Homeostasis Model Assessment Of Β-cell Function Research Articles

Sonic hedgehog N-terminal level correlates with adiponectin level and insulin resistance in adolescents.

Extracellular vesicles (EVs) are small vesicles released by nearly all types of cells. They deliver different types of substances, including proteins and nucleic acids, to nearby or distant cells and play a role in the mediation of cell-to-cell communication. The aim of this study was to explore the association between EVs and insulin resistance in adolescents with obesity or type 2 diabetes mellitus (DM2). The subjects were eight adolescents with DM2(DM2 group; four males and four females; age: 18.1±2.3years), 18 adolescents with simple obesity (obesity group; 12 males and six females; age: 12.2±3.4years), and 20 controls (control group; 10 males and 10 females; age: 13.0±1.4years). As markers of EVs, serum CD9/CD63 and sonic hedgehog N-terminal (Shh-N) levels were measured using enzyme-linked immunosorbent assay. The CD9/CD63 level in the control group was similar to that in the DM2 group, whereas the obesity group had a significantly higher CD9/CD63 level. In the entire study group, correlations were observed between serum Shh-N level and Homeostasis Model Assessment of insulin resistance (HOMA-IR) score (r=0.371, p=0.0143), Homeostasis Model Assessment-β cell function score (r=0.382, p=0.0115), serum insulin level (r=0.350, p=0.0171), and serum adiponectin level (r=0.367, p=0.0122). Multiple regression analysis revealed that serum Shh-N level was the most significant riskfactor for HOMA-IR score and serum insulin level. Shh is correlated with insulin resistance viaits association with adiponectin in adolescents.

Relationship between Habitual Intake of Vitamins and New-Onset Prediabetes/Diabetes after Acute Pancreatitis.

Vitamins have many established roles in human health. However, the role of habitual dietary intake of vitamins in glucose homeostasis in individuals after acute pancreatitis (AP) is yet to be elucidated. The aim was to investigate the associations between habitual intake of fat- and water-soluble vitamins/vitamers and markers of glucose metabolism (fasting plasma glucose (FPG), homeostasis model assessment insulin resistance (HOMA-IR) index, and homeostasis model assessment β-cell function (HOMA-β)) in individuals after AP. A total of 106 participants after AP were included in this cross-sectional study and were grouped based on glycaemic status: new-onset prediabetes/diabetes after AP (NODAP), pre-existing prediabetes/type 2 diabetes (T2DM), and normoglycaemia after AP (NAP). Habitual intake of seven fat-soluble vitamins/vitamers and seven water-soluble vitamins were determined by the EPIC-Norfolk food frequency questionnaire. Multiple linear regression analyses were conducted using five statistical models built to adjust for covariates (age, sex, daily energy intake, visceral/subcutaneous fat volume ratio, smoking status, daily alcohol intake, aetiology of AP, number of AP episodes, cholecystectomy, and use of antidiabetic medications). In the NODAP group, three fat-soluble vitamins/vitamers (α-carotene, β-carotene, and total carotene) were significantly associated with HOMA-β. One water-soluble vitamin (vitamin B3) was also significantly associated with HOMA-β in the NODAP group. None of the studied vitamins were significantly associated with FPG or HOMA-IR in the NODAP group. Prospective longitudinal studies and randomised controlled trials are now warranted to investigate if the observed associations between vitamin/vitamer intake and NODAP are causal and to unveil the specific mechanisms underlying their involvement with NODAP.

Improvement of diabetes-induced metabolic syndrome by millet prolamin is associated with changes in serum metabolomics

Even though the beneficial effect of millet prolamin on diabetes has been demonstrated previously, the underlying mechanism has not yet been researched. The current study aims to evaluate whether millet prolamin supplementation could improve diabetes by modulating serum metabolite disorders. Diabetes was induced in male C57BL/6J mice using a high-fat diet (HFD) and streptozotocin (STZ). Then the diabetic mice were randomly assigned to the HFD/STZ and HFD/STZ-prolamin groups and then administrated with saline or prolamin for five weeks by gavage. Our results showed that prolamin administration alleviated body weight loss, mitigated glucose homeostasis disorder, which manifested a decreased fasting plasma glucose level by 14.21% and an increased homeostasis model assessment-β cell function (HOMA-β) index by 24.86%, and alleviated liver function impairment by downregulating alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in diabetic mice. Metabolomics analysis indicated that serum metabolite disturbance caused by diabetes was partially alleviated by prolamin administration. Notably, retinol metabolism and riboflavin metabolism are the two pathways that contributed the most to the anti-diabetic effect of prolamin. Collectively, the hypoglycemic effect of millet prolamin can be associated with the serum metabolic profile alterations.

