The Mediterranean diet, but not time-restricted eating, mediates the effects of nesfatin on beta cell function among overweight, metabolically healthy individuals.

Nesfatin concentrations are positively correlated with beta cell function. However, it is unclear whether diet composition mediates this relationship. We recruited 27 overweight individuals who practiced Orthodox fasting (OF), a subset of the Mediterranean diet (MedDiet), for 7 weeks. Fourteen overweight people who practiced 16:8 time-restricted eating served as control group. Anthropometric parameters, biochemical data and adipokine levels were evaluated at baseline and after the end of the diet period (7 weeks from baseline). Subsequently, participants were asked to return to their usual eating plans, and an additional evaluation was performed 5 weeks after the end of the research diets (12 weeks from baseline). We observed a significant and negative correlation between HOMA-B and nesfatin values at 12 weeks, only in the OF group (r = -0.455, p = 0.01). In conclusion, returning to normal eating habits after 7 weeks of strict adherence to MedDiet affects the homeostatic balance between insulin secretion and nesfatin.

The Effect of Thiazolidinediones in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterised by insulin resistance and is a risk for type 2 diabetes mellitus (T2DM). The aim of this study was to review the literature on the effect of pioglitazone and rosiglitazone in women with PCOS. METHODS: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science in April 2020 and updated in March 2023. Studies were deemed eligible if they were randomised controlled trials (RCTs) reporting the effect of pioglitazone and rosiglitazone in PCOS. The study follows the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: Out of 814 initially retrieved citations, 24 randomised clinical trials (RCTs) involving 976 participants were deemed eligible. Among women with PCOS, treatment with rosiglitazone compared to metformin resulted in a significant increase in the mean body weight (mean difference (MD) 1.95 kg; 95% CI 0.03-3.87, p = 0.05). Metformin treatment was associated with a reduction in mean body mass index (BMI) compared to pioglitazone (MD 0.85 kg/m2; 95% CI 0.13-1.57, p = 0.02). Both pioglitazone compared to placebo (MD 2.56 kg/m2; 95% CI 1.77-3.34, p < 0.00001) and rosiglitazone compared to metformin (MD 0.74 kg/m2; 95% CI 0.07-1.41, p = 0.03) were associated with a significant increase in BMI. Treatment with pioglitazone compared to placebo showed a significant reduction in triglycerides (MD - 0.20 mmol/L; 95% CI - 0.38 to - 0.03, p = 0.02) and fasting insulin levels (MD - 11.47 mmol/L; 95% CI - 20.20, - 2.27, p = 0.01). Rosiglitazone compared to metformin was marginally significantly associated with a reduction in the luteinising hormone (LH) (MD - 0.62; 95% CI - 1.25-0.00, p = 0.05). CONCLUSION: Both pioglitazone and rosiglitazone were associated with significant increases in body weight and BMI when compared with metformin or placebo. Pioglitazone significantly reduced triglycerides and fasting insulin when compared with placebo while rosiglitazone showed a modest reduction of LH when compared with metformin. PROSPERO REGISTRATION NO: CRD42020178783.

Machine Learning Model Based on Insulin Resistance Metagenes Underpins Genetic Basis of Type 2 Diabetes.

Insulin resistance (IR) is considered the precursor and the key pathophysiological mechanism of type 2 diabetes (T2D) and metabolic syndrome (MetS). However, the pathways that IR shares with T2D are not clearly understood. Meta-analysis of multiple DNA microarray datasets could provide a robust set of metagenes identified across multiple studies. These metagenes would likely include a subset of genes (key metagenes) shared by both IR and T2D, and possibly responsible for the transition between them. In this study, we attempted to find these key metagenes using a feature selection method, LASSO, and then used the expression profiles of these genes to train five machine learning models: LASSO, SVM, XGBoost, Random Forest, and ANN. Among them, ANN performed well, with an area under the curve (AUC) > 95%. It also demonstrated fairly good performance in differentiating diabetics from normal glucose tolerant (NGT) persons in the test dataset, with 73% accuracy across 64 human adipose tissue samples. Furthermore, these core metagenes were also enriched in diabetes-associated terms and were found in previous genome-wide association studies of T2D and its associated glycemic traits HOMA-IR and HOMA-B. Therefore, this metagenome deserves further investigation with regard to the cardinal molecular pathological defects/pathways underlying both IR and T2D.

