humulin-s and Diabetes--Gestational

Diabetes during pregnancy may lead to maternal, fetal and neonatal complications. In order to limit unwarranted outcomes, strict glycemic control is essential. In the past, human insulin was the only insulin formulation administered in pregnancy. However, insulin analogues have also been used for this indication in recent years.. This article reviews the published data regarding the safety of insulin analogue use during pregnancy. We present the qualities, advantages and pitfalls of insulin analogue use in pregnancy compared with human insulin. Insulins lispro, aspart and detemir are safe in pregnant women with type 1 diabetes. Correspondingly, they were reclassified for the treatment of pregnant women with diabetes from category C to category B. For insulin glargine use in pregnancy, most studies are small and retrospective. Yet, no major safety concerns were reported. Insulin glulisine and degludec have not been studied in pregnancy.. Insulin analogues are viable therapeutic options for diabetes in pregnancy, specifically lispro, aspart and detemir. Though data in limited, their safety and efficacy are comparable with human insulin. Remarkably, the analogues are superior to human insulin regarding hypoglycaemia risk. More data, specifically for their use in pregnancies complicated by gestational diabetes or type 2 diabetes, is needed.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Infant, Newborn; Insulin, Regular, Human; Insulins; Pregnancy

We review the recent changes in diagnostic criteria of gestational diabetes mellitus (GDM), describe problems with maintaining and monitoring adequate blood glucose, especially in type 1 diabetes, and provide a brief overview of the currently approved glucose-lowering therapies in pregnancy.. After the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, the definition of GDM was revised under the auspices of the International Association of Diabetes and Pregnancy Study Groups. The guidelines, with minor modifications, were endorsed by WHO in 2013. Intensive debate continues, focused on the expected large increase in prevalence of GDM and shortage of experimental evidence of clinical benefits from the new diagnostic criteria. Despite a very good glycaemic control, the prevalence of macrosomia remains high. This indicates a serious deficiency in current monitoring tools and the available therapies. So far, the only glucose-lowering medications approved for use during pregnancy are insulins.. The HAPO study provides a very suggestive evidence for a strong, continuous association of maternal glucose levels with an increased risk of excessive foetal weight gain. The new definition of GDM results in higher healthcare expenditure, but remains cost-effective. The current therapeutic goals require careful revision to further reduce the risk of adverse outcomes. New glucose-monitoring strategies and markers, and approval of new pharmacotherapies are needed.

Topics: Combined Modality Therapy; Consensus; Diabetes, Gestational; Diet, Diabetic; Evidence-Based Medicine; Female; Fetal Macrosomia; Global Health; Health Transition; Humans; Hypoglycemic Agents; Insulin, Regular, Human; Maternal Nutritional Physiological Phenomena; Practice Guidelines as Topic; Pregnancy; Pregnancy in Diabetics; Prenatal Diagnosis; Recombinant Proteins; Risk

This study strove to investigate the hypothesis that a low dosage of myo-inositol supplementation might decrease the likelihood of gestational diabetes in overweight, pregnant women.. A randomized, double-blind, controlled trial was performed on 60 eligible overweight, pregnant women, at 12-14 weeks of gestation, at two Iranian obstetric clinics. The participants were divided into two groups based on blocked randomization. The myo-inositol group received 2000 mg plus 400 μg folic acid daily and the control group received 400 μg of folic acid daily from 14-24 gestational weeks. The occurrence of gestational diabetes was determined based on 75-g 2-hour oral glucose tolerance test (OGTT) at 24-28 gestational weeks, which was the primary outcome of the study. The secondary outcomes were: the evaluation of insulin therapy, insulin resistance and lipid profile, gestational weight gain, and fetal and maternal outcomes.. The incidence of gestational diabetes in myo-inositol group was noticeably minimized compared to that in the control group (RR=0.29, 95% CI: 0.09-0.94, P=0.037). There were no differences between the two groups in terms of fasting blood sugar, fasting insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), insulin therapy, and triglyceride. There was no report of severe adverse drug reactions.. The absolute risk reduction and the number-needed-to-treat for gestational diabetes were 26.8% (95% CI: 5.6-48) and 3.7 (95% CI: 2.1-18.0), respectively. Hence, it can be concluded that approximately one out of every four overweight pregnant women receiving myo-inositol benefitted from its daily intake.

