Homeostasis Model Assessment Insulin Sensitivity Research Articles

Acrolein Exposure Impaired Glucose Homeostasis and Increased Risk of Type 2 Diabetes: An Urban Adult Population-Based Cohort Study with Repeated Measures

Acrolein is an identified high-priority hazardous air pollutant ubiquitous in daily life and associated with cardiometabolic risk that attracts worldwide attention. However, the etiology role of acrolein exposure in glucose dyshomeostasis and type 2 diabetes (T2D) is unclear. This repeated-measurement prospective cohort study included 3522 urban adults. Urine/blood samples were repeatedly collected for determinations of acrolein metabolites (N-acetyl-S-(3-hydroxypropyl)-l-cysteine, N-acetyl-S-(2-carboxyethyl)-l-cysteine; acrolein exposure biomarkers), glucose homeostasis, and T2D at baseline and a three-year follow-up. We found that each 3-fold increment in acrolein metabolites was cross-sectionally associated with 5.91-6.52% decrement in homeostasis model assessment-insulin sensitivity (HOMA-IS) and 0.07-0.14 mmol/L, 4.02-4.57, 5.91-6.52, 19-20, 18-19, and 23-31% increments in fasting glucose (FPG), fasting insulin (FPI), HOMA-insulin resistance (HOMA-IR), risks of prevalent IR, impaired fasting glucose (IFG), and T2D, respectively; longitudinally, participants with sustained-high acrolein metabolite levels had increased risks of incident IR, IFG, and T2D by 63-80, 87-99, and 120-154%, respectively (P < 0.05). In addition, biomarkers of heme oxygenase-1 activity (exhaled carbon monoxide), lipid peroxidation (8-iso-prostaglandin-F2α), protein carbonylation (protein carbonyls), and oxidative DNA damage (8-hydroxy-deoxyguanosine) mediated 5.00-38.96% of these associations. Our study revealed that acrolein exposure may impair glucose homeostasis and increase T2D risk via mediating mechanisms of heme oxygenase-1 activation, lipid peroxidation, protein carbonylation, and oxidative DNA damage.

Association of SLC22A1, SLC22A2, SLC47A1, and SLC47A2 Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients.

Response to metformin, first-line therapy for type 2 diabetes mellitus (T2DM), exists interindividual variation. Considering that transporters belonging to the solute carrier (SLC) superfamily are determinants of metformin pharmacokinetics, we evaluated the effects of promoter variants in organic cation transporter 1 (OCT1) (SLC22A1 rs628031), OCT2 (SLC22A2 rs316019), multidrug and toxin extrusion protein 1 (MATE1) (SLC47A1 rs2289669), and MATE2 (SLC47A2 rs12943590) on the variation in metformin response. The glucose-lowering effects and improvement of insulin resistance of metformin were assessed in newly diagnosed, treatment-naive type 2 diabetic patients of Han nationality in Chaoshan China (n = 93) receiving metformin. Fasting plasma glucose (FPG), fasting insulin (FINS), glycated hemoglobin A1 (HbA1C), homeostasis model assessment-insulin sensitivity (HOMA-IS), and homeostasis model assessment-insulin resistance (HOMA-IR) were the main metformin efficacy measurements. There were significant correlations between both SLC47A1 rs2289669 and SLC47A2 rs12943590 and the efficacy of metformin in individuals with T2DM. In normal weight T2DM patients, significant associations between the AA and GG genotypes of the rs2289669 variant of SLC47A1 and a greater reduction in FINS and HOMA-IR were detected. A significant correlation was observed between the AG genotype of the rs12943590 polymorphism of SLC47A2 and a greater reduction in HOMA-IR. Gene–environment interaction analysis showed that in the FINS interaction model, the second-order of dose30_g-SLC47A2 rs12943590 was statistically significant. The variants of SLC47A1 rs2289669 and SLC47A2 rs12943590 could be predictors of insulin resistance in type 2 diabetic patients treated with metformin. The second-order interaction of dose30_g-SLC47A2 rs12943590 may have a significant effect on FINS in patients with T2DM on metformin treatment. These findings suggest that promoter variants of SLC47A1 and SLC47A2 are important determinants of metformin transport and response in type 2 diabetes mellitus.

Construction of the experimental rat model of gestational diabetes.