Are HOMA-IR and HOMA-B good predictors for diabetes and pre-diabetes subtypes?

BACKGROUND: To investigate the association between the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Homeostasis Model Assessment of Beta-cell function (HOMA-B) with the incidence of diabetes and pre-diabetes subtypes. METHODS: A total of 3101 normoglycemic people aged 20-70 years were included in the 6-year follow-up study. Multinomial logistic regression was used to calculate the incidence possibility of isolated Impaired Fasting Glucose (iIFG), isolated Impaired Glucose Tolerance (iIGT), Combined impaired fasting glucose & impaired glucose tolerance (CGI), and Diabetes Mellitus (DM) per standard deviation (SD) increment in HOMA-IR and HOMA-B in the crude and multivariable model. RESULTS: In the multivariate model, an increase in one SD change in HOMA-IR was associated with a 43, 42, 75, and 92% increased risk of iIFG, iIGT, CGI, and DM, respectively. There was a positive correlation between the increase in HOMA-B and the incidence of iIGT; however, after adjusting the results for metabolic syndrome components, it was inversely correlated with the incidence of iIFG [Odds Ratio = 0.86(0.75-0.99)]. CONCLUSIONS: HOMA-IR is positively correlated with diabetes and pre-diabetes subtypes' incidence, and HOMA-B is inversely correlated with the incidence of iIFG but positively correlated with iIGT incidence. However, none of these alone is a good criterion for predicting diabetes and pre-diabetes.

Insulinogenic index and early phase insulin secretion predict increased risk of worsening glucose tolerance and of cystic fibrosis-related diabetes.

OBJECTIVE: Measures of stimulated insulin secretion are emerging as important predictors of diabetes mellitus in at-risk populations. We analyzed the utility of clinical estimates of insulin secretion in a prospective cohort at risk for cystic fibrosis-related diabetes (CFRD). METHODS: We divided the profiles of 189 people with CF (pwCF) followed longitudinally in the Montreal CF cohort (mean follow up 6.6 ± 1.2 years) according to quartiles of the insulinogenic index (IGI; (I30-I0)/(G30-G0)); area under the curve for insulin normalized for glucose (AUCins/glu), and HOMA-B at baseline to compare clinical characteristics and risk of CFRD according to quartiles for each measure. We also compared characteristics of 40 pwCF found to have de novo CFRD at baseline. RESULTS: At baseline, IGI and AUCins/glu were lower in subjects with de novo CFRD and those who later developed CFRD than those who never developed CFRD (p < 0.0001 for each). Subjects with the lowest quartiles of IGI, AUCins/glu, and AUCins/glu 0-30 had increased risk of developing CFRD by Kaplan-Meier analysis (p = 0.0244, p = 0.0024, and p = 0.0338, respectively). There was no significant difference in risk between quartiles of HOMA-B. Subjects in the lowest quartile of IGI showed a significant increase in 2-hour OGTT glucose and AUCglu between the initial and final study visits (p = 0.0027 and p = 0.0044, respectively). CONCLUSION: IGI is easily measured in a clinical setting and needs to be validated in prospective studies as a potential tool to improve risk stratification in CFRD with direct relevance to pathogenesis.

Lead exposure and impaired glucose homeostasis in Chinese adults: A repeated measures study with 5 years of follow-up.

