Β-cell Function Index Research Articles

Differential role of insulin resistance and \u03b2-cell function in the development of prediabetes and diabetes in middle-aged and elderly Chinese population

BackgroundThe prevalence of diabetes and prediabetes were estimated to be 10.9% and 35.7% in the Chinese adult population, respectively, and the middle-aged and elderly Chinese are at even higher risk of diabetes and prediabetes than younger population. With the increasing trend of aging in China, the burden of diabetes and related complications will be aggravated.ObjectivesThrough comparing the indices of insulin resistance and β-cell function between subjects with different glucose metabolic status, to analyze the differential role of insulin resistance and β-cell function in the development of prediabetes and type 2 diabetes (T2DM) in the middle-aged and elderly Chinese population.MethodsIn this cross-sectional study, we enrolled 512 participants aged 50 and over. The indices of insulin resistance (homoeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance (Adipo-IR), and indices of β-cell function [HOMA-β), fasting C-peptide to glucose ratio (FCPRI) and postprandial C-peptide to glucose ratio (PCPRI)] were calculated. Association of insulin resistance and β-cell function with prediabetes or T2DM were evaluated by multivariate logistic regression analysis, in which potential confounding factors were adjusted.ResultsOf the 509 participants with complete information, 263 (51.7%) had normal glucose tolerance (NGT), 161 (31.6%) were in prediabetic status and 85 (16.7%) were overt T2DM. With the advancing of unfavorable glucose metabolism, the insulin resistance (HOMA-IR and Adipo-IR) and β-cell function (FCPRI, PCPRI) deteriorated (Ptrend < 0.05 for all indices). We found that increase in insulin resistance expressed by Adipo-IR and HOMA-IR is associated with increased risk of prediabetes, whereas decrease in β-cell function expressed by HOMA-β and PCPRI is associated with increased risk of T2DM. We also demonstrated that Adipo-IR was more closely associated with developing prediabetes than HOMA-IR, and PCPRI was most closely related with developing T2DM among the indices of β-cell function used in this study.ConclusionsInsulin resistance is the main determinant of developing prediabetes, whereas β-cell function is the main determinant of developing T2DM.

Vegetarians have a lower fasting insulin level and higher insulin sensitivity than matched omnivores: A cross-sectional study

Background and aimsPotential associations of vegetarian diet patterns with fasting insulin (FI) and insulin sensitivity remain unclear. We aimed to investigate whether vegetarian diets were associated with FI and insulin sensitivity in a cross-sectional study in Chinese vegetarians and matched omnivores and then to test whether it is independent of body mass index (BMI). Methods and resultsThis study included 279 vegetarians (73 vegans, 206 lacto-ovo-vegetarians) and 279 age- and sex-matched omnivores. Fasting blood glucose (FG) and FI concentrations were measured, and β-cell function (HOMA-β) and insulin resistance index (HOMA-IR) were used to evaluate insulin sensitivity. All blood glucose and insulin sensitivity indices were naturally log-transformed, and multiple-linear regression was used to determine the association between vegetarian diet patterns and insulin sensitivity after adjusting for confounders including BMI, visceral fat area, physical activity, sedentary time, income, alcohol consumption, and daily dietary intakes of macronutrients. Compared to omnivores, both vegan diet [β = −0.25, 95% CI: (−0.38, −0.14)] and lacto-ovo-vegetarian diet [β = −0.10, 95% CI: (−0.18, −0.01)] were negatively associated with HOMA-IR after adjusting for BMI. Vegan diet remained negatively associated with FI [β = −0.16, 95% CI: (−0.30, −0.01)] and HOMA-IR [β = −0.17, 95% CI: (−0.32, −0.03)] after adjusting for all confounders. ConclusionVegetarian diet, especially vegan diet, is negatively associated with FI and IR, independent of BMI.