Topics: Diabetes, Gestational; Dietary Supplements; Female; Folic Acid; Humans; Inositol; Insulin Resistance; Insulin, Regular, Human; Iran; Overweight; Pregnancy; Pregnant Women

To compare body composition, visceral adiposity, adipocytokines, and low-grade inflammation markers in prepubertal offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM).. 172 offspring of 311 mothers randomized to receive metformin (n = 82) or insulin (n = 90) for GDMwere studied at 9 years of age (follow-up rate 55%). Measurements included anthropometrics, adipocytokines, markers of the low-grade inflammation, abdominal magnetic resonance imaging (MRI), magnetic liver spectrometry (MRS), and whole body dual-energy X-ray absorptiometry (DXA).. Serum markers of low-grade inflammation, visceral adipose tissue volume, total fat percentage, and liver fat percentage were similar between the study groups. Serum adiponectin concentration was higher in children in the metformin group compared to insulin group (median 10.37 vs 9.50 µg/ml, p = 0.016). This difference between groups was observed in boys only (median 12.13 vs 7.50 µg/ml, p < 0.001). Leptin/adiponectin-ratio was lower in boys in the metformin group than in the insulin group (median 0.30 vs 0.75; p = 0.016).. Maternal metformin treatment for GDM had no effects on adiposity, body composition, liver fat, or inflammation markers in prepubertal offspring compared to maternal insulin treatment but was associated with higher adiponectin concentration and lower leptin/adiponectin-ratio in boys.

Topics: Adipokines; Adiponectin; Adiposity; Child; Diabetes, Gestational; Female; Humans; Inflammation; Insulin; Insulin, Regular, Human; Leptin; Male; Metformin; Obesity; Pregnancy

To investigate the association between continuous glucose monitoring (CGM) metrics and perinatal outcomes in insulin-treated diabetes mellitus in pregnancy.. In a post-hoc analysis of the GlucoMOMS randomized controlled trial, we investigated the association between the metrics of an offline, intermittent CGM, glycated haemoglobin (HbA1c) and perinatal outcomes per trimester in different types of diabetes (type 1, 2 or insulin-treated gestational diabetes mellitus [GDM]). Data were analysed using multivariable binary logistic regression. Outcomes of interest were neonatal hypoglycaemia, pre-eclampsia, preterm birth, large for gestational age (LGA) and Neonatal Intensive Care Unit (NICU) admission. The glucose target range was defined as 3.5-7.8 mmol/L (63-140 mg/dL).. Of the 147 participants (N = 50 type 1 diabetes, N = 94 type 2 diabetes/insulin-treated GDM) randomized to the CGM group of the GlucoMOMS trial, 115 participants had CGM metrics available and were included in the current study. We found that, in pregnancies with type 1 diabetes, a higher second trimester mean glucose was associated with LGA (odds ratio 2.6 [95% confidence interval 1.1-6.2]). In type 2 and insulin-treated gestational diabetes, an increased area under the curve above limit was associated with LGA (odds ratio 10.0 [95% confidence interval 1.4-72.8]). None of the CGM metrics were associated with neonatal hypoglycaemia, pre-eclampsia, shoulder dystocia, preterm birth and NICU admission rates for pregnancies complicated by any type of diabetes.. In this study, in type 2 diabetes or insulin-treated GDM, the glucose increased area under the curve above limit was associated with increased LGA. In type 1 diabetes, the mean glucose was the major determinant of LGA. Our study found no evidence that other CGM metrics determined adverse pregnancy outcomes.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose; Humans; Hypoglycemia; Infant, Newborn; Insulin; Insulin, Regular, Human; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth

Gestational diabetes mellitus (GDM) is one of the prevalent adverse conditions among pregnant women which needs delicate monitoring and control. GDM is a state in which the pregnant women's blood glucose level exceeds the normal range. Our goal was to determine the best therapeutic method to control the blood glucose level among GDM patients by comparing of the efficacy between two Insulin consisting, Novo-rapid + Levemir Insulin and Regular + NPH Insulin.. In this double-blind, randomized clinical trial study, we enrolled 100 women with GDM as an inpatient. In group A, patients underwent treating with Regular + NPH Insulin, and in group B, patients underwent treating with Novo-rapid + Levemir Insulin. Patient's demographic and clinical information gathered by specified several times during the study and analysis performed by SPSS21.. Despite significant changes in the two groups patient's blood glucose levels; we could not find any remarkable differences between the two groups. In the case of patient and health care system satisfaction and the length of the hospitalization group, B was better than group A.. Altogether, The Novo-rapid and Levemir Insulin in comparing with the Regular and NPH Insulin were practically advantageous due to the simple using method and short hospitalization period of the patient. Thus, we prefer and suggest this beneficial method (using Novo-rapid and Levemir Insulin) to reach therapeutic goals.

