Β-cell Function Index Research Articles

Use of a simple liquid meal test to evaluate insulin sensitivity and beta‐cell function in children

Insulin sensitivity and β-cell function are useful indices of metabolic disease risk but are difficult to assess in young children because of the invasive nature of commonly used methodology. A meal-based method for assessing insulin sensitivity and β-cell function may at least partially alleviate concerns. The objectives of this study were to: (i) determine the association of insulin sensitivity assessed by liquid meal test with that determined by an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT); (ii) examine the association of insulin sensitivity derived from each test with measures of body composition, fat distribution and metabolic health (lipids, fasting insulin and glucose, and surrogate indices of insulin sensitivity); and (iii) examine the associations of indices of β-cell function derived from each test with total and regional adiposity. Forty-seven children (7-12 years) underwent both a liquid meal test and an FSIGT. The insulin sensitivity index derived from the meal test (SI-meal) was positively associated with that from the FSIGT (SI-FSIGT; r = 0.63; P < 0.001), and inversely with all measures of insulin secretion derived from the meal test. Both SI-meal and SI-FSIGT were associated with measures of total and regional adiposity. SI-meal, but not SI-FSIGT, was associated with triglycerides and fasting insulin, after adjusting for ethnicity, gender, pubertal stage and fat mass. Basal insulin secretion measured during the meal test was positively associated with all measures of adiposity, independent of insulin sensitivity. In conclusion, a liquid meal offers a valid and sensitive means of assessing insulin sensitivity and β-cell responsivity in young children.

Preliminary study of the level of visfatin and the relationship with insulin resistance in Chinese patients with chronic hepatitis C.

Many studies have suggested that visfatin expression is closely related to the occurrence of insulin resistance (IR), while the precise role of visfatin in the regulation of IR in chronic hepatitis C (CHC) is not clear. We investigated fasting glucose, fasting insulin (FINS), C peptide, visfatin, visfatin mRNA, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and other parameters of 315 patients with CHC and 150 control cases in China. Meanwhile we collected clinical and other laboratory data for further analysis. Compared with the control group, the CHC group had a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), the AST to platelet ratio index (APRI), ratio of AST to ALT (AAR), gammaglutamyl trans-peptidase, IL-6, TNF-α, visfatin, visfatin mRNA, FINS, fasting C peptide, and IR index. The visfatin, visfatin mRNA, insulin, IR index, Homaβ cell function index (HBCI), and fasting β-cell function index (FBCI) of the subjects with high body mass index (BMI) from the CHC sub-group were significantly higher than the normal BMI sub-group of CHC patients. We found a positive correlation between visfatin, visfatin mRNA and BMI, IL-6, TNF-α, and IR index. Our data suggest that visfatin may be related to IR in Chinese CHC patients.

Women with normal glucose tolerance and a history of gestational diabetes show significant impairment of β-cell function at normal insulin sensitivity

ObjectiveAlthough the nature of gestational diabetes mellitus (GDM) remains unclear, the condition is thought to be related primarily to insulin resistance, overweight and obesity. Most studies include women with a history of GDM and later carbohydrate metabolism abnormalities, while reports of women with previous GDM and subsequent normoglycaemia are scarce. The aim of this study was to assess insulin resistance and β-cell function in normoglycaemic women with a history of GDM. Materials and methodsThe study group included 199 women, aged 38.4±6.6 years, diagnosed with GDM within the last 5–12 years [GDM(+)] and a control group of 50 comparable women in whom GDM was excluded [GDM(−)], according to WHO criteria. Blood glucose and insulin levels were measured at the beginning (fasting) and at 60 and 120min of oral glucose tolerance tests. Indices of insulin resistance (HOMA-IR), insulin sensitivity (HOMA-S%) and β-cell function (HOMA-B%) were calculated. ResultsNormoglycaemia was observed in 57% of GDM(+) and 88% of GDM(−) women (P=0.0003). Diabetes was diagnosed in 13 (6.5%) GDM(+) women and in none of the GDM(−) women. Comparison of 113 normoglycaemic GDM(+) and 44 normoglycaemic GDM(−) women revealed significantly impaired β−cell function (HOMA-B%: 131.1±51.1 vs 144.7±47.1, respectively; P=0.038) with similar normal body mass index (BMI) and no differences in HOMA-IR and HOMA-S%. ConclusionIn this study, more than half of the GDM(+) women were presented with normal glucose tolerance. However, despite normoglycaemia, women with a history of GDM were characterized by significantly impaired insulin secretion, but no signs of increased insulin resistance.