Magnesium intake, insulin resistance and markers of endothelial function among women.

We investigated the association of dietary Mg intake with insulin resistance and markers of endothelial function among Iranian women. A cross-sectional study. Usual dietary intakes were assessed using a validated FFQ. Dietary Mg intake was calculated by summing up the amount of Mg in all foods. A fasting blood sample was taken to measure serum concentrations of glycemic indices (fasting plasma glucose and insulin) and endothelial function markers (E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1). Insulin resistance and sensitivity were estimated using the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), Homeostasis Model Assessment β-cell function (HOMA-β) and quantitative insulin sensitivity check index (QUICKI). Iranian female nurses (n 345) selected by a multistage cluster random sampling method. The Mg intake across energy-adjusted quartiles was 205 (se 7), 221·4 (se 8), 254·3 (se 7) and 355·2 (se 9) mg/d, respectively. After adjustments for potential confounders, QUICKI level was significantly different across quartiles of Mg intake (Q1: 0·34 (se 0·02), Q2: 0·36 (se 0·01), Q3: 0·40 (se 0·01), and Q4: 0·39 (se 0·02), P = 0·02); however, this association disappeared after considering markers of endothelial function, indicating that this relation might be mediated through endothelial dysfunction. After controlling for all potential confounders, Mg intake was inversely, but not significantly, associated with serum concentrations of sICAM (Q1: 239 (se 17), Q2: 214 (se 12), Q3: 196 (se 12), and Q4: 195 (se 17), P = 0·29). There was no other significant association between dietary Mg intake and other indicators of glucose homoeostasis or endothelial markers. Higher dietary Mg intake was associated with better insulin sensitivity in Iranian females. This linkage was mediated through reduced endothelial dysfunction.

Evaluation of the gestational diabetes mellitus diagnostic criteria recommended by the international association of diabetes and pregnancy study group for long-term maternal postpartum outcomes in mainland China.

The gestational diabetes mellitus (GDM) diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Group (IADPSG) were established based on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and have been the most commonly used criteria for determining GDM worldwide. Although individuals from mainland China were not included in the HAPO study, the IADPSG criteria have been used in China since 2011. However, the appropriateness of the criteria for evaluating maternal postpartum outcomes in mainland China are unknown. We conducted this study to determine whether the IADPSG criteria are appropriate for Chinese patients for evaluating long-term maternal postpartum outcomes.Eighty-four patients who were diagnosed with hyperglycemia during pregnancy and had delivery in Peking University First Hospital from February 2007 to December 2009 were enrolled in the study. For patients in Group A, GDM was diagnosed using both the National Diabetes Data Group (NDDG) and the IADPSG criteria, while patients in Group B, gestational impaired glucose tolerance (GIGT) was diagnosed using the NDDG criteria while GDM was diagnosed based on the IADPSG criteria. Anthropometric data, glucose metabolism, lipid profiles, β cell function, and insulin resistance index were evaluated and compared to baseline after 5- to 6-year postpartum period.Patients in group A had significantly higher oral glucose tolerance test (OGTT) fasting, 2-hour and 3-hour plasma glucose levels compared to patients in group B at 24 to 28 weeks of gestation (P < .05). No significant differences were observed between the groups for anthropometric data, postpartum abnormal glucose metabolism (50.91% vs 44.83%, P = .596), type 2 diabetes mellitus (T2DM) (16.36% vs 3.45%, P = .167), lipid profiles, β cell function (homeostasis model assessment β-cell function index (HOMA-β) 1.04 vs 0.99, P = .935) and insulin resistance (homeostasis model assessment insulin resistance index (HOMA-IR) 2.01 vs 1.69, P = .583).Patients diagnosed with GDM using either the NDDG or IADPSG criteria had abnormal glucose levels and lipid metabolism after delivery. Patients with mild hyperglycemia had similar postpartum β-cell functional impairment and insulin resistance to those with moderate hyperglycemia during pregnancy. Hence, with respect to maternal long-term postpartum outcomes, the IADPSG diagnostic criteria for GDM could be appropriate for patients in mainland China.