Numerous methods for modeling gestational diabetes mellitus (GDM) in rats exist. However, their repeatability and stability are unclear. This study aimed to compare the effects of high-fat and high-sugar (HFHS) diet, HFHS diet combined with streptozotocin (STZ) administration, and HFHS diet combined with movement restriction (MR) modeling methods on rat models to confirm the best method for constructing a rat model of GDM. Forty female Sprague-Dawley rats were randomly divided into four groups (n = 10): the normal control (NC), HFHS, HFHS+STZ, and HFHS+MR groups. The rats in the NC group were fed with a standard diet, and those in the remaining groups were fed with a HFHS diet. The rats in the HFHS+STZ group received 25 mg/kg STZ on their first day of pregnancy, and those in the HFHS+MR group were subjected to MR during pregnancy. Bodyweight, food intake, water intake, fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of insulin sensitivity (HOMA-IS), homeostasis model assessment of β-cell function, pancreatic and placental morphology, and the expression levels of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in placentas were then quantified. Moreover, iTRAQ was used to identify placental proteomics. During pregnancy, the rats in the HFHS+STZ group showed FBG levels that were kept stable in a state of moderate hyperglycemia; the typical GDM symptoms of polydipsia, polyphagia, polyuria, and increased body weight; and the modeling rate of 87.5%. On the first and 19th days of pregnancy, the rats in the HFHS group showed higher FBG than that of the NC group, increasing body weight and food intake and the modeling rate of 50%. On the 19th day of pregnancy, the FBG of the rats in the HFHS+MR group was higher than that of the rats in the NC group, and the modeling rate of 42.9%. Comparison with the NC group revealed that the three modeling groups exhibited increased FINS and HOMA-IR, decreased HOMA-IS, and different degrees of pathological changes in pancreases and placentas. Among the groups, the HFHS+STZ group displayed the greatest changes with significant reductions in the numbers of pancreatic and placental cells and appeared cavitation. The expression levels of GLUT1 and GLUT3 in the placentas of the HFHS+STZ and HFHS+MR groups were higher than those in the placentas of the NC and HFHS groups. The above results indicated that the rats in the HFHS+STZ group showed the best performance in terms of modeling indicators. After the changes in placental proteomics in the HFHS+STZ group were compared with those in the NC group, we found that in the HFHS+STZ group, five proteins were up-regulated and 18 were down-regulated; these proteins were enriched in estrogen signaling pathways. HFHS combined with the intraperitoneal injection of 25 mg/kg STZ was the best modeling method for the nonspontaneous model of experimentally induced GDM, and its modeling rate was high. The pathological characteristics of the constructed GDM rat model were similar to those of human patients with GDM. Moreover, the model was stable and reliable. The modeling method can provide a basis for constructing a GDM rat model for subsequent research on the prevention and treatment of GDM.

High-intensity interval training on body composition, functional capacity and biochemical markers in healthy young versus older people

The aim of the following study was to identify the effects of a 12-week high-intensity interval training (HIIT) program on the modification of parameters of body composition, functional capacity as well as lipid and glucose homeostasis markers in healthy young people versus older adults. Experimental trial. Healthy young (YNG, 21±1years, BMI 26.01±2.64kg·m-2, n=10) and older (OLD, 66±5years, BMI 27.43±3.11kg·m-2, n=10) males were subjected to 12weeks of HIIT. Prior to and immediately after the HIIT program, dual-energy X-ray absorptiometry, dominant leg strength one-repetition maximum (1-RM), maximal oxygen uptake (VO2max) and physical performance tests were performed. Blood samples were also taken. Flexibility (P=0.000), static balance (P=0.004), timed up and go test (TUG) (P=0.015), short physical performance battery (SPPB) (P=0.005), dominant leg strength 1-RM(P=0.012), and VO2max (P=0.000) were better in YNG versus OLD. HIIT improved the % whole-body fat mass (P=0.031), leg lean mass (P=0.047), dominant leg strength 1-RM (P=0.025), VO2max (P=0.000), fasting cholesterol (P=0.017) and fasting glucose (P=0.006). TUG was improved by the training only in the OLD group (P=0.016), but insulin (P=0.002) and the homeostasis model assessment - insulin sensitivity (HOMA-IS) (P=0.000) decreased only in the YNG group. HOMA-IS was correlated positive with BMI (R=0.474, P=0.035) and with whole-body fat mass (R=0.517, P=0.019). HIIT for 12weeks improves parameters of body composition, functional capacity and fasting serum lipid and glucose homeostasis markers in healthy young and older participants. Young people are shown as benefiting more.

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis.

