Insulin Resistance Homeostasis Model Research Articles

Effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus: A protocol for systematic review and meta analysis.

Background:There is limited study that has conducted a review investigating the clinical effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus (GDM). Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the effectiveness and safety of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with GDM.Methods:This protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. We will conduct systematic reviews and meta-analyses to identify relevant randomized controlled trials (RCTs) involving vitamin and omega-3 fatty acid co-supplementation on GDM in electronic databases including PubMed, Web of Science, Embase, and the Cochrane Library up to June 2021. Exclusion criteria include observational studies, non-RCTs, review articles, studies with a sample size <50, and studies with insufficient outcome data. The primary outcomes include fasting glucose and insulin. Secondary outcomes are evaluated in a homeostasis model of insulin resistance, total antioxidant capacity, triglycerides, total cholesterol, low-density lipoprotein cholesterol, preterm birth and macrosomia over 4 kg.Results:The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.Registration number:10.17605/OSF.IO/NSW54.

Pro-Neurotensin/Neuromedin N and Risk of Incident Metabolic Syndrome and Diabetes Mellitus in the REGARDS Cohort.

The peptide neurotensin is implicated in insulin resistance, diabetes mellitus (DM), and cardiovascular disease. We studied the association of neurotensin's stable precursor, pro-neurotensin/neuromedin N (pro-NT/NMN) with incident metabolic syndrome (MetS) and DM. We included 3772 participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study who completed the baseline exam (2003-2007), the follow-up exam (2013-2016), and had pro-NT/NMN measured by immunoassay. Weighted logistic regression models were fitted to incident DM, incident MetS, and each MetS component, separately, incorporating demographics, metabolic risk factors, homeostasis model of insulin resistance (HOMA-IR), and diet scores. Incident MetS was defined by 3 or more harmonized criteria at follow-up in those with fewer than 3 at baseline. Incident DM was defined by use of hypoglycemic drugs/insulin, fasting glucose 126 mg/dL or greater, or random glucose 200 mg/dL or greater in those without these at baseline. Median (IQR) plasma pro-NT/NMN was 160 pmol/L (118-218 pmol/L). A total of 564 (of 2770 without baseline MetS) participants developed MetS, and 407 (of 3030 without baseline DM) developed DM. Per SD higher log-pro-NT/NMN, the demographic-adjusted odds ratio (OR) and 95% CI of incident MetS was 1.22 (1.11-1.35), 1.16 (1.00-1.35) for incident low high-density lipoprotein (HDL), and 1.25 (1.11-1.40) for incident dysglycemia. The association of pro-NT/NMN with MetS was attenuated in the model adding HOMA-IR (OR per SD log-pro-NT/NMN 1.14; 95% CI, 1.00-1.30). There was no association with incident DM (OR per SD log-pro-NT/NMN 1.06; 95% CI, 0.94-1.19). Pro-NT/NMN was associated with MetS and 2 components, dysglycemia and low HDL, likely explained by insulin resistance.

Effect of exercise on cardiometabolic health of adults with overweight or obesity: Focus on blood pressure, insulin resistance, and intrahepatic fat-A systematic review and meta-analysis.

SummaryThis systematic review examined the impact of exercise intervention programs on selected cardiometabolic health indicators in adults with overweight or obesity. Three electronic databases were explored for randomized controlled trials (RCTs) that included adults with overweight or obesity and provided exercise‐training interventions. Effects on blood pressure, insulin resistance (homeostasis model of insulin resistance, HOMA‐IR), and magnetic resonance measures of intrahepatic fat in exercise versus control groups were analyzed using random effects meta‐analyses. Fifty‐four articles matched inclusion criteria. Exercise training reduced systolic and diastolic blood pressure (mean difference, MD = −2.95 mmHg [95% CI −4.22, −1.68], p < 0.00001, I 2 = 63% and MD = −1.93 mmHg [95% CI −2.73, −1.13], p < 0.00001, I 2 = 54%, 60 and 58 study arms, respectively). Systolic and diastolic blood pressure decreased also when considering only subjects with hypertension. Exercise training significantly decreased HOMA‐IR (standardized mean difference, SMD = −0.34 [−0.49, −0.18], p < 0.0001, I 2 = 48%, 37 study arms), with higher effect size in subgroup of patients with type 2 diabetes (SMD = −0.50 [95% CI: −0.83, −0.17], p = 0.003, I 2 = 39%). Intrahepatic fat decreased significantly after exercise interventions (SMD = −0.59 [95% CI: −0.78, −0.41], p < 0.00001, I 2 = 0%), with a larger effect size after high‐intensity interval training. In conclusion, exercise training is effective in improving cardiometabolic health in adults with overweight or obesity also when living with comorbitidies.

