnancy and may negatively influence the anthropometric parameters of the newborns.

Topics: Adult; Anthropometry; Antigens, CD; Birth Weight; Body Height; C-Peptide; Cephalometry; Diabetes, Gestational; Female; Humans; Infant, Newborn; Insulin Resistance; Leptin; Pregnancy; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Tumor Necrosis Factor-alpha

The purpose of this study was to identify independent determinants of mild gestational hyperglycemia (MGH) and gestational diabetes mellitus (GDM) and to assess the correlation between fasting glucose and C-peptide levels among control, MGH, and GDM women.. A total of 1,022 consecutive women were evaluated with a 1-h 50-g glucose challenge test (GCT) at between 16 and 33 weeks of gestation. Women with a capillary whole-blood glucose > or =7.8 mmol/l in the GCT underwent a 3-h 100-g oral glucose tolerance test (OGTT). On the basis of a positive GCT, the women with a positive OGTT were classified as GDM, whereas the women with a negative OGTT were classified as MGH. The following data were collected for all women: age, prepregnancy BMI, ethnicity, clinical and obstetric history, pregnancy outcome, and C-peptide level.. A total of 813 women (79.6%) were normal, 138 (13.5%) had MGH, and 71 (6.9%) had GDM. There was a stepwise significant increase in mean fasting glucose (3.6 +/- 0.4, 3.9 +/- 0.4, and 4.7 +/- 0.7 mmol/l, respectively) and C-peptide level (0.60 [0.1-2.4], 0.86 [0.3-2.0], and 1.00 [0.5-1.6] nmol/l, respectively) among the three diagnostic groups. Maternal age, non-Caucasian ethnicity, and prepregnancy BMI were associated with GDM, whereas only maternal age and prepregnancy BMI were associated with MGH. A positive correlation between levels of fasting glucose and C-peptide was found in control women (r = 0.39 [95% CI 0.31-0.46]). A similar result was seen in MGH women (r = 0.38 [95% CI 0.23-0.52]), whereas the correlation between fasting glucose and C-peptide was nearly lost in GDM women (r = 0.14 [CI -0.09 to 0.36]). The fasting C-peptide-to-glucose ratio was reduced by 60% in GDM patients versus control subjects and MGH patients (0.41 +/- 0.25 vs. 0.70 +/- 0.20 and 0.73 +/- 0.23, P < 0.001).. Of the well-known independent determinants of GDM, only maternal age and prepregnancy BMI were associated with MGH. It appears that additional factors promoting loss of beta-cell function distinguish MGH from GDM. One of these factors appears to be ethnicity.

Topics: Adult; Apgar Score; Blood Glucose; Body Mass Index; C-Peptide; Diabetes, Gestational; Ethnicity; Family; Fasting; Female; Gestational Age; Glucose Tolerance Test; Humans; Hyperglycemia; Hypertension; Infant, Newborn; Maternal Age; Netherlands; Parity; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Pregnancy, High-Risk; Reference Values; White People

The aim of the study was to investigate the pathophysiological role of the tumor necrosis factor (TNF) system in insulin resistance in patients with gestational diabetes (GDM) and during the course of normal pregnancy.. Thirty women with GDM (16-39 gestational weeks), 35 healthy pregnant women (15 first, nine second and 11 third trimester) and 25 healthy age-matched non-pregnant women were studied. Serum TNF-alpha, and its soluble receptors 1 and 2 (sTNFR-1 and -2) were measured.. In non-diabetic pregnant women in the third trimester all measures were significantly higher (P<0.05 or less) than in the first trimester and in non-pregnant women (BMI 27.6 +/- 4.1 (+/- S.D.), 24.1 +/- 2.6, 22.4 +/- 2.4 kg/m(2)), serum TNF-alpha (4.6 +/- 0.6, 4.1 +/- 0.4, 4.1 +/- 0.4 ng/l), sTNFR-1 (2.7 +/- 0.9, 2.0 +/- 0.5, 2.0 +/- 0.1 microg/l), sTNFR-2 (5.6 +/- 2.6, 4.6 +/- 2.1, 3.3 +/- 0.2 microg/l), C-peptide (3.1 +/- 1.7, 1.1 +/- 0.7, 1.1 +/- 0.8 microg/l), and C-peptide:blood glucose ratio (0.6 +/- 0.2, 0.2 +/- 0.1, 0.2 +/- 0.1 microg/mmol). In GDM these measures were even higher than in any subgroup of healthy pregnant women (BMI) (33.4 +/- 6.4 kg/m(2), TNF-alpha) (6.3 +/- 0.6 microg/l), sTNFR-1 (3.0 +/- 0.5 microg/l), sTNFR-2 (10.0 +/- 6.9 microg/l, C-peptide 6.0 +/- 2.7 microg/l, C-peptide:blood glucose ratio: 1.2 +/- 0.5 microg/mmol, P<0.01). Significant (P<0.01) positive linear correlations were found in gestational diabetic and non-diabetic women between serum TNF-alpha, C-peptide levels, and BMI. In gestational diabetic women, in multivariate analysis studying the dependency of C-peptide only BMI remained significant (r(2)=0.67, P=0.01).. Our observation emphasizes the obesity-related component of insulin resistance driven by adipocytokines, such as TNF-alpha and its receptors during the course of normal pregnancy and GDM.

Topics: Antigens, CD; Blood Glucose; Body Mass Index; C-Peptide; Diabetes, Gestational; Female; Fructosamine; Glycated Hemoglobin; Health Status; Humans; Insulin Resistance; Pregnancy; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Reference Values; Regression Analysis; Tumor Necrosis Factor-alpha

We have determined prehepatic insulin secretion rates (ISRs) in seven patients with gestational diabetes mellitus (GDM) and in eight age- and weight-matched nondiabetic pregnant women during late gestation (third trimester) and again postpartum. Plasma glucose concentrations were raised to approximately 8.9 mM with iv glucose (hyperglycemic clamping), and ISRs were determined by deconvolution of peripheral C-peptide concentrations using C-peptide kinetic parameters that were obtained in every patient during late gestation and again postpartum. Plasma insulin levels were measured by RIA with an antibody with minimal (<0.2%) cross-reactivity with proinsulin. During late gestation, women with GDM were more insulin resistant than nondiabetic controls and had significantly lower ISRs (689 vs. 849 pmol/min, P < 0.05) and glucose uptake rates (30.6 vs. 49.4 micromol/kg.min, P < 0.05) in response to hyperglycemia. Postpartum, ISRs and insulin resistance decreased in women with GDM and controls (ISR by 43% and 43%, respectively, and insulin resistance by 75% and 118%, respectively), and both groups had similar ISRs (352 vs. 408 pmol/min, nonsignificant). Women with GDM, however, continued to be more insulin resistant than controls. In summary, patients with GDM during late pregnancy not only had severe deficiencies in ISR but, in addition, were more insulin resistant than controls. Postpartum, insulin resistance and ISRs (and plasma insulin levels) improved in both groups, and ISRs (and plasma insulin levels) were no longer significantly different in patients with GDM and controls. Insulin resistance, however, remained higher in women with GDM, and their glucose uptake remained lower. We concluded that the women with GDM had a major ss-cell defect that made it impossible for them to compensate for their increased level of insulin resistance, which occurred during late pregnancy.