Both type 2 prediabetes/diabetes (T2DM) and new-onset prediabetes/diabetes after acute pancreatitis (NODAP) are characterized by impaired tissue sensitivity to insulin action. Although the outcomes of NODAP and T2DM are different, it is unknown whether drivers of insulin resistance are different in the two types of diabetes. This study aimed to investigate the associations between abdominal fat phenotypes and indices of insulin sensitivity in non-obese individuals with NODAP, T2DM, and healthy controls. Indices of insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA-IS), Raynaud index, triglyceride and glucose (TyG) index, Matsuda index) were calculated in fasting and postprandial states. Fat phenotypes (intra-pancreatic fat, intra-hepatic fat, skeletal muscle fat, visceral fat, and subcutaneous fat) were determined using magnetic resonance imaging and spectroscopy. Linear regression and relative importance analyses were conducted. Age, sex, and glycated hemoglobin A1c were adjusted for. A total of 78 non-obese individuals (26 NODAP, 20 T2DM, and 32 healthy controls) were included. Intra-pancreatic fat was significantly associated with all the indices of insulin sensitivity in the NODAP group, consistently in both the unadjusted and adjusted models. Intra-pancreatic fat was not significantly associated with any index of insulin sensitivity in the T2DM and healthy controls groups. The variance in HOMA-IS was explained the most by intra-pancreatic fat (R2 = 29%) in the NODAP group and by visceral fat (R2 = 21%) in the T2DM group. The variance in the Raynaud index was explained the most by intra-pancreatic fat (R2 = 18%) in the NODAP group and by visceral fat (R2 = 15%) in the T2DM group. The variance in the TyG index was explained the most by visceral fat in both the NODAP group (R2 = 49%) and in the T2DM group (R2 = 25%). The variance in the Matsuda index was explained the most by intra-pancreatic fat (R2 = 48%) in the NODAP group and by visceral fat (R2 = 38%) in the T2DM group. The differing association between intra-pancreatic fat and insulin resistance can be used to differentiate NODAP from T2DM. Insulin resistance in NODAP appears to be predominantly driven by increased intra-pancreatic fat deposition.

Insulin Resistance in Nonobese Renal Allograft Recipients on Maintenance Doses of Cyclosporine or Tacrolimus

PurposeIn comparison to cyclosporine (CsA), tacrolimus (Tac) seems to be more diabetogenic in renal transplant recipients, and post-transplant diabetes mellitus is more common in patients using Tac, especially during the first year after transplantation. However, at maintenance doses, there are no comparative data of insulin resistance (IR) in patients using Tac or CsA. The purpose of this study was to investigate the IR indexes in patients on maintenance doses of CsA or Tac. MethodsForty-five nondiabetic and nonobese renal transplant recipients participated in the study (M:F, 30:15; age, 36 ± 9 years); 27 patients were on CsA, and 18 were on Tac. All had stable graft function, were transplanted at least 6 months previously, and were receiving maintenance doses of steroids (5.0 mg/d), azathioprine or mycophenolate mofetil, and calcineurin inhibitors (CsA [2.14 ± 0.46 mg/kg/d] or Tac [0.06 ± 0.03 mg/kg/d]). IR was evaluated by the homeostasis model assessment (HOMA) index and composite body insulin sensitivity index. ResultsWe did not determine any significant difference in the HOMA and composite body insulin sensitivity index levels among patients using CsA or Tac (1.5 ± 1.3 vs 1.5 ± 1.1, P > .05, and 9.9 ± 5.8 vs 14.6 ± 11.7, P > .05, respectively). There was a significant correlation between creatinine and HOMA values. ConclusionThere was no difference in IR indexes in renal transplant recipients receiving maintenance doses of either CsA or Tac.

Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women.

Hyperglycaemia and type 2 diabetes (T2D) are associated with impaired insulin secretion and/or insulin action. Since few studies have addressed the relation between DNA methylation patterns with elaborated surrogates of insulin secretion/sensitivity based on the intravenous glucose tolerance test (IVGTT), the aim of this study was to evaluate the association between DNA methylation and an insulin sensitivity index based on IVGTT (calculated insulin sensitivity index (CSi)) in peripheral white blood cells from 57 non-diabetic female volunteers. The CSi and acute insulin response (AIR) indexes, as well as the disposition index (DI = CSi × AIR), were estimated from abbreviated IVGTT in 49 apparently healthy Chilean women. Methylation levels were assessed using the Illumina Infinium Human Methylation 450k BeadChip. After a statistical probe filtering, the two top CpGs whose methylation was associated with CSi were cg04615668 and cg07263235, located in the catenin delta 2 (CTNND2) and lipoprotein lipase (LPL) genes, respectively. Both CpGs conjointly predicted insulin sensitivity status with an area under the curve of 0.90. Additionally, cg04615668 correlated with homeostasis model assessment insulin-sensitivity (HOMA-S) and AIR, whereas cg07263235 was associated with plasma creatinine and DI. These results add further insights into the epigenetic regulation of insulin sensitivity and associated complications, pointing the CTNND2 and LPL genes as potential underlying epigenetic biomarkers for future risk of insulin-related diseases.