Experimental studies suggest the diabetogenic effects of lead, but relevant data in humans are limited and have been primarily based on cross-sectional study design. We aimed to prospectively examine the association between lead exposure and glucose homeostasis in general population using repeated measurements. This cohort study included 5505 Chinese adults free of glucose-lowering medication use at baseline in 2014 and followed up 5 years later. Blood lead and glucose metabolic traits including fasting plasma glucose (FPG), fasting serum insulin, the homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA of beta-cell function (HOMA-B) were measured at baseline and follow-up. Linear mixed models and linear regression models were performed to evaluate the associations between blood lead and markers of glucose homeostasis. After full adjustment for confounders including BMI, an interquartile range (IQR) increase in blood lead levels was associated with a 2.26 % increase in FPG (95 % CI: 0.16 %, 4.39 %) and an 11.3 % decrease in HOMA-B (95 % CI: - 19.1 %, - 2.71 %) in women. The odds ratios of hyperglycemia and beta-cell dysfunction corresponding to an IQR increase in blood lead levels were 1.39 (95 % CI: 0.99, 1.95) and 1.74 (95 % CI: 1.00, 3.03), respectively. Similar results were found for 5-year changes of glucose metabolic markers. Compared with the first quartile of baseline lead levels, the highest lead quartile was associated with an additional 3.03 % increase in FPG (95 % CI: 0.84 %, 5.26 %) and an additional 13.3 % decrease in HOMA-B (95 % CI: - 20.4 %, - 5.53 %) in women during follow-up. We observed no overall associations between blood lead levels and glucose metabolic markers in men. Our findings provide suggestive evidence that environmental exposure to lead might contribute to sex-dependent disruption of glucose homeostasis in general adult population.

The Relationship between the Lipid Accumulation Product and Beta-cell Function in Korean Adults with or without Type 2 Diabetes Mellitus: The 2015 Korea National Health and Nutrition Examination Survey.

AIMS: This study was conducted to assess the relationship between the lipid accumulation product index (LAP) and the homeostasis model assessment for insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) in Korean adults with or without type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The study was carried out using data from the 2015 Korean National Health and Nutrition Examination Survey (KNHANES) and included 4,922 adults aged 20 or older. RESULTS: There were several key findings. First, in overall population, after adjusting for related variables, HOMA-IR (p < .001) and HOMA-B (p < .001) level were positively associated with quartiles of LAP. Second, in non-T2DM group, HOMA-IR (p < .001) and HOMA-B level (p < .001) were positively associated with quartiles of LAP. Third, in T2DM group, HOMA-IR (p < .001) level was positively associated with the quartiles of LAP, but HOMA-B (p = .153) level was not significant. In addition, HOMA-B level was increased with an increasing metabolic syndrome component in non-T2DM (p < .001) but not in T2DM (p = .267). CONCLUSIONS: LAP was positively associated with both HOMA-IR and HOMA-B in non-diabetic Korean adults. However, LAP was positively associated with HOMA-IR in Korean adults with T2DM, while the association with HOMA-B was not significant.

Metabolic characteristics and adverse pregnancy outcomes for women with hyperglycaemia in pregnancy as a function of insulin resistance.

AIM: Recent studies have shown that women with hyperglycaemia in pregnancy and insulin resistance have a greater risk of adverse pregnancy outcomes than women with normoglycaemic pregnancies. This study aimed to determine adverse pregnancy outcomes of women with hyperglycaemia in pregnancy only as a function of insulin resistance. METHODS: From a prospective cohort study, we included 1,423 women with hyperglycaemia in pregnancy whose insulin resistance was evaluated using homoeostatic model assessment for insulin resistance (HOMA-IR) when care was first provided for this condition. We compared the adverse pregnancy outcomes for different tertiles of HOMA-IR (intertertile range 1.9 and 3.3). RESULTS: Increasing HOMA-IR tertiles were positively associated with the rate of insulin therapy (tertile 1, 2 and 3: 32.7, 47.0 and 58.7%, P < 0.0001), caesarean section (23.7, 26.0 and 32.2%, respectively, P < 0.01), gestational hypertension (1.3, 2.8 and 5.4% respectively, P < 0.01), preeclampsia (1.5, 2.8 and 4.5% respectively, P < 0.05), large-for-gestational-age infant (13.3, 10.4 and 17.6% respectively, P < 0.05), and neonatal hypoglycaemia (0.8, 1.5 and 3.2% respectively, P < 0.05). Women in the 3rd HOMA-IR tertile were more likely to have insulin therapy (odds ratio 2.09 (95% interval confidence 1.61-2.71)), hypertensive disorders (2.26 (1.42-3.36)), and large-for-gestational-age infant (1.42 (1.01-1.99)) than those in the 1st and 2nd tertiles combined in multivariable logistic regression analyses adjusted for gestational age at HOMA-IR measurement, glycaemic status, age, body mass index, family history of diabetes, parity and ethnicity. CONCLUSION: Despite suitable care and increased rates of insulin therapy during pregnancy, higher insulin resistance in women with hyperglycaemia in pregnancy was associated with a greater risk of adverse pregnancy outcomes.