Topics: Adult; Blood Glucose; Diabetes, Gestational; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Pregnancy; Young Adult

Evaluation of adjuvant insulin therapy effects on glycemic control, perinatal outcome and postpuerperal glucose tolerance in impaired glucose tolerance (IGT) pregnant women who failed to achieve desired glycemic control by dietary regime.. A total of 280 participants were classified in two groups: Group A patients continued with dietary regime and Group B patients were treated with adjuvant insulin therapy. Glycemic control was assessed by laboratory and ultrasonograph means. Pregnancy outcomes were evaluated by prevalence of pregnancy induced hypertension (PIH), high birth weight, neonatal hypoglycemia and caesarean section rates. Postpuerperal glucose tolerance was assessed by oral glucose tolerance test (oGTT).. All laboratory and ultrasound indicators of glycemic control had significantly lower values in Group B. Group A women were more likely to develop the EPH (Edema, Proteinuria, Hypertension) syndrome, 20% versus 7.86% (p = 0.003). High birth weight occurred more frequently in Group A, but the difference was not significant (p = 0.197). Higher rate of caesarean delivery was in Group A than in Group B, 16.43% versus 26.43% (p = 0.041). The difference in neonatal hypoglycemia was not significant (p = 0.478). Pathological oGTT results were observed in 73 Group A patients and in 15 Group B patients.. Lower caesarean section rates and the EPH syndrome incidence are the benefits of adjuvant insulin therapy in IGT patients.

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; Chemotherapy, Adjuvant; Diabetes, Gestational; Diet Therapy; Drug Administration Schedule; Drug Therapy, Combination; Exercise Therapy; Female; Glucose Metabolism Disorders; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Regular, Human; Insulin, Regular, Pork; Isophane Insulin, Human; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Treatment Outcome; Young Adult

Topics: Adult; Blood Glucose; Diabetes, Gestational; Female; Fetal Macrosomia; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Insulin, Regular, Pork; Isophane Insulin, Human; Patient Compliance; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Pregnancy Trimester, Third; Prospective Studies

To evaluate changes in insulin physiology in euglycemic pregnancy and gestational diabetes mellitus (GDM).. Participants underwent oral glucose tolerance tests at ≤15 weeks' gestation (early pregnancy), 24-32 weeks' gestation (mid-late pregnancy), and 6-24 weeks postpartum. We evaluated longitudinal changes in insulin secretory response (log Stumvoll first-phase estimate) and insulin sensitivity (log Matsuda index) using linear mixed models. We then evaluated participants who met GDM criteria in early pregnancy (early GDM) and mid-late pregnancy (classic GDM) separately from those without GDM. We derived the pregnancy insulin physiology (PIP) index to quantify β-cell compensation for insulin resistance.. Among 166 participants, 21 had early GDM and 24 developed classic GDM. Insulin sensitivity was reduced slightly in early pregnancy (β = -0.20, P < 0.001) and substantially in mid-late pregnancy (β = -0.47, P < 0.001) compared with postpartum. Insulin secretory response (adjusted for insulin sensitivity) was augmented in early pregnancy (β = 0.16, P < 0.001) and mid-late pregnancy (β = 0.16, P = 0.001) compared with postpartum. Compared with postpartum, the PIP index was augmented in early pregnancy (β = 215, P = 0.04) but not mid-late pregnancy (β = 55, P = 0.64). Early GDM was distinguished by a substantial reduction in early pregnancy insulin sensitivity (β = -0.59, P < 0.001) compared with postpartum. Both early and classic GDM lacked evidence of early pregnancy augmentation of insulin secretory response (adjusted for insulin sensitivity) and the PIP index (P > 0.1 vs. postpartum). Early pregnancy PIP index predicted GDM independent of participant characteristics (area under the curve without PIP index 0.70 [95% CI 0.61-0.79], area under the curve with PIP index 0.87 [95% CI 0.80-0.93]).. β-Cell function is enhanced in early pregnancy. Deficient first-trimester β-cell function predicts GDM.