Associations of Physical Behaviours and Behavioural Reallocations with Markers of Metabolic Health: A Compositional Data Analysis.

Standard statistical modelling has shown that the reallocation of sitting time to either standing or stepping may be beneficial for metabolic health. However, this overlooks the inherent dependency of time spent in all behaviours. The aim is to examine the associations between physical behaviours and markers of metabolic health (fasting glucose, fasting insulin, 2-h glucose, 2-h insulin, Homeostasis Model Assessment of Insulin Sensitivity (HOMA-IS), Matsuda Insulin Sensitivity Index (Matsuda-ISI) while quantifying the associations of reallocating time from one physical behaviour to another using compositional analysis. Objectively measured physical behaviour data were analysed (n = 435) using compositional analysis and compositional isotemporal substitutions to estimate the association of reallocating time from one behaviour to another in a population at high risk of type 2 diabetes mellitus (T2DM). Stepping time was associated with all markers of metabolic health relative to all other behaviours. Reallocating 30 min from sleep, sitting, or standing to stepping was associated with 5–6 fold lower 2-h glucose, 15–17 fold lower 2-h insulin, and higher insulin sensitivity (10–11 fold via HOMA-IS, 12–15 fold via Matsuda-ISI). Associations of reallocating time from any behaviour to stepping were maintained for 2-h glucose, 2-h insulin, and Matsuda-ISI after further adjusting for body mass index (BMI). Relocating time from stepping into sleep, sitting, or standing was associated with lower insulin sensitivity. Stepping time may be the most important behavioural composition when promoting improved metabolic health in adults at risk of T2DM.

Renal function markers and insulin sensitivity after 3\xa0years in a healthy cohort, the EGIR-RISC study

BackgroundPeople with chronic renal disease are insulin resistant. We hypothesized that in a healthy population, baseline renal function is associated with insulin sensitivity three years later.MethodsWe studied 405 men and 528 women from the European Group for the study of Insulin Resistance - Relationship between Insulin Sensitivity and Cardiovascular disease cohort. Renal function was characterized by the estimated glomerular filtration rate (eGFR) and by the urinary albumin-creatinine ratio (UACR). At baseline only, insulin sensitivity was quantified using a hyperinsulinaemic-euglycaemic clamp; at baseline and three years, we used surrogate measures: the Matsuda insulin sensitivity index (ISI), the HOmeostasis Model Assessment of Insulin Sensitivity (HOMA-IS). Associations between renal function and insulin sensitivity were studied cross-sectionally and longitudinally.ResultsIn men at baseline, no associations were seen with eGFR, but there was some evidence of a positive association with UACR. In women, all insulin sensitivity indices showed the same negative trend across eGFR classes, albeit not always statistically significant; for UACR, women with values above the limit of detection, had higher clamp measured insulin sensitivity than other women. After three years, in men only, ISI and HOMA-IS showed a U-shaped relation with baseline eGFR; women with eGFR> 105 ml/min/1.73m2 had a significantly higher insulin sensitivity than the reference group (eGFR: 90–105 ml/min/1.73m2). For both men and women, year-3 insulin sensitivity was higher in those with higher baseline UACR. All associations were attenuated after adjusting on significant covariates.ConclusionsThere was no evidence to support our hypothesis that markers of poorer renal function are associated with declining insulin sensitivity in our healthy population.

Flavonoid intake from fruit and vegetables during adolescence is prospectively associated with a favourable risk factor profile for type 2 diabetes in early adulthood.

Flavonoid consumption during adolescence could contribute to preventing adult onset of type 2 diabetes mellitus. We investigated the prospective association between habitual intake of flavonoids from fruit and vegetables (FlavFV) during adolescence and risk markers of type 2 diabetes in early adulthood. This analysis included participants of the DONALD Study, who had provided a fasting blood sample in adulthood (18-39years), data on FlavFV-intake during adolescence (females: 9-15years, males: 10-16years) and relevant covariates. Habitual FlavFV-intake was either estimated using repeated 3-day weighed dietary records (n = 268), or the validated biomarker hippuric acid (uHA)-excretion in repeated 24-h urine samples (n = 241). Multivariable linear regressions were performed to analyse the prospective associations of FlavFV or uHA with homeostasis model assessment insulin sensitivity (HOMA2-%S), hepatic steatosis index (HSI), fatty liver index (FLI) and a pro-inflammatory score. Higher FlavFV-intake was independently related to higher HOMA2-%S among females (Ptrend=0.03), but not among males. Both FlavFV-intake and uHA-excretion were inversely associated with HSI (Ptrend<0.0001 and Ptrend=0.02, respectively) and the pro-inflammatory score (Ptrend=0.02 and Ptrend=0.008, respectively), but not with FLI. Our data indicate that flavonoid consumption from fruit and vegetables during adolescence is associated with a favourable risk factor profile for type 2 diabetes in early adulthood.