Lipoprotein Insulin Resistance Score: Validation and Utility in African Ancestry Populations

Lipoprotein insulin resistance (LPIR) is an emerging biomarker of insulin resistance (IR), and a score of >48 is a strong predictor of incident cardiometabolic disease disease in a predominantly European ancestry population. LPIR is derived from a composite score of nuclear magnetic resonance (NMR) lipoprotein (Lp) parameters: triglyceride-rich (TRLp), low density (LDLp), and high density (HDLp). Yet, there is a paucity of data in African ancestry population, in whom there is low-normal TRLp despite high rates of IR and diabetes. Therefore, we examined Lp profiles and LPIR in a large African ancestry cohort, stratified by sex to determine the relationship of LPIR with established markers of IR. This is a secondary analysis from 2 studies (The Africans in America and Federal Women’s Study) designed to evaluate the genetic, biological and socio-environmental factors of diabetes risk in those of African ancestry. All participants self-identified as healthy and lived in the DC metro area, n= 518: 87.7% African immigrant,12.3% African American; age 39±10 (20-65y); BMI 28.1±4.8 (18.2–45.2 kg/m2); 58% male; 31% with obesity, and 37% with abnormal glucose tolerance; mean±SD (range); median (25th-75th percentile). Fasting measures of IR (LPIR, triglyceride/HDL (TG/HDL) ratio and homeostasis model of insulin resistance (HOMA-IR)) were compared with the whole-body insulin sensitivity index (WBISI) obtained during a multi-sample 75g OGTT, using spearman correlations. Lp particle size and subclass concentrations were measured by the amplitudes of the lipid-methyl group signals (NMR LipoProfile®). Men had lower BMI (27.1±3.9 vs 29.3±5.6 kg/m2), fat mass (23.5±5.5 vs 37.9±6.8 %), insulin resistance (WBISI: 6.2 (3.7–10.1) vs 4.9 (3.2–8.6), HOMA-IR: 1.3 (0.7–2.0) vs 1.6 (0.9–2.4), TG/HDL: 1.4 (1.0–2.2) vs 1.1 (0.8–1.5)), all P<0.001. LDLp (1226 (959–1531) vs 1239 (981–1553) nmol/L) and HDLp (17.6 (16.2–19) vs 17.5 (15.9–19.7) µmol/L) were similar by sex, P>0.6, while small LDLp 734 (523–1039) vs 541 (370–805) nmol/L and TRLp 80.5 (52.2–116.4) vs 53.6 (28.7 -89.3) nmol/L were higher in men. The total mean LPIR score was 28.9±18.7 and was higher in men (34±19 vs. 23±17), P<0.001. LPIR and TG/HDL ratio correlated with WBISI (r≥-0.40) and HOMA-IR (r≥0.40), P<0.001 with no differences by sex. HOMA-IR correlated with WBISI (r=-0.95, P<0.001). Overall, African ancestry individuals had high rates of abnormal glucose tolerance, obesity and LDLp but LPIR was 20 points lower than the established score for predicting cardiometabolic disease. It’s utility for detecting IR was modest but it may be an important adjunct for early cardiometabolic risk stratification in African ancestry populations in whom traditional screening methods have lower sensitivity.

Leukocyte telomere length is inversely associated with a metabolic risk score in Mesoamerican children.