Effect of caffeine on the possible amelioration of diabetic neuropathy: A spectroscopic study.

IMPORTANCE: One of the consequential and alarming complications of diabetes mellitus is diabetic neuropathy (DN). DN is assured to be caused chiefly by excess sorbitol levels in the body. The harmful consequences of DN alike peripheral nerve damage with extremity ulcers may be dodged with timely detection and treatment. The therapeutic methods for DN are scarce and expensive. Therefore economic and user friendly methodologies to prevent acquiring the disease need proper attention. OBJECTIVE: The present research has been conducted (1) to analyse the levels of sorbitol in diabetic blood samples and compare them with non-diabetic ones and (2) to study the reduction in sorbitol levels upon addition of an important biochemical compounds caffeine in both sample groups. RESEARCH DESIGN, SETTING, PARTICIPANTS AND METHOD: Sorbitol-caffeine interaction analysis of blood samples of 16 patients with type 2 diabetes from KPC Medical College, Kolkata, India was made. The spectroscopic analysis and their interpretations were compared with 16 healthy subjects. MAIN OUTCOMES AND MEASURES: Present work describes that caffeine can be helpful in reducing the sorbitol level in diabetics, so the chances of development and progression of diabetic neuropathy can be controlled with the introduction of caffeine. RESULTS: A total number of 32 blood samples of patients (aged 35-70 years); mean age ranges were 52.06 ± 2.68 and 53.50 ± 2.66 years for non-diabetic and diabetic ones respectively, glucose and sorbitol screening examination were done by enzymatic methodologies where concentrations were assessed by means of either absorption or fluorescence spectroscopy. The calibration range was 18.2-1119.3 mg/dL (Linear regression analysis r2 = 0.996). The sensitivity of this screening program in detecting DN with the healthy adults has been inquired and found efficient. Results of fasting insulin analyses have also been analysed for HOMA-IR (homeostasis model assessment - insulin resistance) and HOMA-B (homeostasis model assessment - pancreatic ß cell function) values. Statistical significance of the results in non-diabetic and diabetic groups were performed and found to be statistically significant. CONCLUSIONS: We have defined the relationship between blood glucose level, insulin level, sorbitol and caffeine in human body and utilized them in the plausible remediation of DN.

Impact of pharmacological interventions on insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterized by insulin resistance and is a major risk factor for type 2 diabetes mellitus (T2DM). The objective was to review the literature on the effect of different pharmacological interventions on insulin resistance in women with PCOS. DESIGN: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science in April 2020 and updated in March 2021. The study follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-ana. Reviwers extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: In 58 randomized controlled trials there were significant reductions in the fasting blood glucose (FBG) with metformin versus placebo (standardized mean difference [SMD]: -0.23; 95% confidence interval [CI]: -0.40, -0.06; I² = 0%, low-grade evidence), and acarbose versus metformin (mean difference [MD]: -10.50 mg/dl; 95% CI: -15.76, -5.24; I² = 0%, low-grade evidence). Significant reductions in fasting insulin (FI) with pioglitazone versus placebo (SMD: -0.55; 95% CI: -1.03, -0.07; I² = 37%; p = .02, very-low-grade evidence). A significant reduction in homoeostatic model assessment of insulin resistance (HOMA-IR) was seen with exenatide versus metformin (MD: -0.34; 95% CI: -0.65, -0.03; I² = 0%, low-grade evidence). No effect on homoeostatic model assessment of beta cells (HOMA-B) was observed. CONCLUSIONS: Pharmacological interventions, including metformin, acarbose, pioglitazone and exenatide have significant effects on FBG, FI, HOMA-IR but not on HOMA-B.

Superiority of Purple Okra (Abelmoschus esculentus) to Green Okra in Insulin Resistance and Pancreatic ß Cell Improvement in Diabetic Rats.