Comparative effect of vildagliptin and teneligliptin on HbA1c, glycemic efficacy and insulin sensitivity

Background: Vildagliptin, a potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor, increases the availability of endogenous incretin hormones, glucagon-like peptide (GLP-1), and glucose-dependent insulinotropic polypeptide, thereby improving glycemic control. The objective of this study is to further investigate the insulin sensitizing properties of Vildagliptin in comparison to those of Teneligliptin.Methods: Naive subjects with T2DM were administered 50-100mg/day Vildagliptin monotherapy (n = 53). As a comparator, monotherapy, 20mg/day Teneligliptin monotherapy was performed in a non-randomized manner (n=58). No other drugs were administered. At 3 month, levels of diabetic parameters were compared with those at baseline.Results: At 3 months, while similar reductions of glycated hemoglobin (HbA1c) levels were observed with these two drugs, indexes for insulin sensitivity homeostasis model assessment (HOMA)-R ameliorated only with Vildagliptin. Then, the subjects were divided into two groups representing distinct degrees of insulin resistance; high HOMA-R (C4) and low HOMA-R (2) groups. With Vildagliptin, similar decreases of HbA1c levels were observed in high (10.85-8.66%, p\0.0005) and low (11.12-8.91%, p\0.01) HOMA-R groups. HOMA-R (-31.9%, p\0.05) and non-high density lipoprotein cholesterol (non-HDL-C, -7%, p\0.05) levels significantly decreased. HOMA-B levels increased in both groups with significant inter-group differences (102.1 % in low HOMA-R group vs. 53.4 % in high HOMA-R group). Group 2. With Teneligliptin similar decreases of HbA1c levels were observed from those of vildagliptin in either high or low HOMA-R group, but no changes of HOMA-R, non-HDL-C levels were noted. Increases of HOMA-B levels with teneligliptin were comparable to those with vildagliptin in either high or low HOMA-R group.Conclusions: These results indicate that vildagliptin ameliorates insulin sensitivity and non-HDL-C levels in subjects with high degrees of insulin resistance and vildagliptin also shows glycemic efficacy by decreasing HbA1c. This is not the case with teneligliptin though similar glycemic efficacies were observed.

The Influence of GH Treatment on Glucose Homeostasis in Girls With Turner Syndrome: A 7-Year Study.

Growth hormone (GH) influences glucose homeostasis mainly by negatively affecting insulin sensitivity. To longitudinally study insulin sensitivity [via homeostasis model assessment of insulin sensitivity (HOMA-S)], insulin secretion [insulinogenic index (IGI)], and capacity of β cells to adapt to changes in insulin sensitivity [oral disposition index (ODI)] in girls with Turner syndrome (TS) undergoing GH treatment. Longitudinal, retrospective, 7-year study conducted in a tertiary pediatric endocrine unit and university pediatric clinic. We studied 104 patients with TS (mean age ± standard deviation, 9.1 ± 3.4 years) for a median of 7.2 years. Every year, the children underwent an oral glucose tolerance test, which was used to calculate HOMA-S, IGI, and ODI. HOMA-S, IGI, and ODI did not significantly change. The results are reassuring, showing no negative influence of GH treatment on insulin sensitivity and on β-cell secretory capacity in girls with TS.

Inclusion of Konjac Flour in the Gestation Diet Changes the Gut Microbiota, Alleviates Oxidative Stress, and Improves Insulin Sensitivity in Sows.