Leukocyte telomere length (LTL) may be involved in the etiology of the metabolic syndrome (MetS). We examined the associations of LTL with MetS and its components among Mesoamerican children and their adult parents, in a region where MetS prevalence is high. We conducted a cross-sectional study of 151 children aged 7-12 years and 346 parents from the capitals of Belize, Honduras, Nicaragua, Costa Rica, Panama, and Chiapas State, Mexico. We quantified LTL by qPCR on DNA extracted from whole blood. In children, we created an age- and sex-standardized metabolic risk score using waist circumference (WC), the homeostasis model of insulin resistance (HOMA-IR), blood pressure, serum high-density lipoprotein (HDL) cholesterol, and serum triglycerides. In adults, MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III definition. We estimated mean differences in metabolic risk score and prevalence ratios of MetS across quartiles of LTL using multivariable-adjusted linear and Poisson regression models, respectively. In children, every 1 LTL z-score was related to an adjusted 0.05 units lower (95% CI: -0.09, -0.02, P= 0.005) MetS risk score, through WC, HOMA-IR, and HDL. Among adults, LTL was not associated with MetS prevalence; however, every 1 LTL z-score was associated with an adjusted 34% lower prevalence of high fasting glucose (95% CI: 3%, 55%, p=.03). Among Mesoamerican children, LTL is associated with an improved metabolic profile; among adults, LTL is inversely associated with the prevalence of high fasting glucose.

Hippocampal cellular changes in androgen deprived insulin resistant rats.

Androgen deprivation can be achieved through testosterone antagonists (chemical castration) with or without orchidectomy. We use a rat model to characterize hippocampal structural and functional changes that might be associated with a subset population of androgen deprived insulin-resistant patients. Adult male Wistar rats assigned into six (6) groups: control group (distilled water/sham), orchiectomy group (bilateral orchiectomy), flutamide group (oral flutamide; 11mg/kg body weight), diabetes group (multiple low-dose of streptozotocin (STZ; 30mg/kg body weight intraperitoneally), orchiectomy and diabetic group (bilateral orchiectomy with 30mg/kg body weight of STZ), and orchiectomy/diabetic/flutamide group (bilateral orchiectomy with 30mg/kg body weight of STZ with 11mg/kg body weight of flutamide). Animals were sacrificed at 30 and 60days respectively. Spatial learning and working memory behavior were assessed; while total plasma; testosterone, insulin levels, and fasting blood glucose were assayed; the Homeostasis model for insulin resistance was also calculated. Histological examinations by H&E and CFV, while immunohistochemical analysis of astrocytes, P53 protein, and NSE were performed. Androgen deprived insulin-resistant state caused altered learning and cognitive behavior through decreased percentage correct alternation to an increased escape latency period. Significant bidirectional correlates exist between the hormonal profiles relative to the control group (p < 0.05), especially in the 60days post-orchiectomy. While histological and immunohistochemical data indicate microcellular derangement. That the summate effects of androgen deprivation and impaired insulin signaling exacerbate hippocampal neurodegenerative changes that merit further studies.

Association between insulin resistance and post-ischaemic stroke outcome in patients without diabetes: protocol for a systematic review and meta-analysis

IntroductionInsulin resistance is an independent risk factor for atherosclerosis, coronary artery disease and ischaemic stroke. Currently, insulin resistance is not usually included in post-stroke risk stratification. This systematic review and...

Retrospective analysis on pregnancy outcomes and fat-related factors of treatment of endomorph PCOS infertility patients by acupuncture of 8 acupoints around umbilicus

