Β-cell Function Index Research Articles

The 1-hour post-load glucose level is more effective than HbA1c for screening dysglycemia.

To assess the performance of HbA1c and the 1-h plasma glucose (PG≥155mg/dl; 8.6mmol/l) in identifying dysglycemia based on the oral glucose tolerance test (OGTT) from a real-world clinical care setting. This was a diagnostic test accuracy study. For this analysis, we tested the HbA1c diagnostic criteria advocated by the American Diabetes Association (ADA 5.7-6.4%) and International Expert Committee (IEC 6.0-6.4%) against conventional OGTT criteria. We also tested the utility of 1-h PG≥mg/dl; 8.6mmol/l. Prediabetes was defined according to ADA-OGTT guidelines. Spearman correlation tests were used to determine the relationships between HbA1c, 1-h PG with fasting, 2-h PG and indices of insulin sensitivity and β-cell function. The levels of agreement between diagnostic methods were ascertained using Cohen's kappa coefficient (Κ). Receiver operating characteristic (ROC) curve was used to analyze the performance of the HbA1c and 1-h PG test in identifying prediabetes considering OGTT as reference diagnostic criteria. The diagnostic properties of different HbA1c thresholds were contrasted by determining sensitivity, specificity and likelihood ratios (LR). Of the 212 high-risk individuals, 70 (33%) were identified with prediabetes, and 1-h PG showed a stronger association with 2-h PG, insulin sensitivity index, and β-cell function than HbA1c (P<0.05). Furthermore, the level of agreement between 1-h PG≥155mg/dl (8.6mmol/l) and the OGTT (Κ[95% CI]: 0.40[0.28-0.53]) diagnostic test was stronger than that of ADA-HbA1c criteria 0.1[0.03-0.16] and IEC criteria (0.17[0.04-0.30]). The ROC (AUC[95% CI]) for HbA1c and 1-h PG were 0.65[0.57-0.73] and 0.79[0.72-0.85], respectively. Importantly, 1-h PG≥155mg/dl (8.6mmol/l) showed good sensitivity (74.3% [62.4-84.0]) and specificity 69.7% [61.5-77.1]) with a LR of 2.45. The ability of 1-h PG to discriminate prediabetes was better than that of HbA1c (∆AUC: -0.14; Z value: 2.5683; P=0.01022). In a real-world clinical practice setting, the 1-h PG≥155mg/dl (8.6mmol/l) is superior for detecting high-risk individuals compared with HbA1c. Furthermore, HbA1c is a less precise correlate of insulin sensitivity and β-cell function than the 1-h PG and correlates poorly with the 2-h PG during the OGTT.

Associations among the plasma amino acid profile, obesity, and glucose metabolism in Japanese adults with normal glucose tolerance.

BackgroundAmino acids (AAs) are emerging as a new class of effective molecules in the etiology of obesity and diabetes mellitus. However, most investigations have focused on subjects with obesity and/or impaired glucose regulation; the possible involvement of AAs in the initial phase of glucose dysregulation remains poorly understood. Furthermore, little attention has been given to possible associations between the pattern/degree of fat deposition and the plasma AA profile. Our objective was therefore to determine the relationships between plasma AA concentrations and the type/degree of obesity and glucose regulation in Japanese adults with normal glucose tolerance.MethodsEighty-three subjects with normal glucose tolerance were classified as obese or nonobese and as visceral obesity or nonvisceral obesity. Correlations between the plasma levels of 23 AAs and somatometric measurements, visceral fat area (VFA), subcutaneous fat area (SFA), and 75-g oral glucose tolerance test results were analyzed.ResultsObesity or visceral obesity was associated with higher levels of branched-chain AAs (isoleucine, leucine, and valine), lysine, tryptophan, cystine, and glutamate but lower levels of asparagine, citrulline, glutamine, glycine, and serine (p < 0.04). Age- and gender-adjusted analyses indicated that VFA was positively correlated with tryptophan and glutamate levels, whereas VFA and SFA were negatively correlated with citrulline, glutamine, and glycine levels (p < 0.05). The fasting and 2-h plasma glucose levels or the homeostasis model assessment of insulin resistance were positively correlated with valine, glutamate, and tyrosine levels but negatively correlated with citrulline, glutamine, and glycine levels. The homeostasis model assessment for the β-cell function index was positively correlated with leucine, tryptophan, valine, and glutamate levels but negatively correlated with citrulline, glutamine, glycine, and serine levels (p < 0.05).ConclusionsThe present study identified specific associations between 10 AAs and the type/degree of obesity, and indices of glucose/insulin regulation, in Japanese adults with preserved glucose metabolism. With the growing concern about the increasing prevalence of obesity and diabetes, the possible roles of these AAs as early markers and/or precursors warrant further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-015-0059-5) contains supplementary material, which is available to authorized users.