Indices of Insulin Secretion during a Liquid Mixed-Meal Test in Obese Youth with Diabetes

To compare indices of insulin secretion, insulin sensitivity (IS), and oral disposition index (oDI) during the liquid mixed-meal test in obese youth with clinically diagnosed type 2 diabetes mellitus (T2DM) and negative autoantibodies (Ab(-)) versus those with T2DM and positive autoantibodies (Ab(+)) to examine whether differences in β-cell function can be detected between the 2 groups. Twenty-seven youth with Ab(-) and 15 youth with Ab(+) clinically diagnosed T2DM underwent a mixed-meal test (Boost; 55% carbohydrate, 25% protein, and 20% fat). Fasting and mixed-meal-derived insulin and C-peptide indices of IS, secretion (30-minute insulinogenic [ΔI(30)/ΔG(30)] and C-peptide [ΔC(30)/ΔG(30)]), and oDI were calculated. Indices of insulin secretion were ~40%-50% lower in patients with Ab(+) T2DM compared with those with Ab(-) T2DM. After controlling for body mass index, ΔI(30)/ΔG(30), ΔC(30)/ΔG(30), C-peptide area under the curve (AUC)/glucose AUC, and insulin AUC/glucose AUC were significantly (P < .05) lower in the Ab(+) group compared with the Ab(-) group. Sensitivity indices were significantly higher in the Ab(+) group. The oDI, 1/fasting insulin × ΔI(30)/ΔG(30) (0.04 ± 0.02 vs 0.12 ± 0.02 mg/dL(-1); P = .005), and 1/fasting C-peptide × ΔC(30)/ΔG(30) (0.02 ± 0.009 vs 0.05 ± 0.006 mg/dL(-1); P = .018) were lower in the Ab(+) group. Receiver operating characteristic curve analyses revealed that fasting C-peptide <3.2 ng/mL had 87% sensitivity and 74% specificity and ΔC(30)/ΔG(30) <0.075 ng/mL per mg/dL had 93% sensitivity and 80% specificity for identifying youth with Ab(+) T2DM. During a liquid mixed-meal test, indices of β-cell function were lower and IS was higher in patients with Ab(+) T2DM versus those with Ab(-) T2DM, with high sensitivity and specificity for fasting and stimulated C-peptide as markers of Ab(+) status. Indices of insulin secretion during this standardized mixed-meal test could be used to assess β-cell function in therapeutic trials of β-cell restoration in youth with T2DM.

Increment of C-peptide after glucagon injection determines the progressive nature of Japanese type 2 diabetes: A long-term follow-up study

Type 2 diabetes (T2D) is characterized by a steady worsening of β-cell dysfunction as the disease progresses. The objective of this study was to estimate the decline of insulin secretion in Japanese type 2 diabetic patients (T2D-patients) by glucagon injection over an observation period of more than 10 years. Thirty-three T2D-patients were followed for 10.4 ± 1.4 years. Fasting C-peptide immunoreactivity (FCPR), the 6 min value of CPR after glucagon injection (6MCPR), and the increment of CPR (ΔCPR) were measured at baseline and follow-up. FCPR, 6MCPR, ΔCPR were significantly lower at follow-up than at baseline (p<0.05, p<0.005, and p<0.0005, respectively). The annual change of ΔCPR was significantly (p<0.05) greater than the annual change of FCPR (-0.062 ± 0.076 ng/mL/year and -0.025 ± 0.067 ng/mL/year, respectively). In contrast, CPR-index (an index of β-cell function) and SUIT-index (secretory units of islets in transplantation) calculated based on fasting blood samples were unaltered. The annual changes of FCPR, 6MCPR, and ΔCPR were negatively correlated with the FCPR, 6MCPR, and ΔCPR values at baseline, respectively. Duration of diabetes, BMI, diabetic retinopathy, and secondary sulfonylurea failure at baseline were not correlated with the annual changes of FCPR, 6MCPR, and ΔCPR. In conclusion, our longitudinal observations suggest that β-cell function progressively declines in Japanese T2D-patients. The annual declines of ΔCPR were more prominent than the annual declines of FCPR. ΔCPR after glucagon injection may be more useful for estimating individual longitudinal insulin secretion than fasting blood samples.