To assess the therapeutic effect of acupuncture of eight acupoints around the umbilicus in improving the metabolic level and reproductive function in endomorph polycystic ovary syndrome (PCOS) infertile patients. Retrospective analysis was performed on 96 cases of endomorph type PCOS infertility patients who were admitted to the clinic of the Reproductive Center of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from October 2015 to June 2018. Among them, fifty-six cases of the acupuncture group received treatment with acupuncture stimulation of eight acupoints (Shuifen ［CV9］, Yinjiao ［CV7］, Tianshu ［ST25］, Wailing ［ST26］, Huaroumen ［ST24］, etc.) around the umbilicus, and 40 cases of the control group were treated by oral administration of Letrozole. Acupuncture was performed once every other day, and Letrozole (2.5 mg/day) given once daily for 5 days, if no pregnancy got, the treatment procedure was repeated once again next menstruation cycle, continuously for 3 months. The pregnancy outcomes including the pregnancy rate, persistent pregnancy rate, ovulation rate and the first trimester abortion rate, and the levels of fat-related factors including body mass index (BMI), waist-to-hip ratio (WHR), homeostasis model of insulin resistance (HOMA-IR=fasting insulin x fasting blood glucose /22.5), leptin(LEP) and adiponectin(APN) of the two groups were compared. The ovulation rate (number of effective ovulation cycles/ number of observation cycles) x 100%, the first trimester abortion rate (number of spontaneous abortion within 12 weeks÷pregnancy cases) X100% were calculated. The fasting blood samples were taken for assaying serum LEP and APN contents using ELISA, blood glucose level using hexokinase assay, and serum insulin by using chemiluminescent microparticle immunoassay, separately. After the treatment, the pregnancy rate and the level of APN were significantly higher (P<0.05), and the BMI, WHR, HOMA-IR and LEP levels were all obviously lower in the acupuncture group than in the control group (P<0.05). There were no significant differences between the two groups in the persistent pregnancy rate, abortion rate and ovulation rate (P>0.05). Acupuncture at the eight points around the umbilicus can raise the pregnancy rate in obese type PCOS patients, which may be related to its effects in up-regulating serum APN and lowering BMI, WHR, HOMA-IR, and serum LEP levels.

Efficacy and safety of Shenqi Jiangtang Granules plus oral hypoglycemic agent in patients with type 2 diabetes mellitus: A protocol for systematic review and meta-analysis of 15 RCTs.

Objective:Shenqi Jiangtang Granules (SQJTG) has been widely used to treat patients with type 2 diabetes mellitus (T2DM). But whether there exists sufficient evidence on the efficacy of SQJTG in the treatment of T2DM is unclear. In order to assess the effects of SQJTG for T2DM, a systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out.Methods:Eight databases, namely, PubMed, The Cochrane Library, EMBASE, Web of Science, Chinese National Knowledge Infrastructure, Chinese Scientific Journals Full-Text Database, CBM, and Wanfang database were searched up to May 2020. According to the Cochrane standards, the selection of study, the extraction of data, the assessment of study quality, and the analyses of data were carried out strictly. Then a fixed or random effects model was applied to analyze the outcomes.Results:Fifteen studies (N = 1392) in total conformed the inclusion criteria to this meta-analysis. Two subgroups were identified, based on different dose of SQJTG: oral hypoglycemic agent (OHA) vs OHA plus SQJTG (1 g); OHA vs. OHA plus SQJTG (1.5–3 g). The pooled results showed that, in comparison with OHA, OHA plus SQJTG significantly reduced fasting plasma glucose in both 1 g subgroup and 1.5–3 g subgroup; 2-hour post-meal blood glucose was also greatly reduced in the SQJTG 1 g subgroup and the SQJTG 1.5–3 g subgroup. Compared with OHA, SQJTG 1 g subgroup significantly reduced levels of glycated hemoglobin A1c, as well as the SQJTG 1.5–3 g subgroup. Homeostasis model-insulin resistance index was also reduced in both SQJTG 1 g subgroup and SQJTG 1.5–3 g subgroup; SQJTG group can also significantly reduce the total adverse events especially in reducing the incidence of hypoglycemia.Conclusions:SQJTG is an effective and safe complementary treatment for T2DM patients. This meta-analysis provides an evidence for the treatment in patients with T2DM. While owing to the high heterogeneity and the trials’ small sample size, it's crucial to perform large-scale and strict designed studies.

Insulin resistance in transgender individuals correlates with android fat mass.