Although dietary fibers contribute to health and physiology primarily via the fermentative actions of the gut microbiota of the hosts, few studies have focused on how these interactions influence the metabolic status of sows. Here, the effects of inclusion of konjac flour (KF) in a gestation diet on oxidative stress status, insulin sensitivity, and gut microbiota were investigated to elucidate the correlation between the microbiota and metabolic changes in sows. Sows were assigned to either control or 2.2% KF dietary treatment during gestation. The gut microbiota population in sows during gestation and lactation was assessed by 16S rRNA gene sequencing. The oxidative stress parameters, homeostasis model assessment (HOMA) values, and fatty acids in the blood of sows were also assessed. Compared to the control diet group, KF significantly reduced the serum levels of reactive oxygen species (ROS) and 8-hydroxy-deoxyguanosine (8-OHdG) but increased the serum concentrations of glutathione peroxidase (GSH-Px) in sows on day 1 in lactation. Additionally, sows in the KF group had a lower HOMA insulin resistance value but a higher HOMA insulin sensitivity (HOMA-IS) value. KF induced changes in the gut microbial composition at the phylum and genus levels. The increased relative abundances of Akkermansia and Roseburia in the KF group were positively correlated with the HOMA-IS. Overall, dietary KF alleviated oxidative stress and improved insulin sensitivity of sows, and the changes in the gut microbiota in response to KF may have been correlated with the host metabolism response. To date, the effect of dietary fiber on metabolism responses and gut microbiota in sows has not been investigated. Here, KF supplementation of a gestation diet in sows was found to alleviate oxidative stress and to improve insulin sensitivity. Pyrosequencing analysis revealed that KF treatment induces changes in the gut microbiota composition at the phylum and genus levels. Moreover, the changes of gut microbiota in response to KF may be correlated with the host metabolism response.

Association between insulin dosage and insulin usage time, and coronary artery lesions in patients with type 2 diabetes and coronary heart disease.

Insulin is used in the treatment of type 2 diabetes, with its usage reaching 30–50% in Western countries. The aim of the present study was to determine the association between insulin dosage (ID)/insulin usage time (IT) and coronary artery lesions in patients of type 2 diabetes with coronary heart disease. Based on the insulin using dosage, 353 type 2 diabetes patients were divided into the high-dose (≥0.5 IU/kg) and low-dose (<0.5 IU/kg) group. Selected coronary angiography was performed and the Gensini score was used to determine the degree of the coronary artery lesions. The homeostasis model assessment-insulin sensitivity (HOMA-IS) index was assessed by HOMA2. Data including age, gender, smoking, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), glucose (Glu), hemoglobin A1c (HbA1c), C-peptide, ID, IT, diabetes duration time (DT), and IT/DT were collected. The association between insulin usage (both dose and time) and the coronary artery lesions in these patients was then determined. Statistical differences for the two groups for factors including C-peptide, HbA1c, ID, IT, DT, IT/DT and the Gensini score values (P<0.05) were identified. By contrast, no significant differences for factors such as gender, smoking history, age, BMI, TC, TG, LDL, HDL, fasting insulin, Glu, SBP and DBP were observed. The coronary artery damage Gensini score in insulin-insensitive individuals was significantly greater than that in the insulin-sensitive individuals. The Spearman analysis revealed that ID and IT, DT and IT/DT were positively correlated with the coronary artery damage Gensini score. The multivariate regression, the interquartile range method and receiver operating characteristic analyses showed that ID, ID/DT, IT had a greater effect on coronary vascular damage compared with DT. In conclusion, the degree of coronary artery lesions were correlated with ID, IT, DT, IT/DT. High doses of insulin or a high IT/DT ratio may aggravate coronary artery damage.

Increased concentration of circulating visfatin associates with post-challenged hyperglycaemia and insulin resistance in IGT subjects

Abstract Objectives The cytokine visfatin is increased in obesity and type 2 Diabetes; however, its role in the development of diabetes is still unsettled. The present study aimed to investigate the serum visfatin levels in prediabetic subjects. Methods Seventeen subjects with Impaired Fasting Glucose (IFG), 44 Impaired Glucose Tolerant (IGT), 16 IFG-IGT and 51 healthy subjects were recruited. Fasting insulin and visfatin were measured using enzyme-linked immunosorbent assay (ELISA) techniques. The Insulin sensitivity Homeostasis Model Assessment (HOMA%S) and B-cell secretory capacity (HOMA%B) were estimated using HOMA-CIGMA software. Results HOMA%B was significantly lower in IFG (p = 0.0001) and IFG-IGT (p = 0.001) subjects. HOMA%S in IGT (p = 0.0001) and IFG-IGT (p = 0.001) subjects were significantly lower compared to controls. The fasting serum visfatin (ng/ml) level was significantly higher in IFG (5.08 ± 2.16, p = 0.0001), IGT (4.75 ± 2.81, p = 0.0001) and IFG-IGT subjects (4.33 ± 2.68, p = 0.013) compared to controls (2.60 ± 1.2). In binary logistic regression analysis, visfatin has found significantly associated with IFG (B = 0.198, p = 0.040), IGT (B = 0.162, p = 0.043) and IFG-IGT (B = 0.188, p = 0.044). Visfatin was also found significantly correlated with postprandial serum glucose and blood pressure in IGT subjects. Frequency of IFG, IGT and IFG-IGT subjects increased with increasing visfatin concentrations. Conclusions Serum visfatin appear to be associated with IFG, IGT and IFG-IGT. Postprandial serum glucose and blood pressure are positively associated with visfatin levels in IGT subjects.