Short communication: Effect of supplementation with Lactobacillus casei Shirota on insulin sensitivity, β-cell function, and markers of endothelial function and inflammation in subjects with metabolic syndrome—A pilot study

Based on animal studies, intake of probiotic bacteria was suggested to improve insulin sensitivity by reducing endotoxinemia and inflammation. The objective of this study was to determine the effects of supplementation with the probiotic strain Lactobacillus casei Shirota (LcS) over 12wk on insulin sensitivity, β-cell function, inflammation, and endothelial dysfunction parameters in subjects with metabolic syndrome. In a randomized-controlled study, 30 subjects with metabolic syndrome either received Lactobacillus casei Shirota 3 times daily for 12wk or served as controls with standard medical therapy. Fasting blood samples were taken and a 75-g oral glucose tolerance test was performed to derive indices for insulin sensitivity and β-cell function. In addition, parameters to assess endothelial function and inflammation markers were determined. Even though the insulin sensitivity index significantly improved after 3mo of probiotic supplementation (0.058±0.021 vs. 0.038±0.025), the change was not significantly different compared with the control group. No improvements were seen in additional indices of insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity by oral glucose tolerance test, and homeostasis model assessment for insulin resistance) and β-cell function (first and second phase insulin secretion, and homeostasis model assessment for β-cell function). Probiotic supplementation resulted in a significant reduction in soluble vascular cell adhesion molecule-1 (sVCAM-1) level (1,614±343 vs. 1,418±265ng/mL). No significant changes in parameters used to assess low-grade inflammation or endothelial dysfunction were observed. Intake of LcS for 12wk in subjects with metabolic syndrome did not improve insulin sensitivity, β-cell function, endothelial function, or inflammation markers in this trial.

Exenatide plus metformin compared with metformin alone on β‐cell function in patients with Type 2 diabetes

To quantify how much exenatide added to metformin improves β-cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone. A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to exenatide (5 μg twice a day for the first 4 weeks and forced titration to 10 μg twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and β-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-α. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation. Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment β-cell function index (HOMA-β) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity-C reactive protein and tumour necrosis factor-α. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin. Exenatide is effective not only on glycaemic control, but also in protecting β-cells and in reducing inflammation.

Glucose Intolerance Is Associated with Increased Intimal Medial Thickness of the Carotid Artery and Increased Pulse Wave Velocity in Renal Transplant Recipients

Background: New-onset diabetes after transplantation has a significant negative impact on allograft and patient survival, and glucose intolerance (impaired fasting glucose; IFG and/or impaired glucose tolerance; IGT) is asymptomatic hyperglycemia and borderline diabetes. Previous reports have shown that glucose intolerance is a risk factor for diabetes and cardiovascular disease in general populations. However, the clinical significance of glucose intolerance in renal transplant recipients has not been identified. Measurements of the intimal-medial thickness (IMT) of the carotid arteries by B-mode ultrasound and pulse wave velocity (PWV) have been identified as non-invasive methods for assessing atherosclerosis. Our study was designed to determine whether glucose intolerance affects the occurrence of atherosclerosis by the evaluation of IMT and PWV in renal transplant recipients. Patients and methods: A total of 32 renal transplant recipients without prior evidence of diabetes (at least a year after transplantation) at our institution was enrolled in this study. Transplant recipients were divided into two groups (normal glucose tolerance (NGT) group and glucose intolerance group) according to the results of their oral glucose tolerance test with 75 g of glucose (OGTT). NGT was defined as fasting plasma glucose (FPG) < 110 mg/dl and 2h plasma glucose < 140 mg/dl, IFG as 110-126 mg/dl and < 140 mg/dl, IGT as < 110 mg/dl and 140-200 mg/dl, and diabetes mellitus (DM) as >126 mg/dl and >200 mg/dl, respectively. Glucose intolerance included IFG, IGT, IFG/IGT, and DM. Categories of glucose tolerance were defined according to the World Health Organization criteria. NGT was detected in 19 patients as assessed by OGTT, while 13 patients had glucose intolerance; 6 had IGT, 2 had IFG, and 5 had IGT and IFG. No patients had DM. Bilateral brachial-ankle PWV (baPWV) and IMT were measured as markers of atherosclerosis and compared between the subjects with glucose intolerance and those with NGT among the renal transplant recipients. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-R), and pancreatic β-cell function was evaluated by the homeostasis model assessment of β-cell function (HOMA-β) and insulinogenic index. Results: The patients in the glucose intolerance group showed significantly greater baPWV and IMT than the patients in the NGT group. There was no significant difference in HOMA- β between the two groups, whereas insulinogenic index was significantly lower in the glucose intolerance group than in the NGT group. HOMA-R in the glucose intolerance group was significantly higher than that in the NGT group. Liner regression analysis showed that the rise in IMT in the renal transplant recipients significantly correlated with HOMA-R. Conclusions: This present study demonstrated that renal transplant recipients with glucose intolerance had increased IMT and baPWV. Our results suggested that glucose intolerance in renal transplant recipients may induce atherosclerosis, and that the rise in insulin resistance may contribute to the increased IMT in renal transplant recipients.