C-Peptide-Based Index Is More Related to Incident Type 2 Diabetes in Non-Diabetic Subjects than Insulin-Based Index.

BackgroundDiabetes can be efficiently prevented by life style modification and medical therapy. So, identification for high risk subjects for incident type 2 diabetes is important. The aim of this study is to identify the best β-cell function index to identify high risk subjects in non-diabetic Koreans.MethodsThis is a retrospective longitudinal study. Total 140 non-diabetic subjects who underwent standard 2-hour 75 g oral glucose tolerance test from January 2007 to February 2007 at Kangbuk Samsung Hospital and followed up for more than 1 year were analyzed (mean follow-up, 54.9±16.4 months). The subjects were consist of subjects with normal glucose tolerance (n=44) and subjects with prediabetes (n=97) who were 20 years of age or older. Samples for insulin and C-peptide levels were obtained at 0 and 30 minutes at baseline.ResultsThirty subjects out of 140 subjects (21.4%) developed type 2 diabetes. When insulin-based index and C-peptide-based index are compared between progressor and non-progressor to diabetes, all C-peptide-based indices were statistically different between two groups, but only insulinogenic index and disposition index among insulin-based index were statistically different. C-peptide-based index had higher value of area under receiver operating characteristic curve (AROC) value than that of insulin-based index. "C-peptidogenic" index had highest AROC value among indices (AROC, 0.850; 95% confidence interval, 0.761 to 0.915). C-peptidogenic index had significantly higher AROC than insulinogenic index (0.850 vs. 0.731 respectively; P=0.014).ConclusionC-peptide-based index was more closely related to incident type 2 diabetes in non-diabetic subjects than insulin-based index.

Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassemia

▪Background: Increased intestinal iron absorption has been shown in non-transfusion-dependent thalassemia (NTDT) and thus results in mild to moderate iron excess. Therefore, these patients should theoretically have increased risks of pre-diabetes and diabetes. However, there have been no studies addressing insulin and glucose metabolism in these patients. We, therefore, hypothesize that NTDT with iron excess may have impaired β-cell function and reduced insulin sensitivity and their improvements may occur following iron chelation therapy.Objective: To assess insulin sensitivity and β-cell function in NTDT with iron excess pre- and post-iron chelation therapy.Study design: non-randomized open-labelled prospective cohort studyPatients:Inclusion criteria: NTDT patients, aged older than 10 years who have had serum ferritin >300 ng/mL and/or transferrin saturation ≥70% and/or liver iron (Fe) concentration (LIC) of at least 5 mg Fe per gram of dry weight.Exclusion criteria: Known case of type I or type II DM and taking medications affecting glucose metabolism or iron chelation therapy within one month prior to study.Methods: The complete patient histories were obtained and physical examinations were performed initially and at 3- and 6-month follow-up. Deferasirox at the dose of 10 mg/kg was prescribed daily to the studied patients for 6 months. Iron status indicators including serum ferritin, serum iron, total iron biding capacity (TIBC), transferrin saturation, non-transferrin-binding iron (NTBI) and hepcidin were determined pre- and 6-month post-chelation. For assessment of glucose metabolism, an oral glucose tolerance test (OGTT) and serum adiponectin were determined pre- and 6-month post-chelation. During an OGTT, serum insulin and plasma glucose at 0, 30, 60, 90 and 120 min were obtained. Insulin resistance, insulin sensitivity and β-cell function indices including homeostatic model assessment-insulin resistance (HOMA-IR), whole body insulin sensitivity index (WBISI) and disposition index (WBISI x insulinogenic index), were calculated. Also, MRI of the heart, liver and pancreas were monitored pre- and 6-month post-chelation.Results: Ten patients (7 males) with a median age of 17.4 years enrolled in the study. Seven patients were b-thalassemia /Hb E disease of either b0 or b+ thalassemia genes and three patients were non-deletion type of Hb H disease with Hb Constant Spring or Hb Pakse. One of these three patients had additional Hb E resulting in AE Bart's disease. The severity of the thalassemia diseases was classified using a scoring system for b-thal/HbE revealing severe (n=1), moderate (n=6) and mild (n=3) degrees.For iron status indicators, the median pre-chelation serum ferritin was significantly higher than that of post-chelation (551.4 vs. 486.1 ng/mL, p=0.049). Also, the median pre-chelation TIBC was significantly lower than that of post-chelation (211.5 vs. 233.5 µg/dL, p=0.006). The median pre-chelation NTBI was higher than that of post-chelation (6.2 vs 4.0 µM, p =0.068) but no statistical significance. Also, the median pre-chelation hepcidin was lower than that of post-chelation but no statistical significance.For glucose metabolism, the median pre-chelation serum adiponectin was not different from that of post-chelation (46.41 vs. 48.77 ng/mL, p=0.508). All patients had normal glucose tolerance both pre- and post-chelation with no significant changes of body mass index during the 6-month period. However, there was a significant reduction of fasting plasma glucose after iron chelation (85.0 vs.79.5 mg/dL, p =0.045). In comparison between pre- and post-chelation, there were trends towards decreasing insulin resistance index expressed as HOMA-IR (0.8 vs. 0.2, p =0.219) and increasing insulin sensitivity indices expressed as WBISI (11.5 vs. 19.8, p =0.105). Also, there was a trend towards improving β-cell function expressed as disposition index (5.1 vs. 6.2, p=0.064). MRI revealed no significant changes of iron accumulation in liver, pancreas and myocardium following 6-month iron chelation therapy. No adverse effects following oral iron chelation therapy were detected.Conclusions: There was a trend towards improving insulin sensitivity and β-cell function following 6-month iron chelation therapy. Longer term of iron chelating agent treatment may demonstrate a significant beneficial effect on glucose metabolism. DisclosuresNo relevant conflicts of interest to declare.