Effect of Vitamin D3 Supplementation on Insulin Resistance and β-Cell Function in Prediabetes: A Double-Blind Randomised Placebo Controlled Trial

Background: Observational studies have suggested an inverse association between low serum 25(OH)D concentrations and development of type 2 diabetes. High-quality trials are required to test the hypothesis that vitamin D is a direct contributor to type 2 diabetes pathogenesis. The purpose of this double-blind randomised placebo controlled trial was to investigate the effect of vitamin D3 supplementation on insulin resistance and β-cell function in people with prediabetes and suboptimal vitamin D status(<50nmol/l). Methods: Sixty-six individuals were randomised to receive 3000IU(75µg) vitamin D3 or placebo daily for 26 weeks. Compliance was monitored by pill count and change in serum 25(OH)D concentration using liquid chromatography-mass spectrometry. The primary endpoint was between-group difference in change in insulin resistance assessed using a two-step euglycaemic hyperinsulinaemic clamp combined with infusion of tritiated glucose. An oral glucose tolerance test was performed pre and post-intervention to calculate indices of β-cell function. Between group comparisons were made using analysis of covariance(ANCOVA). Findings: 64 participants completed the study. Baseline serum 25(OH)D in the vitamin D3 and placebo group was 30.7 and 30.0nmol/l with status increasing by 70.5nmol/l and 5.3nmol/l respectively(between group difference in vitamin D=65.8nmol/l(95% CI 54.2, 77.3, p<0.01),after supplementation. There was no difference between groups in measures of whole-body,peripheral or hepatic insulin resistance or in any measure of glycaemic control or β-cell function. Interpretation: This study employed a robust assessment of insulin resistance and β-cell function and targeted a high-risk population with low 25(OH)D status at baseline and found that Vitamin D3 supplementation had no effect on insulin action in people with prediabetes. Trial Registration Number: This trial was registered on clinicaltrials.gov as NCT01889810. Funding Statement: This research was funded by a N.I. HSC R&D Fellowship, NI Chest, Heart & Stroke and The Royal Victoria Hospital Belfast Metabolic Unit Research Fund. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: Ethical approval for this trial was obtained from the Office for Research Ethics Committee Northern Ireland (ORECNI) (Project ID 117728).

Study on the correlation between the changes of TNFR1, TNF-α, and adiponectin in patients with gestational diabetes mellitus and insulin resistance

Gestational diabetes mellitus (GDM) refers to pregnant women with impaired glucose tolerance, which could bring high risk to the mother and fetus. However, the early diagnosis and treatment of GDM remained unclear. In this study, 60 patients with GDM were selected as the research group and 50 healthy pregnant women as the control group. Tumor necrosis factor receptor 1 (TNFR1), tumor necrosis factor-α (TNF-α), and adiponectin (ADP) in the serum were measured by enzyme-linked immunosorbent assays (ELISAs). The levels of fasting blood glucose (FBG), fasting insulin (FINS), and glycosylated hemoglobin (HbA1c) were also detected to calculate homeostasis model assessment insulin resistance index (HOMA-IR) and pancreatic β-cell function index (HOMA-HBCl). Compared with the control group, the serum levels of TNFR1, TNF-α, and HbA1c in research group were significantly increased ( P &lt; 0.05), while ADP showed lower levels ( P &lt; 0.01). Furthermore, FBG, FINS, and HOMA-IR were evidently increased ( P &lt; 0.05), while homeostasis model assessment insulin secretion index (HOMA-β) and insulin sensitivity index (ISI) were decreased ( P &lt; 0.05) in research group. TNFR and TNF-α were positively correlated with FBG, FINS, and HOMA-IR ( P &lt; 0.05). In addition, there was a significant negative correlation between ADP and FINS and HOMA-IR ( P &lt; 0.01). From logistic regression analysis, age, gestational age, FBG, FINS, TNFR1, TNF-α, and ADP ( P &lt; 0.05) were shown to be risk factors to affect the function of islet β-cells. In conclusion, the high levels of TNFR1 and TNF-α and the low levels of ADP in the second trimester of pregnancy are the risk factors of GDM, which are related to the insulin resistance and impaired pancreatic β-cell function.

Ventilation inhomogeneity is associated with OGTT-derived insulin secretory defects in cystic fibrosis.