Glucose Intolerance Is Associated with Increased Intimal Medial Thickness of the Carotid Artery and Increased Pulse Wave Velocity in Renal Transplant Recipients

Background: New-onset diabetes after transplantation has a significant negative impact on allograft and patient survival, and glucose intolerance (impaired fasting glucose; IFG and/or impaired glucose tolerance; IGT) is asymptomatic hyperglycemia and borderline diabetes. Previous reports have shown that glucose intolerance is a risk factor for diabetes and cardiovascular disease in general populations. However, the clinical significance of glucose intolerance in renal transplant recipients has not been identified. Measurements of the intimal-medial thickness (IMT) of the carotid arteries by B-mode ultrasound and pulse wave velocity (PWV) have been identified as non-invasive methods for assessing atherosclerosis. Our study was designed to determine whether glucose intolerance affects the occurrence of atherosclerosis by the evaluation of IMT and PWV in renal transplant recipients. Patients and methods: A total of 32 renal transplant recipients without prior evidence of diabetes (at least a year after transplantation) at our institution was enrolled in this study. Transplant recipients were divided into two groups (normal glucose tolerance (NGT) group and glucose intolerance group) according to the results of their oral glucose tolerance test with 75 g of glucose (OGTT). NGT was defined as fasting plasma glucose (FPG) < 110 mg/dl and 2h plasma glucose < 140 mg/dl, IFG as 110-126 mg/dl and < 140 mg/dl, IGT as < 110 mg/dl and 140-200 mg/dl, and diabetes mellitus (DM) as >126 mg/dl and >200 mg/dl, respectively. Glucose intolerance included IFG, IGT, IFG/IGT, and DM. Categories of glucose tolerance were defined according to the World Health Organization criteria. NGT was detected in 19 patients as assessed by OGTT, while 13 patients had glucose intolerance; 6 had IGT, 2 had IFG, and 5 had IGT and IFG. No patients had DM. Bilateral brachial-ankle PWV (baPWV) and IMT were measured as markers of atherosclerosis and compared between the subjects with glucose intolerance and those with NGT among the renal transplant recipients. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-R), and pancreatic β-cell function was evaluated by the homeostasis model assessment of β-cell function (HOMA-β) and insulinogenic index. Results: The patients in the glucose intolerance group showed significantly greater baPWV and IMT than the patients in the NGT group. There was no significant difference in HOMA- β between the two groups, whereas insulinogenic index was significantly lower in the glucose intolerance group than in the NGT group. HOMA-R in the glucose intolerance group was significantly higher than that in the NGT group. Liner regression analysis showed that the rise in IMT in the renal transplant recipients significantly correlated with HOMA-R. Conclusions: This present study demonstrated that renal transplant recipients with glucose intolerance had increased IMT and baPWV. Our results suggested that glucose intolerance in renal transplant recipients may induce atherosclerosis, and that the rise in insulin resistance may contribute to the increased IMT in renal transplant recipients.

Comprehensive Intensive Therapy for Chinese Gestational Diabetes Benefits Both Newborns and Mothers

