Homeostasis Model Assessment Β-cell Research Articles

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.

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.

In utero exposure to phenanthrene induced islet cell dysfunction in adult mice: Sex differences in the effects and potential causes

Epidemiological studies show that the burden of polycyclic aromatic hydrocarbons in human body is associated with the occurrence of insulin resistance and diabetes. In the present study, pregnant mice were exposed to phenanthrene (Phe) at doses of 0, 60 and 600 μg/kg body weight of by gavage once every 3 days. The female F1 mice at 120 days of age showed no change in their fasting glucose levels (FGLs) but exhibited significantly decreased homeostasis model assessment (HOMA) β-cell (49% and 43%) and significantly downregulated pancreatic proinsulin gene (ins2) transcription. The downregulation of transcription factors, such as PDX1, PAX4 and FGF21, indicated impaired development and function of β-cells. The significantly reduced α-cell mass in 60 and 600 μg/kg groups, and the significantly downregulated expression of proglucagon gene gcg and ARX in the 600 μg/kg group suggested that the development and function of α-cells had been impacted. The males exhibited significantly increased FGLs (1.14- and 1.15-fold) in Phe exposed treatments and significantly elevated HOMA β-cell (3.15-fold) in the 600 μg/kg group. Upregulated ins2 transcription and FGF21 protein in male mice prenatally exposed to 600 μg/kg Phe suggested that these animals appeared compensatory enhancement in β-cell function. The reduced serum estradiol levels and downregulated pancreatic estrogen receptor α and β were responsible for the dysfunction of β-cells in the females. In the males, the significantly elevated androgen levels in the 600 μg/kg group might be related to the upregulated ins2 transcription, and the increased expression of pancreatic FGF21 further demonstrated the enhancement of β-cell potential. The results will be helpful for assessing the risk of developing diabetes in adulthood after prenatal exposure to phenanthrene.

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.

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.

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.

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.

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.

Insulin Resistance and Excess Risk of Diabetes in Mexican-Americans: The San Antonio Heart Study

Mexican-Americans have more diabetes than non-Hispanic whites, but the extent to which insulin resistance and insulin secretion explain the ethnic difference is unknown. We analyzed selected indices of insulin resistance and secretion for both the ethnic difference and predictive discrimination. The San Antonio Heart Study is a longitudinal population-based study with a follow-up period of 7.5 yr. A total of 1540 nondiabetic individuals aged 25-64 yr were enrolled from January 1984 to December 1988. Homeostasis model assessment (HOMA) of insulin resistance and secretion were estimated by available formulas (HOMA-IR and HOMA β-cell) and computer program (HOMA2S and HOMA2B). Matsuda index and insulinogenic index from 0 to 30 and 0 to 120 min (ΔI0-30/ΔG0-30 and ΔI0-120/ΔG0-120) were also calculated. Incident diabetes was defined by the 2003 American Diabetes Association criteria. Incident diabetes was in excess in Mexican-Americans [odds ratio 2.26 (95% confidence interval, 1.53-3.34)]. Matsuda index explained a larger proportion of the ethnic difference than did HOMA-IR (49.2 vs. 31.0%; P<0.001). The ethnic difference was not explained by measures of insulin secretion. Matsuda index and ΔI0-30/ΔG0-30 had a better predictive discrimination than their HOMA equivalents and ΔI0-120/ΔG0-120. HOMA estimates by the computer program offered no advantage over simple formulas for HOMA. Insulin resistance accounts for a large and significant proportion of the excess risk of diabetes in Mexican-Americans. Matsuda index is better than HOMA-IR for both explaining the ethnic difference and predicting diabetes.

The Association of Unintentional Changes in Weight, Body Composition, and Homeostasis Model Assessment Index with Glycemic Progression in Non-Diabetic Healthy Subjects

BackgroundWe performed a retrospective longitudinal study on the effects of changes in weight, body composition, and homeostasis model assessment (HOMA) indices on glycemic progression in subjects without diabetes during a four-year follow-up period in a community cohort without intentional intervention.MethodsFrom 28,440 non-diabetic subjects who participated in a medical check-up program in 2004, data on anthropometric and metabolic parameters were obtained after four years in 2008. Body composition analyses were performed with a bioelectrical impedance analyzer. Skeletal muscle index (SMI, %) was calculated with lean mass/weight×100. Subjects were divided into three groups according to weight change status in four years: weight loss (≤-5.0%), stable weight (-5.0 to 5.0%), weight gain (≥5.0%). Progressors were defined as the subjects who progressed to impaired fasting glucose or diabetes.ResultsProgressors showed worse baseline metabolic profiles compared with non-progressors. In logistic regression analyses, the increase in changes of HOMA-insulin resistance (HOMA-IR) in four years presented higher odds ratios for glycemic progression compared with other changes during that period. Among the components of body composition, a change in waist-hip ratio was the strongest predictor, and SMI change in four years was a significant negative predictor for glycemic progression. Changes in HOMA β-cell function in four years was a negative predictor for glycemic progression.ConclusionIncreased interval changes in HOMA-IR, weight gain and waist-hip ratio was associated with glycemic progression during a four-year period without intentional intervention in non-diabetic Korean subjects.