Progressive deterioration of β-cell function is the main mechanism underlying diabetes in cystic fibrosis (CF). Diabetes negatively impacts the clinical status of CF patients years before its onset. We aimed to evaluate if OGTT-derived indices of β-cell function are associated with early markers of lung disease. We carried out a cross-sectional study on 80 CF patients who performed OGTT, spirometry, and nitrogen-multiple breath washout test. β-cell glucose sensitivity and the insulinogenic indices were used as markers of β-cell function and first-phase insulin response to glucose stimulus. We used sex- and age-adjusted multiple linear regression models to estimate the association between OGTT-derived indices and lung function measures. An increment of β-cell glucose sensitivity equal to its interquartile range was associated with an increase in ppFEV1 of 7.6 points (95%CI: 0.8; 14.4) as well as with a decrease in LCI of -1.96 units (95%CI: -3.40; -0.51) and in Scond of -0.016 L-1 (95%CI: -0.026; -0.007). The corresponding figures for insulinogenic index were: 8.6 (95%CI: 3.4; 13.9) for ppFEV1 , -2.03 (95%CI: -3.13; -0.94) for LCI, and -0.014 L-1 (95%CI: -0.021; -0.071) for Scond . When adjusting also for 2-h plasma glucose, both β-cell glucose sensitivity and insulinogenic index remained inversely associated with Scond . Deterioration of β-cell function is related to early lung disease in young patients with mild to normal pulmonary function. This relationship is independent from hyperglycemia and mainly involves conductive airways.

Milk Powder Co-Supplemented with Inulin and Resistant Dextrin Improves Glycemic Control and Insulin Resistance in Elderly Type 2 Diabetes Mellitus: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial.

The objective of the present study is to evaluate the effects of milk powder co-supplemented with inulin and resistant dextrin (MPCIR) on elderly patients with type 2 diabetes mellitus (T2DM). A randomized, double-blind, placebo-controlled clinical trial is carried out among elderly T2DM patients. The subjects recruited from the community are randomly assigned to either the MPCIR group or placebo group for 12 weeks intervention. Each group receives 45 g milk powder with or without inulin and resistant dextrin. Anthropometric and metabolic variables are measured. For the MPCIR group, systolic blood pressure (BP) and diastolic BP are reduced significantly by 5.45 and 4.56 mmHg (p < 0.001, vs placebo group), respectively. Compared with the placebo group, the fasting and 2-h postprandial plasma glucose levels, glycosylated serum protein, and insulin resistance index of the MPCIR group are significantly decreased by 0.96 mmolL-1 , 1.47 mmolL-1 , 16.33 μmolL-1 , and 0.65 respectively (p < 0.001). The MPCIR group shows an increase by 7.09 μIUmL-1 and 20.43 in 2-h postprandial insulin (p = 0.016) and β-cell function index (p < 0.001), respectively. MPCIR supplementation helps to improve glycemic control, insulin resistance, and blood pressure.

Serum ferritin levels are associated with insulin resistance in Chinese men and post-menopausal women: the Shanghai Changfeng study.

Associations between ferritin and insulin sensitivity have been described in recent studies. The possible association showed conflicting results by sex and menopausal status. We aimed to investigate the cross-sectional association of ferritin levels with insulin resistance and β-cell function. A total of 2518 participants (1033 men, 235 pre-menopausal women and 1250 post-menopausal women) were enrolled from the Changfeng Study. A standard interview was conducted, as well as anthropometric measurements and laboratory analyses, for each participant. The serum ferritin level was measured using electrochemiluminescence immunoassay. Insulin resistance and β-cell function indices were derived from a homeostasis model assessment. The results showed that the serum ferritin levels were 250·4 (sd 165·2), 94·6 (sd 82·0) and 179·8 (sd 126·6) ng/ml in the men, pre-menopausal and post-menopausal women, respectively. In fully adjusted models (adjusting for age, current smoking, BMI, waist:hip ratio, systolic blood pressure, diastolic blood pressure, TAG, HDL-cholesterol, LDL-cholesterol, log urine albumin:creatinine ratio, leucocytes, alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transpeptidase), serum ferritin concentrations are significantly associated with insulin resistance in men and post-menopausal females, and the null association was observed in pre-menopausal females. Interestingly, an increased β-cell function associated with higher ferritin was observed in post-menopausal participants, but not in male participants. In conclusion, these results suggested that elevated serum ferritin levels were associated with surrogate measures of insulin resistance among the middle-aged and elderly male and post-menopausal women, but not in pre-menopausal women.