This study identified the impact of intensive therapy on neonatal outcomes in women with gestational diabetes mellitus (GDM) and determined the effects on the postpartum metabolic status of the mothers. In total, 127 pregnant women with GDM were randomly selected to receive an intensive treatment regimen, which included one-to-one education, lifestyle intervention, scheduled clinic visits, strict glucose control, and frequent glucose self-monitoring. Meanwhile, 148 age-matched pregnant women with GDM were selected as controls and given the standard treatment regimen. Pregnancy outcomes including parameters related to the GDM mothers and to their neonates were comparatively analyzed between the two treatment groups. GDM patient follow-up (range, 1-3 years after delivery) included an oral glucose tolerance test and measurements of lipid concentration and insulin secretion. The insulinogenic index (ΔInsulin(30 min)/ΔBlood glucose(30 min)) and homeostasis model assessment index of β-cell function and insulin resistance were calculated. The patients' demographic and anthropometric data were also recorded for comparative analysis. Compared with GDM patients receiving standard treatment, GDM patients receiving intensive treatment had lower instances of premature delivery (2.4% vs. 8.3%, P<0.05) and neonatal care unit admission (21.3% vs. 33.3%, P<0.05) and lower neonatal birth weight (3.26±0.53 vs. 3.45±0.55 kg, P<0.0001). At follow-up, GDM patients from the intensive treatment group had a smaller waist circumference (75.83±3.11 vs. 78.34±4.20 cm, P<0.01), lower 30-min glucose levels after a 75-g glucose load (8.26±1.85 vs. 9.46±2.74 mmol/L, P<0.05), and higher high-density lipoprotein levels (1.30±0.24 vs. 1.18±0.23 mmol/L, P<0.05). The intensive GDM treatment regimen led to healthier outcomes for the women, the neonates, and the birth event and was associated with better maternal metabolic situations in the months and years after delivery.

Vitamin D Levels and Insulin Resistance in Children Born with Severe Growth Restriction

This study was designed to examine differences in serum 25(OH)D levels between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) prepubertal children in correlation with birth weight and indices of insulin resistance and β-cell function. Sixty-five nonobese children were examined at age 5-7.5 years; 27 born SGA and 38 matched AGA. Body weight, height, BMI, and waist circumference were recorded and fasting serum levels of glucose, insulin, 25(OH)D, and parathyroid hormone (PTH) were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) and the β-cell function index (HOMA-β%) were estimated. The mean level of 25(OH)D was higher in the SGA group (26.2±10 vs. 17.2±7 ng/ml, p<0.01) but that of PTH was no different. The insulin resistance and β-cell function indices were higher in the SGA group: HOMA-IR 1.34±0.67 vs. 0.99±0.53, and HOMA-β% 135±56 vs. 97±60 in the SGA and AGA groups, respectively. In the SGA group, 25(OH)D was correlated with HOMA-β% but not with HOMA-IR or insulin. In multiple regression, in the total cohort 25(OH)D and HOMA-IR were independently negatively correlated with birth weight (β= - 0.31, β= - 0.36, p<0.05) respectively. In conclusion, at prepuberty severely in utero growth restricted children have increased birth weight dependent levels of 25(OH)D, which might exert a regulatory role on β-cell function.

Pioglitazone Ameliorates Endothelial Dysfunction in Those with Impaired Glucose Regulation among the First-Degree Relatives of Type 2 Diabetes Mellitus Patients

Objective: To study the effects of pioglitazone on endothelial dysfunction of subjects with impaired glucose regulation (IGR) among the first-degree relatives of patients with type 2 diabetes mellitus (T2DM). Subjects and Methods: The first-degree relatives of T2DM patients were screened with oral glucose test and IGR was diagnosed. IGR subjects whose blood glucose was still above the level after 1-month exercise were randomized to receive pioglitazone (15 mg/day) or vehicle for 12 weeks. Endothelial function was assessed as endothelium-dependent and -independent vasodilation. Blood nitric oxide (NO), blood pressure, body mass index, insulin and serum lipids were also measured. Area under the curve of glucose (AUC_glu) and insulin (AUC_INS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of β-cell function (HOMA-β) and early insulin secretion index (ΔI₃₀/ΔG₃₀) were calculated. Results: After pioglitazone treatment, fasting plasma, 2-hour plasma glucose, triglyceride (TG), fasting insulin, AUC_glu, HOMA-β and HOMA-IR, 2-hour insulin, AUC_INS and ΔI₃₀/ΔG₃₀ decreased. Endothelium-dependent vasodilation and NO were significantly improved in the treatment group. Furthermore, the changes of endothelium-dependent vasodilation were negatively correlated with changes in AUC_INS but positively with NO and HOMA-β. Stepwise multivariate regression analysis showed that changes in NO and HOMA-β were both independent parameters for improvement of endothelial dysfunction. Conclusion: Pioglitazone decreased blood glucose and TG, increased insulin sensitivity, and ameliorated endothelial dysfunction of IGR subjects among the first-degree relatives of T2DM patients. Increased NO production may be associated with the improvement of endothelial dysfunction.