Effects of dynamic change in fetuin-A levels from the first to the second trimester on insulin resistance and gestational diabetes mellitus: a nested case–control study

ObjectiveTo examine the effects of dynamic change in fetuin-A levels before the diagnosis of gestational diabetes mellitus (GDM) on insulin resistance and GDM.Research design and methodsA total of 135 women...

Selenium supplementation and insulin resistance in a randomized, clinical trial

ObjectiveWhile controversial, observational and randomized clinical trial data implicate the micronutrient selenium (Se) in the development of type 2 diabetes (T2D). The aim of this study was to test the...

Involvement of RBP4 in Diabetic Atherosclerosis and the Role of Vitamin D Intervention.

The purposes of this study were to evaluate the expression of retinol-binding protein 4 (RBP4) in diabetic rats with atherosclerosis and to investigate the role of vitamin D intervention. Male Wistar rats were randomly divided into 4 groups, including the control group (NC), the diabetic rats (DM1), the untreated diabetic atherosclerosis rats (DM2), and the vitamin D-treated diabetic atherosclerosis rats (DM3). The levels of serum and adipose RBP4, fasting insulin (FINS), fasting plasma glucose (FPG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), 25-hydroxyvitamin D [25(OH)D], C-reactive protein (CRP), and systolic blood pressure (SBP) were measured. Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment β-cell function index (HOMA-β), and atherogenic indexes (AI) were calculated. Compared with group NC, the levels of RBP4, TG, LDL-c, FPG, FINS, CRP, AI1, AI2, SBP, and HOMA-IR increased, while the levels of HDL-c, 25(OH)D, and HOMA-β decreased in groups DM1 and DM2. After 8 weeks of vitamin D supplementation in group DM3, the levels of 25(OH)D and HOMA-β increased and the levels of LDL-c, TC, HOMA-IR, FINS, CRP, RBP4, AI1, AI2, and SBP decreased significantly when compared with group DM2 (P < 0.05); Pearson analysis showed that serum RBP4 was positively correlated with TG, FINS, HOMA-IR, SBP, CRP, and AI and negatively correlated with 25(OH)D. In addition, multivariable logistic regression analysis showed that serum RBP4, SBP, and HDL-c were predictors for the presence of diabetic atherosclerosis. These findings suggested that RBP4 could involve in the improvement of diabetic atherosclerosis; vitamin D had the ability to decrease the level of RBP4 and eventually played an important role in preventing atherosclerosis in diabetes.

The Effects of Exenatide and Metformin on Endothelial Function in Newly Diagnosed Type 2 Diabetes Mellitus Patients: A Case-Control Study.

IntroductionExenatide is a new antidiabetic glucagon-like peptide-1 receptor agonist. In addition to its hypoglycemic effect, exenatide may have a potential protective benefit on vascular endothelial function. This study attempted to compare the effects of exenatide and traditional antidiabetic drug metformin treatment on endothelial function in overweight patients with type 2 diabetes.MethodsNinety overweight patients with newly diagnosed type 2 diabetes were recruited; 45 patients received exenatide (Exe) treatment and 45 patients received metformin (Met) treatment for 12 weeks. The control groups included 37 overweight and 24 non-overweight individuals. The parameters of glucose and lipid metabolism and endothelial function were measured before and after treatment. Vascular endothelial dysfunction was measured by reactive hyperemia index.ResultsNewly diagnosed patients with type 2 diabetes had more serious vascular endothelial dysfunction than both overweight and normal-weight control groups. The levels of body mass index, glucose, HbA1c, homeostasis model assessment insulin resistance, and homeostasis model assessment β-cell function were improved significantly by both exenatide and metformin treatment. Both exenatide and metformin treatment can improve vascular endothelial function (Exe group: 1.67 ± 0.52 vs 1.98 ± 0.67, P < 0.05; Met group: 1.68 ± 0.29 vs 1.82 ± 0.24, P < 0.05). Exenatide treatment was no less effective than metformin in improving endothelial function (0.31 ± 0.70 vs 0.13 ± 0.24, P > 0.05).ConclusionsNewly diagnosed patients with type 2 diabetes may have vascular endothelial dysfunction. Both exenatide and metformin treatment can improve vascular endothelial dysfunction, and exenatide was no less effective than metformin treatment.