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Postpartum Period; Pregnancy; Pregnancy Trimester, Third; Racial Groups; Radioimmunoassay; Reference Values

Insulin resistance as well as marked changes in body weight and energy metabolism are associated with pregnancy. Its impact on plasma leptin is not known and was determined in this longitudinal study in both diabetic and normal pregnancy.. At 28 gestational weeks plasma concentrations of leptin and B-cell hormones were measured at fasting and after an oral glucose load (OGTT:75 g) in women with gestational diabetes and pregnant women with normal glucose tolerance and compared with women who were not pregnant (C).. Plasma leptin (ng/ml) was higher (p < 0.001) in women with gestational diabetes (24.9 +/- 1.6) than in women with normal glucose tolerance (18.2 +/- 1.5) and increased in both groups when compared with the non-pregnant women (8.2 +/- 1.3; p < 0.0005). No change in plasma leptin concentrations was induced by OGTT in any group. Basal insulin release was higher (p < 0.05) in women with gestational diabetes compared with the pregnant women with normal glucose tolerance. Marked insulin resistance was confirmed by a 20 % lower (p < 0.05) insulin sensitivity in subgroup analysis and a decrease of almost 40% in fasting glucose/insulin ratio (p < 0.005) in women with gestational diabetes. Leptin correlated in women with gestational diabetes with basal plasma concentrations of glucose (p < 0.02), insulin (p < 0.004) and proinsulin (p < 0.01) as well as with BMI (p < 0.001) and overall pregnancy induced maternal weight gain (p < 0.009). With normalisation of blood glucose 8 weeks after delivery in women with gestational diabetes their plasma leptin decreased (p < 0.0005) to 17.3 +/- 1.9 ng/ml but did not completely normalize (p < 0.05 vs non-pregnant women).. Our data show that women with gestational diabetes without any change in plasma leptin upon oral glucose loading have increased plasma leptin concentrations during and after pregnancy, a clear association of plasma leptin with the respective concentration of glucose and insulin resistance as well as with changes in body weight, and a failure to normalize spontaneously BMI to the same extent as pregnant women with normal glucose tolerance when compared with matched control subjects.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Diabetes, Gestational; Fasting; Female; Gestational Age; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Insulin Resistance; Insulin Secretion; Leptin; Postpartum Period; Pregnancy; Proinsulin; Regression Analysis; Weight Gain

The sulphonylurea receptor-1 (SUR-1) regulates glucose-induced insulin secretion by controlling K+-ATP channel activity of the pancreatic beta-cell membrane. In this study, we investigated the putative role of a T/G-polymorphism (exon 33, codon 1369; S1369A) in the adenosine diphosphate-sensing nucleotide-binding fold-2 (NBF-2) of the SUR-1 on glucose-induced insulin secretion during an oral glucose tolerance test in pregnant women (PW; n=182). Compared to PW with the T/T genotype, statistically significant elevated C-peptide concentrations were found 60 min after glucose intake in PW with the T/G and G/G genotype (T/T 9.0+/-0.4 ng/ml vs T/G 10.8+/-0.4 ng/ml or G/G 10.8+/-0.7 ng/ml, p=0.01). Furthermore, compared to PW with T/T genotype the deltaC-peptide (60/0 min) was significantly enhanced in PW with T/G or G/G genotype (T/T 6.7+/-0.3 vs T/G 8.9+/-0.4 or G/G 8.9+/-0.7, p=0.0009). A significant correlation of C-peptide concentrations with blood glucose (BG) 60 min after glucose intake was only found in PW with the T/T genotype (r=0.6, p<0.0004). Similarly, a significant correlation of insulin concentrations with BG 60 min after glucose intake was observed in PW with T/T genotype (r=0.5, p<0.0001) and T/G genotype (r=0.24, p<0.03) but not in PW with G/G genotype (r=0.01, p=0.9). From our data we conclude that in PW with the alanine substitution in the NBF-2 region, the insulin response of the pancreatic beta-cell after glucose intake is enhanced and does not correlate with actual BG levels.

Topics: Alanine; ATP-Binding Cassette Transporters; Binding Sites; Blood Glucose; C-Peptide; Codon; Diabetes, Gestational; Exons; Female; Genetic Variation; Glucose; Humans; Insulin; Insulin Secretion; Polymorphism, Genetic; Potassium Channels; Potassium Channels, Inwardly Rectifying; Pregnancy; Receptors, Drug; Serine; Sulfonylurea Receptors

To test the hypothesis that fetal pancreatic exocrine and endocrine function are stimulated in parallel in the diabetic pregnancy, 68 mothers with gestational and pregestational diabetes who underwent amniocenteses after 34 weeks' for the evaluation of fetal lung maturity were enrolled. Amniotic fluid specimens were analyzed for C-peptide and trypsin content. Amniotic fluid specimens were obtained from 92 non-diabetic women undergoing amniocenteses for lung maturity, preterm labor, or premature rupture of membranes. Groups were compared using the Wilcoxon rank-sum test, Kruskal Wallis rank sum test, and Spearman's rank correlation test. C-peptide amniotic fluid concentrations were significantly greater in diabetics (median 0.6 ng/ml) than non-diabetics (median 0.4 ng/ml, P= 0.0001), in pregestational (median 0.6 ng/ml) vs. gestational diabetics (median 0.4 ng/ml, P = 0.006), and greater in proportion to severity of disease according to diabetic class (A1 = 0.4 ng/ml, A2 = 0.55 ng/ml, B = 0.6 ng/ml, C = 0.7 ng/ml, D = 0.85 ng/ml, P = 0.04). No significant differences were detected in amniotic fluid trypsin between the diabetic and non-diabetic or the gestational and non-gestational diabetic groups. There was no correlation between C-peptide and trypsin within the diabetic groups. Stimulation of the exocrine and endocrine pancreas does not occur in parallel in the fetus of the diabetic mother. Although originating as a single organ, pancreatic exocrine and endocrine functions are distinct in both physiologic and pathologic conditions.