Plasma 25-Hydroxyvitamin D Levels Are Favorably Associated With β-Cell Function

The association of hypovitaminosis D with type 2 diabetes is well recognized. Although hypovitaminosis D is associated with insulin resistance, there is much less information about its impact on β-cell function in humans. We enrolled 150 healthy, glucose-tolerant subjects for the assessment of β-cell function (acute insulin response) and insulin sensitivity index (ISI) using a hyperglycemic clamp. Adjusted β-cell function (ABCF) was defined as the product of acute insulin response and ISI. The relations of plasma 25-hydroxyvitamin D [25(OH)D] level with insulin sensitivity and ABCF were examined. Plasma 25(OH)D levels were positively associated with ABCF (P = 0.00004) and ISI (P < 0.00001). The associations remained significant after adjustment for age, sex, body mass index, physical activity, ethnicity, and season of study. Plasma 25(OH)D levels are positively association with both β-cell function and insulin sensitivity. Our observations suggest the roles of vitamin D deficiency in the dual defect of type 2 diabetes.

The serum lipopolysaccharide level in people with different glucose tolerances and its relationship with insulin resistance and β-cell secretory function

Objective To investigate serum lipopolysaccharide (LPS) level in people with different glucose tolerances and to explore the relationship between LPS and insulin resistance/β-cell secretory function.Methods Sixty-seven subjects were recruited,including 23 with newly diagnosed type 2 diabetes ( T2DM),21 impaired glucose tolerance ( IGT),and 23 normal glucose tolerance (NGT).Serum LPS was assayed by limulus amebocyte lysate test ;expression of LPS toll-like receptor 4 (TLR4) on surface of plasma monocytes was measured by flow cytometric assays,and the changes of LPS levels by 0.5 hours and 2 hours after a high-fat diet were detected.Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR); β-cell secretory function was evaluated by homeostasis model assessment for β3 cell function ( HOMA-β )/HOMA-IR,increment in insulin in the first 30 minutes/increment in glucose in the first 30 minutes ( AIns30/ΔG30)/HOMA-IR,AUCIns120min/HOMA-IR.Results 2 h LPS levels after a high-fat diet were significantly higher than fasting LPS levels [ NGT:0.96(0.33,0.99)vs 0.62 (0.22,0.64),IGT:1.08(0.53,1.22)vs 0.71 (0.39,0.82),T2DM:1.23 (0.62,1.43)vs 0.86( 0.45,0.94 ),EU/ml,all P＜0.01 ].Fasting,0.5 h,and 2 h LPS levels and fasting TLR4 levels of T2 DM group and IGT group were respectively higher than those of NGT group [ fasting LPS:0.86( 0.45,0.94 ),0.71 ( 0.39,0.82 ) vs 0.62(0.22,0.64),EU/ml;0.5 h LPS:1.10(0.55,1.18),0.84(0.50,1.07) vs 0.73(0.31,0.76),EU/ml;2 h LPS:1.23(0.62,1.43),1.08(0.53,1.22)vs 0.96(0.33,0.99),EU/ml; fasting TLR4:36.96( 17.22,55.19),30.34 ( 15.00,45.18 )vs 15.66 (6.09,9.76),MIF/105 cells,all P＜0.01 ].Fasting LPS,AUCLPS 120 min,and fasting TLR4 were positively correlated with insulin resistance index and negatively correlated with β-cell secretory function index ( P＜0.05 ).Multiple linear regression analysis showed that fasting LPS was an independent correlative factor of HOMA-IR and 0.5 h LPS was an independent correlative factor of (AIns30/AG30)/HOMA-IR and AUCIns Ins120min/HOMA-IR.Conclusion People with different glucose tolerances show differed LPS levels and its receptor TLR4 levcls,both of which are correlated with insulin resistance and β-cell secretory function,suggesting that LPS is associated with the pathogenesis of abnormal glucose regulation. Key words: Lipopolysaccharide ; Toll-like receptor 4 ; Insulin resistance ; β-cell secretory function

Vildagliptin Added to Metformin on β-Cell Function After a Euglycemic Hyperinsulinemic and Hyperglycemic Clamp in Type 2 Diabetes Patients