Reduction of Specific Circulating Lymphocyte Populations with Metabolic Risk Factors in Patients at Risk to Develop Type 2 Diabetes

Low-grade inflammation, characterized by increased pro-inflammatory cytokine levels, is present in patients with obesity-linked insulin resistance, hyperglycemia and hyperlipidemia and considered to play a leading role to progression into type 2 diabetes (T2D). In adipose tissue in obese patients and in pancreatic islets in T2D patients cellular inflammation is present. However, the systemic leukocyte compartment and the circulating endothelial/precursor compartment in patients at risk to develop T2D has so far not been analyzed in detail. To address this, peripheral blood cells from a cohort of 20 subjects at risk to develop diabetes with normal to impaired glucose tolerance were analyzed by flow cytometry using a wide range of cellular markers and correlated to known metabolic risk factors for T2D i.e. fasting plasma glucose (FPG), 2 h plasma glucose (2 h PG), HbA1c, body mass index (BMI), homeostasis model assessment of β-cell function (HOMA-B), homeostasis model assessment of insulin sensitivity (HOMA-IS) and fasting insulin (FI). The four highest ranked cell markers for each risk factor were identified by random forest analysis. In the cohort, a significant negative correlation between the number of TLR4+ CD4 T cells and increased FPG was demonstrated. Similarly, with increased BMI the frequency of TLR4+ B cells was significantly decreased, as was the frequency of IL-21R+ CD4 T cells. Unlinked to metabolic risk factors, the frequency of regulatory T cells was reduced and TLR4+ CD4 T cells were increased with age. Taken together, in this small cohort of subjects at risk to develop T2D, a modulation of the circulating immune cell pool was demonstrated to correlate with risk factors like FPG and BMI. This may provide novel insights into the inflammatory mechanisms involved in the progression to diabetes in subjects at risk.

WHR: common anthropometric indicators for identifying insulin sensitivity and resistance in female

Diabetes mellitus has reached epidemic level worldwide. South Asians are known for increased predisposition of diabetes which has become an important health problem. Obesity is a well-established risk factor for diabetes mellitus and Insulin resistance. Early detection of reduced insulin sensitivity (IS) and insulin resistance (IR) is need of the time. The aim of the present study was to assess most suitable anthropometric indicator for identifying IR or IS and determine the cutoff points of the most effective indicators. A total of 742 subjects were included in this cross-sectional study. Hormone and glucose levels were estimated using standard protocols. Body mass index (BMI), waist circumference (WC), waist-to-hip ratio, waist-to-height ratio (WHtR) and the HOMA-IS and HOMA-IR were determined. The correlations between the anthropometric indices and IS and IR were determined. ROC analysis was used to determine the areas under the curve (AUC) and cutoff points. Among the obese non diabetic females, WHR (r = -0.386; P = <0.001) showed substantially significant correlation with HOMA-IS (homeostasis model assessment of insulin sensitivity). The ROC curve demonstrated statistical significance for BMI, WC and WHR, and the best cutoff points were 28.06 kg/m2, 94.75 cm and 0.91, respectively. It also showed substantial significance for WHR (AUC = 0.65±0.06; P = 0.021), and the best cutoff points was 0.85 in all studied anthropometric indices. Among the obese non diabetic female, WHR showed substantially greater correlation with IR/IS.

Insulin resistance and increased muscle cytokine levels in patients with mitochondrial myopathy.

