c-peptide and Non-alcoholic-Fatty-Liver-Disease

This study investigates the connection between abnormal liver enzymes and macro vascular disease in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). Clinical data from 276 T2DM patients with NAFLD were retrospectively examined and divided into two groups based on the presence or absence of macro vascular disease. Various biochemical markers were tested, including fasting C-peptide, total bilirubin (TBil), total protein (TP), albumin (Alb), C-reactive protein (CRP) and the insulin resistance index (HOMA-IR). The study found no significant differences in demographic variables between the two groups. However, patients with macro vascular disease had significantly higher levels of fasting C-peptide, CRP, HOMA-IR, TBil, TP, Alb and certain blood lipid markers. The study concludes that in T2DM patients with NAFLD, increased blood lipids, liver function and inflammatory factors are risk factors for macro vascular disease, suggesting the importance of clinical management to lower macro vascular disease prevalence.

Topics: Albumins; Bilirubin; C-Peptide; C-Reactive Protein; Diabetes Mellitus, Type 2; Humans; Non-alcoholic Fatty Liver Disease; Retrospective Studies; Risk Factors; Vascular Diseases

Glucolipid metabolism plays an important role in the occurrence and development of diabetes mellitus. However, there is limited research on the characteristics of glucolipid metabolism and complications in different subgroups of newly diagnosed diabetes. This study aimed to investigate the characteristics of glucolipid metabolism and complications in novel cluster-based diabetes subgroups and explore the contributions of different glucolipid metabolism indicators to the occurrence of complications and pancreatic function.. This retrospective study included 547 newly diagnosed type 2 diabetes patients. Age, body mass index (BMI), glycated hemoglobin (HbA. Total cholesterol (TC), triglycerides (TG), triglyceride glucose index (TyG), HbA. There were differences in the characteristics of glucolipid metabolism as well as complications among different subgroups of newly diagnosed type 2 diabetes. 2hCP, FCP, FINS, FPG, TyG, HbA

Topics: Blood Glucose; C-Peptide; Cholesterol, HDL; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; Lipoproteins, HDL; Non-alcoholic Fatty Liver Disease; Renal Insufficiency, Chronic; Retrospective Studies; Triglycerides

While for individuals with obesity an association between hyperleptinemia and an increased risk of non-alcoholic fatty liver disease (NAFLD) is assumed, a leptin deficiency is also related to the development of NAFLD early in life in. To investigate the association of circulating leptin levels in pre-pubertal children with obesity and steatosis hepatis.. The cross-sectional study consisted data of n=97 (n. One-third of the children with obesity were diagnosed with steatosis hepatis (I°: 63.6%, II°/III°: 36.4%). Children with steatosis hepatis had significantly lower z-scores of circulating leptin levels compared to children with an unremarkable liver ultrasonography (-2.1 ± 0.8 vs. -0.7 ± 0.6). Z-scores of circulating leptin levels correlate negatively with degree of steatosis hepatis. Children with low z-scores of circulating leptin levels had significantly higher triglyceride, fasting insulin and c-peptide levels compared to children with normal z-scores of circulating leptin levels.. Prepubertal children with NAFLD and obesity and partial leptin deficiency might be defined as a clinical subgroup.

Topics: Body Mass Index; C-Peptide; Child; Cross-Sectional Studies; Female; Humans; Insulin; Leptin; Male; Non-alcoholic Fatty Liver Disease; Pediatric Obesity; Triglycerides

Nonalcoholic fatty liver disease (NAFLD) is the commonest etiology of chronic hepatic problems in children with obesity. This study aimed to assess whether urinary C-peptide creatinine ratio (UCPCR) might be a potential indicator of NAFLD in obese children.. The study included 240 children with simple obesity. Hepatic ultrasonic examination, anthropometric and laboratory measurements including fasting plasma glucose, fasting insulin, fasting C peptide, liver, renal profile, lipid profile, and UCPCR were obtained in all cases. According to the results of the hepatic ultrasonography, cases were classified into two categories, those with NAFLD (n=98) and without NAFLD (n= 142).. In cases with NAFLD, UCPCR was significantly higher than those without NAFLD (P < 0.001). A significant positive correlation between UCPCR and waist circumference (WC SDS), triglyceride, fasting C-peptide, HOMA-IR and alanine aminotransferase (ALT) was found (P < 0.001 for each). Adjusting for other variables, UCPCR was the most significant predictor of NAFLD in children with obesity with higher odds ratio (OR = 3.26) than fasting C peptide (OR = 2.87), triglyceride (OR = 1.89), ALT (OR = 2.20), WC SDS (OR = 1.32) and age (OR=1.27) . UCPCR cut-off value of 0.755 nmol/mmol was able to discriminate cases with NAFLD from those without NAFLD with a sensitivity of 95%, a specificity of 87%.. We concluded that UCPCR is a useful, practical and non-invasive predictor of NAFLD in children with obesity with high sensitivity and specificity.