This study evaluated the effect of vildagliptin + metformin on glycemic control and β-cell function in type 2 diabetes patients. One hundred seventy-one type 2 diabetes patients, naive to antidiabetes therapy and with poor glycemic control, were instructed to take metformin for 8±2 months up to a mean dosage of 2,500±500 mg/day; then they were randomly assigned to add vildaglipin 50 mg twice a day or placebo for 12 months. We evaluated at 3, 6, 9, and 12 months: body mass index, glycemic control, fasting plasma insulin, homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment β-cell function index (HOMA-β), fasting plasma proinsulin, proinsulin/fasting plasma insulin ratio, C-peptide, glucagon, adiponectin, and high-sensitivity C-reactive protein. Before and at 12 months after the addition of vildagliptin, patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation, to assess insulin sensitivity and insulin secretion. After 12 months of treatment, vildagliptin + metformin gave a better decrease of body weight, glycemic control, HOMA-IR, and glucagon and a better increase of HOMA-β compared with placebo + metformin. Regarding the measures of β-cell function, treatment-induced changes in M-value, first- and second-phase C-peptide response to glucose, and C-peptide response to arginine were significantly higher in the vildagliptin + metformin group compared with the placebo + metformin group. The addition of vildagliptin to metformin gave a better improvement of glycemic control, insulin resistance, and β-cell function compared with metformin alone.

Variations in Inflammatory Biomarkers Following the Addition of Sitagliptin in Patients with Type 2 Diabetes not Controlled with Metformin

The effects of dipeptidyl peptidase-4 (DPP-4) inhibition on adipose tissue inflammation remain obscure. The aim of this study was to evaluate the effects of the addition of sitagliptin on the β-cell function and various inflammatory biomarkers in type 2 diabetic patients. After a run-in period of taking metformin, 178 diabetic patients with poor glycemic control were randomized to take sitagliptin at a dose of 100 mg once a day or a placebo in addition to metformin for 12 months. We evaluated the following parameters at three, six, nine and twelve months: body mass index (BMI), glycemic control, the homeostasis model assessment insulin resistance index (HOMA-IR), the homeostasis model assessment β-cell function index (HOMA-β), the proinsulin/fasting plasma insulin ratio (Pr/FPI ratio) and the levels of fasting plasma insulin (FPI), fasting plasma proinsulin (FPPr), C-peptide, glucagon, resistin, vaspin, omentin-1 and tumor necrosis factor-α (TNF-α). Before and twelve months after the addition of sitagliptin, the patients underwent combined euglycemic hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation to assess insulin sensitivity and secretion. Treatment with sitagliptin + metformin was more effective than placebo + metformin in improving glycemic control, the HOMA-IR and the glucagon level and increasing the HOMA-β and all β-cell measurements after combined euglycemic hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation. Regarding inflammatory biomarkers, sitagliptin + metformin more effectively reduced the levels of resistin, vaspin and omentin-1 than placebo + metformin. When treatment with metformin alone is not adequate for obtaining glycemic control, the addition of sitagliptin can be considered due to its actions in preserving the β-cell function and reducing the levels of biomarkers of inflammation.

The effect of FOXA2rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals

BackgroundVariations within the FOXA family have been studied for a putative contribution to the risk of type 2 diabetes (T2D), and recently the minor T-allele of FOXA2 rs1209523 was reported to associate with decreased fasting plasma glucose levels in a study using a weighted false discovery rate control procedure to enhance the statistical power of genome wide association studies in detecting associations between low-frequency variants and a given trait.Thus, the primary aim of this study was to investigate whether the minor T-allele of rs1205923 in FOXA2 associated with 1) decreased fasting plasma glucose and 2) a lower risk of developing T2D. Secondly, we investigated whether rs1205923 in FOXA2 associated with other glucose-related phenotypes.MethodsThe variant was genotyped in Danish individuals from four different study populations using KASPar® PCR SNP genotyping system. We examined for associations of the FOXA2 genotype with fasting plasma glucose and estimates of insulin release and insulin sensitivity following an oral glucose tolerance test in 6,162 Danish individuals from the population-based Inter99 study while association with T2D risk was assessed in 10,196 Danish individuals including four different study populations.ResultsThe FOXA2 rs1209523 was not associated with fasting plasma glucose (effect size (β) = -0.03 mmol/l (95%CI: -0.07; 0.01), p = 0.2) in glucose-tolerant individuals from the general Danish population. Furthermore, when employing a case-control setting the variant showed no association with T2D (odds ratio (OR) = 0.82 (95%CI: 0.62-1.07), p = 0.1) among Danish individuals. However, when we performed the analysis in a subset of 6,022 non-obese individuals (BMI < 30 kg/m2) an association with T2D was observed (OR = 0.68 (95%CI: 0.49-0.94), p = 0.02). Also, several indices of insulin release and β-cell function were associated with the minor T-allele of FOXA2 rs1209523 in non-obese individuals.ConclusionsWe failed to replicate association of the minor T-allele of FOXA2 rs1209523 with fasting plasma glucose in a population based sample of glucose tolerant individuals. More extensive studies are needed in order to fully elucidate the potential role of FOXA2 in glucose homeostasis.