INTRODUCTION: Antidiabetic medicinal plants are increasingly used in the treatment of diabetes as they are generally assumed to pro-duce minimal side effects. Okra is a quercetin-containing plant which can induce pancreas regeneration and has antidiabetic effect. There has been a lot of research that demonstrate that purple okra contains more quercetin than green okra. AIM: To demonstrate the advantages of purple okra over green okra on the diabetic markers improvement in diabetic rats. MATERIALS AND METHODS: Fifteen male 2-month-old Wistar rats were injected intraperitoneally with 65 mg streptozotocin and 110 mg niacinamide. Their blood glucose levels were measured three days after the injection. The induction of diabetes was deemed  successful if the glucose level of the rats got higher than 250 mg/dL, and then such rats were considered diabetic. The diabetic rats were divided into three groups: an acarbose group, a purple okra powder group, and a green okra powder group. The latter two were given, respectively, purple and green okra powder for 28 days. Blood serum was taken to examine the fasting blood glucose, insulin, HOMA-B and GLUT-4 levels. Pancreas was examined histologically for damage using hematoxylin eosin staining. RESULTS: Fasting blood glucose, insulin, HOMA-B, and GLUT-4 levels of diabetic rats that received purple okra powder (p<0.05) were better than those of the rats that received green okra powder. The least damage (p<0.05) to pancreatic beta cells was found in the purple okra powder group. CONCLUSIONS: Purple okra is superior to green okra in terms of improving the diabetic markers of rats.

Insulin secretory defect may be the major determinant of GDM in lean mothers.

AIMS: To compare the insulin sensitivity and secretion indices of pregnant Bangladeshi women with GDM and normal glucose tolerance (NGT). METHODS: This cross sectional study was performed with 40 GDM and equal number of NGT pregnant women diagnosed on basis of WHO criterion-2013 during 24-40 weeks of gestation. Glucose was measured by glucose oxidase method and fasting insulin by chemiluminescent immunoassay. Equations of homeostatic model assessment (HOMA) were used to calculate indices of insulin resistance (HOMA-IR), ß-cell function (HOMA-B) and insulin sensitivity (HOMA-%S). RESULTS: The GDM group had significantly higher insulin resistance as indicated by higher fasting insulin value [GDM vs. NGT; 10.23 (7.94-14.50) vs. 7.07 (5.28-11.07) µIU/ml] and HOMA-IR [GDM vs. NGT; 2.47 (1.75-3.43) vs. 1.50 (0.99-2.22)] and poor ß-cell secretion [GDM vs. NGT; HOMA-B: 113.37 (90.30-191.35) vs. 150.98 (109.85-271.72), median (IQR); p < 0.001 for all]. HOMA-B was significantly lower in GDM than NGT with BMI < 23 kg/m2 [GDM vs. NGT; 63.37 (49.19-83.83) vs. 134.89 (93.50-193.17) ng/ml; p = 0.010] despite having statistically comparable difference in IR. BMI was found to be a significant predictor of HOMA-IR in GDM. CONCLUSIONS: Though impairments of both insulin secretion and sensitivity are hallmarks in the pathogenesis of GDM, ß-cell dysfunction contributes more to development of GDM in those with relatively lower BMI in our population.

Association between cognitive impairment patient with solid cancer and insulin resistance.

OBJECTIVES: In an aging population, an increase in the number of elderly cancer patients with cognitive impairment is expected. The possible association between cancer and cognitive impairment is important to elucidate, because it can have a serious impact on quality of life. Here, we focused on glucose metabolism as a factor that links cancer and cognitive impairment. RESULTS: Thirteen subjects with solid cancers and cognitive impairment were recruited. As a control group, 14 subjects with cognitive impairment alone and 8 subjects with cancer alone were recruited. A Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and that of ß-cell function (HOMA-B) were used. In comparison with patients with solid cancer alone, those with cognitive impairment alone and those with both cancer and cognitive impairment had increased HOMA-IR values. Insulin resistance was increased in patients with cognitive impairment alone and those with both cognitive impairment and solid cancer than in patients without cognitive impairment; however, ß-cell function was not affected. The present data indicated that elderly cancer patients with high HOMA-IR score may be at a relatively high risk for developing cognitive impairment. Furthermore, early treatment to reduce insulin sensitivity may prevent cognitive impairment.

Urinary bisphenol A concentration and glucose homeostasis in non-diabetic adults: a repeated-measures, longitudinal study.