Topics: Body Mass Index; C-Peptide; Child; Creatinine; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Pediatric Obesity; Triglycerides

To determine the prognostic value of C-peptide in long-term nonalcoholic fatty liver disease (NAFLD) mortality.. A total of 4670 participants with NAFLD were enrolled in this study. Multivariable Cox regression models evaluated the links between C-peptide levels and all-cause and cardiovascular disease (CVD) mortality risk using adjusted hazard ratios (aHR). In addition, a two‑piecewise Cox model with penalized splines was adapted to investigate the nonlinear relationships between C-peptide and mortality.. After a mean follow‑up period of 20 years, 1714 deaths from all causes were recorded. In an adjusted Cox regression analysis, using the low C-peptide group as the reference (quartile 1), higher C-peptide (quartile 4) was notably associated with increased all-cause mortality (aHR =1.39; 95% CI: 1.18-1.65) and CVD death (aHR = 1.97; 95% CI: 1.41-2.76). Spline analyses demonstrated that the association between C-peptide levels and all-cause mortality was U-shaped, with a threshold value of 0.41 nmol/L. Below the threshold, every one-unit increment in C-peptide had a 70% reduced risk of all-cause death (aHR = 0.30, 95% CI: 0.1-0.7). Above the threshold, the C-peptide levels were associated with a higher probability of all-cause death (aHR = 1. 3, 95% CI:1.2-1.4).. In the US NAFLD population defined by ultrasound, a U-shaped association was detected between baseline serum C-peptide level and all-cause mortality.

Topics: C-Peptide; Cardiovascular Diseases; Humans; Non-alcoholic Fatty Liver Disease; Proportional Hazards Models; Regression Analysis; Risk Factors

This study aimed to retrospectively assess the association between prolactin (PRL) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).. A retrospective, cross-sectional study was conducted at a single hospital in Anhui, China.. A total of 406 patients with T2DM (230 men and 176 women) was included.. P values for the independent t-test, the Mann-Whitney rank-sum test, the Spearman correlation analysis and multiple logistic regression models were used to explore the association between PRL and NAFLD in patients with T2DM.. The results indicated that in both men and women, the levels of PRL were significantly lower in the T2DM with NAFLD group than in the T2DM without NAFLD group (men: 9.56 ng/mL vs 10.36 ng/mL, women: 10.38 ng/mL vs 12.97 ng/mL). In male patients, the levels of PRL were negatively correlated with hip circumference (r=-0.141, p=0.032), homoeostasis model assessment for insulin resistance (C-peptide) (r=-0.141, p=0.032) and triglyceride (TG) (r=-0.252, p=0.000) values and inversely correlated with high-density lipoprotein (r=0.147, p=0.025) levels. In female patients, PRL levels were negatively related to body mass index (r=-0.192, p=0.011), diastolic blood pressure (r=-0.220, p=0.003), waist circumference (r=-0.152, p=0.044), hip circumference (r=-0.157, p=0.037) and TG (r=-0.258, p=0.001) values. Logistic regression analysis revealed a negative relationship between PRL and NAFLD (men: OR 0.891, 95% CI 0.803 to 0.989, p=0.031; women: OR 0.874, 95% CI 0.797 to 0.957, p=0.004). As PRL levels increased, NAFLD prevalence decreased in both sexes (men: p=0.012, women: p=0.013).. Our results suggest that low levels of PRL in the physiological range were markers of NAFLD in patients with T2DM and that PRL within the biologically high range may play a protective role in the pathogenesis of NAFLD.

Topics: C-Peptide; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Hospitals; Humans; Lipoproteins, HDL; Male; Non-alcoholic Fatty Liver Disease; Prolactin; Retrospective Studies; Triglycerides

To explore relationships between polyunsaturated fatty acids (PUFA) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes, and whether insulin action has an interactive effect with PUFA on NAFLD progression.. We extracted clinical and omics data of 482 type 2 diabetes patients from a tertiary hospital consecutively from April 2018 to April 2019. NAFLD was estimated by ultrasound at admission. Plasma fasting n3 and n6 fatty acids were quantified by liquid chromatography-tandem mass spectrometry analysis. Restricted cubic spline nested in binary logistic regression was used to select the cut-off point, and estimate odds ratios and 95% confidence intervals. Additive interactions of the n6 : n3 ratio with insulin action for NAFLD were estimated using relative excess risk due to interaction, attributable proportion due to interaction and synergy index. Relative excess risk due to interaction >0, attributable proportion due to interaction >0 or synergy index >1 indicates biological interaction. Spearman correlation analysis was used to obtain partial correlation coefficients between PUFA and hallmarks of NAFLD.. Of 482 patients, 313 were with and 169 were without NAFLD. N3 ≥800 and n6 PUFA ≥8,100 μmol/L were independently associated with increased NAFLD risk; n6 : n3 ratio ≤10 was associated with NAFLD (odds ratio 1.80, 95% confidence interval 1.20-2.71), and the effect size was amplified by high C-peptide (odds ratio 8.89, 95% confidence interval 4.48-17.7) with significant interaction. The additive interaction of the n6 : n3 ratio and fasting insulin was not significant.. Decreased n6 : n3 ratio was associated with increased NAFLD risk in type 2 diabetes patients, and the effect was only significant and amplified when there was the co-presence of high C-peptide.