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.

Serum uric acid to creatinine ratio correlates with β-cell function in type 2 diabetes.

The correlation between serum uric acid (SUA) and β-cell function remains controversial. The present study aims to use a new index, renal function-normalized SUA, to observe its correlation with β-cell function in patients with type 2 diabetes (T2DM). A total of 713 patients with T2DM received standard 75-g oral glucose tolerance and insulin release test. Renal function-normalized SUA was calculated using SUA/creatinine and β-cell function was assessed by HOMA-B. Binary logistic regression analysis was used to estimate the association between SUA/creatinine and β-cell function. There are positive correlations between SUA/creatinine and HOMA-B (r=0.143, P<0.001), as well as other indexes of β-cell function including modified β-cell function index (r=0.104, P=0.007), InsAUC30 (r=0.100, P=0.008), and InsAUC120 (r=0.124, P=0.001). SUA/creatinine also positively correlates with insulin resistance (HOMA-IR: r=0.161, P<0.001). Moreover, multivariate analysis revealed that SUA/creatinine was significantly associated with preserved β-cell function, independently of potential confounders including sex, BMI, and renal function. SUA to creatinine ratio correlates with β-cell function in T2DM patients.

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).

The Effect of Alpha-Lipoic Acid on Liver Function and Metabolic Markers in Obese Patients with Non-Alcoholic Fatty Liver Disease: A Double - Blind Randomized Controlled Trial

Background: Insulin resistance has a pivotal role in the occurrence of impaired glucose tolerance and dyslipidemia in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). There is evidence of possible beneficial effects of Alpha-Lipoic Acid (ALA) on insulin resistance and metabolic disorders. Objectives: This study aimed at examining the effects of ALA supplementation on liver enzymes, insulin sensitivity, glucose markers, and lipid profile in obese patients with NAFLD. Methods: In this double-blind placebo-controlled randomized clinical trial, 50 obese patients with NAFLD were randomly allocated to “ALA group” (received 1200 mg ALA as two capsules per day) or “Placebo group” (received placebo containing cornstarch as two capsules per day) for 12 weeks. Anthropometric measures, dietary intakes, liver enzymes as well as glucose markers and lipid profile were assessed at baseline and after 12 weeks of intervention. Results: Forty-five patients completed the study (ALA group = 23; placebo group = 22). Liver enzymes were not significantly altered by the intervention group. Alpha Lipoic Acid supplementation led to a significant attenuation in serum levels of insulin (13.4 ± 5.4 vs. 18.1 ± 8.6; P = 0.019) and triglyceride (146.9 ± 60.6 vs. 186.3 ± 54.2; P = 0.037) in comparison with the placebo group, yet did not affect other lipid profile parameters, Fasting Serum Glucose (FSG) and β-cell function index (HOMA-B) in patients with NAFLD. furthermore, quantitative insulin sensitivity check index (QUICKI) increased significantly in the ALA group compared to the placebo (0.329 ± 0.025 versus 0.317 ± 0.020; P = 0.033). Conclusions: Patients with NAFLD may benefit from ALA supplementation, at least partially through augmented insulin sensitivity and improvement of lipid profile.

Somatostatin Analogs and Glucose Metabolism in Acromegaly: A Meta-analysis of Prospective Interventional Studies.