Impaired endocrine-metabolic homeostasis: underlying mechanism of its induction by unbalanced diet.

To characterize the intrinsic mechanism by which sucrose induces β-cell dysfunction. Normal rats received for 3 weeks a standard diet supplemented with 10% sucrose in the drinking water (high sucrose (HS)) with/out an antioxidant agent (R/S α-lipoic acid). We measured plasma glucose, insulin, triglyceride, leptin, and lipid peroxidation levels; homeostasis model assessment (HOMA)-insulin resistance (HOMA-IR) and HOMA for β-cell function (HOMA-β) indexes were also determined. Insulin secretion, β-cell apoptosis, intracellular insulin and leptin mediators, and oxidative stress (OS) markers were also measured in islets isolated from each experimental group. HS rats had increased plasma triglyceride, insulin, leptin, and lipid peroxidation (OS marker) levels associated with an insulin-resistant state. Their islets developed an initial compensatory increase in glucose-induced insulin secretion and mRNA and protein levels of β-cell apoptotic markers. They also showed a significant decrease in mRNA and protein levels of insulin and leptin signaling pathway mediators. Uncoupling protein 2 (UCP2), peroxisome proliferator-activated receptor (PPAR)-α and -δ mRNA and protein levels were increased whereas mRNA levels of Sirtuin-1 (Sirt-1), glutathione peroxidase, and catalase were significantly lower in these animals. Development of all these endocrine-metabolic abnormalities was prevented by co-administration of R/S α-lipoic acid together with sucrose. OS may be actively involved in the mechanism by which unbalanced/unhealthy diet induces β-cell dysfunction. Since metabolic-endocrine dysfunctions recorded in HS rats resembled those measured in human pre-diabetes, knowledge of its molecular mechanism could help to develop appropriate strategies to prevent the progression of this metabolic state toward type 2 diabetes (T2D).

Diabetic Retinopathy in Newly Diagnosed Subjects With Type 2 Diabetes Mellitus: Contribution of β-Cell Function.

The association of hyperglycemia and diabetic retinopathy (DR) in established type 2 diabetes mellitus (T2DM) subjects is well accepted. However, the association between β-cell responsiveness and insulin sensitivity leading to fasting and postprandial hyperglycemia with DR in newly diagnosed treatment-naïve T2DM subjects remain unreported. A total of 544 newly diagnosed treatment-naïve T2DM subjects were screened for DR (digital photography) and underwent a standardized meal tolerance test. Serial plasma glucose and insulin levels were measured, and fasting (M0) and postprandial β-cell responsiveness calculated Calculating Pancreatic Response Program along with homeostasis model assessment-β cell function (HOMA-B) and HOMA-Insulin Sensitivity. A subgroup of 201 subjects also underwent a frequently sampled IV glucose tolerance test and the acute insulin response to glucose, insulin sensitivity, and glucose effectiveness (SG) estimated (MINMOD model). A total of 16.5% (90) subjects had DR at diagnosis. Subjects with DR had significantly reduced M0, HOMA-B and SG leading to higher fasting and postprandial (2 hour) glucose and significantly lower fasting and postprandial (2 hour) insulin. Factors independently associated with DR in multivariate logistic regression analysis were M0, HOMA-B, and SG with fasting and postprandial (2 hour) glucose and insulin. There was no statistical difference in glycated hemoglobin, systolic blood pressure, acute insulin response to glucose, and insulin sensitivity between those with or without DR. In this cohort of newly diagnosed T2DM subjects, DR is associated with reduced β-cell responsiveness, resulting from β-cell failure rather than insulin resistance, leading to fasting and postprandial hyperglycemia and hypoinsulinemia.