Topics: Aged; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Inpatients; Insulin; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Odds Ratio

Patients with nonalcoholic fatty liver disease (NAFLD) are characterized by insulin resistance and hyperinsulinism. However, insulin resistance measurements have not been shown to be good diagnostic tools to predict NAFLD in prior studies.. We aimed to assess a newly validated method to measure intact molecules of insulin by mass spectrometry to predict NAFLD.. Patients underwent a 2-hour oral glucose tolerance test (OGTT), a liver magnetic resonance spectroscopy (1H-MRS), and a percutaneous liver biopsy if they had a diagnosis of NAFLD. Mass spectrometry was used to measure intact molecules of insulin and C-peptide.. A total of 180 patients were recruited (67% male; 52 ± 11 years of age; body mass index [BMI] 33.2 ± 5.7 kg/m2; 46% with diabetes and 65% with NAFLD). Intact fasting insulin was higher in patients with NAFLD, irrespective of diabetes status. Patients with NAFLD without diabetes showed ~4-fold increase in insulin secretion during the OGTT compared with all other subgroups (P = 0.008). Fasting intact insulin measurements predicted NAFLD in patients without diabetes (area under the receiver operating characteristic curve [AUC] of 0.90 [0.84-0.96]). This was significantly better than measuring insulin by radioimmunoassay (AUC 0.80 [0.71-0.89]; P = 0.007). Intact fasting insulin was better than other clinical variables (eg, aspartate transaminase, triglycerides, high-density lipoprotein, glucose, HbA1c, and BMI) to predict NAFLD. When combined with alanine transaminase (ALT) (intact insulin × ALT), it detected NAFLD with AUC 0.94 (0.89-0.99) and positive and negative predictive values of 93% and 88%, respectively. This newly described approach was significantly better than previously validated noninvasive scores such as NAFLD-LFS (P = 0.009), HSI (P < 0.001), and TyG index (P = 0.039).. In patients without diabetes, accurate measurement of fasting intact insulin levels by mass spectrometry constitutes an easy and noninvasive strategy to predict presence of NAFLD.

Topics: Adult; Alanine Transaminase; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Liver; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Middle Aged; Non-alcoholic Fatty Liver Disease; Reproducibility of Results

Objective The correlation between the insulin secretion levels and the risk of hepatocarcinogenesis is clinically important. The aim of the present study was to determine the effects of various clinical parameters on C-peptide (CPR) levels in patients with non-alcoholic fatty liver disease (NAFLD). Methods In this retrospective cohort study, the effects of clinical parameters on insulin resistance (HOMA-IR) and insulin secretion levels (HOMA-β and fasting CPR) were investigated. Patients A total of 244 Japanese patients with histopathologically confirmed NAFLD were evaluated. Of these, 77 underwent the meal tolerance test (MTT) to evaluate the association of various clinical parameters with the CPR levels at 120 minutes. Results A multivariate analysis identified fasting plasma glucose (FPG) (≥110 mg/dL), aspartate aminotransferase (≥1.0×ULN IU/L), and a large waist circumference as independent predictors of insulin resistance (HOMA-IR ≥2.5) or high fasting CPR levels. Significant parameters for a low insulin secretion capacity (HOMA-β <30%) were not detected, except for the parameters mentioned in the diagnostic criteria of diabetes mellitus. Regarding the MTT, the CPR levels at 120 minutes were significantly higher in patients with fibrosis stage 3-4 than in those with stage 0-2. Body composition and genetic variation did not affect the CPR levels at 120 minutes. A multivariate analysis identified fibrosis stage (3-4), hyperuricemia, FPG (≥110 mg/dL), and procollagen III peptide (>1.0 U/mL) as independent predictors of high CPR levels at 120 minutes. Conclusion The present study showed that high plasma glucose levels and severe liver fibrosis stage influence insulin secretion levels in Japanese patients with NAFLD. Conservation of delayed insulin secretion levels was confirmed in patients with severe liver fibrosis.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Blood Glucose; C-Peptide; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Japan; Liver Cirrhosis; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Predictive Value of Tests; Retrospective Studies; Risk Factors; Young Adult

Whether fasting C-peptide can be a potential indicator for nonalcoholic fatty liver disease (NAFLD) in obese children is unknown. This study aimed to assess whether fasting C-peptide represented a risk factor for NAFLD.. A total of 520 obese children (376 male, 144 female) aged 3.4-17.1 years were divided into two groups, obese with NAFLD and non-NAFLD, according to hepatic ultrasound results. Fasting plasma glucose, fasting C-peptide, hemoglobin A1c, renal function, liver function, blood lipid, fasting insulin and blood routine indices were measured. Insulin resistance by homoeostasis model (HOMA-IR) was calculated.. Compared with the non-NAFLD group, the obese children with NAFLD had higher fasting C-peptide, fasting insulin and HOMA-IR (P < 0.001). Stepwise multiple logistic regression models showed that fasting C-peptide (odds ratio: OR = 2.367) was independent indicator of the presence of NAFLD in obese children as well as white blood cell (OR = 1.113), albumin (OR = 1.124), alanine aminotransferase (OR = 1.030), triglycerides (OR = 1.335), and waist circumference (OR = 1.047). Furthermore, after adjustment for confounding variables, the prevalence of NAFLD in obese children was significantly higher according to increased serum fasting C-peptide levels. The adjusted OR for NAFLD according to fasting C-peptide tertiles were 1.00 (as references), 1.896(1.045-3.436), and 4.169(1.822-9.537).. Our data suggested that obese children with high level of fasting C-peptide had an increased risk for developing NAFLD.