Somatostatin analogs (SSAs) effectivelycontrol growth hormone secretion in first and second line treatmentof acromegaly. Their effect onglucose metabolism is still debated. to address the following questions: 1) Do SSAs affect fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated hemoglobin (HbA1c), glucose load (2h-OGTT), HOMA-I, HOMA-β, triglycerides (TGD), weight (W) or body mass index (BMI)? 2) Do lanreotide (LAN) and octreotide LAR (OCT) affect metabolism differently? 3)Does their effect depend on disease control? We performed a meta-analysis of prospective interventional trialstreating acromegaly with SSAs. Inclusion criteria: all studies reporting glyco-metabolic outcomes before and after SSAs with a minimum 6-month follow-up. The inclusion criteria were met by 47 studies treating 1297 subjects (631 F). SSA treatment effectively lowered FPI (effect size [ES] -6.67 mU/L, 95%CI: -8.38 to -4.95mU/L; p<0.001), HOMA-I (ES -1.57, CI: -2.42 to -0.72; p<0.001), HOMA-β (ES -47.45, CI: -73.15 to -21.76; p<0.001) and TGD (ES -0.37 mmol/L, CI: -0.47 to -0.27 mmol/L; p<0.001). SSAs worsened 2h-OGTT (ES 0.59 mmol/L, CI: 0.05 to 1.13 mmol/L; p=0.032), but not FPG. A mild but significant increase in HbA1c (ES 0.12%, CI: 0.00to 0.25%; p=0.044) was found in OCT treated subjects. SSA treatment in acromegaly patients-while improving disease control- reduces insulin levels, increases after load glucose and, ultimately, increases HbA1c levels without affecting FPG. The findings suggest that clinicians treating acromegaly with SSAs should consider targeting post-prandial glucose.

Serum Phthalate and Triclosan Levels Have Opposing Associations With Risk Factors for Gestational Diabetes Mellitus.

Certain phthalates and bisphenol A (BPA) have been associated with insulin resistance and type 2 diabetes in non-pregnant adults, but studies of gestational diabetes mellitus (GDM) have reported conflicting results for phthalates and no associations with BPA. Our aim was to investigate the relationship between maternal serum levels of phthalate metabolites and phenols at 10–17 weeks of gestation and glucose homeostasis at 28 weeks of gestation. 232 women aged ≥16 years without type 1 or 2 diabetes with singleton male pregnancies were recruited from a single UK maternity centre between 2001 and 2009 as part of a prospective observational study (Cambridge Baby Growth Study). Serum levels of 16 phthalate metabolites and 9 phenols (including BPA) were measured using liquid chromatography/tandem mass spectrometry. Oral glucose tolerance tests were performed at 28 weeks. 47/232 (20.3%) women had GDM. First-trimester triclosan (TCS) was inversely associated with incident GDM (adjusted odds ratio per log increase in concentration 0.54, 95% confidence interval 0.34–0.86, p = 0.010). Amongst women without GDM, first-trimester mono-(2-ethylhexyl) phthalate and mono(carboxyisooctyl) phthalate levels were positively associated with 120-min plasma glucose (adjusted β 0.268 and 0.183, p = 0.0002 and 0.010, respectively) in mid-pregnancy. No other monotonic associations were detected between phthalate or phenol levels and fasting or stimulated plasma glucose, β-cell function, insulin resistance, or 60-min disposition index. Our results support a glycaemia-raising effect of phthalates during pregnancy, consistent with findings in non-pregnant populations and suggest a possible protective effect of exposure to TCS against GDM.

The association between elevated serum uric acid levels and islet β-cell function indexes in newly diagnosed type 2 diabetes mellitus: a cross-sectional study.

BackgroundSerum uric acid (UA) has been reported as a risk factor for type 2 diabetes mellitus (T2DM). However, whether serum UA is associated with insulin resistance and insulin secretion, and the effect of gender on it in the case of the existed association, both remain undefined.MethodsA cross-sectional study was designed and performed, which enrolled a total of 403 newly diagnosed T2DM patients (mean age, 50.21 ± 13.34 years (62.5% males)). Clinical characteristics and islet function indexes of all participants were analyzed based on gender-specific tertiles of serum UA levels. In addition, multiple linear regression analysis was conducted to investigate covariates associated with islet function indexes.ResultsThe mean levels of serum UA were 331.05 μmol/L (interquartile range (IQR): 60.6, 400.9 μmol/L) and 267.9 μmol/L (IQR: 204.7, 331.9 μmol/L) in men and women, respectively. The values of insulin secretion indexes involving AUCins30/glu30, AUCins120/glu120 and total insulin disposition index (DI120) in females were significantly higher than those in males. Apart from the homeostasis model assessment insulin resistance of men, serum UA was positively associated with insulin secretion and insulin resistance indexes both in men and women. Multivariable linear regression analysis showed serum UA exerted an independent impact on insulin secretion in females, but not on insulin resistance. In males, islet function was simultaneously affected by serum UA age, body mass index (BMI), and serum lipids.ConclusionSerum UA harbored a positive correlation with insulin secretion and insulin resistance indexes in newly diagnosed T2DM patients, which was influenced by gender, BMI, serum lipids. Hence, serum UA may be considered as a predictor for islet function in clinical practice.