Mitochondrial dysfunction has been proposed to cause insulin resistance and that might stimulate cytokine production. The objective of the study was to elucidate the association between mitochondrial myopathy, insulin sensitivity, and cytokine levels in muscle. This was an experimental, controlled study in outpatients. Eight overnight-fasted patients (P) with various inherited mitochondrial myopathies and eight healthy subjects (C) matched for sex, age, weight, height, and physical activity participated in the study. The intervention included a 120-minute hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus lateralis muscles for 4 hours, including one-legged, knee extension exercise for 30 minutes, was performed. Glucose infusion rate during 90-120 minutes of insulin infusion was measured. Cytokine concentrations in dialysate were also measured. Muscle strength, percentage fat mass, and creatine kinase in plasma did not differ between groups. The maximal oxygen uptake was 21 ± 3 (SE) (P) and 36 ± 3(C) mL/kg·min (2P < .05). Basal insulin, C-peptide, and glucagon were higher in P (55 ± 10, 980 ± 92, and 102 ± 13 pM) than in C (36 ± 12, 712 ± 98, and 44 ± 10 pM) (two-sided significance testing [2P ]< .05). The homeostasis model assessment insulin sensitivity index and glucose infusion rate (6.8 ± 1.0 vs 9.4 ± 1.3 mg/min·kg) were lower, and free fatty acids and glycerol at 120 minutes were higher in P vs C (2P < .05). Dialysate concentrations of TNF-α, IL-6, IL-8, IL-10, and monocyte chemoattractant protein-1 were higher in P vs C (2P < .05). Dialysate concentrations of these cytokines and of IL-1 receptor antagonist increased during exercise (2P < .05), identically in P and C. No differences existed in plasma cytokine concentrations. In patients with a variety of mitochondrial myopathies, insulin sensitivity of muscle, adipose tissue, and pancreatic A cells is reduced, supporting that mitochondrial function influences insulin action. Furthermore, a local, low-grade inflammation of potential clinical importance exists in the muscle of these patients.

Effects of dairy vs. sugar‐sweetened products on insulin sensitivity, pancreatic β‐cell function and plasma lipids in men and women at risk for type 2 diabetes mellitus (117.3)

This randomized, controlled, crossover trial assessed the effects of dairy (2 servings/d 2% milk and 1 serving/d low‐fat yogurt) vs. sugar‐sweetened (2 servings/d non‐diet soda and 1 serving/d non‐dairy pudding) product consumption for 3 wk on insulin sensitivity, β‐cell function, and plasma lipids. Subjects were 34 consumers of sugar‐sweetened beverages (蠅2 servings/d), 50% female, mean age 53.8 y and BMI 32.2 kg/m2, with multiple risk factors for type 2 diabetes mellitus (T2DM). A liquid meal tolerance test (LMTT) was administered at baseline (BL) and the end of each treatment. Changes from BL (dairy condition shown first) were significantly different between conditions for mean homeostasis model assessment insulin sensitivity (HOMA‐%S; 17.8 vs. ‐17.3%; P = 0.01; BL = 127.1%), LMTT disposition index (‐0.03 vs. ‐0.36; P = 0.01; BL = 2.59), and HDL‐C (0.8 vs. ‐4.2%; P = 0.01; BL = 44.3 mg/dL). Median changes from BL in LMTT Matsuda insulin sensitivity index (0.54 vs. ‐0.26; BL = 4.16) and HOMA β‐cell function (0.5 vs. 3.8%; BL = 68.4%) did not differ significantly between treatments. These results suggest that dairy consumption, compared with sugar‐sweetened products, improves HOMA‐%S, LMTT disposition index, and HDL‐C in men and women at‐risk for T2DM.Grant Funding Source: Dairy Research Institute

Impact of dietary fiber intake on glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry

BackgroundDietary fiber is beneficial for the treatment of type 2 diabetes mellitus, although it is consumed differently in ethnic foods around the world. We investigated the association between dietary fiber intake and obesity, glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese type 2 diabetic patients.MethodsA total of 4,399 patients were assessed for dietary fiber intake using a brief self-administered diet history questionnaire. The associations between dietary fiber intake and various cardiovascular risk factors were investigated cross-sectionally.ResultsBody mass index, fasting plasma glucose, HbA1c, triglyceride and high-sensitivity C-reactive protein negatively associated with dietary fiber intake after adjusting for age, sex, duration of diabetes, current smoking, current drinking, total energy intake, fat intake, saturated fatty acid intake, leisure-time physical activity and use of oral hypoglycemic agents or insulin. The homeostasis model assessment insulin sensitivity and HDL cholesterol positively associated with dietary fiber intake. Dietary fiber intake was associated with reduced prevalence of abdominal obesity, hypertension and metabolic syndrome after multivariate adjustments including obesity. Furthermore, dietary fiber intake was associated with lower prevalence of albuminuria, low estimated glomerular filtration rate and chronic kidney disease after multivariate adjustments including protein intake. Additional adjustments for obesity, hypertension or metabolic syndrome did not change these associations.ConclusionWe demonstrated that increased dietary fiber intake was associated with better glycemic control and more favorable cardiovascular disease risk factors including chronic kidney disease in Japanese type 2 diabetic patients. Diabetic patients should be encouraged to consume more dietary fiber in daily life.