AIMS/HYPOTHESIS: Bisphenol A (BPA) has been shown to be potentially associated with type 2 diabetes; however, there is little evidence associating BPA exposure with glucose metabolic outcomes prior to diabetes onset. We aimed to examine BPA exposure in relation to glucose homeostasis among non-diabetic individuals. METHODS: This longitudinal cohort study comprised 2336 Chinese adults aged 40 years or above (62.8% women) and free of diabetes at baseline in 2009, followed for 4 years. Urinary BPA and glucose metabolic traits including fasting plasma glucose (FPG), 2 h post-load plasma glucose, fasting serum insulin, HOMA-IR and HOMA-B were measured at baseline and follow-up. Repeated-measures analysis was performed to evaluate associations of urinary BPA concentration with markers of glucose homeostasis. RESULTS: After full adjustment for confounders including BMI, each tenfold increase in urinary BPA concentrations was associated with a 3.39% increase in FPG (95% CI 2.24%, 4.55%) and an 11.6% decrease in HOMA-B (95% CI -15.8%, -7.18%) in women. The inverse association between urinary BPA and HOMA-B was more prominent among overweight or obese individuals (change -13.7%; 95% CI -19.3%, -7.61%) compared with those who were of normal weight (change -6.74%; 95% CI -13.2%, 0.20%) (pinteraction = 0.07). Moreover, the ORs of fasting hyperglycaemia and beta cell dysfunction corresponding to a tenfold increase in urinary BPA concentrations were 1.37 (95% CI 1.10, 1.72) and 1.30 (95% CI 1.02, 1.65) in women, respectively. No significant associations existed between urinary BPA and glucose metabolic markers in men. CONCLUSIONS/INTERPRETATION: Our findings suggest that exposure to BPA was independently associated with impaired glucose homeostasis before the development of diabetes in middle-aged and elderly women.

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits.

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E-04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E-03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E-06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.

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 ß-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 ß-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 ß-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.

Anti-diabetic effects of Sargassum oligocystum on Streptozotocin-induced diabetic rat.

OBJECTIVES: Diabetes is a metabolic syndrome which is associated with the worldwide major public health problems. There are many natural compounds from the sea-market, as a valuable aquatic source, along with the variety of health and therapeutic benefits. In the present research, with respect to the traditional and ethnic uses of Sargassum oligocystum algae for healing of some diseases which have similar metabolic mechanism to the diabetes, its anti-diabetic effects in animal model was proposed. MATERIALS AND METHODS: The animals (rat) were divided into the normal control, diabetic control, positive control and, the test groups. The test groups were gavaged with oral doses of 150 and 300 mg/kg of algae hydroalcoholic extracts. After 30 days of intervention the serum glucose, cholesterol, triglyceride, HDLC, LDLC, insulin, insulin resistance, ß-cells function and, the histopathology of pancreatic tissue were evaluated. RESULTS: In animals that were fed with algae extracts a significant decrease in the fasting blood glucose, triglyceride and HOMA-IR and an increase in the HOMA-B with no significant impacts on the insulin, cholesterol and HDL were observed. Also, the histopathology evaluations in the groups which were treated with algae extract revealed the regeneration and reconstitution of damaged pancreatic ß-cells. CONCLUSION: The results give evidence that, the S. oligocystum algae extract has a healing effect on diabetes which can be considered as a new research prospect for the natural therapy of diabetes.

The presence of the 1068 G>A variant of P2X7 receptors is associated to an increase in IL-1Ra levels, insulin secretion and pancreatic ß-cell function but not with glycemic control in type 2 diabetes patients.

It has been reported that an increased function of the P2X7 purinergic receptor is associated with an increase in both insulin sensitivity and secretion. Accordingly, we explored the possible effect of the 1068 G>A polymorphism of the gene P2RX7 on glucose homeostasis and the levels of the anti-inflammatory cytokine IL-1Ra in T2D patients. The presence of the 1068 G>A polymorphism in T2D patients (n = 100) and healthy subjects (n = 100) was determined by DNA sequencing, and serum levels of IL-1Ra were measured by ELISA. Pancreatic ß-cell function, insulin resistance, blood glucose levels and glycated hemoglobin (HbA1c) were also analyzed. We detected a significant negative association between T2D and the 1068 G>A SNP (Odds ratio 0.3916, p = 0.0045). In addition, we observed that T2D patients bearing the 1068 G>A variant showed higher serum levels of IL-1Ra compared to both, patients with the GG genotype or healthy individuals (GG or G>A). Moreover, T2D patients bearing the 1068 G>A SNP showed increased insulin levels and a better pancreatic ß-cell function (p < 0.05 in both cases) compared to patients with the wild type genotype. However, the HbA1c levels, fasting glucose levels and the degree of insulin resistance were similar in T2D patients carrying or not the G>A SNP. Our results suggest that although the 1068 G>A polymorphism of the P2RX7 gene is associated with an increased ß-cell function and IL-1Ra release in T2D patients, the glycemic control is not significantly affected by the presence of this SNP.