Acute Effects of Blood Transfusion on Insulin Sensitivity and Pancreatic β-Cell Function in Children with β-Thalassemia/Hemoglobin E Disease

Objective:To assess the acute effects of blood transfusion on insulin sensitivity and pancreatic β-cell function in thalassemia patients.Methods:Fifty children and adolescents with β-thalassemia/HbE disease were enrolled in a prospective cohort study. Hemoglobin, serum ferritin and oral glucose tolerance test (OGTT) were performed prior to, and one week after blood transfusion. Insulin sensitivity indices [homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR), whole body insulin sensitivity index (WBISI)] and β-cell function indices [HOMA of β-cell function (HOMA-β), insulinogenic index (IGI), and disposition index (DI)] were calculated from glucose and insulin levels obtained during the OGTT.Results:Following blood transfusion, hemoglobin and serum ferritin increased significantly; 8.5 to 10.1 g/dL (p<0.001) and 1764 to 2160 ng/mL (p<0.001), respectively. β-Cell function indices also increased significantly [median HOMA-β: 74.3 vs. 82.7 (p=0.033); median IGI: 59.6 vs. 79.3 (p=0.003); median DI: 658 vs. 794 (p=0.01)]. However, the insulin sensitivity index (WBISI) tended to decrease and the insulin resistance index (HOMA-IR) tended to increase although this did not reach significance. Multivariate analysis showed that pre-transfusion serum ferritin was the major factor negatively associated with WBISI and positively associated with HOMA-IR, but pre-transfusion hemoglobin had no significant association with insulin sensitivity indices post-transfusion.Conclusion:This study demonstrated that acute increases in serum ferritin and hemoglobin following blood transfusion in patients with thalassemia might contribute to an increase in insulin secretion and to a trend towards increased insulin resistance.

Beta-cell Function and Metabolic Clearance Rate of Glucose in Patients with Major Mental Health Disorders on Antipsychotic Drug Treatment

BackgroundInsulin resistance and metabolic alteration continue to be essential features of major mental health disorders (MMHD) with poorly understood and multifaceted mechanisms. This study was carried out to provide information on insulin resistance, beta-cell function, metabolic clearance rate of glucose and their possible interplay with duration of antipsychotic use in patients with major mental health disorders. MethodologyPlasma levels of glucose and insulin were determined in 124 patients with MMHD after an overnight fast and at 30 and 120 min of standard Oral Glucose Tolerance Test. Thereafter, indices of insulin resistance, beta-cell function and estimated metabolic clearance rate of glucose (eMCR) were calculated appropriately. Statistical analysis was done using ANOVA, Kruskal Wallis, independent Student's t-test and Mann-Whitney U. P-values less than 0.05 were considered as statistically significant. ResultsMetabolic factors (fasting and postprandial glucose and insulin), indices of insulin sensitivity and β-cell function were not significantly different when patients with schizophrenia, bipolar and depression were compared with one another. Postprandial insulin level at 30 min (30 min PPI), estimated First and Second Phases of Insulin Release (eFPIR, eSPIR) were significantly lower in patients on atypical antipsychotic drugs [18.15 (3.57-40.35) μIU/ml), 617.63 (320.06-911.31) pmol/l, 180.30 (114.82–249.39) pmol/l] compared with patients on typical antipsychotic drugs [27.48 (13.33–47.68) μIU/ml, 767.69 (530.58-1198.35) pmol/l, 209.89 (154.01-310.97) pmol/l]. Furthermore, the mean waist circumference and body mass index were significantly higher in patients who have been on anti-psychotic drug for more than 10 years compared with patients with less than 5 years history of anti-psychotic use. eMCR of glucose progressively declined with increasing duration of antipsychotic use and it was significantly lower in patients who have been on antipsychotic drugs for more than 10 years [8.09 (5.90-9.44) ml.kg−1.min−1] compared with patients who have been on the drugs for less than 5 years [9.03 (7.47-10.04) ml.kg−1.min−1]. ConclusionPatients on atypical antipsychotics seem to have insulin secretion phases consistent with β-cell dysfunction. Also, chronicity of antipsychotic treatment predisposes patients with major mental health disorders to central adiposity and low metabolic clearance rate of glucose, a forerunner of glucose intolerance.