Topics: Blood Glucose; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Postpartum Period; Pregnancy

To describe the clinical and sociodemographic characteristics of pregnant women diagnosed with gestational diabetes mellitus (GDM) and to assess factors potentially associated with out-of-target glycemic control and the need for insulin.. Retrospective descriptive cohort. Women with GDM delivered at a reference hospital between January 2018 and September 2020 were included; women delivered in a different institution were excluded. Measured variables were age, body mass index (BMI) at the start of pregnancy, family history of diabetes, gestational age at the time of diagnosis, blood glucose levels at baseline and following oral glucose tolerance test, fructosamine, Hba1c, and insulin therapy use. A descriptive exploratory analysis of factors associated with poor glycemic control was conducted using uni and multivariate analyses.. Of the patients with GDM, 44 % were out of target for blood glucose with lifestyle and dietary measures. The exploratory analyses revealed a potential increase in the risk of poor glycemic control associated with initial blood glucose level on OGTT (raw OR: 3.57; 95 % CI: 2.1 - 6.1), BMI > 25 kg/m2 (OR: 1.97, 95 % CI: 1.15 - 3.34), and more advanced gestational age at the time of diagnosis as a protective factor against the need for insulin therapy (OR: 0.45, 95 % CI: 0.27- 0.75). However, these associations were not confirmed in the multivariate analysis.. A baseline blood glucose value greater than 95 mg/dl and BMI of more than 25 kg/m2 could be associated with poor glycemic control in women with GDM. Studies that assess these variables and control for confounding factors are needed in order to identify the factors associated with insulin requirement in pregnant women.. describir las características clínicas y sociodemográficas de las gestantes con diagnóstico de diabetes mellitus gestacional (DMG) y evaluar posibles factores asociados al control glucémico fuera de objetivo y requerimiento de insulina.. cohorte retrospectiva descriptiva. Se incluyeron mujeres con DMG atendidas en un hospital de referencia entre enero de 2018 y septiembre de 2020; se excluyeron mujeres con parto realizado en otra Institución. Las variables medidas fueron edad, índice de masa corporal al inicio del embarazo, antecedentes familiares de diabetes, edad gestacional al diagnóstico, glucemia basal y glucemia post prueba de tolerancia oral a la glucosa, fructosamina, Hba1c, y uso de insulinoterapia. Se realizó un análisis descriptivo y exploratorio de los factores asociados al mal control glucémico por medio del análisis uni y multivariado.. el 44 % de las pacientes con DMG presentaron control glucémico fuera de objetivo con medidas higiénico-dietéticas. El análisis exploratorio mostró que podría haber un incremento en el riesgo del mal control glucémico asociado al valor inicial de la glucemia durante la PTOG (OR crudo: 3,57, IC 95 %: 2,1 - 6,1), el IMC > 25 kg/m2 (OR: 1,97, IC 95 %: 1,15 - 3,34) y la mayor edad gestacional al momento del diagnóstico como factor protector del requerimiento de la insulinoterapia (OR: 0,45, IC 95 %: 0,27 - 0,75). Sin embargo, estas asociaciones no se confirmó en el análisis multivariado.. el valor de la glucemia basal mayor a 95 mg/dl, el IMC mayor a 25 kg/m2 podrían estar asociadas al mal control glucémico en las mujeres con DMG. Se necesitan estudios que evalúen estas variables con control de los factores de confusión para determinar los factores que indican el uso de insulina en mujeres gestantes.