Circulating Levels of Betatrophin and Irisin Are Not Associated with Pancreatic β-Cell Function in Previously Diagnosed Type 2 Diabetes Mellitus Patients.

Betatrophin and irisin are two recently identified hormones which may participate in regulating pancreatic β-cell function. However, the associations of these two hormones with β-cell function remain unclear. The present study aims to demonstrate the associations of circulating betatrophin and irisin levels with β-cell function, assessed by the area under the curve (AUC) of C-peptide, and the possible correlation between these two hormones in previously diagnosed type 2 diabetes mellitus (T2DM) patients. In total, 20 age-, sex-, and body mass index- (BMI-) matched normal glucose tolerance (NGT) subjects and 120 previously diagnosed T2DM patients were included in this study. Partial correlation analysis was used to evaluate the relationships between these two hormones and indexes of β-cell function and insulin resistance. Our results showed that betatrophin levels were significantly elevated, while irisin levels were significantly decreased, in patients with T2DM compared with NGT subjects. However, partial correlation analysis showed that betatrophin levels did not correlate with β-cell function-related variables or insulin resistance-related variables before or after controlling multiple covariates, while irisin correlated positively with insulin sensitivity but is not associated with β-cell function-related variables. Besides, no correlation was observed between betatrophin and irisin levels. Hence we concluded that betatrophin and irisin were not associated with β-cell function in previously diagnosed T2DM patients.

β-Cell Function and Insulin Sensitivity in Normal Glucose-Tolerant Subjects Stratified by 1-Hour Plasma Glucose Values.

This study was designed to assess β-cell function and insulin sensitivity indices among normal glucose tolerance (NGT) subjects stratified by 1-h plasma glucose (1hPG) values during an oral glucose tolerance test (OGTT). One hundred sixty-six NGT subjects underwent a five-point OGTT, and glucose and insulin levels were estimated. We calculated the following indices: (a) β-cell function (homeostasis assessment model-β-cell function [HOMA-β] and Insulinogenic Index [IGI]) and (b) insulin sensitivity (homeostasis assessment model-insulin resistance [HOMA-IR], Matsuda Index, and Insulin Sensitivity Index [ISI]). NGT subgroups with elevated 1hPG values (i.e., 1hPG ≥143 to <155 mg/dL and 1hPG ≥155 mg/dL) did not differ from those with 1hPG <143 mg/dL by HOMA-β (P = 0.236) but had significantly lower IGIs (367 ± 239 vs. 257 ± 243 vs. 246 ± 239; P = 0.019). With respect to ISIs, HOMA-IR was not significantly different among the groups (P = 0.103). However, the Matsuda Index (11.2 ± 5.0 vs. 7.4 ± 4.8 vs. 5.5 ± 4.9; P < 0.001) and ISI (0.015 ± 0.010 vs. 0.012 ± 0.006 vs. 0.011 ± 0.011; P = 0.028) were significantly lower in subjects with elevated 1hPG values. NGT subjects with elevated 1hPG levels have alterations in β-cell function and insulin sensitivity compared with those with normal 1hPG levels.

Serum vascular endothelial growth factor B is elevated in women with polycystic ovary syndrome and can be decreased with metformin treatment.