Clinical Characteristics of People with Newly Diagnosed Type 2 Diabetes between 2015 and 2016: Difference by Age and Body Mass Index

BackgroundWe evaluated the clinical characteristics of insulin resistance and β-cell dysfunction in newly diagnosed, drug-naive people with type 2 diabetes by analyzing nationwide cross-sectional data.MethodsWe collected the clinical data of 912 participants with newly diagnosed diabetes from 83 primary care clinics and hospitals nationwide from 2015 to 2016. The presence of insulin resistance and β-cell dysfunction was defined as a homeostatic model assessment of insulin resistance (HOMA-IR) value ≥2.5 and fasting C-peptide levels <1.70 ng/mL, respectively.ResultsA total of 75.1% and 22.6% of participants had insulin resistance and β-cell dysfunction, respectively. The proportion of participants with insulin resistance but no β-cell dysfunction increased, and the proportion of participants with β-cell dysfunction but no insulin resistance decreased as body mass index (BMI) increased. People diagnosed with diabetes before 40 years of age had significantly higher HOMA-IR and BMI than those diagnosed over 65 years of age (HOMA-IR, 5.0 vs. 3.0; BMI, 28.7 kg/m2 vs. 25.1 kg/m2). However, the β-cell function indices were lower in people diagnosed before 40 years of age than in those diagnosed after 65 years of age (homeostatic model assessment of β-cell function, 39.3 vs. 64.9; insulinogenic index, 10.3 vs. 18.7; disposition index, 0.15 vs. 0.25).ConclusionWe observed that the main pathogenic mechanism of type 2 diabetes is insulin resistance in participants with newly diagnosed type 2 diabetes. In addition, young adults with diabetes are more likely to have higher insulin resistance with obesity and have higher insulin secretory defect with severe hyperglycemia in the early period of diabetes than older populations.

Insulin Sensitivity, Inflammation, and Basal Metabolic Rate in Adults with Sickle Cell Anemia.

Background:Chronic inflammation and elevated basal metabolic rate (BMR) are established features of sickle-cell anemia (SCA). However, there is little information on the possible impacts of these afore-mentioned features on glycemia and insulin sensitivity status of this group of people.Aim:This study aims to determine the insulin sensitivity status as well the effect of BMR on glycemia in adults with SCA in steady state.Materials and Methods:Fifty participants comprising 30 adults with SCA in steady state and 20 age- and gender-matched apparently healthy adults with hemoglobin genotype AA (HbAA) genotype that served as controls. Anthropometric and clinical indices were obtained using standard methods. After an overnight fast, fasting plasma glucose (FPG), and serum insulin levels were determined using the glucose oxidase method and ELISA, respectively. Indices of insulin sensitivity and β-cell function as well as BMR were appropriately calculated.Results:The mean fasting insulin resistance (IR) index, homeostatic model of assessment of IR (HOMA-IR) and of β-cell function (HOMA2-β%), and mean insulin level were significantly lower while the mean HOMA of insulin sensitivity (HOMA2-S%), quantitative insulin sensitivity check index, inverse of insulin sensitivity (1/FI), glucose-insulin ratio, C-reactive protein (CRP), and BMR was significantly higher in patients with SCA compared with the controls. The mean FPG and insulin levels and the mean values of indices of insulin sensitivity and secretion were not significantly different in SCA patients with elevated BMR compared with SCA patients with lower BMR. In addition, BMR had no significant correlation with FPG and HOMA-IR in patients with SCA.Conclusion:Despite the established chronic inflammation in SCA patients in steady state, they seem to have better insulin sensitivity status but impaired β-cell activity when compared with adults with HbAA. Furthermore, BMR does not have any pronounced effect on glycemic and insulin sensitivity status in SCA patients in steady state.