Background:Transgender individuals receiving gender-affirming hormone therapy (GAHT) are at increased risk of adverse cardiovascular outcomes. This may be related to effects on body composition and insulin resistance.Aims:To examine relationships between body fat distribution and insulin resistance in transgender individuals on established GAHT.Methods:Comparisons of body composition (dual energy X-ray absorptiometry) and insulin resistance [Homeostasis Model of Insulin Resistance (HOMA2-IR)] were made between transgender individuals (43 trans men and 41 trans women) on established GAHT (>12 months) and age-matched cisgender controls (30 males and 48 females). Multiple linear regressions were used to examine the relationship between HOMA2-IR and fat mass with gender, adjusting for age and total duration of GAHT and Pearson correlation coefficients are reported.Results:Compared with control cisgender women, trans men had mean difference of +7.8 kg (4.0, 11.5), p < 0.001 in lean mass and higher android:gynoid fat ratio [0.2 (0.1, 0.3), p < 0.001], but no difference in overall fat mass or insulin resistance. Compared with control cisgender men, trans women had median difference in lean mass of −6.9 kg (–10.6, –3.1), p < 0.001, fat mass of +9.8 kg (3.9, 14.5), p = 0.001, lower android:gynoid fat ratio −0.1 (–0.2,–0.0), p < 0.05), and higher insulin resistance 1.6 (1.3–1.9), p < 0.001). Higher HOMA2-IR correlated with higher android (r2 = 0.712, p < 0.001) and gynoid (r2 = 0.572, p < 0.001) fat mass in both trans men and trans women.Conclusion:Android fat more strongly correlates with insulin resistance than gynoid fat in transgender individuals. Higher fat mass and insulin resistance in trans women may predispose to increased cardiovascular risk. Despite adverse fat distribution, insulin resistance was not higher in trans men.

Cafeteria diet induces global and Slc27a3-specific hypomethylation in male Wistar rats

ABSTRACT Increased visceral adipose tissue (VAT) is associated with metabolic dysfunction, while subcutaneous adipose tissue (SAT) is considered protective. The mechanisms underlying these differences are not fully elucidated. This study aimed to investigate molecular differences in VAT and SAT of male Wistar rats fed a cafeteria diet (CD) or a standard rodent diet (STD) for three months. The expression of fatty acid metabolism genes was analysed by quantitative real-time PCR. Global and gene-specific DNA methylation was quantified using the Imprint® Methylated DNA Quantification Kit and pyrosequencing, respectively. Bodyweight, retroperitoneal fat mass, insulin resistance, leptin and triglyceride concentrations and adipocyte hypertrophy were higher in CD- compared to STD-fed rats. The expression of solute carrier family 27 member 3 (Slc27a3), a fatty acid transporter, was 9.6-fold higher in VAT and 6.3-fold lower in SAT of CD- versus STD-fed rats. Taqman probes confirmed increased Slc27a3 expression, while pyrosequencing showed Slc27a3 hypomethylation in VAT of CD- compared to STD-fed rats. The CD decreased global methylation in both VAT and SAT, although no depot differences were observed. Dysregulated fatty acid influx in VAT, in response to a CD, provides insight into the mechanisms underlying depot-differences in adipose tissue expansion during obesity and metabolic disease. Abbreviations: CD: cafeteria diet; E2F1: E2F Transcription Factor 1; EMSA: electrophoretic mobility shift assay; EGFR: epidermal growth factor receptor; GCF: GC-Rich Sequence DNA-Binding Factor; HOMA-IR: Homeostasis model for insulin resistance; NKX2-1: NK2 homeobox 1; PCR: Polymerase chain reaction; qRT-PCR: quantitative real-time PCR; RF: retroperitoneal fat; SAT: subcutaneous adipose tissue; Slc27a3: solute carrier family 27 member 3; STD: standard diet; TNFα: tumour necrosis factor alpha; TTS: transcriptional start site; T2D: Type 2 Diabetes; VAT: visceral adipose tissue; WT1 I: Wilms’ tumour protein 1

Association of Adiponectin−11377 C/G (rs266729) Gene Polymorphism with Nonalcoholic Fatty Liver Disease and Metabolic Features in Egyptian Women