Topics: C-Peptide; Child; Fasting; Female; Humans; Male; Non-alcoholic Fatty Liver Disease; Pediatric Obesity; Risk Factors

We aimed to determine the immediacy of exercise intervention on liver-specific metabolic processes in nonalcoholic fatty liver disease.. We undertook a short-term (7-d) exercise training study (60 min·d treadmill walking at 80%-85% of maximal heart rate) in obese adults (N = 13, 58 ± 3 yr, 34.3 ± 1.1 kg·m, >5% hepatic lipid by H-magnetic resonance spectroscopy). Insulin sensitivity index was estimated by oral glucose tolerance test using the Soonthorpun model. Hepatic insulin extraction (HIE) was calculated as the molar difference in area under the curve (AUC) for insulin and C-peptide (HIE = 1 - (AUCInsulin/AUCC-Pep)).. The increases in HIE, V˙O2max, and insulin sensitivity index after the intervention were 9.8%, 9.8%, and 34%, respectively (all, P < 0.05). Basal fat oxidation increased (pre: 47 ± 6 mg·min vs post: 65 ± 6 mg·min, P < 0.05) and carbohydrate oxidation decreased (pre: 160 ± 20 mg·min vs post: 112 ± 15 mg·min, P < 0.05) with exercise training. After the intervention, HIE correlated positively with adiponectin (r = 0.56, P < 0.05) and negatively with TNF-α (r = -0.78, P < 0.001).. By increasing HIE along with peripheral insulin sensitivity, aerobic exercise training rapidly reverses some of the underlying physiological mechanisms associated with nonalcoholic fatty liver disease, in a weight loss-independent manner. This reversal could potentially act through adipokine-related pathways.

Topics: Blood Glucose; C-Peptide; Carbohydrate Metabolism; Exercise; Glucagon-Like Peptide 1; Heart Rate; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Liver; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Oxygen Consumption

A higher prevalence of nonalcoholic steatohepatitis (NASH) and advanced stages of fibrosis was observed in type 2 diabetes. We aim to investigate whether C-peptide is associated with nonalcoholic fatty liver disease (NAFLD) progression in type 2 diabetic adults.. A total of 4937 diabetic participants were enrolled from China in 2018. Liver steatosis was detected by ultrasound. Subjects with NAFLD were categorized into simple NAFLD and probable NASH by the concurrent presence of metabolic syndrome. NAFLD fibrosis score was used to identify patients with probable advanced fibrosis.. Individuals with a longer history of type 2 diabetes had a lower C-peptide level and a lower prevalence of probable NASH but a higher prevalence of advanced fibrosis. C-peptide was positively associated with simple NAFLD and probable NASH, with odds ratios (ORs) of 4.55 [95% confidence interval (CI) 3.16, 6.55] and 5.28 (95% CI 3.94, 7.09), respectively, comparing quartile 4 with quartile 1 (both p for trend <0.001). However, C-peptide quartiles were negatively associated with the probable presence of advanced fibrosis (Q4 vs. Q1, OR 0.59, 95% CI 0.36, 0.97, p for trend <0.05). A 1-SD increment of ln(C-peptide) was also significantly associated with inflammatory and fibrotic progression (OR 1.34, 95% CI 1.27, 1.41; OR 0.88, 95% CI 0.79, 0.98, respectively).. Significant but opposite associations between C-peptide and inflammatory and fibrotic progression of NAFLD were observed. Understanding islet hormone changes during type 2 diabetes and differentiating the stage of NAFLD may help to personalize treatment strategies for NAFLD patients with type 2 diabetes.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Disease Progression; Female; Follow-Up Studies; Humans; Inflammation; Liver Cirrhosis; Male; Metabolic Syndrome; Middle Aged; Non-alcoholic Fatty Liver Disease; Prognosis; Severity of Illness Index; Young Adult