To determine serum vascular endothelial growth factor B (VEGF-B) levels in polycystic ovary syndrome, their association with insulin resistance and β-cell dysfunction, and the effect of metformin on serum VEGF-B levels. A cross-sectional, interventional study. We recruited 103 women with polycystic ovary syndrome and 96 age-matched healthy controls. Serum VEGF-B levels were determined in all participants, and 44 polycystic ovary syndrome patients randomly received metformin. We measured VEGF-B levels in healthy controls and women with polycystic ovary syndrome before and after metformin treatment. Women with polycystic ovary syndrome had higher serum VEGF-B levels, which decreased with metformin treatment. In the lean and overweight/obese groups, patients with polycystic ovary syndrome had higher plasma VEGF-B levels than did healthy controls (P < 0·05). VEGF-B levels were correlated with body mass index, body fat percentage, M values, homeostasis model assessment of insulin resistance and β-cell function indices. A multiple linear regression analysis showed that VEGF-B level was associated with M values after adjusting for age, body mass index, serum sex hormones and serum lipids in women with polycystic ovary syndrome. Serum VEGF-B is significantly higher in women with polycystic ovary syndrome and is closely and positively related to insulin resistance. Metformin treatment reduces VEGF-B levels and ameliorates insulin resistance.

Improved glycemic control due to sitagliptin is not related to cortisol or the surrogate marker IGFBP-1 for hepatic insulin sensitivity

ImportanceElevated cortisol levels and dysregulated insulin-like growth factor binding protein-1 (IGFBP-1; a marker of hepatic insulin sensitivity) are both related to insulin resistance and glucose abnormalities. It is unknown whether improvement in these parameters is related to improved glucose metabolism during treatment with sitagliptin. ObjectiveTo determine whether improved insulin sensitivity and beta-cell function during treatment with sitagliptin is related to lower cortisol levels and/or improved regulation of IGFBP-1 in patients with recent acute coronary syndrome (ACS) and newly discovered glucose abnormalities. DesignSamples were taken from The BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction (BEGAMI) trial, a double-blinded, placebo-controlled randomized clinical trial on the efficacy and safety of sitagliptin for patients with ACS and newly discovered glucose abnormalities. SettingCardiology departments (cardiac ICU and outpatient clinic) in two hospitals in Stockholm, Sweden. ParticipantsSubjects hospitalized (or recently hospitalized) for ACS, in whom an oral glucose tolerance test revealed previously unknown glucose abnormalities. InterventionsSubjects were randomized to sitagliptin 100mg once daily (n=34) or placebo (n=37) for twelve weeks. Oral glucose tolerance test (OGTT) and randomization occurred after stabilization median 7days after ACS. Main outcomes and measuresFasting serum cortisol and IGFBP-1 were analyzed before OGTT, around 8a.m., and after at 10a.m. The latter time point was chosen as the spread in cortisol levels around is small then, allowing improved chances to detect differences between groups. ResultsGlucose tolerance and insulin sensitivity improved in both groups, while HbA1c and indices of β-cell function improved only in the sitagliptin group as reported previously. Both groups displayed decreased cortisol levels around 10a.m. (from 338±21 to 278±14nmol/L, p=0.038, in the sitagliptin group; from 343±17 to 302±15nmol/L, p=0.017, in the placebo group), and improved correlation between fasting log-IGFBP-1 and insulin. Conclusions and relevanceThese findings suggest that a stress-related elevation in cortisol may have negative impact on glucose tolerance in patients with recent ACS. However, improved glycemic control with sitagliptin does not appear to be related to changes in cortisol levels or hepatic insulin sensitivity as assessed by IGFBP-1.

Association between the NF-E2 Related Factor 2 Gene Polymorphism and Oxidative Stress, Anti-Oxidative Status, and Newly-Diagnosed Type 2 Diabetes Mellitus in a Chinese Population.

Oxidative stress is a major risk factor in the onset and progression of type 2 diabetes mellitus (T2DM). NF-E2 related factor 2 (NRF2) is a pivotal transcription factor in oxidative stress related illnesses. This study included 2174 subjects with 879 cases of newly-diagnosed T2DM and 1295 healthy controls. Compared to individuals with the CC genotype, those with the AA genotype had lower total anti-oxidative capacity, superoxide dismutase, catalase, glutathione, glutathione peroxidase activity; and lower homeostasis model assessment of β-cell function index. Those with the AA genotype also had a higher malondialdehyde concentration and homeostasis model assessment of insulin resistance index values. The frequency of allele A was significantly higher in T2DM subjects (29.4%), compared to control subjects (26.1%; p = 0.019). Individuals with the AA genotype had a significantly higher risk of developing T2DM (OR 1.56; 95% CI 1.11, 2.20; p = 0.011), relative to those with the CC genotype, even after adjusting for known T2DM risk factors. Our results suggest that the NRF2 rs6721961 polymorphism was significantly associated with oxidative stress, anti-oxidative status, and risk of newly-diagnosed T2DM. This polymorphism may also contribute to impaired insulin secretory capacity and increased insulin resistance in a Chinese population.