The present cross-sectional study included 150 unrelated non-alcoholic fatty liver disease (NAFLD) patients and 150 healthy subjects. ADIPOQ (-11377C / G) variant was genotyped with polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) method for both patients and controls. Anthropometric and biochemistry parameters were measured. The Homeostasis Model Insulin Resistance Assessment (HOMA-IR) was used to assess the insulin resistance. The rs266729 polymorphism was associated with NAFLD with significant increase in CG genotype compared to those with the wild genotype CC (OR = 9.24, 95% CI = 4.96 - 17.21, p<0.001) in co dominant tested inheritance model as well in dominant tested inheritance model with CG/GG genotype (OR = 9.58, 95% CI = 5.32 – 17.28, p< 0.001). The G allele increased the risk of NAFLD (OR = 6.06, 95% CI = 3.65 - 10.05, p< 0.001) in comparison with C allele. Subgroup comparison in NAFLD revealed significant higher levels of waist circumference (WHR), HOMA-IR, systolic blood pressure (SBP), fasting glucose and LDL-C in GG and GC carriers compared to CC genotype and significant lower levels of serum adiponectin. Conclusions: The study suggests that ADIPOQ gene polymorphism can be used as a helpful biomarker for NAFLD and abnormal metabolic parameters. Our study sheds light on its role that might be played in the pathogenesis of NAFLD. Proper evaluation of NAFLD is likely to improve therapy effectiveness and safety management.

Fibre Intake Is Associated with Cardiovascular Health in European Children.

Background: We aimed at analysing the association between dietary fibre intake during childhood and cardiovascular health markers. Methods: We used observational longitudinal analysis and recorded diet using 3-day diaries at the ages of 3, 4, 5, 6, and 8 years in children from the EU Childhood Obesity Project Trial. At the age of 8, waist circumference, systolic and diastolic blood pressure (SBP and DBP) and biochemical analyses (lipoproteins, triglycerides and homeostasis model for insulin resistance (HOMA-IR)) were evaluated. Those parameters were combined into a cardiometabolic risk score through the sum of their internal z-scores. Results: Four-hundred children (51.8% girls) attended to the 8-year visit with a 3-day diary. Adjusted linear regression models showed that children who repeatedly stayed in the lowest tertile of fibre intake during childhood had higher HOMA-IR (p = 0.004), higher cardiometabolic risk score (p = 0.02) and a nonsignificant trend toward a higher SBP at 8 years. The higher the dietary intake of soluble fibre (from fruits and vegetables) at 8 years, the lower the HOMA-IR and the cardiometabolic risk score (p = 0.002; p = 0.004). SBP was directly associated with fibre from potatoes and inversely with fibre from nuts and pulses. Conclusion: A diet rich in dietary fibre from fruits, vegetables, pulses and nuts from early childhood was associated to a healthier cardiovascular profile, regardless of children’s weight.

A randomized controlled clinical trial comparing calcitriol versus cholecalciferol supplementation to reduce insulin resistance in patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world with no definite treatment. Insulin resistance (IR) and low serum vitamin D are closely linked to NAFLD. Since there is no comparative study on the effect of calcitriol with cholecalciferol on NAFLD based on homeostasis model of insulin resistance (HOMA-IR) as an IR indicator, so we designed this research. A double blind randomized clinical trial was conducted on patients with NAFLD with concomitant vitamin D deficiency/insufficiency at two referral tertiary teaching medical centers, from July 2017 to January 2019. Patients were randomly divided into two groups: calcitriol (1mcg/day) and cholecalciferol (50,000IU/week) for 8 weeks. Before and after the intervention, anthropometric and laboratory data were measured and HOMA-IR was calculated for each patient. 54 patients completed the trial. In total, calcitriol supplementation improved serum insulin levels as well as IR based on the HOMA-IR index, significantly compared to the cholecalciferol group. HOMA-IR decreased 1.8 times more in patients receiving calcitriol than in those receiving cholecalciferol, which was clinically meaningful. The observed changes were more pronounced in patients with higher baseline body mass index. Moreover, calcitriol was more associated with a significant decrease in liver enzymes and cholesterol levels comparing to cholecalciferol. Based on the findings of this study, the use of calcitriol supplementation significantly reduced HOMA-IR as an IR indicator in NAFLD patients, compared to cholecalciferol. To confirm this findings, further studies with larger sample sizes are recommended.

GALNT2 Gene Variant rs4846914 Is Associated with Insulin and Insulin Resistance Depending on BMI in PCOS Patients: a Case-Control Study.