Topics: Argentina; Blood Glucose; Diabetes, Gestational; Female; Hospitals; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human; Pregnancy; Retrospective Studies; Risk Factors

Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, RAMPs are present in mouse pancreatic islets and co-localized with insulin. The expressions of ADM, CRLR and RAMP2 in islets from pregnant mice are reduced compared to that of non-pregnant mice. NIT-1-β cells express ADM and its receptor mRNA, and glucose dose-dependently stimulates expressions. Furthermore, ADM inhibits NIT-1-β cell growth, and this inhibition is reversed by ADM antagonist, ADM22-52. The glucose-induced insulin secretion was suppressed by ADM in NIT-1-β cells and isolated pancreatic islets from pregnant mice. These inhibitory effects are accompanied by upregulation of endoplasmic reticulum (ER) stress biomarker genes in NIT-1-β cells. This study unveils that reduced ADM and its receptors may play a role in β-cell adaptation during pregnancy, while increased plasma ADM in GDM may contribute to the β-cells dysfunction, and blockade of ADM may reverse β-cell insulin production.

Topics: Adrenomedullin; Animals; Diabetes, Gestational; Female; Glucose; Humans; Insulin; Insulin-Secreting Cells; Insulin, Regular, Human; Mice; Pregnancy; Receptors, Adrenomedullin

South Asian women have a higher risk of type 2 diabetes after gestational diabetes mellitus (GDM) than Nordic women; however, the mechanisms behind this difference remain unclear. We investigated insulin sensitivity, β-cell function, and hepatic insulin clearance in 179 South Asian and 108 Nordic women ∼17 months after GDM (mean age 35.3 years, BMI 29.1 kg/m2) by oral glucose tolerance test using deconvolution of C-peptide kinetics. Thirty-one percent of South Asian and 53% of Nordic participants were normoglycemic at the time of measurement. South Asian women had higher areas under the curve (AUCs) for glucose, prehepatic insulin, and peripheral insulin and lower insulin sensitivity, disposition index, and fasting hepatic insulin clearance than Nordic women. In the group with prediabetes or diabetes, South Asian women had similar AUCs for glucose and prehepatic insulin but a higher AUC for peripheral insulin, lower disposition index, and lower fasting hepatic insulin clearance than Nordic women. The waist-to-height ratio mediated ∼25-40% of the ethnic differences in insulin sensitivity in participants with normoglycemia. Overall, our novel data revealed that South Asian women with normoglycemia after GDM showed lower insulin secretion for a given insulin resistance and lower hepatic insulin clearance than Nordic women. South Asian women are at high risk of developing type 2 diabetes after GDM, and preventive efforts should be prioritized.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Kinetics; Pregnancy

We previously reported an increased risk of being small for gestational age (SGA) and a decreased risk of being large for gestational age (LGA) after in utero exposure to metformin compared with insulin exposure. This follow-up study investigated if these observations remain when metformin exposure (henceforth, metformin cohort) is compared with non-pharmacological antidiabetic treatment of gestational diabetes mellitus (GDM; naïve cohort), instead of insulin. RESEARCH DESIGN AND METHODS : This was a Finnish population register-based cohort study from singleton children born during 2004-2016. Birth outcomes from metformin cohort (n=3964) and the naïve cohort (n=82 675) were used in the main analyses. Additional analyses were conducted in a subcohort, restricting the metformin cohort to children of mothers with GDM only (n=2361). Results were reported as inverse probability of treatment weighted OR (wOR), with the naïve cohort as reference. RESULTS  : No difference was found for the outcome of SGA between the cohorts in the main analyses (wOR 0.97, 95% CI 0.73 to 1.27) or in the additional analyses (wOR 1.01, 95% CI 0.75 to 1.37). No difference between the cohorts was found for the risk of LGA (wOR 0.91, 95% CI 0.75 to 1.11) in the main analyses but a decreased risk was observed in the additional analyses (wOR 0.72, 95% CI 0.56 to 0.92). CONCLUSIONS : This follow-up study found no increase in the risk of SGA or LGA after in utero exposure to metformin, compared with drug-naïve GDM. The decreased risk of LGA in mothers with GDM may suggest residual confounding. The lack of increased SGA risk aligns with findings from studies using metformin in non-diabetic pregnancies. In contrast, lower birth weight and increased SGA birth risk were observed in GDM pregnancies for metformin versus insulin. Metformin should be avoided with emerging growth restriction in utero. The interplay of intrauterine hyperglycemia and pharmacological treatments needs further assessment.

Topics: Child; Cohort Studies; Diabetes, Gestational; Female; Follow-Up Studies; Humans; Infant, Newborn; Insulin; Insulin, Regular, Human; Metformin; Pregnancy; Weight Gain