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease which becomes a rapidly growing health problem in the Western countries. The development of the disease is most often connected to obesity. NAFLD is also considered as the hepatic manifestation of metabolic syndrome. Transforming growth factor b1 (TGF-b1) plays an important role in the pathogenesis of liver fibrosis, being involved in activation of hepatic stellate cells, stimulation of collagen gene transcription, and suppression of matrix metalloproteinase expression. The objective of the study was to evaluate by immunohistochemistry the expression of TGF-b1 in the liver tissue of NAFLD patients and correlate it with anthropometric, biochemical and routine histological parameters.. The study group consisted of 48 patients with diagnosed NAFLD. Liver steatosis, NAFLD Activity Score (NAS) and METAVIR score of fibrosis were evaluated in liver biopsies. The immunoreactivity of TGF-b1 was evaluated semi-quantitatively separately in portal, septal, lobular hepatocytic and lobular sinu-soidal liver compartments. The results were analyzed in regard to patients' clinical and biochemical parameters.. Neither steatosis nor NAS correlated with TGF-b1 expression in any liver compartment, whereas METAVIR score of fibrosis was associated with increased immunoreactivity of TGF-b1 in most of the studied liver compartments. TGF-b1 immunoreactivity showed positive correlation with patients' age and its expression in septal compartment disclosed positive correlation with body mass index, and waist and hip circumference. Hyaluronic acid serum level was positively and iron concentration was negatively associated with TGF-b1 ex-pression in the selected consecutive liver compartments.. The immunohistochemical expression of TGF-b1 may be complementary to routine methods of liver fibrosis evaluation.

Topics: Adult; C-Peptide; Fatty Liver; Female; Glycated Hemoglobin; Haptoglobins; Humans; Hyaluronic Acid; Immunohistochemistry; Iron; Liver; Liver Cirrhosis; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Transforming Growth Factor beta1

In patients with type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and liver fibrosis is frequent and presumably associated with increased cardiovascular disease risk and mortality. The objective was to investigate risk factors associated with hepatic fibrosis in patients with type 2 diabetes and NAFLD to provide a basis for the prevention and treatment.. Liver stiffness measurements (LSM) expressed in kilopascals (kPa) and controlled attenuation parameter (CAP) expressed in dB/m were diagnosed by transient elastography. Hepatic steatosis and significant fibrosis were defined as having a CAP score ≥ 260 dB/m and an LSM score ≥ 8 kPa, respectively. Associations between fibrosis categories with anthropometric and metabolic variables were determined; then, variables with statistical significance in the univariate analysis were included in multivariate model.. A total of 108 participant with type 2 diabetes and NAFLD (mean age: 44.69 ± 5.57 years; mean duration of diabetes 4.68 ± 4.24 years) were recruited. In these patients, body mass index, obesity, fat mass, waist circumferences, resting energy expenditure, CAP score, fasting insulin, C-peptide, HbA1C, hs-CRP as well as liver enzymes and systolic blood pressure and diastolic blood pressure were positively associated with fibrosis (all p < 0.05). Using multivariate logistic regression, serum aspartate aminotransferase (OR 1.12; 95% CI 1.06-1.19), waist circumferences (odds ratio [OR] 1.15; 95% CI 1.05-1.25) and C-peptide (OR 3.81; 95% CI 1.5-9.7) remained as independently associated with liver fibrosis.. For participants with type 2 diabetes with coexisting NAFLD, stratification by independent risk factors for fibrosis could have important prognostic value.

Topics: Adult; Aspartate Aminotransferases; Blood Pressure; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Liver Cirrhosis; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Waist Circumference

Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans.. This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75-g OGTT. Fasting serum Sfrp5 was measured by ELISA. Associations were assessed with several indices of insulin sensitivity and beta-cell function derived from glucose, insulin and C-peptide concentrations during the OGTT.. Circulating Sfrp5 associated inversely with the insulinogenic index based on C-peptide (rs = -0·244, P = 0·001), but not with the insulinogenic index based on insulin levels (rs = -0·007, P = 0·926) after adjustment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulin sensitivity in the model adjusted for age and sex (rs = -0·149, P = 0·039). These associations were not influenced by the additional adjustment for hepatic steatosis index.. The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Eye Proteins; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Membrane Proteins; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity

The severity of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) population compared with that in normal glucose tolerance (NGT) individuals has not yet been quantitatively assessed. We investigated the prevalence and the severity of NAFLD in a T2DM population using controlled attenuation parameter (CAP).. Subjects who underwent testing for biomarkers related to T2DM and CAP using Fibroscan® during a regular health check-up were enrolled. CAP values of 250 dB/m and 300 dB/m were selected as the cutoffs for the presence of NAFLD and for moderate to severe NAFLD, respectively. Biomarkers related to T2DM included fasting glucose/insulin, fasting C-peptide, hemoglobin A1c (HbA1c), glycoalbumin, and homeostasis model assessment of insulin resistance of insulin resistance (HOMA-IR).. Among 340 study participants (T2DM, n=66; pre-diabetes, n=202; NGT, n=72), the proportion of subjects with NAFLD increased according to the glucose tolerance status (31.9% in NGT; 47.0% in pre-diabetes; 57.6% in T2DM). The median CAP value was significantly higher in subjects with T2DM (265 dB/m) than in those with pre-diabetes (245 dB/m) or NGT (231 dB/m) (all p<0.05). Logistic regression analysis showed that subjects with moderate to severe NAFLD had a 2.8-fold (odds ratio) higher risk of having T2DM than those without NAFLD (p=0.02; 95% confidence interval, 1.21-6.64), and positive correlations between the CAP value and HOMA-IR (ρ0.407) or fasting C-peptide (ρ0.402) were demonstrated.. Subjects with T2DM had a higher prevalence of severe NAFLD than those with NGT. Increased hepatic steatosis was significantly associated with the presence of T2DM, and insulin resistance induced by hepatic fat may be an important mechanistic connection.