GALNT2 is a GalNAc transferase that regulates insulin signaling, lipogenesis, and serum lipid fractions. The objective of this study was to investigate the association of GALNT2 rs2144300 and rs4846914 single nucleotide polymorphisms (SNPs) with the risk of polycystic ovary syndrome (PCOS) and related traits. The two SNPs were genotyped in 616 PCOS patients and 482 control subjects. Genetic associations with related traits were also analyzed. The genotype distributions of the two SNPs in PCOS patients were similar to those of normal controls. However, significant differences were noted across the three groups of genotypes with respect to the examined variables. In the PCOS group, subjects with genotype AA at the rs4846914 SNP exhibited an increased fasting serum insulin and homeostasis model insulin resistance (HOMA-IR) index compared with that of corresponding GG or GA genotype carriers (all P < 0.05). When PCOS patients were further separated into obese and non-obese subgroups, the genotype-related effects on insulin and HOMA-IR were more obvious, and variations in BMI and FSH levels were exclusively observed in obese PCOS subjects (all P < 0.05). In addition, fasting plasma glucose levels were affected by the genotypes of the rs2144300 SNP in normal control women (P < 0.05). rs4846914 and rs2144300 polymorphisms in the GALNT2 gene are associated with insulin and HOMA-IR, BMI, and FSH levels in obese PCOS patients and glucose levels in normal control women, respectively, but not with PCOS. GALNT2 rs4846914 AA carrier status may be associated with insulin resistance and related traits in obese patients.

The association of dietary and plasma fatty acid composition with FTO gene expression in human visceral and subcutaneous adipose tissues.

The human obesity susceptibility gene, FTO, associates with body mass and obesity in humans through regulation of energy expenditure and intake. We aimed to determine how fatty acids in plasma and in diet associate with FTO gene expression in subcutaneous and visceral adipose tissues. In this study, 97 participants aged ≥ 18years were selected from patients admitted to the hospital for abdominal surgeries. Habitual dietary intake of participants was collected using a valid and reliable food frequency questionnaire (FFQ), from which the intake of fatty acids was quantified. Plasma fatty acids were assessed by gas-liquid chromatography. The mRNA expression of the FTO gene in visceral and subcutaneous adipose tissues obtained by biopsy was measured by Real-Time Quantitative Reverse Transcription PCR. Standardized β-coefficients were calculated by multivariable linear regression. After adjusting for age, homeostasis model insulin resistance index (HOMA-IR), and body mass index, total fatty acid intake was significantly associated with FTO gene expression in visceral (STZβ = 0.208, P = 0.037) and subcutaneous (STZβ = 0.236, P = 0.020) adipose tissues. Dietary intake of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) had positive significant associations with the expression of FTO in visceral (STZβ = 0.227, P = 0.023; STZβ = 0.346, P < 0.001, respectively) and subcutaneous (STZβ = 0.227, P = 0.026; STZβ = 0.274, P = 0.006, respectively) adipose tissues. There were no associations between plasma fatty acids and FTO mRNA expression in either subcutaneous or visceral adipose tissues. The weak association of dietary total fatty acids, MUFA, and PUFA with FTO gene expression in both adipose tissues may highlight the importance of dietary fatty acids composition along with total fat intake in relation to FTO gene expression.

Epigallocatechin-3-gallate ameliorates glucolipid metabolism and oxidative stress in type 2 diabetic rats.

Aims:The objective of this study was to explore the effects of epigallocatechin-3-gallate (EGCG) on type 2 diabetes mellitus (T2DM).Main methods:Male Sprague–Dawley rats were allocated into six groups. The control group received a conventional diet. The diabetic group received a high-sucrose high-fat (HSHF) diet for 4 weeks and then was fasted and injected with streptozotocin (STZ); subsequently, the rats received a HSHF diet for another 4 weeks to develop diabetes. The four treatment groups were diabetic rats that received intragastric metformin (500 mg/kg/day) or EGCG (25, 50, and 100 mg/kg/day) for 10 weeks. All groups except the control group received a HSHF diet throughout the experiment. Several biochemical parameters such as fasting blood glucose (FBG), postprandial blood glucose (PBG), liver glycogen, muscle glycogen, fasting serum insulin (FSI), homeostasis model of insulin resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFA), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to assess the effects of EGCG on glycemic control, insulin resistance, lipid profile, and oxidative stress. Furthermore, oxidative stress in pancreatic islet β cells was detected by dihydroethidium staining.Key findings:A HSHF diet and STZ injection induced T2DM, as indicated by changed blood glucose and body weight, which was accompanied by insulin resistance, an altered lipid profile, and oxidative stress. Interestingly, EGCG treatment dose-dependently recovered these indexes.Significance:EGCG successfully ameliorated glycemic control and insulin sensitivity while reducing the lipid profile and oxidative stress in a T2DM rat model.