Effect of serum 25-hydroxyvitaminD3 on insulin resistance and β-cell function in newly diagnosed type2 diabetes patients.

To evaluate serum 25-hydroxyvitamin D3 (25(OH)D3) in newly diagnosed type 2 diabetes patients and to explore the associations of 25(OH)D3 with insulin resistance and β-cell function. A total of 97 newly diagnosed type 2 diabetes patients and 69 healthy controls were recruited. Serum 25(OH)D3 was determined using high-pressure liquid chromatography. Insulin resistance was measured using a homeostasis model assessment of insulin resistance (HOMA-IR). β-Cell function was determined using the HOMA β-cell function index (HOMA-β), early-phase insulin secretion index (ΔI30/ΔG30) and area under the insulin curve (AUCins). Correlation analysis was carried out using Pearson's correlation and multiple stepwise regression analysis. Serum 25(OH)D3 was much lower in patients with newly diagnosed type 2 diabetes (t = -13.00, P < 0.01), and the prevalence of hypovitaminosis 25(OH)D3 was 62.9% (61/97) in diabetic patients. Among the diabetic patients, patients with hypovitaminosis 25(OH)D3 showed higher glycosylated hemoglobin and AUCglu (P < 0.01) as well as lower HOMA-β, ΔI30/ΔG30 and AUCins. Serum 25(OH)D3 was independently positively correlated with ΔI30/ΔG30 and AUCins (P < 0.05), but was not significantly correlated with either HOMA-IR or HOMA-β. Only triglycerides, glycosylated hemoglobin and ΔI30/ΔG30 emerged as independent factors associated with serum 25(OH)D3 in both diabetes patients and the health control group. The present results further showed a low serum 25(OH)D3 concentration in patients with newly diagnosed type 2 diabetes. 25(OH)D3 deficiency is associated with disturbances in glucose metabolism and lipid metabolism. Serum 25(OH)D3 is not correlated with basal insulin resistance or β-cell function, but is significantly positively correlated with glucose-stimulated insulin secretion and β-cell function.

Biomarkers of Alzheimer Disease, Insulin Resistance, and Obesity in Childhood

To answer the question of whether onset of insulin resistance (IR) early in life enhances the risk of developing dementia and Alzheimer disease (AD), serum levels of 2 molecules that are likely associated with development of AD, the amyloid β-protein 42 (Aβ42) and presenilin 1 (PSEN1), were estimated in 101 preschoolers and 309 adolescents of various BMI. Participants (215 boys; 48.8%) were normal weight (n = 176; 40%), overweight (n = 135; 30.7%), and obese (n = 129; 29.3%). The HOmeostasis Model of IR (HOMA-IR), HOMA percent β-cell function (HOMA-β) and QUantitative Insulin-sensitivity Check Index (QUICKI) were calculated. Obese adolescents had values of Aβ42 higher than overweight and normal-weight peers (190.2 ± 9.16 vs 125.9 ± 7.38 vs 129.5 ± 7.65 pg/mL; P < .0001) as well as higher levels of PSEN1 (2.34 ± 0.20 vs 1.95 ± 0.20 vs 1.65 ± 0.26 ng/mL; P < .0001). Concentrations of Aβ42 were significantly correlated with BMI (ρ = 0.262; P < .0001), HOMA-IR (ρ = 0.261; P < .0001) and QUICKI (ρ = -0.220; P < .0001). PSEN1 levels were correlated with BMI (ρ = 0.248; P < .0001), HOMA-IR (ρ = 0.242; P < .0001), and QUICKI (ρ = -0.256; P < .0001). Western blot analysis confirmed that PSEN1 assays measured the full-length protein. Obese adolescents with IR present higher levels of circulating molecules that might be associated with increased risk of developing later in elderly cognitive impairment, dementia, and AD.

The effect of metformin and pioglitazone on glucagon of patients with diabetes and metabolic syndrome