Particulate matter and markers of glycemic control and insulin resistance in type 2 diabetic patients: result from Wellcome Trust Genetic study.

There is growing evidence that air pollution is associated with increased risk of type 2 diabetes (T2DM). However, information related to whether particulate matter (PM) contributing to worsened metabolic control in T2DM patients is inconsistent. We examined the association of PM10 exposure with glucose-function parameters in young-onset T2DM patients. We investigated the association between a year ambient concentration of PM10 at residential places, using AERMOD dispersion model, with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), 2 h post meal plasma glucose (2hPG), homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-β) and disposition index (DI) in 1213 diabetic patients from the Wellcome Trust Genetic study at the Diabetes Unit, KEM Hospital Research Center, Pune, India. We used linear regression models and adjusted for a variety of individual and environmental confounding variables. Possible effect modification by age, gender, waist-to-hip ratio (WHR) and smoking status were investigated. Sensitivity analysis assessed the impact of relative humidity (RH) and temperature a day before examination and anti-diabetic and HHR medication (Hydralazine, Hydrochlorothiazide and Reserpine). We found that 1 SD increment in background concentration of PM10 at residential places (43.83 µg/m3) was significantly associated with 2.25 mmol/mol and 0.38 mmol/l increase in arithmetic means of HbA1c and 2hPG, respectively. A similar increase in PM10 was also associated with 4.89% increase in geometric mean of HOMA-IR. The associations remained significant after adjustment to RH and temperature, and WHR and smoking enhanced the size of the effect. Our study suggests that long-term exposure to PM10 is associated with higher glycaemia and insulin resistance. In context of our previous demonstration of association of SO2 and NO x and plasma C-reactive protein, we suggest that air pollution could influence progression of diabetes complications. Prospective studies and interventions are required to define mechanism and confirm causality.

Effects of immediate-release niacin and dietary fatty acids on acute insulin and lipid status in individuals with metabolic syndrome.

The nature of dietary fats profoundly affects postprandial hypertriglyceridemia and glucose homeostasis. Niacin is a potent lipid-lowering agent. However, limited data exist on postprandial triglycerides and glycemic control following co-administration of high-fat meals with a single dose of niacin in subjects with metabolic syndrome (MetS). The aim of the study was to explore whether a fat challenge containing predominantly saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated (LCPUFAs) fatty acids together with a single dose of immediate-release niacin have a relevant role in postprandial insulin and lipid status in subjects with MetS. In a randomized crossover within-subject design, 16 men with MetS were given a single dose of immediate-release niacin (2 g) and ∼15 cal kg-1 body weight meals containing either SFAs, MUFAs, MUFAs plus omega-3 LCPUFAs or no fat. At baseline and hourly over 6 h, plasma glucose, insulin, C-peptide, triglycerides, free fatty acids (FFAs), total cholesterol, and both high- and low-density lipoprotein cholesterol were assessed. Co-administered with niacin, high-fat meals significantly increased the postprandial concentrations of glucose, insulin, C-peptide, triglycerides, FFAs and postprandial indices of β-cell function. However, postprandial indices of insulin sensitivity were significantly decreased. These effects were significantly attenuated with MUFAs or MUFAs plus omega-3 LCPUFAs when compared with SFAs. In the setting of niacin co-administration and compared to dietary SFAs, MUFAs limit the postprandial insulin, triglyceride and FFA excursions, and improve postprandial glucose homeostasis in MetS. © 2017 Society of Chemical Industry.