Topics: Adult; Aged; Biomarkers; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Odds Ratio; Prevalence

This study investigated the relationship among β-cell function, metabolic control, and diabetic microvascular complications in patients with type 2 diabetes mellitus (T2DM).. In total, 885 patients with type 2 diabetes mellitus (DM) were recruited from January 2012 to January 2014 and grouped into three groups according to the area under the curve of C-peptide [AUC(C-pep)] during the 75-g oral glucose tolerance test. Logistic regression analyses were used to evaluate the association between C-peptide and microvascular complications.. The prevalence of diabetic microvascular complications decreased from the first to the third AUC(C-pep) tertile (P < 0.01 for all), whereas the rates of nonalcoholic fatty liver disease (NAFLD) was positively associated with AUC(C-pep) values. Patients with lower AUC(C-pep) tertile exhibited higher levels of glycosylated hemoglobin and high-density lipoprotein cholesterol and longer duration of DM; however, levels of triglycerides, fasting C-peptide, 2-h C-peptide, body mass index, and homeostasis model assessment of insulin resistance index were lower compared with the third tertile. Comparison among patients with a similar DM duration showed a higher level of AUC(C-pep) was inversely associated with prevalence of microvascular complications. The odds ratios for nephropathy, retinopathy, and neuropathy in the lowest versus the highest AUC(C-pep) tertile were 3.10 (95% confidence interval, 2.01-4.78), 2.83 (1.73-4.64), and 2.04 (1.37-3.04) after adjustment for confounding factors.. Higher AUC(C-pep) levels were associated with a decreased prevalence of microvascular complications and a good level of glycemic control, whereas higher endogenous insulin levels were linked to the components of metabolic syndrome and increased rates of NAFLD.

Topics: Adult; Aged; Area Under Curve; Blood Glucose; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fasting; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Insulin-Secreting Cells; Logistic Models; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Odds Ratio; Prevalence; Triglycerides

To investigate the clinical features of non-alcoholic fatty liver disease (NAFLD) and its relationship with serum C-peptide levels in patients with latent autoimmune diabetes in adults (LADA).. A total of 155 patients with LADA who had no drinking history and were hospitalized in department of endocrinology and metabolism from January 2007 to June 2009 were divided into two groups, including patients with LADA but without NAFLD and patients with both LADA and NAFLD, according to Chinese medical association's guidelines of NAFLD and hepatic ultrasound result. Their clinical data and results of laboratory examinations were collected and analyzed, including medications, blood pressure, weight, height, waist circumference, hip circumference, fasting plasma glucose, 2 h postprandial plasma glucose, fasting C-peptide, 2 h postprandial C-peptide, hemoglobin A1c, renal function, liver function, blood lipid and C-reactive protein. The clinical features between two groups were compared and the relationship between serum C-peptide and NAFLD were also analyzed.. Compared to the patients with LADA but without NAFLD, patients with both LADA and NAFLD had higher alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γ-GT) (all P<0.01), but the serum total bilirubin (TBI) and direct bilirubin (DBI) level had no significant inter-group difference (P>0.05). The patients with both LADA and NAFLD had higher fasting C-peptide [0.62(0.33-0.93) vs 0.17 (0.05-0.50) nmol/L, P<0.001], 2 h postprandial C-peptide [1.57(0.78-1.88) vs 0.42(0.06-1.01) nmol/L, P<0.001] and more severe insulin resistance [0.8(1.0-2.5) vs 0.6(0.2-1.3), P<0.001]. Logistic regression analysis showed that there was a significant association between fasting C-peptide and the presence of NAFLD after controlling other confounding factors in patients with LADA.. The patients with both LADA and NAFLD had more severe metabolic disorders and insulin resistance. Serum fasting C peptide was independently associated with the presence of NAFLD in patients with LADA.

Topics: Adult; Alanine Transaminase; Asian People; Aspartate Aminotransferases; C-Peptide; C-Reactive Protein; Diabetes Mellitus, Type 1; gamma-Glutamyltransferase; Glucose Intolerance; Glycated Hemoglobin; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Waist Circumference