Oral Disposition Index in Obese Youth from Normal to Prediabetes to Diabetes: Relationship to Clamp Disposition Index

We sought to assess the glucose disposition index using an oral glucose tolerance test (OGTT; oDI) compared with the glucose disposition index measured from the combination of the euglycemic-hyperinsulinemic and hyperglycemic clamps (cDI) in obese pediatric subjects spanning the range of glucose tolerance. Overweight/obese adolescents (n = 185) with varying glucose tolerance (87 normal, 54 impaired, 31 with type 2 diabetes, and 13 with type 1 diabetes) completed an OGTT and both a hyperinsulinemic-euglycemic and a hyperglycemic clamp study. Indices of insulin sensitivity and β-cell function were calculated, and 4 different oDI estimates were calculated as the products of insulin and C-peptide-based sensitivity and secretion indices. Mirroring the differences across groups by cDI, the oDI estimates were greatest in normal glucose tolerance adolescents and lowest in type 2 diabetes mellitus and obese with type 1 diabetes mellitus adolescents. The insulin-based oDI estimates correlated with cDI overall (r ≥ 0.74, P < .001) and within each glucose tolerance group (r ≥ 0.40, P < .001). Also, oDI and cDI predicted 2-hour OGTT glucose similarly. The oDI is a simple surrogate estimate of β-cell function relative to insulin sensitivity that can be applied to obese adolescents with varying glucose tolerance in large-scale epidemiological studies where the applicability of clamp studies is limited due to feasibility, cost, and labor intensiveness.

The once-daily human glucagon-like peptide-1 analog, liraglutide, improves β-cell function in Japanese patients with type 2 diabetes.

Aims/Introduction: β-cell function was evaluated by homeostasis model assessment of β-cell function (HOMA-B) index, proinsulin:insulin and proinsulin:C-peptide ratios in adult, Japanese type 2 diabetes patients receiving liraglutide. Data from two randomized, controlled clinical trials (A and B) including 664 Japanese type 2 diabetes patients (mean values: glycated hemoglobin [HbA1c] 8.61-9.32%; body mass index [BMI] 24.4-25.3 kg/m(2)) were analyzed. In two 24-week trials, patients received liraglutide 0.9 mg (n = 268) or glibenclamide 2.5 mg (n = 132; trial A), or liraglutide 0.6, 0.9 mg (n = 176) or placebo (n = 88) added to previous sulfonylurea therapy (trial B). Liraglutide was associated with improved glycemic control vs sulfonylurea monotherapy or placebo. In liraglutide-treated groups in trials A and B, area under the curve (AUC) insulin 0-3 h was improved (P < 0.001 for all) and the AUCinsulin 0-3 h:AUCglucose 0-3 h ratio was increased (estimated treatment difference [liraglutide-comparator] 0.058 [0.036, 0.079]). HOMA-B significantly increased with liraglutide relative to comparator in trial B (P < 0.05), but not in trial A. The reduction in fasting proinsulin:insulin ratio was 50% greater than in comparator groups. In Japanese type 2 diabetes patients, liraglutide was associated with effective glycemic control, restoration of prandial insulin response and indications of improved β-cell function. This trial was registered with Clinicaltrials.gov (trial A: no. NCT00393718/JapicCTI-060328 and trial B: no. NCT00395746/JapicCTI-060324). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00193.x, 2012).

Relationship of a single-sample urinary C-peptide/creatinine ratio and 24 h urinary C-peptide with islet β-cell function in type 2 diabetic patients

Blood C-peptide,first-void fasting urinary C-peptide/creatinine ratio ( UCPCR ),second-void fasting UCPCR,and 24 h urinary C-peptide (UCP) were determined in 90 type 2 diabetics and 30 health volunteers.The results showed that first-void fasting UCPCR and second-void fasting UCPCR were positively related to 24 h UCP and the index of islet β-cell function( all P＜0.01 ). Key words: Urinary C-peptide/creatinine ratio; Diabetes mellitus, type 2 ; Void fasting urine; 24 h urine; Islet β-cell function