Topics: Adult; Amniocentesis; Amniotic Fluid; C-Peptide; Diabetes, Gestational; Female; Humans; Islets of Langerhans; Pancreas; Pregnancy; Pregnancy in Diabetics; Trypsin

Leptin has been implicated in the regulation of body weight and energy balance; Leptin is produced by adipocytes and placental tissue. Chronic fetal hyperinsulinemia and accelerated fetal growth with increased amounts of body fat are frequent findings in the offspring of diabetic mothers. In this study, we examined whether leptin levels in cord blood of infants of type 1 diabetic mothers (n = 29), gestational diabetic mothers (n = 6 and controls (n = 96) correlated with level of maternal glucose control, maternal leptin level at delivery, gender, fetal and placental size, and C-peptide in cord blood at birth. Leptin was significantly elevated in infants of type 1 diabetic (24.7 ng/ml) and gestational diabetic mothers (29.3 ng/ml) as compared to controls (7.9 ng/ml). C-peptide was also significantly higher in infants of type 1 diabetic (0.91 nmol/l) and gestational diabetic mothers (0.99 nmol/l) vs controls (0.34 nmol/l). Infants of type 1 diabetic mothers with a leptin level in cord blood above the upper normal range, i.e. > 30 ng/ml (n = 13), had an average maternal HbA1c level of 5.4% (normal < 5.5%) that was not different from 5.2% in infants with a leptin level < 30 ng/ml (n = 15). In both neonatal groups of diabetic mothers, leptin in cord blood did not correlate with maternal leptin concentrations, placental weight, birthweight, gender and cord blood C-peptide. In controls, leptin in cord blood was higher in girls than in boys (p = 0.044) and correlated significantly with birthweight (p = 0.41, p < 0.001) and cord blood C-peptide (p = 0.44, p < 0.001) but not with maternal leptin level or placental weight. The 3-4 times higher leptin levels in the offspring of diabetic mothers than normal could reflect increased adipose tissue mass and/or increased contribution from other sources such as placental tissue.

Topics: Birth Weight; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Leptin; Male; Organ Size; Placenta; Pregnancy; Pregnancy in Diabetics; Proteins; Sex Characteristics

To observe the different changes of plasma insulin and c-peptide in patients with gestational diabetes mellitus (GDM), gestational impaired glucose tolerance (GIGT), normal pregnant women, and to detect the function of beta-cell in patients with gestational impaired glucose metabolism.. Test the plasma insulin, c-peptide in 48 cases of GDM(group I), 39 cases of GIGT (group II), 39 cases of normal pregnant women (group III) and 22 cases of healthy non-pregnant women (group IV) by radioimmunoassay.. (1) In third trimester of group III, insulin, c-peptide levels were higher than those of group IV (P < 0.01). They increased from 28-34 weeks to 38-40 weeks, peaked during delivery. Insulin levels of group I and group II were higher than those of group III (P < 0.01, P < 0.05), but tended to decrease by the end of the third trimester and peaked during delivery. During delivery, there was no significant differences among the three groups. At 28-40 weeks, c-peptide of group I was significantly higher than those in groups II and III (P < 0.01) and was lower than that in group III during delivery (P < 0.05). Insulin and c-peptide of these 3 groups dropped gradually within 2 months after delivery but in group I and II they were significantly higher than those of group III (P < 0.01).. In third trimester insulin and c-peptide of group I-III increased till delivery, the reason maybe associated with insulin resistance. GDM had the same peaking secretion during delivery with normal pregnant women and GIGT group, this maybe due to the stress during delivery. Insulin levels of most GDM and GIGT were still higher than normal after two month postpartum, and should be followed up carefully.

Topics: Adult; C-Peptide; Diabetes, Gestational; Female; Glucose Intolerance; Humans; Insulin; Pregnancy

We aimed to evaluate gestational impaired glucose tolerance (GIGT) in untreated patients using umbilical cord blood insulin and connecting peptide (C-peptide) concentrations to indicate fetal hyperinsulinemia. A 75 g, 2-hour oral glucose tolerance test, evaluated using WHO criteria, was performed in 722 antenatal patients. Cord C-peptide (p = 0.001) and insulin (p = 0.008) concentrations were significantly higher in patients with GIGT in comparison to those with normal glucose tolerance. The WHO test failed to identify abnormal C-peptide concentrations (p = 0.057), but did identify abnormal insulin concentrations (p = 0.006) and cases where either or both were raised (p = 0.002), with a low Youden's index (range 8.1-11.3) in all 3 cases. A significant biochemical difference exists in patients with GIGT. The WHO criteria for GIGT predict abnormal biochemical outcomes, but they do so poorly.

Topics: Biomarkers; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Fetal Diseases; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperinsulinism; Pregnancy; Pregnancy Complications

Gestational diabetes mellitus (GDM) and positive parental history of type 2 diabetes are predictors of the future development of type 2 diabetes in several populations. However, the relative importance of parental history of diabetes and/or history of GDM as risk factors for the pathogenesis of diabetes in African-Americans remains unknown. Thus, the objectives of the present study were 1) to characterize the glucose homeostatic regulations and 2) to examine the contribution of parental history of type 2 diabetes to the potential metabolic alterations found in nondiabetic African-American women with a history of GDM (HGDM).. We evaluated beta-cell secretion, insulin sensitivity (SI), and glucose-dependent glucose disposal (SG) in 15 glucose-tolerant African-American women with a parental history of type 2 diabetes and prior GDM (HGDM) and 35 women with a parental history of type 2 diabetes but without prior GDM (NHGDM). Fifteen healthy nonobese nondiabetic subjects without a family history of diabetes served as control subjects. Body composition was determined by bioelectrical impedance analyzer, and body fat distribution pattern was determined by waist-to-hip ratio (WHR). Insulin-modified frequently sampled intravenous glucose tolerance (FSIGT) test was performed in each subject. SI and SG were determined by the minimal model method.. The mean age, BMI, percent body fat content, and lean body mass were not different between the subgroups of relatives with and without a history of GDM, but were greater than those of the healthy control subjects. Mean fasting and postchallenge serum glucose levels were slightly but significantly greater in the HGDM versus NHGDM subjects and the healthy control subjects. However, the 2-h glucose levels were greater in the relatives with and without GDM when compared with the healthy control subjects. In contrast, mean postprandial serum insulin responses were significantly lower between t = 30 and 120 min in the HGDM versus NHGDM groups and the healthy control subjects. The mean serum insulin levels were not different in the NHGDM subjects and healthy control subjects. During the FSIGT test, acute first-phase insulin release (t = 0-5 min) was significantly lower in the HGDM versus NHGDM groups and healthy control subjects. Mean SI was significantly (P < 0.05) lower in the HGDM versus NHGDM subjects and healthy control subjects (1.87 +/- 0.47 vs. 2.87 +/- 0.35 and 3.09 +/- 0.27 x 10(-4).min-1.[microU/ml]-1, respectively). SG was significantly lower in HGDM than NHGDM subjects and healthy control subjects (2.11 +/- 0.15 vs. 3.25 +/- 0.50 and 2.77 +/- 0.22 x 10(-2).min-1, respectively). Mean glucose effectiveness at zero insulin concentrations (GEZI) was significantly lower in the HGDM subjects when compared with the NHGDM and healthy control subjects.. The present study demonstrates that in African-American women with a parental history of type 2 diabetes and GDM, defects in early-phase beta-cell secretion, as well as a decreased SI, SG, and GEZI, persist when compared with those without GDM. We suggest that African-American women with a positive history of GDM have additional genetic defects that perhaps differ from that conferred by a parental history of diabetes alone. Alternatively, the metabolic and hormonal milieu during GDM may be associated with permanent alterations in beta-cell function, SI, and glucose effectiveness in African-American women. These defects could play a significant role in the development of GDM, and perhaps in the subsequent development of type 2 diabetes, in African-American women.