Studies have indicated that low serum sex hormone-binding globulin (SHBG) and testosterone levels are associated with nonalcoholic fatty liver disease (NAFLD). However, it remains unclear whether an association exists between SHBG and NAFLD independent of testosterone.. This study was aimed to investigate the relationship between SHBG and both total and free testosterone levels with NAFLD.. One hundred and twenty patients with NAFLD and 120 age-, sex- and BMI-matched patients with non-NAFLD were enrolled into a case-control study. Serums SHBG, total testosterone (TT), liver enzymes, lipids, insulin, C-peptide and plasma glucose were measured. Free testosterone (FT) and fatty liver index were calculated.. Serum SHBG levels were significantly lower in NAFLD group than in non-NAFLD group (24·5 ± 11·0 vs 37·6 ± 14·4 nm, P < 0·001). After adjustment for age, smoking status, alcohol use, duration of diabetes, BMI and fasting C-peptide, serum SHBG levels in men and women were inversely associated with NAFLD, with odds ratio (OR) and 95% confidence interval (CI) in the forth quartile as 0·05 (0·01-0·30) and 0·25 (0·08-0·77) compared with the first quartile (OR = 1·00). Additional adjustment for TT in men and FT in women did not materially alter the association. The relationship between serum TT (for men) and FT (for women) with NAFLD was attenuated and even diminished after multivariable adjustment for known risk factors and SHBG.. Low serum SHBG levels, but not TT or FT, are associated with NAFLD in type 2 diabetic patients.

Topics: Adult; Aged; Anthropometry; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Fatty Liver; Female; Humans; Male; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Odds Ratio; Sex Hormone-Binding Globulin; Testosterone

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) often coexist and have adverse outcomes. The aim of our study was to elucidate metabolic abnormalities in patients with DM-NAFLD versus those with T2DM alone.. Patients were divided into two groups: 26 T2DM patients with NAFLD and 26 gender-, age-, and body mass index-matched patients with T2DM alone. Patients took a 75-g oral glucose tolerance test (OGTT), which measured serum insulin and C-peptide (C-p) levels at baseline (0 min), 30 min, 60 min, and 120 min after glucose challenge.. Patients with DM-NAFLD or T2DM alone had similar blood glucose levels. β-cell hypersecretion was more obvious in patients with DM-NAFLD. In addition, fasting, early-phase, and late-phase C-peptide levels were significantly increased in patients with DM-NAFLD (ΔC-p 0-30 min, P < 0.05; Area Under the Curve (AUC) C-p/PG 30-120 min ratio, P < 0.01; and AUC C-p 30-120 min, P < 0.01). Hepatic and extrahepatic insulin resistance during the OGTT did not differ significantly between groups. Hepatic insulin sensitivity independently contributed to the early phase (0-30 min) of the OGTT in patients with T2DM and NAFLD, whereas a significant deficit in late insulin secretion independently contributed to the 30-120 min glucose status in patients with T2DM only.. In patients with similar levels of insulin resistance and hyperglycemia, DM-NAFLD was associated with higher serum insulin levels than T2DM alone. Hyperinsulinemia is caused mainly by β-cell hypersecretion. The present study demonstrates pathophysiological differences in mechanisms of insulin resistance in patients with DM-NAFLD versus T2DM alone.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fatty Liver; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease

Current literature lacks data on markers of non-alcoholic fatty liver disease (NAFLD) in newly diagnosed type 2 diabetes mellitus (T2DM) patients. We therefore, conducted a cross-sectional study to examine modifiable clinical and lifestyle factors associated with elevated alanine aminotransferase (ALT) levels as a marker of NAFLD in new T2DM patients.. Alanine aminotransferase levels were measured in 1026 incident T2DM patients enrolled in the nationwide Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. We examined prevalence of elevated ALT (>38 IU/L for women and >50 IU/L for men) and calculated prevalence ratios associated with clinical and lifestyle factors using Poisson regression. We examined the association with other biomarkers by linear regression.. The median value of ALT was 24 IU/L (interquartile range: 18-32 IU/L) in women and 30 IU/L (interquartile range: 22-41 IU/L) in men. Elevated ALT was found in 16% of incident T2DM patients. The risk of elevated ALT was increased in patients who were <40 years old at diabetes debut [adjusted prevalence ratio (aPR): 1.96, 95% confidence interval (CI): 1.15-3.33], in those with alcohol overuse (>14/>21 drinks per week for women/men) (aPR: 1.60, 95% CI: 1.03-2.50), and in those with no regular physical activity (aPR: 1.42, 95% CI: 1.04-1.93). Obesity and metabolic syndrome per se showed no association with elevated ALT when adjusted for other markers, whereas we found positive associations of ALT with increased C-peptide (β = 0.14, 95% CI: 0.06-0.21) and fasting blood glucose (β = 0.07, 95% CI: 0.03-0.11).. Among newly diagnosed T2DM patients, several modifiable clinical and lifestyle factors are independent markers of elevated ALT levels.

Topics: Adult; Alanine Transaminase; Alcohol Drinking; Biomarkers; C-Peptide; Cohort Studies; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 2; Female; Humans; Linear Models; Male; Non-alcoholic Fatty Liver Disease; Poisson Distribution; Prevalence; Sedentary Behavior; Sex Factors; Weight Gain; Young Adult

Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM), but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, β-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases) and nonketotic onset group (78 cases). After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC) of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β) and insulin resistance (HOMA-IR). Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD) than nonketotic group (P = 0.04). Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC(0-0.5), AUC₀₋₁, AUC₀₋₃ (P < 0.05). Moreover, this group also had higher HOMA-β and HOMA-IR than nonketotic group (P < 0.05). From these data, we concluded that ketosis onset T2DM had better islet β-cell function and more serious insulin resistance than nonketotic onset T2DM.