The relationship between chronic kidney function and homeostasis model assessment of insulin resistance and beta cell function in Korean adults with or without type 2 diabetes mellitus.

The present study was conducted to assess the relationship between chronic kidney disease (CKD) and the homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in Korean adults with or without type 2 diabetes mellitus (T2DM). This study included 5,188 adults aged 20 or older using the 2015 Korea National Health and Nutrition Examination Survey (KNHANES) data, which represents national data in Korea. A covariance test adjusted for covariates was performed for HOMA-IR and HOMA-B in relation to CKD. The present study has several key findings. First, in T2DM, HOMA-IR (p = 0.035) was higher in the CKD group than in the non-CKD group after adjusting for the related variables but HOMA-B (p = 0.141) was not significant. Second, in non-T2DM, HOMA-IR (p = 0.163) and HOMA-B (p = 0.658) were not associated with CKD after adjusting for the related variables (except age). However, when further adjusted for age, HOMA-IR (p = 0.020) and HOMA-B (p = 0.006) were higher in the CKD group than in the non-CKD group. In conclusion, insulin resistance was positively associated CKD with in Korean adults with or without T2DM. Beta cell function was positively associated CKD with in Korean adults without T2DM but not in Korean adults with T2DM.

Synbiotic supplementation and the effects on clinical and metabolic responses in patients with rheumatoid arthritis: a randomised, double-blind, placebo-controlled trial.

Synbiotic intake may be associated with reduced inflammation in patients with rheumatoid arthritis (RA) due to optimised inflammatory markers, oxidative stress and insulin resistance. This research was conducted to assess the effects of synbiotic supplementation on the clinical and metabolic parameters of patients with RA. A total of fifty-four patients with RA were allocated into two groups to receive either a synbiotic capsule (n 27) or a placebo (n 27) for 8 weeks in this randomised, double-blind, placebo-controlled trial. Fasting blood samples were taken at baseline and week 8 of the study to quantify related markers. After the 8-week intervention, compared with the placebo, synbiotic supplementation resulted in a significant reduction in serum high-sensitivity C-reactive protein (hs-CRP) levels (-1427·8 (sd 3267·2) v. +2833·4 (sd 5639·7) ng/ml, P=0·001). In addition, compared with the placebo, synbiotic supplementation improved disease activity score-28 joints (DAS-28) (-1·6 (sd 0·8) v. -0·3 (sd 0·5), P<0·001) and visual analogue scales (VAS) pain (-30·4 (sd 18·7) v. -11·5 (sd 15·9), P<0·001). In addition, a significant elevation in plasma nitric oxide (NO) (+0·8 (sd 4·4) v. -2·6 (sd 4·5) µmol/l, P=0·008), and significant reductions in insulin values (-13·8 (sd 26·4) v. +4·2 (sd 28·2) pmol/l, P=0·01), homoeostasis model of assessment-estimated insulin resistance (HOMA-IR) (-0·5 (sd 1·0) v.+0·1 (sd 1·1), P=0·03) and homoeostatic model assessment-ß-cell function (HOMA-B) (-9·4 (sd 17·9) v. +3·3 (sd 18·9), P=0·01) following supplementation with the synbiotic compared with the placebo. Compared with the placebo, synbiotic supplementation also resulted in a significant increase in plasma GSH (+36·6 (sd 63·5) v. -58·5 (sd 154·4) µmol/l, P=0·005). Overall, our study demonstrated that synbiotic supplementation for 8 weeks among patients with RA had beneficial effects on hs-CRP, DAS-28, VAS, NO, insulin levels, HOMA-IR, HOMA-B and GSH levels.