Objective To observe and evaluate the effects of metformin and pioglitazone on blood glucose, insulin, glucagon, β-cell function and insulin resistance among patients with diabetes and metabolic syndrome, so as to discuss the role of pancreatic α cells in pathogenesis of type 2 diabetes mainly caused by insulin resistance and the change of α-cell function after treatment. Methods A total of 60 patients diagnosed with diabetes and metabolic syndrome were selected in Beijing Chaoyang District Diabetes Center from April 2012 to April 2013 and divided with random number table into metformin group (treated with metformin 0.5 g orally thrice a day for 1 year, n=30) and pioglitazone group (treated with pioglitazone 15 mg orally once a day for 1 year, n=30). 30 normal healthy people who had physical examination at the Center during the same period were enrolled into the control group, matched in age and gender with the intervention groups. The general condition of the 3 groups, and blood levels of glucose, insulin, and glucagon, insulin sensitivity index (ISI)-Matsuda, homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function index (HOMA-β), 1-phase index, 2-phase index, and insulin secretion sensitivity index (ISSI) at baseline in the 3 groups and after treatment in the metformin group and the pioglitazone group were measured and calculated. Results Compared with the control group before treatment, the intervention groups as a whole had significantly higher fasting glucagon level [(146.22±25.41) pmol/L vs. (21.31±7.85) pmol/L, P=0.002] and area under curve (AUC) of glucagon [(469.84±13.12) pmol/(L·h) vs. (100.94±7.73) pmol/(L·h), P=0.006]. Compared with the results before treatment, the metformin group exhibited significantly reduced fasting glucose [(6.46±1.38) mmol/L vs. (7.54±0.43) mmol/L, P=0.031], fasting insulin [(119.22±69.01) pmol/L vs. (139.38±71.13) pmol/L, P=0.042], fasting glucagon [(91.69±22.11) pmol/L vs. (142.81±24.56) pmol/L, P=0.029], AUC of glucose [(25.19±1.31) mmol/(L·h) vs. (32.68±1.12) mmol/(L·h), P=0.043], AUC of insulin [(468.65±20.10) pmol/(L·h) vs. (786.32±21.37) pmol/(L·h), P=0.017], and AUC of glucagon [(280.60±8.26) pmol/(L·h) vs. (487.14±14.31) pmol/(L·h), P=0.032]; while the pioglitazone group after treatment also showed significantly decreased fasting glucose [(6.58±2.21) mmol/L vs. (7.68±0.59) mmol/L, P=0.028], fasting insulin [(107.92±17.81) pmol/L vs. (144.66±74.43) pmol/L, P=0.033], fasting glucagon [(76.07±20.57) pmol/L vs. (148.34±28.94) pmol/L, P=0.025], AUC of glucose [(25.58±1.22) mmol/(L·h) vs. (35.07±1.38) mmol/(L·h), P=0.038], AUC of insulin [(435.54±19.30) pmol/(L·h) vs. (854.75±20.61) pmol/(L·h), P=0.013], and AUC of glucagon [(223.43±5.83) pmol/(L·h) vs. (458.55±12.96) pmol/(L·h), P=0.026]. The before-after-treatment differences were significantly smaller in the metformin group than in the pioglitazone group in terms of fasting insulin [(20.16±2.98) mmol/L vs. (36.74±2.88) mmol/L, P=0.011], fasting glucagon [(51.12±3.67) pmol/L vs. (72.27±4.58) pmol/L, P=0.016], AUC of insulin [(317.67±13.45) pmol/(L·h) vs. (419.21±15.44) pmol/(L·h), P=0.031] and AUC of glucagon [(206.54±9.66) pmol/(L·h) vs. (235.12±10.29) pmol/(L·h), P=0.046]. Conclusions Glucagon in patients with diabetes and metabolic syndrome is higher than that in normal individuals. Metformin and pioglitazone can decrease the level of glucagon in patients with metabolic syndrome and diabetes as well as improve the glucose control, β-cell function and insulin resistance, suggesting improving effect of these two drugs on α-cell function. Pioglitazone manifests a stronger effect than metformin does. Key words: Metformin; Pioglitazone; Glucagon; Insulin

Glucolipid metabolism of lipoprotein lipase heterozygous mice and the mechanism of insulin resistance

Objective To investigate the glucolipid metabolism in lipoprotein lipase (LPL) gene knockout mice, and to explore the possible mechanisms of insulin resistance. Methods 16- and 40-week old LPL gene knockout heterozygous mice(LPL+ /-) and wild type(WT) C57 mice were selected and divided into 4 groups: 16-week LPL+ /-(n=6), 16-week WT(n=6), 40-week LPL+ /-(n=6), and 40-week WT(n=6) group. LPL activity of post-heparin serum was examined. Serum triglyceride(TG) and free fatty acid(FFA) were measured. Intraperitoneal glucose tolerance test(IPGTT) in 4 groups of mice were performed. The glucose area under the curve(AUCG) and homeostasis model assessment for insulin resistance index and β-cell function index(HOMA-IR, HOMA-β) were calculated to evaluate insulin sensitivity and the function of islet β-cells. Serum malondialdehyde(MDA) and total antioxidant capacity(TAOC) levels were determined by means of colorimetric method. Using dihydroethidium(DHE) fluorescent staining method, reactive oxygen species(ROS) levels in liver and skeletal muscle were determined. Results LPL activity levels of both 16- and 40-week LPL+ /- mice were significantly lower than that in WT mice of the same age. Serum TG and FFA of 40-week old LPL+ /- mice were significantly higher than those in WT mice of the same age(P<0.05), and they were also higher than those of 16-week old LPL+ /- mice(P<0.05). IPGTT showed that compared with WT mice, blood glucose level in LPL+ /- mice was significantly higher than that in WT group at 30 and 120 minute(P<0.05), and fasting insulin and HOMA-IR were increased significantly(P<0.05). Serum MDA of 40-week old LPL+ /- mice was evidently higher than that in WT mice by the same week(P<0.05), while TAOC level was lower than that of WT mice (P<0.05). ROS in skeletal muscle of 16-week old LPL+ /- mice was significantly increased. Meanwhile, ROS in both liver and skeletal muscle of 40-week old LPL+ /- mice was significantly higher than that in WT mice of the same age. Conclusion As time goes by, lipid and glucose disorders of LPL+ /- mice are aggravating, and insulin resistance develops evidently. Insulin resistance in LPL+ /- mice with dyslipidemia may be related to oxidative stress. (Chin J Endocrinol Metab, 2015, 31: 143-147) Key words: Lipoprotein lipase; Insulin resistance; Oxidative stress