Topics: Adult; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Fasting; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Liver; Models, Biological; Ohio; Pregnancy; Reference Values; Risk Factors

Leptin can be considered as a peripheral signal which informs the centers about the mass of energy stores. Studies done on the human adult population have demonstrated that degree of adiposity and insulin levels play a major role as determinants of leptin circulating levels. The aim of this study was to evaluate which factors may influence leptin levels at birth. We examined the role played by baby size and by the metabolic environment the fetus was exposed to during pregnancy. We considered 85 newborns from normal (n = 60), gestational (GDM, n = 17) and pregestational (IDDM = 8) diabetes mellitus mothers. At delivery, blood was taken from the umbilical cord vein. Babies from normal and GDM mothers were subdivided into AGA (appropriate for gestational age) and LGA (large for gestational age). There was no difference in leptin levels between babies from normal or GDM mothers belonging to the same weight category, but leptin levels were always higher in LGA than in AGA newborns, and highly correlated with birth weight (r = 0.34, P = 0.001). Moreover, IDDM mothers gave birth to newborns with significantly higher levels of leptin and insulin when compared with normal and GDM mothers. Diabetes of both GDM and IDDM mothers was clinically well controlled (HbA1c was 4.0 and 7.2, respectively). The correlation between leptin and insulin was significant only when newborns from IDDM mothers were included in the regression analysis (r = 0.39, P = 0.0002). Our results suggest that degree of adiposity is one of the main regulators of leptin concentration in the human newborn and that babies exposed to an altered, though clinically controlled, metabolic environment, as in IDDM mothers, have increased levels of leptin.

Topics: Adipose Tissue; Adult; Birth Weight; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Glycated Hemoglobin; Humans; Infant, Newborn; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Leptin; Multivariate Analysis; Pregnancy; Proteins; Regression Analysis; Testosterone

Free insulin cannot cross the placenta but insulin complexed to anti-insulin antibodies has been demonstrated in cord blood. We studied whether antibody-bound insulin in diabetic patients can evoke fetal macrosomia independently of maternal metabolic control. In 457 non insulin-treated controls and 173 insulin-treated diabetic patients we measured 1187 anti-insulin antibody levels and maternal blood glucose, maternal fructosamine, cord blood insulin, cord blood C-peptide, cord blood fructosamine and amniotic fluid insulin. Mean anti-insulin antibody levels in maternal blood and cord blood were significantly higher in insulin treated diabetic patients (4.6 and 5.4 U/ml) than in controls (1.8 and 1.7 U/ml) with maxima of 89.2 in maternal and 120.0 U/ml in cord blood, respectively. In insulin treated diabetic patients 16.6% (maternal blood) and 22% (cord blood) anti-insulin antibody levels were above the 97th percentile. There was a high significant correlation between maternal and cord blood anti-insulin antibodies (R = 0.987, P = < 0.0001), but no correlation of anti-insulin antibodies with maternal (glucose, fructosamine) or fetal (insulin, C-peptide, and fructosamine in cord blood, amniotic fluid insulin) metabolic parameters. While maternal and fetal metabolic parameters correlated with birth weight neither maternal nor cord blood anti-insulin antibody levels correlated with birth weight. These findings do not support the hypothesis that maternal anti-insulin antibodies independently influence fetal weight.

Topics: Amniotic Fluid; Autoantibodies; Birth Weight; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fetal Blood; Fructosamine; Humans; Infant, Newborn; Insulin; Pregnancy; Pregnancy in Diabetics

Recent research indicates that islet amyloid pancreatic polypeptide (IAPP) might have a regulatory effect on beta-cell insulin processing and secretion. To study such interaction in more detail, IAPP secretion and kinetics and the serum concentrations of proinsulin were assessed both before and after delivery in lean pregnant women with gestational diabetes mellitus (GDM patients) in comparison to those with normal glucose tolerance (NGT) and to nonpregnant healthy lean (control) and obese insulin-resistant women during oral glucose tolerance tests. Kinetic analysis of IAPP was performed with mathematical modeling, providing indirect estimates of its secretion and fractional clearance. Total insulin secretion per 180 min was elevated by 30% in GDM patients (35 +/- 3 pmol/l) versus control subjects (27 +/- 1 pmol/l) (P < 0.05), but increased even more (190-250%) in obese insulin-resistant women, compared with all other groups (68 +/- 7 pmol/l, P < 0.0005). Pregnancy induced a more marked fourfold increase in apparent total IAPP secretion rate (TIR) (GDM patients, 172 +/- 31 pmol x 1(-1) x 3 h(-1); NGT subjects, 166 +/- 31 pmol x 1(-1) x 3 h(-1); control subjects, 40 +/- 1 pmol 1(-1) x 3 h(-1)) and a twofold rise in its fractional clearance versus control subjects (P < 0.01), whereas in GDM patients a 30% increase of IAPP secretion and a decreased clearance was found, compared with obese insulin-resistant women (TIR, 112 +/- 14 pmol x 1(-1) x 3 h(-1)). The increase in IAPP secretion in both pregnant groups was much higher than that of the insulin groups, resulting in a marked change of the IAPP-insulin cosecretion factor when compared with lean or obese nonpregnant women (P < 0.0005). Associated serum proinsulin and the postprandial (total divided by 180 min) proinsulin-to-insulin ratio were greater in GDM patients versus NGT and control subjects (0.11 +/- 0.01 vs. 0.07 +/- 0.01 and 0.08 +/- 0.01 pmol/l, P < 0.05), while the fasting proinsulin-to-insulin ratio was only increased in GDM patients versus control subjects (0.22 +/- 0.03 vs. 0.13 +/- 0.01 pmol/l, P < 0.05). After delivery, total IAPP secretion (52.4 +/- 1.5 pmol/l) was completely normalized in the GDM group, as were the clearance rate and the IAPP-insulin cosecretion factor. Similarly, serum proinsulin concentrations returned to normal, whereas proinsulin-to-insulin ratios remained elevated. In conclusion, IAPP hypersecretion is characteristic for pregnancy and might partially decrease hyperinsu

Topics: Adult; Amyloid; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin; Islet Amyloid Polypeptide; Islets of Langerhans; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Proinsulin

The aetiology of the metabolic syndrome remains unknown. This study investigated whether two components of this syndrome, higher blood pressure and higher plasma insulin concentrations, are related at birth. Neonates in the study were from 23 European, 25 Maori, 22 South Asian, and 25 Pacific Islands women having normal singleton pregnancies as well as 6 Maori, 5 Indian, and 19 Pacific Islands women with gestational diabetes (diagnosed by a 3 h 100 g oral glucose tolerance test at 28-32 weeks). Additional fasting glucose and fructosamine concentrations were measured at 36-38 weeks. Umbilical cord blood was taken for insulin, C-peptide, fructosamine and insulin-like growth factor I. Neonatal anthropometry and blood pressure were measured 24 h after delivery. Compared with those with a lower systolic blood pressure (SBP), neonates with a higher SBP had higher umbilical cord insulin (45.6 (39.6-52.8) vs 63.0 (54.6-72.6) pM, p < 0.01), C-peptide (0.22 (0.20-0.25) vs 0.28 (0.26-0.30) nmol l-1, p < 0.001) and fructosamine concentrations, higher maternal fructosamine concentrations and heavier placentas. These data suggest that neonatal hyperinsulinaemia, possibly driven by minor elevations in maternal glycaemia, may be linked to a higher neonatal SBP.