Sustained Decrease of Early-Phase Insulin Secretion in Japanese Women with Gestational Diabetes Mellitus Who Developed Impaired Glucose Tolerance and Impaired Fasting Glucose Postpartum.

OBJECTIVEThe aim of this study was to compare glucose intolerance in the antenatal and the postpartum periods using a 75-g oral glucose tolerance test (OGTT) in the Japanese women with gestational diabetes mellitus (GDM) using a retrospective design.PATIENTS AND METHODSData were obtained from 85 Japanese women with GDM who delivered from April 2011 through April 2015 and who underwent an OGTT 6–14 weeks postpartum. The women were divided into two groups based on the results of the postpartum OGTT: one group with normal glucose tolerance (NGT) and the other with impaired glucose tolerance (IGT) as well as impaired fasting glucose (IFG). We analyzed the associations between postpartum IGT–IFG and various factors.RESULTSAntenatally, a significant difference was observed between the groups only in the 1-hour plasma glucose level of the 75-g OGTT. Postpartum results of plasma glucose level were significantly higher at 0.5, 1, and 2 hours in the IGT–IFG group than those in the NGT group. Moreover, a significant decrease in the levels of 0.5-hour immunoreactive insulin and insulinogenic index was observed in the IGT–IFG group compared to those in the NGT group. Homeostasis model assessment-insulin resistance and homeostasis model assessment β-cell function of both groups were found to significantly decrease in the postpartum period; however, there was no significant change in the insulinogenic index of either group.CONCLUSIONSOur study clearly showed that the postpartum IGT and IFG levels of Japanese women with GDM are affected by impaired early-phase insulin secretion; however, insulin resistance promptly improves.

Decreased circulating levels of oxytocin in obesity and newly diagnosed type 2 diabetic patients.

Oxytocin can affect energy homeostasis and has interesting potential as a metabolic disease therapeutic. We detected serum oxytocin levels in obese (OB) and type 2 diabetes mellitus (T2DM) subjects and investigated the relationships between serum oxytocin levels and glycolipid metabolism, insulin resistance, pancreatic β-cell function, and inflammation. A total of 176 subjects were enrolled in the study, including 88 patients with newly diagnosed T2DM and 88 subjects with normal glucose tolerance (NGT). NGT and T2DM groups were divided into normal-weight (NW) and OB subgroups. We analyzed the concentrations of oxytocin by ELISA. Oral glucose tolerance testing was done, and hemoglobin A1c (HbA1c), blood lipids, and highly sensitive C-reactive protein (hs-CRP) were also measured. Insulin resistance and pancreatic β-cell function were assessed by homeostasis model assessment (HOMA). Serum oxytocin levels were lower in the T2DM group than in the NGT group (P < .01). The levels of serum oxytocin in OB subjects were also lower than those in NW subjects (P < .01). Serum oxytocin levels were negatively correlated with body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), HbA1c, fasting plasma glucose (FPG), 2-hour plasma glucose, fasting insulin (FINS), 2-h insulin, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), HOMA of insulin resistance (HOMA-IR), and hs-CRP and positively correlated with HOMA of β-cell function (HOMA-β) (P < .05). Multiple stepwise regression analysis showed that 2-hour plasma glucose, BMI, and TC were associated with serum oxytocin levels (P < .05). Logistic regression analyses demonstrated that serum oxytocin was significantly associated with T2DM (P < .01). Serum oxytocin levels were decreased in T2DM as well as OB subjects.