Visceral adiposity index and insulin secretion and action in first-degree relatives of subjects with type 2 diabetes.

To explore the predictive performance of the newly established visceral adiposity index for diabetes and prediabetes, as well as the relationships between the visceral adiposity index and the parameters of insulin secretion and action. Eight hundred twenty-four first-degree relatives of individuals with type 2 diabetes who had no known history of abnormal glucose regulation were selected. Diabetes and prediabetes were diagnosed using the standard oral glucose tolerance test. The visceral adiposity index values were greater for the subjects with prediabetes and diabetes than for those with normal glucose regulation. Among the subjects with normal glucose regulation, the visceral adiposity index was higher for those whose levels were above the median value of the incremental area under the curve for glucose than for the subjects whose levels fell below the median value. The visceral adiposity index was negatively correlated with the homeostasis model assessment of the β-cell function index (Homa-β) and with the insulinogenic index (ΔI30 /ΔG30 ). The visceral adiposity index was found to be a valuable predictor of diabetes, but it was not superior to triglyceride levels, waist circumference, or lipid accumulation production. The first degree relatives of people with type 2 DM who have prediabetes or diabetes have progressively higher visceral adiposity index in association with progressive hyperglycemia, and it was found to correlate with the Homa-β and the ΔI30 /ΔG30 .

Vigorous Physical Activity May Be Important for the Insulin Sensitivity in Immigrants from the Middle East and Native Swedes

Purpose: To compare physical activity measures and their associations with insulin sensitivity, β-cell function and body mass index (BMI) between Iraqi immigrants and native Swedes. Methods: A cross-sectional study of 493 Iraqis (58% men) and 469 Swedes (54% men) aged 30 to 75 years living in the city of Malmö, Sweden. Accelerometry was used for physical activity measures (sedentary time, breaks in sedentary time, moderate and vigorous physical activity, total counts). Insulin sensitivity index and oral disposal index were determined from an oral glucose tolerance test and BMI by body weight and height. Results: Iraqi men were less physically active than Swedish men, while the physical activity was more similar in the women. BMI was a strong predictor of insulin sensitivity and β-cell function and frequently associated with the physical activity measures. BMI modified the associations of insulin sensitivity and β-cell function with the physical activity measures to such extent that only VPA and total counts show direct associations with insulin sensitivity in addition to the indirect associations via BMI. Iraqi women demonstrated weaker associations compared with Swedish women. Conclusions: Physical activity and performed at vigorous intensity may be important mainly for the insulin sensitivity in Iraqi immigrants and native Swedes.

Decreased Insulin Secretion in Women with Previous Gestational Diabetes Mellitus

Objectives: Gestational diabetes mellitus (GDM) affects 2%–4% of the all pregnant women, and it is a major risk factor for development of type 2 DM. We performed this cross-sectional study to determine whether there were defects in insulin secretory capacity or insulin sensitivity in women with previous GDM. Methods: On 6–8 weeks after delivery, 75 g oral glucose tolerance test was performed in 36 women with previous GDM and 19 non-pregnant control women matched with age and weight. Intravenous glucose tolerance test was performed on 10–14 weeks after delivery. Insulin secretory capacity measured as the acute insulin response to glucose (AIRg) and insulin sensitivity as minimal model derived sensitivity index (SI) were obtained. AIRg×SI (β-cell disposition index) was used as an index of β-cell function. Results: Women with previous GDM were classified into normal glucose tolerance (postpartum-NGT, n=19) and impaired glucose tolerance (postpartum-IGT, n=17). Postpartum fasting glucose levels were significantly higher in postpartum-IGT compared to postpartum-NGT and control (P<0.05). AIRg×SI was significantly lower in postpartum-IGT compared to control (P<0.05). SI was lower in postpartum-NGT and postpartum-IGT compared to control, but the difference did not have the statistical significance. Frequency of parental history of type 2 diabetes was significantly greater in postpartum-IGT compared to postpartum-NGT (P<0.05). Conclusion: Women with previous GDM showed impaired insulin secretion although their glucose tolerance states were restored to normal. It suggests impaired early insulin secretion may be a major pathophysiologic factor for development of type 2 DM, and this defect may be genetically determined. (Ewha Med J 2015;38(1):30-35)

Effects of Sitagliptin on Insulin and Glucagon Levels in Type 2 Diabetes Mellitus.