Topics: Asia; Birth Weight; Blood Glucose; Blood Pressure; Body Constitution; C-Peptide; Diabetes, Gestational; Diastole; Female; Fetal Blood; Fructosamine; Glucose Tolerance Test; Humans; India; Infant, Newborn; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Labor, Obstetric; Maternal Age; New Zealand; Pacific Islands; Parity; Prediabetic State; Pregnancy; Reference Values; Regression Analysis; Systole; White People

The significance of gestational diabetes mellitus (GDM) results from its short-term detrimental effects on the fetus and its long-term prediction of NIDDM in the mother. We compared several variables associated with insulin resistance between GDM and non-GDM pregnant women to show the similarities between GDM and NIDDM (and thus insulin resistance).. On the basis of a 3-h oral glucose tolerance test (OGTT), 52 GDM patients and 127 non-GDM patients were recruited from pregnant, non-diabetic women who had a nonfasting 1-h-50-g glucose screening test > or = 7.2 mmol/l (130 mg/dl) performed between 16 and 33 weeks of gestation (a total of 518 of 3,041 women drawn from six community health care prenatal clinics were screened positive). During the OGTT, several potential markers of insulin resistance were measured at fasting and 2-h time points, in addition to the standard glucose measurements. The relationship of these variables with the diagnosis of GDM was studied.. GDM patients, compared with non-GDM patients, had 1) higher prepregnancy weight (P = 0.011), prepregnancy BMI (P = 0.006), C-peptide at fasting (P = 0.002) and at 2 h (P < 0.001), insulin at fasting (P = 0.001) and at 2 h (P < 0.001), triglycerides at fasting (P = 0.005) and at 2 h (P = 0.003), free fatty acids at fasting (P = 0.017), beta-hydroxybutyrate at fasting (P = 0.007); and 2) lower HDL cholesterol at fasting (P = 0.029). These variables were all predictive of GDM (P < 0.036) individually. Using stepwise logistic regression with all of these variables available, fasting (P = 0.019) and 2-h (P < 0.001) insulin levels, fasting free fatty acids (P = 0.031), and fasting beta-hydroxybutyrate (P = 0.036) were statistically significant as jointly predictive of GDM. Comparisons between GDM patients and non-GDM patients matched by BMI confirmed that the metabolic abnormalities persisted when difference in BMI was taken into account. Concomitant blood pressure measurements in women with GDM did not differ significantly from those without GDM.. Our results show that many of the known metabolic components of the syndrome of insulin resistance (syndrome X) are predictive of GDM. These results are in keeping with the argument that GDM is one phase of the syndrome of insulin resistance. We suggest that GDM be looked upon as a component of the syndrome of insulin resistance that provides an excellent model for the study and prevention of NIDDM in a relatively young age-group.

Topics: Adolescent; Adult; Analysis of Variance; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Lipids; Lipoproteins; Odds Ratio; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Reference Values

In order to define the islet amyloid polypeptide (IAPP) levels in gestational diabetes mellitus (GDM) and their interrelationship with the insulin levels, we studied (1) the placental RNA from 10 women (5 with GDM and 5 normals) for IAPP expression by Northern blotting and (2) 10 women with GDM during a 100-gram oral glucose tolerance test and compared these with 11 normal women matched for obesity and age. Plasma levels of glucose, IAPP, insulin, and C peptide were determined. No IAPP expression was detected in any of the placentae after a long exposure. We could not demonstrate any differences in plasma IAPP levels (basal or stimulated) between the two groups of pregnant women. However, in women with GDM we found a lower IAPP/insulin ratio (p < 0.05) and a lower maximal IAPP/maximal insulin response ratio during the oral glucose tolerance test (p < 0.05) than in normal women. Therefore, IAPP does not appear to be directly involved in the development of GDM. The peripheral levels of IAPP relative to insulin are lower in GDM, a finding similar to that described in type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus). This observation further confirms that GDM resembles the early stages of type 2 diabetes mellitus.

Topics: Adult; Amyloid; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Gene Expression; Glucose Tolerance Test; Humans; Insulin; Islet Amyloid Polypeptide; Placenta; Pregnancy

To examine the impact of gestational diabetes mellitus(GDM) on perinatal outcome in a setting where influences of maternal age and obesity would be minimal.. A case-control study was done to compare the outcome of pregnancy in 65 women with GDM and 153 women with normal carbohydrate metabolism matched for age, height, and prepregnancy weight.. The frequencies of preeclampsia and primary cesarean sections were higher and delivery was earlier in pregnancies complicated by GDM. Birth weight, symmetry index, and chest circumference were greater, and macrosomia and need for phototherapy were more common in offspring of mothers with GDM. Cord-serum C-peptide and insulin concentrations were higher in the infants of mothers with GDM and were strongly correlated with birth weight and symmetry index. However, maternal age, prepregnancy weight, and prepregnancy BMI were not correlated with birth weight. Postprandial glucose levels during the first 2 weeks after diagnosis of GDM had associations with the infants' birth weight, symmetry index, and cord insulin concentration in the diet-treated patients with GDM.. Antepartum maternal glucose metabolism was significantly associated with fetal hyperinsulinemia and excessive fetal growth in relatively nonobese Korean women. These findings support a direct role for metabolic factors in the adverse outcomes in pregnancies complicated by GDM.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Case-Control Studies; Cesarean Section; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Gestational Age; Humans; Infant, Newborn; Jaundice, Neonatal; Korea; Maternal Age; Morbidity; Obesity; Parity; Phototherapy; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Regression Analysis

To evaluate beta-cell secretion and glucose metabolism in lean subjects with gestational diabetes mellitus (GDM) compared with that in subjects with normal pregnancy and obesity.. Insulin secretion, insulin sensitivity (S1), and hepatic insulin extraction were assessed in pregnant women with GDM before and after delivery and in those with normal glucose tolerance (NGT) in comparison to healthy nonpregnant lean and obese women. Kinetic analysis of glucose, insulin, and C-peptide plasma concentrations during oral and intravenous glucose tolerance tests was performed by mathematical modeling.. S1 was blunted in pregnant women with GDM by 84% and in those with NGT by 66% compared with lean nonpregnant women (P < 0.005 vs. healthy nonpregnant lean control subjects; P < 0.05, GDM vs. pregnant women with NGT), whereas glucose effectiveness was decreased by 33% in both pregnant groups (P < 0.05 vs. healthy nonpregnant lean control subjects). Insulin secretion was 30% higher (P < 0.05) in subjects with GDM than in pregnant women with NGT or in nonpregnant lean women, but decreased (P < 0.005) when compared with obese women with a comparable degree of insulin resistance. Fractional hepatic insulin extraction was similar in both pregnant groups, being lower (P < 0.0001) by 30% versus nonpregnant females. beta-cell sensitivity to glucose for insulin release was decreased in subjects with GDM versus pregnant women with NGT as well as nonpregnant women by 40-50% (P < 0.01). Twelve weeks after delivery, GDM returned to normal glucose tolerance, but S1 remained 50% lower than that in lean nonpregnant women, while beta-cell sensitivity to glucose did not change (P < 0.01 vs. healthy nonpregnant lean control subjects).. Pregnancy is characterized by insulin resistance, diminished hepatic insulin extraction, and glucose effectiveness. Lean subjects with GDM are additionally characterized by having more pronounced insulin resistance and inadequate insulin secretion, which persist after delivery. Compared with other insulin-resistant prediabetic states like impaired glucose tolerance (IGT), defective insulin secretion seems to be a predominant defect in lean GDM subjects, indicating that it might represent a specific prediabetic condition.