The Changes of Blood Glucose Control and Lipid Profiles after Short-Term Smoking Cessation in Healthy Males

ObjectiveOur aim was to evaluate the changes in blood glucose control and lipid profiles after 2-months of smoking cessation in healthy males.MethodsSmoking abstinence was evaluated through self-report and urine cotinine levels. 12 individuals who succeeded in quitting smoking were analyzed. Fasting values of glucose and insulin were used to estimate the β-cell activity and insulin resistance was evaluated using the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI).ResultsThe data showed that the subjects had a significant increase in weight, body mass index and fasting plasma glucose levels after smoking cessation. The HOMA-Insulin Resistance and the HOMA β-cell function increased significantly (p=0.005, p=0.047 respectively). The QUICKI showed a significant decrease (p=0.005). In addition, the low-density lipoprotein cholesterol levels decreased significantly (p=0.028); however, changes in the high-density lipoprotein cholesterol, the triglyceride and total cholesterol levels were not significant (p=0.284, p=0.445 respectively).ConclusionDuring the initial stage of smoking abstinence, insulin resistance increased and insulin sensitivity decreased due to elevated body weight and fat composition. Therefore, it is important to educate individuals that stop smoking about the necessity of weight control during smoking cessation programs.

Plasma gastric inhibitory polypeptide and glucagon-like peptide-1 levels after glucose loading are associated with different factors in Japanese subjects.

Aims/Introduction: Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins that potentiate insulin secretion from pancreatic β-cells. The factors responsible for incretin secretion have been reported in Caucasian subjects, but have not been thoroughly evaluated in Japanese subjects. We evaluated the factors associated with incretin secretion during oral glucose tolerance test (OGTT) in Japanese subjects with normal glucose tolerance (NGT). We measured plasma GIP and GLP-1 levels during OGTT in 17 Japanese NGT subjects and evaluated the factors associated with GIP and GLP-1 secretion using simple and multiple regression analyses. GIP secretion (AUC-GIP) was positively associated with body mass index (P < 0.05), and area under the curve (AUC) of C-peptide (P < 0.05) and glucagon (P < 0.01), whereas GLP-1 secretion (AUC-GLP-1) was negatively associated with AUC of plasma glucose (P < 0.05). The insulinogenic index was most strongly associated with GIP secretion (P < 0.05); homeostasis model assessment β-cell was the most the strongly associated factor in GLP-1 secretion (P < 0.05) among the four indices of insulin secretion and insulin sensitivity. Several distinct factors might be associated with GIP and GLP-1 secretion during OGTT in Japanese subjects. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00078.x, 2011).

Exenatide Versus Glibenclamide in Patients with Diabetes

Incretin-based therapies have provided additional options for the treatment of type 2 diabetes mellitus. The aim of our study was to evaluate the effects of exenatide compared to glibenclamide on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state in patients with diabetes. One hundred twenty-eight patients with uncontrolled type 2 diabetes mellitus receiving therapy with metformin were randomized to take exenatide 5 microg twice a day or glibenclamide 2.5 mg three times a day and titrated to exenatide 10 microg twice a day or glibenclamide 5 mg three times a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance (HOMA-IR) index, homeostasis model assessment beta-cell function (HOMA-beta) index, plasma proinsulin (PPr), PPr/FPI ratio, resistin, retinol binding protein-4 (RBP-4), and high-sensitivity C-reactive protein (Hs-CRP) at baseline and after 3, 6, 9, and 12 months. Body weight and BMI decreased with exenatide and increased with glibenclamide. A similar improvement of HbA(1c), FPG, and PPG was obtained in both groups, whereas FPI decreased with exenatide and increased with glibenclamide. The HOMA-IR index decreased and the HOMA-beta index increased with exenatide but not with glibenclamide. A decrease of PPr was reported in both groups, but only glibenclamide decreased the PPr/FPI ratio. Resistin and RBP-4 decreased with exenatide and increased with glibenclamide. A decrease of Hs-CRP was obtained with exenatide, whereas no variations were observed with glibenclamide. Both exenatide and glibenclamide gave a similar improvement of glycemic control, but only exenatide gave improvements of insulin resistance and beta-cell function, giving also a decrease of body weight and of inflammatory state.