Effects of Sitagliptin on Insulin and Glucagon Levels in Type 2 Diabetes Mellitus.

Pregnancy complications and glucose intolerance in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by insulin resistance and hyperandrogenism. The interaction of these factors might result in increased risks of miscarriage and pregnancy complications such as gestational diabetes mellitus (GDM). To examine the pregnancy risks in women with PCOS, we compared obstetrical outcomes between patients with and without PCOS. We also studied the differences in maternal characteristics, glucose intolerance and pregnancy complications between PCOS patients with and without GDM, with and without obesity, and between successful pregnancies and miscarriages. We observed a high incidence of GDM and prevalence of GDM diagnosis in the first trimester in PCOS. Patients with GDM had higher body mass index (BMI) and lower homeostasis model assessment of β-cell function (HOMA-β) at preconception than those without GDM. Obese pregnant women with PCOS demonstrated a high incidence of GDM with severe insulin resistance, including high fasting insulin, HOMA of insulin resistance (HOMA-IR), and HOMA-β at preconception compared with normal-weight patients. BMI was significantly correlated with HOMA-IR or HOMA-β, and both indices were lower in PCOS patients with than without GDM for the same BMI. There were no significant differences in maternal characteristics (excluding maternal age) between PCOS patients with successful pregnancy and PCOS patients with miscarriages. Our data suggest that pregnant women with PCOS have an increased risk of GDM, especially if they have obesity and/or poorer insulin secretion. Measure of β-cell function, such as HOMA-β, at preconception might be a useful predictor of the risk of GDM in pregnant PCOS patients.

Relationship between elevated triglyceride levels with the increase of HOMA-IR and HOMA-β in healthy children and adolescents with normal weight.

To test the hypothesis that mildly elevated triglyceride levels are associated with the increase of homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-β) indices in healthy children and adolescents with normal weight, we conducted a cross-sectional population study. Based on fasting triglyceride levels, participants were allocated into groups with and without triglyceride levels ≥1.2 mmol/L. Normal weight was defined by body mass index between the 15th and 85th percentiles, for age and gender. Insulin resistance and insulin secretion were estimated using HOMA-IR and HOMA-β indices. A total of 1660 children and adolescents were enrolled, of them 327 (19.7%) with mildly elevated triglycerides. The multivariate linear regression analysis showed that mildly elevated triglyceride levels in children were associated with HOMA-IR (β = 0.214, p < 0.001), HOMA-β (β = 0.139, p = 0.001), systolic (β = 0.094, p = 0.01), and diastolic blood pressure (β = 0.102, p = 0.007), whereas in adolescents, HOMA-IR (β = 0.267, p < 0.001) and HOMA-β (β = 0.154, p < 0.001), but not systolic (β = 0.029, p = 0.38) and diastolic blood pressure (β = 0.015, p = 0.642), showed association with mildly elevated triglycerides. Mildly elevated triglyceride levels are associated with increased HOMA-IR and HOMA-β indices in healthy children and adolescents with normal weight.

Positive association of free triiodothyronine with pancreatic β-cell function in people with prediabetes.

To analyse the effects of thyroid hormones on β-cell function and glucose metabolism in people with prediabetes who are euthyroid. A total of 111 people who were euthyroid underwent 75-g oral glucose tolerance tests, of whom 52 were assigned to the normal glucose tolerance and 59 to the prediabetes groups. Homeostatic model assessment of β-cell function, insulinogenic index and areas under the curve for insulin and glucose were evaluated as indices of pancreatic β-cell function. In both groups, BMI, fasting insulin, homeostasis model assessment ratio and HDL cholesterol correlated significantly with all indices of pancreatic β-cell function. Free triiodothyronine correlated positively with all insulin secretion indices in the prediabetes group. Multiple linear regression analysis showed that free triiodothyronine was an independent variable that had a positive correlation with all indices of β-cell function in the prediabetes group. By contrast, no such correlation was found in the normal glucose tolerance group. Free triiodothyronine is associated with both basal and glucose-stimulated insulin secretion in people with prediabetes who are euthyroid; therefore, the regulation of insulin secretion by thyroid hormones is a potentially novel therapeutic target for the treatment of diabetes.