Topics: Adult; Blood Glucose; C-Peptide; Cohort Studies; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Reference Values

Postprandial substrate and hormone responses to a standard mixed meal (400 kcal) was determined at two occasions, A and B, in 11 women with gestational diabetes (GDMs) and 11 normoglycaemic controls, matched for age, body mass index, and gestational age. Levels of circulating glucose, non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate (3-HBA), individual amino acids, insulin, and C-peptide were analysed. A was performed when GDMs were considered inadequately controlled with diet alone, B later during gestation following initiation of insulin therapy because of hyperglycaemia. Fasting glucose, glycerol, total and individual amino acids (alanine, valine, isoleucine, leucine), insulin, and C-peptide were not different from normal during A and B, neither were postprandial amino acid levels. During test A, GDMs had elevated fasting and postprandial 3-HBA (p < 0.001), greater postprandial rise of glucose (p < 0.001), elevated NEFA (p < 0.05), but normal and parallel decreases of NEFA and glycerol. Insulin and C-peptide responses were delayed and prolonged. During B, GDMs had higher glucose response (p < 0.005), higher fasting 3-HBA (p < 0.02) but similar and parallel decreases of NEFA, glycerol, and 3-HBA as controls. The C-peptide response was not significantly different from normal; insulin response was higher (p < 0.05). In conclusion, the relative insulin deficiency characterizing GDMs, also when treated with insulin, is associated with selected defects in insulin action; mainly affecting glucoregulation, whereas suppression of lipolysis and proteolysis remain normal.

Topics: 3-Hydroxybutyric Acid; Adolescent; Adult; Amino Acids; Blood Glucose; Body Mass Index; C-Peptide; Diabetes, Gestational; Diet, Diabetic; Energy Intake; Fatty Acids, Nonesterified; Female; Gestational Age; Glycerol; Humans; Hydroxybutyrates; Hypoglycemic Agents; Insulin; Postprandial Period; Pregnancy; Reference Values; Time Factors

Our purpose was to investigate insulin sensitivity and insulin secretion in women with previous gestational diabetes.. Twelve women with previous gestational diabetes and 11 controls were examined by oral and intravenous glucose tolerance tests and a hyperinsulinemic euglycemic clamp including indirect calorimetry. All women were lean and had normal oral glucose tolerance test results. Activities of glycogen synthase, phosphofructokinase, and hexokinase were measured in vastus lateralis muscle biopsy specimens obtained in the basal state and after insulin stimulation.. Women with previous gestational diabetes had a decreased glucose disposal rate (p<0.01) because of a reduced insulin-stimulated nonoxidative glucose metabolism (6.63 +/- 0.47 vs 9.04 +/- 0.57 mg/kg fat-free mass per minute, p<0.01). The muscle activities of glycogen synthase, phosphofructokinase, and hexokinase were similar in the two groups. The first-phase insulin response to the intravenous glucose tolerance test was, in absolute terms, comparable in the two groups. However, when the decreased insulin sensitivity was taken into account, women with previous gestational diabetes had a relative insulin secretion deficiency.. Women with previous gestational diabetes have a decreased insulin sensitivity and a relative impairment of insulin secretion.

Topics: Adult; Biopsy; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Glycogen Synthase; Hexokinase; Humans; Insulin; Insulin Secretion; Lipids; Liver; Muscle, Skeletal; Phosphofructokinase-1; Pregnancy

To evaluate if an increased proinsulin-to-insulin ratio (PI/I) in former gestational diabetes mellitus (GDM) subjects could be a marker for later impairment of glucose tolerance.. This study is a prospective follow-up. In a previous follow-up study of former GDM subjects 3-4 years after an index pregnancy, an increased PI/I was found also in normoglycemic nonobese former GDM subjects compared with control subjects. A 75-g oral glucose tolerance test (OGTT) was performed 3 years after the first follow-up, i.e., 6-7 years after the index pregnancy in 97 of the former GDM subjects and in 23 control subjects. A 75-g OGTT according to the World Health Organization was performed. Glucose, insulin, proinsulin, and C-peptide were determined at 0, 30, 60, 90, 120, 150, and 180 min after the glucose intake.. Since the first follow-up, an additional 3 in 97 (3.1%) and 15 in 97 (15.5%) of the former GDM subjects had NIDDM or impaired glucose tolerance (IGT), respectively. All control subjects still had a normal OGTT. The fasting PI/I at follow-ups 1 and 2 was significantly correlated in the former GDM subjects (r = 0.41, P < 0.001) and in the control group (r = 0.46, P < 0.05). There was no significant correlation between the PI/I in follow-up 1 and the fasting or 2-h glucose values at follow-up 2. If GDM subjects with a PI/I in the upper quartile in the first follow-up were compared with those with a lower PI/I, there were no significant differences in outcome of OGTT in the second follow-up.. The hypothesis that an increased fasting PI/I is a marker for later development of NIDDM or IGT in former GDM subjects could not be supported.

Topics: Adult; Biomarkers; Birth Weight; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Middle Aged; Predictive Value of Tests; Pregnancy; Proinsulin; Reference Values; Statistics, Nonparametric; Time Factors

Although gestational diabetes affects as many as 3% of all pregnant women, specific aspects of glucose and protein metabolism in this population have not been clearly delineated. We tested the hypothesis that gestational diabetes mellitus (GDM) results in increased glucose production and proteolysis during fasting.. Using tracer isotope infusions, the rate of appearance (Ra) of glucose, leucine, phenylalanine and tyrosine, phenylalanine hydroxylation, leucine oxidation, and urea nitrogen excretion were determined after an overnight fast in 10 GDM subjects, within 2 weeks of diagnosis and before initiation of treatment, and in a matched control group of nine healthy nondiabetic pregnant women.. Fasting glucose Ra was similar in GDM patients and control subjects (GDM, 12.8 +/- 1.1 vs. control subjects, 12.8 +/- 0.9 mumol . kg-1 . min-1). Leucine and phenylalanine Ra (reflecting proteolysis) also were not different between GDM patients and control subjects (GDM leucine Ra, 128 +/- 14 vs. control subjects, 124 +/- 5; phenylalanine Ra GDM, 35 +/- 4 vs. control subjects, 40 +/- 2 mumol . kg-1 . h-1). Furthermore, leucine oxidation and phenylalanine hydroxylation were not increased in GDM subjects, urea nitrogen excretion was actually lower in GDM patients. However, fasting insulin concentrations were significantly elevated in GDM subjects (GDM, 165 +/- 35 vs. control subjects, 30 +/- 5 pmol/l; P < 0.01).. Hepatic glucose release and whole-body proteolysis in GDM patients were remarkably similar to matched pregnant control subjects. This was achieved with insulin concentrations three- to fivefold higher than normal, suggesting significant insulin resistance for both glucose and protein metabolism in GDM.