Short-Term Continuous Subcutaneous Insulin Infusion Combined with Insulin Sensitizers Rosiglitazone, Metformin, or Antioxidant α-Lipoic Acid in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Short-term continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes has been proved effective in improving metabolic control and β-cell function, thus inducing long-term drug-free remission. A randomized controlled trial was conducted to investigate whether CSII in combination with rosiglitazone, metformin, or α-lipoic acid separately brings about extra benefits. One hundred sixty patients with newly diagnosed type 2 diabetes were randomized to one of four treatment groups: CSII alone, CSII in combination with rosiglitazone or metformin for 3 months, or CSII with α-lipoic acid intravenous infusion for 2 weeks. Duration of CSII treatment was identical in the four groups. Glucose and lipid profiles, homeostasis model assessment (HOMA) indices, acute insulin response (AIR), intramyocellular lipid (IMCL) level, and malondialdehyde level were compared before and after intervention. The near-normoglycemia rate at the third month in CSII alone and that in combination with rosiglitazone, metformin, or α-lipoic acid was 72.5%, 87.5%, 90%, and 75%, respectively (metformin group vs. CSII alone, P=0.045). The metformin group achieved euglycemia in a shorter time (2.6 ± 1.3 vs. 3.7 ± 1.8 days, P=0.020) with less daily insulin dosage and was more powerful in lowering total cholesterol, increasing AIR and HOMA β-cell function, whereas reduction of IMCL in the soleus was more obvious in the rosiglitazone group but not in the metformin group. The efficacy of combination with α-lipoic acid was similar to that of CSII alone. Short-term CSII in combination with rosiglitazone or metformin is superior to CSII alone, yet the efficacy of the two differs in some way, whereas that with α-lipoic acid might not have an additive effect.

Chromium Nicotinate Has No Effect on Insulin Sensitivity, Glycemic Control, and Lipid Profile in Subjects with Type 2 Diabetes

Objective: To investigate the effect of chromium nicotinate supplementation on insulin sensitivity, glycemic control, and lipid profile in subjects with type 2 diabetes. Materials and Methods: In a double-blind clinical trial, 56 overweight individuals with type 2 diabetes were randomized into 3 groups: placebo (NC0), 50 μg (NC50), and 200 μg (NC200) of chromium as chromium nicotinate. Chromium status, sensitivity to insulin, glycemic control, and lipid profile were assessed at the beginning of the study and 45 days and 90 days after. Results: In the beginning, most subjects showed low concentrations of serum chromium (71.88%), regular levels of urinary chromium (80.65%), and insulin resistance (73.80%). The serum chromium concentrations did not differ among the groups over time (p = 0.2549). The changes in serum chromium and urine concentrations did not relate to changes in fasting glucose (p > 0.05). At 90 days of intervention, there was no significant difference between groups in fasting glucose, glycosylated hemoglobin, homeostasis model assessment insulin resistance (HOMA-IR), total cholesterol, and low-density lipoprotein (LDL); there was increase in homeostasis model assessment β-cell function (HOMA-β; p = 0.0349) and high-density lipoprotein (HDL; p = 0.0425) in the NC0 group and a reduction of triglycerides in the NC0 (p = 0.0177) and NC50 (p = 0.0336) groups. Conclusion: Supplementation at 50 and 200 μg of chromium as chromium nicotinate did not promote glycemic control, increase insulin sensitivity, or change the lipid profile of subjects with diabetes.

Variation in Inflammatory Markers and Glycemic Parameters After 12 Months of Exenatide Plus Metformin Treatment Compared with Metformin Alone: A Randomized Placebo-Controlled Trial