Topics: Adolescent; Adult; Aged; C-Peptide; Case-Control Studies; China; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fatty Liver; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Ketone Bodies; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Prevalence; Retrospective Studies; Young Adult

Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease.. We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease.. The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3±8.9 ng/dl, p<0.001) compared with those of the control group (20±13.6 ng/dl).. In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed.

Topics: Adult; Albuminuria; Blood Glucose; C-Peptide; Creatinine; Fasting; Female; Humans; Insulin; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Outpatients; Regression Analysis; Seasons; Vitamin D; Vitamin D Deficiency

Insulin is pivotal in regulating hepatic lipid synthesis, metabolism, and export.. We tested the hypothesis that intrahepatic insulin exposure is an important determinant of intrahepatocellular lipid (IHCL), taking into account regional adiposity and both glucoregulatory and antilipolytic insulin sensitivity.. We compared 21 European males with known nonalcoholic fatty liver disease (NAFLD) with 19 healthy male controls. Insulin sensitivity, secretion, and percentage hepatic extraction were derived from iv glucose tolerance test (IVGTT) glucose, insulin, and C-peptide concentrations. Intrahepatic insulin exposure was calculated as percentage hepatic insulin extraction multiplied by basal or IVGTT insulin secretion. IHCL was quantified by proton magnetic resonance spectroscopy. Total and regional adipose tissue was measured using whole body magnetic resonance imaging.. Percentage hepatic extraction of newly secreted insulin differed between cases with NAFLD and controls at borderline significance (median, 76 vs. 83%; P = 0.07). Cases had higher intrahepatic insulin exposure than controls, both in the basal (34 vs. 18 pmol; P = 0.0002) and glucose-stimulated states (58 vs. 24 pmol; P = 0.01). IHCL was significantly related to both basal (r(s) = 0.62; P < 0.0001) and IVGTT intrahepatic insulin exposure (r(s) = 0.47; P = 0.002). As predictors of IHCL, both basal and IVGTT intrahepatic insulin exposure were dependent on the waist-to-hip ratio and homeostasis model assessment insulin resistance, but not on magnetic resonance imaging fat measures or IVGTT insulin sensitivity.. Men with NAFLD have higher intrahepatic insulin exposure than controls. This correlates with IHCL, but the principal determinants of IHCL were fat distribution and hepatic rather than peripheral insulin resistance.

Topics: Adipose Tissue; Adult; Aged; Blood Glucose; C-Peptide; Cohort Studies; Fatty Liver; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Lipid Metabolism; Liver; Magnetic Resonance Imaging; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Young Adult

NASH (non-alcoholic steatohepatitis) is considered the hepatic manifestation of the metabolic syndrome (MS). We aimed to analyze lipid, carbohydrate, and iron metabolism in NASH.. 37 patients with MS (17 M/20 F, 51+/-15 years), elevated transaminases; 25 patients had histologically proven NASH (NAS score≥5), 12 patients had toxic background (nonNASH). 37 age, sex, BMI-matched healthy controls. Lipid variables, LDL-subfractions, iron, ferritin, transferrin (T), transferrin saturation (TS), and hepcidin (H) were measured in patients/controls. Oral glucose tolerance tests were performed.. NASH patients with steatosis gr. 2 and 3 (>33% hepatic fat) had higher sd-LDL (mg/dl) concentrations than patients with steatosis gr. 1 (<33%) (p=0.002), nonNASH patients (p=0.03) and controls (p=0.001). Sd absolute (mg/dl) correlated directly with the steatosis grade only in patients with NASH and steatosis >33% (p=0.04). NASH-patients showed higher insulin, C-peptide and IRI values than nonNASH patients (p=0.034; 0.032; 0.04). H was increased in patients versus controls (p<0.001). H correlated with ferritin in MS-patients (p=0.01), correlated directly with sd-LDL (mg/dl) (p=0.017) and IRI (p<0.001) and indirectly with HDL (p=0.05) in NASH. No associations between hepatic inflammation/iron content on liver biopsy and variables of lipid metabolism were found but hepcidin correlated with hepatic inflammation in all patients and with NAS scores in NASH.. NASH-patients show insulin resistance and increased sd-LDL subfractions, suggesting an atherogenic profile. The correlation of H with sd-LDL and IRI, without relation to hepatic iron content suggests a putative link between inflammation, carbohydrate and lipid metabolism in NASH.

Topics: Adult; Aged; Antimicrobial Cationic Peptides; C-Peptide; Carbohydrate Metabolism; Cholesterol, LDL; Fatty Liver; Female; Ferritins; Glucose Tolerance Test; Hepcidins; Humans; Insulin; Iron; Lipid Metabolism; Male; Metabolic Syndrome; Metabolome; Middle Aged; Non-alcoholic Fatty Liver Disease; Transferrin