Topics: Adult; Amino Acids; Blood Glucose; C-Peptide; Calorimetry; Carbon Dioxide; Carbon Isotopes; Diabetes, Gestational; Female; Glucose; Humans; Infusions, Intravenous; Insulin; Leucine; Oxygen Consumption; Phenylalanine; Pregnancy; Reference Values; Regression Analysis

Gestational diabetes affects 2-3% of pregnant women and is associated with foetal complications including macrosomia and an increased likelihood of developing diabetes in later life. We have therefore studied seven women with gestational diabetes and five control women both during the third trimester of pregnancy and again 2-3 months post-partum, using the minimal model analysis of the frequently sampled labelled ([6,6-2H2]-glucose) intravenous glucose tolerance test. Glucose tolerance (glucose Kd) was significantly reduced in the women with gestational diabetes compared with the normal pregnant women both in pregnancy (1.16 +/- 0.11 vs 1.78 +/- 0.23%/min; p < 0.05) and post-partum (1.47 +/- 0.22 vs 2.59 +/- 0.43%/min; p < 0.05) and increased significantly in the control women after delivery (p < 0.05). Glucose effectiveness was not significantly different between the women with gestational diabetes and the control group either during or after pregnancy. Insulin sensitivity was significantly lower during pregnancy than after delivery in the women with gestational diabetes (p < 0.05). There was no significant difference in basal insulin secretion in the two groups during pregnancy or post-partum. However, during pregnancy the control subjects significantly increased (p < 0.001) their insulin secretion over a period of 20 min in response to an intravenous glucose tolerance test (96.2 +/- 42.7 pmol/kg) compared with post-partum values (58.3 +/- 25.2 pmol/kg) while in the women with gestational diabetes insulin secretion was similar in pregnancy (65.5 +/- 9.3 pmol/kg) and after delivery (57.7 +/- 15.7 pmol/kg). These data suggest that the glucose intolerance in gestational diabetes compared to normal pregnancy is due to reduced insulin sensitivity and an impaired ability in gestational diabetes to increase insulin secretion in response to glucose.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Fasting; Female; Humans; Insulin; Insulin Secretion; Postpartum Period; Pregnancy; Reference Values; Sensitivity and Specificity

The aim of the study was to evaluate glucose levels and insulin secretion early in pregnancy and at a time when gestational diabetes mellitus frequently occurs in order to define reference values for glucose tolerance during pregnancy. The results were also related to maternal factors that might identify subjects at risk of developing gestational diabetes mellitus as well as foetal factors that might be a result of impaired glucose tolerance during pregnancy.. A prospective study.. All Caucasian women attending one antenatal out-patient care unit were offered a 75 g oral glucose tolerance test at the 17th and 32nd week of gestation.. A total of 586 consecutive pregnant women were included in the study. All 586 women were examined by repeated blood glucose measurements and 298 agreed to perform oral glucose tolerance tests as well.. Venous whole blood glucose values were measured in the fasting state and in samples obtained 15, 30, 45, 60, 75, 90 and 120 min after oral intake of 75 g glucose. Serum insulin and C-peptide were also measured at these times. In all subjects, a random blood glucose sample was taken at the first visit, and thereafter at the 20th, 30th and 36th week of gestation. Information was also obtained from all subjects regarding body mass index, weight gain during pregnancy, smoking habits, family history of diabetes and hypertension, hypertension during pregnancy, past obstetric history, parity, and fetal outcome.. The glucose tolerance was significantly impaired at the 32nd week of gestation compared with the 17th week of gestation. The mean +2SD 2 h glucose value during the oral glucose tolerance test at the 32nd week of gestation was 8.0 mmol L-1. Impaired glucose tolerance was characterised by increased insulin resistance, with a significant rise in serum insulin and C-peptide concentrations and in the insulin/glucose index during the oral glucose tolerance test at the 32nd week of gestation. Maternal factors associated with an impaired glucose tolerance were a family history of diabetes mellitus, smoking, a weight gain more than 18 kg during pregnancy, and glucosuria, while a family history of hypertension and hypertension present during pregnancy were not. Foetal factors that might be a result of impaired glucose tolerance during pregnancy, e.g. macrosomia and prematurity as well as complicated deliveries such as vacuum extraction/forceps or Caesarean section, all tended to be associated with higher blood glucose values. The same pattern was seen when the Apgar score was < 7.. The results from this study show that the present cut-off values for diagnosis of gestational diabetes mellitus should be revised. Even if some maternal factors might indicate an increased risk for impaired glucose tolerance during pregnancy, they are probably not enough to detect women with gestational diabetes mellitus. Therefore, a screening programme for gestational diabetes should be considered.

Topics: Adult; Area Under Curve; Blood Glucose; C-Peptide; Diabetes, Gestational; Diagnosis, Differential; Female; Glucose Tolerance Test; Humans; Insulin; Pregnancy; Reference Values

Our purpose was to determine the prevalence of autoantibodies to glutamic acid decarboxylase in women who had had gestational diabetes, including those in whom insulin-requiring or non-insulin-requiring diabetes mellitus has since developed.. The study group comprised 734 women with previous gestational diabetes who were consecutive attendees to a follow-up clinic. These women were tested for autoantibodies to glutamic acid decarboxylase with a radioimmunoprecipitation assay. We similarly tested 104 women in whom permanent diabetes mellitus developed after gestational diabetes, of whom 20 were using insulin and 84 were not. Those using insulin also had fasting C-peptide levels measured.. Thirteen of the 734 (1.8%, 95% confidence interval 0.9% to 3.0%) women with previous gestational diabetes were positive for autoantibodies to glutamic acid decarboxylase. Of the 20 women with diabetes treated with insulin, 12 had insulin deficiency confirmed by low levels of C peptide; all 12 were positive for autoantibodies to glutamic acid decarboxylase. Of the 84 women with diabetes not requiring insulin, 6 (7.1%, 95% confidence interval 2.7% to 14.9%) were positive for autoantibodies to glutamic acid decarboxylase.. The prevalence of autoantibodies to glutamic acid decarboxylase in women with previous gestational diabetes was 1.8%. Our data also showed that insulin-dependent diabetes mellitus will develop in 1.7% of women with gestational diabetes. A positive test for autoantibodies to glutamic acid decarboxylase may help in the early identification of insulin-dependent diabetes mellitus. Adult-onset insulin-dependent diabetes mellitus developed in only 5.2% (12/230) of women with previous gestational diabetes who later had diabetes mellitus.