To evaluate the effects of exenatide on some inflammatory markers and to quantify the effect of exenatide on β-cell function. A randomized, double-blind, placebo-controlled trial. Seven hospitals in Italy. A total of 174 white treatment-naive adults with type 2 diabetes and a glycated hemoglobin (HbA(1c)) level higher than 7.5%. After an open-label run-in period of 8 ± 2 months with metformin, patients were randomized to take exenatide (5 μg twice/day for the first 4 weeks, 10 μg twice/day thereafter) or a placebo volume equivalent for 12 months. Body mass index, HbA(1c), fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index, homeostasis model assessment β-cell function index (HOMA-β), fasting plasma proinsulin (FPPr), proinsulin-to-fasting plasma insulin ratio (Pr:FPI ratio), C-peptide, glucagon, vaspin, chemerin, and resistin were evaluated at baseline, at randomization, and at 3, 6, 9, and 12 months. Patients also underwent a combined euglycemic, hyperinsulinemic, and hyperglycemic clamp with subsequent arginine stimulation to assess insulin sensitivity and insulin secretion. HbA(1c) was significantly improved with exenatide plus metformin compared with placebo plus metformin. Exenatide plus metformin was also significantly more effective than placebo plus metformin in increasing HOMA-β C-peptide, and all measures of β-cell function after the euglycemic hyperinsulinemic and hyperglycemic clamp. We observed that exenatide plus metformin also reduced resistin compared with placebo plus metformin. No variations in vaspin and chemerin were noted in group-to-group comparisons. We observed a significant correlation between M value increase, an index of insulin sensitivity, and a decrease in inflammatory parameters in the exenatide plus metformin group. The combination of exenatide plus metformin was more effective than metformin alone in improving glycemic control, β-cell function, and inflammatory parameters.

Insulin Sensitivity among College Athletes with Smoking Behavior

It has been shown that athletes have higher smoking rate than regular college students. But the association between smoking behavior and insulin sensitivity in college athletes is still unclear. The purpose of this cross-sectional study was to investigate the smoking behavior on insulin sensitivity in college athletes. Five hundred and fifty two nonsmoking and ninety eight smoking (8.4 ± 0.7 cigarette per day) athletes were recruited for this study. Indices of glucose metabolism (glucose, insulin, HbA1c), inflammation (white blood cells, WBC) and liver function test markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) were measured for all subjects under fasting condition. We found that gender-, alcohol consumption- and age-adjusted insulin, HOMA-IR (homeostasis model assessment of insulin resistance), HOMA-β (homeostasis model assessment β-cell function) and WBC number were higher in smokers than nonsmokers in ANCOVA. QUICKI (quantitative insulinsensitivity check index) and AST levels were lower in smokers compared to nonsmokers. Simple linear regression and multiple linear regression analyses were used to determine whether the smoking amount was associated with markers in metabolism. We found that smoking amount was positively associated with serum insulin, HOMAIR, HOMA-β, HbA1c and WBC count, and negatively associated with QUICKI before and after adjusting the gender, alcohol consumption and age. Smoking was also negatively related with adjusted AST. However, WBC is positively correlated with HOMA-IR and HOMA-β, and negatively correlated with QUICKI. These findings conclude that athletes with smoking behavior have low insulin sensitivity; the possible reason might be due to the increased chronic low-grade inflammation.

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.

Associations of serum vitamin D concentrations with obstetric glucose metabolism in a subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study cohort

To assess associations between maternal serum vitamin D concentration and glucose metabolism in a cohort of pregnant women living in an Australian subtropical environment. Cross-sectional assessment of 25-hydroxy vitamin D concentrations in 399 Hyperglycemia and Adverse Pregnancy Outcome ancillary study participants, treated at an obstetric teaching hospital in Brisbane, Australia. All patients underwent a blinded 75-g oral glucose tolerance test at 24-32 (target 28) weeks' gestation. The mean (± standard deviation) fasting plasma glucose was 4.5 ± 0.4 mmol/l. Mean (± standard deviation) serum 25-hydroxy vitamin D was 132.5 ± 44.0 nmol/l. A difference of one standard deviation in maternal 25-hydroxy vitamin D was inversely related to fasting glucose (fasting glucose lower by 0.047 mmol/l, P=0.012) when assessed with multiple linear regression after adjusting for confounders. Maternal 25-hydroxy vitamin D correlated with β-cell function as estimated by the log-transformed homeostasis model assessment-β-cell function equation (r=0.131, P=0.009), but not with the homeostasis model assessment of insulin resistance. An association between mid-gestational 25-hydroxy vitamin D and fasting glucose was confirmed in a largely normoglycaemic and vitamin D-replete pregnant population. The correlation between 25-hydroxy vitamin D and β-cell function suggests that vitamin D may influence glucose metabolism through this mechanism. Intervention studies are required to determine causality and the role of vitamin D replacement in deficient individuals.

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.