Topics: Adult; Autoantibodies; C-Peptide; Confidence Intervals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Glutamate Decarboxylase; Humans; Middle Aged; Pregnancy; Reference Values; Time Factors

C-peptide concentrations in the cord blood of 29 macrosomic neonates born of nondiabetic mothers were higher than in 23 control infants whose birth weight was appropriate for gestational age, and there was a significant direct correlation between birth weight and C-peptide concentration. Six of the macrosomic infants studied (20%) had hypoglycemia in the first 24 hours of life, compared with none of the infants born with appropriate weight. We conclude that chronic fetal hyperinsulinemia may be one of the causes of macrosomia and neonatal hypoglycemia in infants of nondiabetic mothers.

Topics: Birth Weight; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Gestational Age; Humans; Hypoglycemia; Infant, Newborn; Pregnancy; Radioimmunoassay

Topics: C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fetal Blood; Humans; Infant, Newborn; Insulin; Islets of Langerhans; Mothers; Pilot Projects; Pregnancy; Proinsulin; Retrospective Studies

Because women with gestational diabetes mellitus have a risk of up to 60% for the later development of type II diabetes, we used the intravenous glucagon stimulation test to evaluate beta-cell function in pregnant women.. Twenty-seven pregnant women with one or more risk factors for gestational diabetes had an intravenous beta-cell stimulation test. Glucose, C-peptide and insulin levels were measured at baseline and 5, 10 and 15 min after the administration of 1 mg glucagon. The women were classified using the 75-g oral glucose tolerance test according to World Health Organization criteria. During the oral glucose tolerance test glucose, C-peptide and insulin levels were measured at baseline and at 2 h.. Insulin and C-peptide responses were significantly lower in pregnant women with impaired glucose tolerance and diabetes compared with women with normal glucose tolerance.. This study shows gradually decreasing insulin secretion from normal to subnormal in pregnant women without and with glucose intolerance, and diabetes mellitus, respectively.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes, Gestational; Fasting; Female; Glucagon; Humans; Insulin; Islets of Langerhans; Kinetics; Pregnancy; Risk Factors

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Diabetic Ketoacidosis; Female; Fetal Diseases; Glucose Tolerance Test; Humans; Hydrocephalus; Pregnancy; Pregnancy Trimester, Second

to investigate whether differences in the glucose-insulin axis are present at birth in neonates from ethnic groups at high risk of diabetes.. fructosamine samples were taken from Maori, European and Pacific Island expectant mothers at their 28 week appointment at the public outpatients clinic at National Women's Hospital, Auckland. Umbilical cord samples for insulin, C-peptide and fructosamine assay were taken at delivery and babies had their subscapular skinfold fat thickness measured by callipers.. the mean maternal 28 week fructosamine was similar in the three populations in spite of a higher prevalence of gestational diabetes among Pacific Islanders. Of the 1066 deliveries, cord samples were available for 207 Europeans, 81 Maoris and 113 Pacific Islanders. Both Pacific Island and Maori babies had higher cord fructosamine concentrations than European babies. However, Pacific Island babies were also heavier, and had higher cord insulin concentrations and subscapular skinfold thickness than European babies.. the elevated cord fructosamine concentrations suggest that Maori and Pacific Island babies, who share a high risk of noninsulin dependent diabetes mellitus later in life, are hyperglycaemic at birth. The paradoxical insulin results and the cause for the relative neonatal hyperglycemia warrant further investigation.

Topics: Adult; Anthropometry; Birth Weight; Body Height; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Ethnicity; Europe; Female; Fetal Blood; Fructosamine; Head; Hexosamines; Hospitals, Maternity; Hospitals, Public; Humans; Hyperinsulinism; Infant, Newborn; Insulin; New Zealand; Parity; Polynesia; Pregnancy; Prevalence; Risk Factors; Skinfold Thickness

Urinary C-peptide excretion was measured during the last trimester of pregnancy in 12 non-diabetic control women and in 32 women with gestational diabetes. The urine was sampled in two 12-hour periods between 06h00 and 18h00 and 18h00 and 06h00. At the end of the sampling period a fasting plasma sample was analysed for insulin, C-peptide, glycerol, free fatty acids and 3-hydroxybutyrate. The women with gestational diabetes had a significantly lower excretion of C-peptide during the daytime period. In this group women with diabetic heredity had lower C-peptide excretion during the day-time and the 24-hour period compared with women without diabetic heredity. In the non-diabetic group there was significant correlation between body mass index and urinary C-peptide during the night-time and the total 24-hour period. The gestational diabetic women had fasting plasma concentrations of glycerol, free fatty acids and 3-hydroxybutyrate acid that were significantly above the levels found in the control group.

Topics: C-Peptide; Diabetes, Gestational; Female; Humans; Insulin; Insulin Secretion; Pregnancy; Pregnancy Trimester, Third

Gestational diabetes mellitus (GDM) is a strong predictor of glucose intolerance later in life. Former GDM (n = 145) and control (n = 41) subjects were studied 3-4 yr after the index pregnancy. They were subjected to a 75-g oral glucose tolerance test (OGTT) with measurements of insulin, C-peptide, and proinsulin in the basal state and every 30 min for 180 min. In the former GDM group, 5 subjects (3.4%) had developed non-insulin-dependent diabetes mellitus (NIDDM), and 32 (22%) had developed impaired glucose tolerance (IGT; by World Health Organization criteria). In the control group, 2 (4%) had IGT. In the GDM group, IGT or NIDDM was significantly associated with obesity (body mass index [BMI] greater than or equal to 25 kg/m2) and earlier diagnosis of GDM during pregnancy (P less than 0.001). Nonobese (BMI less than 25 kg/m2) GDM subjects with normal glucose tolerance at follow-up had significantly higher mean glucose (P less than 0.01), insulin (P less than 0.05), and proinsulin (P less than 0.001) values during the OGTT than control subjects, whereas there was no significant difference in C-peptide values. A comparison between control subjects with normal OGTT and BMI less than 25 kg/m2 (n = 39) and GDM subjects (n = 39) selected to have a comparable area under the glucose curve, BMI, and age demonstrated no group differences in glucose, C-peptide, or insulin levels, whereas the proinsulin levels were significantly higher (P less than 0.001) during the glucose load. The molar ratio between proinsulin and insulin was also significantly higher among the former GDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Pregnancy; Proinsulin

All newborn children to mothers with gestational diabetes mellitus (GDM) in the county of Orebro were investigated during a one year prospective study. Neonatal macrosomia (birthweight greater than 3 SD) was observed in 27% of children of mothers with GDM and was significantly correlated to the cord C-peptide concentration. Hypoglycaemia (B-glucose less than 1.5 mmol/l) was observed in 38% of the children, most frequently two hours after delivery. Hypoglycaemia was not more common in macrosomic children and could not be predicted by the blood glucose concentration of the mother at delivery or by the cord C-peptide level. It is concluded that mothers with GDM must be intensively treated in order to avoid the occurrence of macrosomia in their infants and that the newborn child must be carefully observed and treated in order to avoid neonatal hypoglycaemia.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fetal Macrosomia; Glycated Hemoglobin; Humans; Hypoglycemia; Infant, Newborn; Insulin; Pregnancy; Pregnancy in Diabetics