Serum Bisphenol A, glucose homeostasis, and gestational diabetes mellitus in Chinese pregnant women: a prospective study.

Lab studies have suggested that exposure to Bisphenol A (BPA) could disturb glucose homeostasis, but epidemiologic studies are limited and show inconsistent results for pregnant women. For this, 535 pregnant women were selected from a pregnant women cohort established in Tangshan City in North China between 2013 and 2014. Serum concentrations of BPA were measured in the early term of pregnancy, and fasting glucose and insulin levels were repeatedly measured in each of three terms of pregnancy (early, middle, and late). Gestational diabetes mellitus (GDM) were examined by Oral Glucose Tolerance Test (OGTT) in the middle and late terms of pregnancy. BPA was detected in 97.5% of pregnant women with a median of 6.50ng/ml. Natural log-transformed BPA (Ln BPA) was positively associated with fasting glucose level (β (95% CI): 0.038 (0.015~0.061)), fasting insulin level (0.195 (0.069~0.321)), and homeostasis model insulin resistance index (HOMA-IR) (0.226 (0.087~0.364)) in the middle term of pregnancy by multiple linear regression model after adjusting for potential confounders. After serum BPA levels were divided into three groups (low, middle, and high), BPA showed a positive dose-response relationship with blood glucose, insulin, and HOMA-IR in the middle term of pregnancy. Increased BPA concentration tended to increase the RR of GDM although not statistically significant (risk ratio: 2.51 (95% CI: 0.68~9.30) for high vs low tertile of BPA concentrations). These findings suggested that exposure to BPA might affect glucose homeostasis and the middle term of pregnancy was a potentially sensitive period.

The Product of Red Blood Cells and Hematocrit Can Be Used as a Novel Indicator of Impaired Fasting Blood Glucose Status.

ObjectiveTo explore whether the red blood cell count multiplied by hematocrit index (RBCHct) in blood routine parameters can indicate the risk of impaired fasting blood glucose (IFG), and whether it is related to insulin resistance and inflammation.MethodsIn this cross-sectional study, previous history of diabetes was excluded, and people with normal and impaired IFG were included. We use Spearman analysis to evaluate the correlation between RBCHct index and fasting plasma glucose, insulin resistance homeostasis model assessment (HOMA-IR), and hypersensitive C-reactive protein (hs-CRP). Binary logistic regression analysis was used to evaluate the RBCHct index for assessing the potential risk of IFG, and the receiver operating characteristic (ROC) curve was used to evaluate the RBCHct index for diagnosing insulin resistance and chronic low-grade inflammatory efficacy among those with IFG.ResultsCorrelation analysis showed that the RBCHct index and fasting plasma glucose (r=0.088, P=0.003); HOMA-IR (r=0.199, P<0.001); and hs-CRP (r=0.097, P=0.001) were positively correlated. After adjusting for confounding factors, the risk of IFG in the third and fourth quartiles of the RBCHct index increased to 1.889 and 3.048 times. The area under the ROC curve of the RBCHct index for diagnosis of insulin resistance state (HOMA-IR) was 0.695 (p<0.001), and the area under the ROC curve of the RBCHct index for the diagnosis of chronic low-inflammatory state (hs-CRP) was 0.641 (P=0.010).ConclusionThe RBCHct index may be a potential indicator for assessing the risk of prediabetes and is closely related to whether the body is in a state of insulin resistance and inflammation under IFG.

DNA methylation of FKBP5 in South African women: associations with obesity and insulin resistance

BackgroundDisruption of the hypothalamic–pituitary–adrenal (HPA) axis, a neuroendocrine system associated with the stress response, has been hypothesized to contribute to obesity development. This may be mediated through epigenetic modulation of HPA axis-regulatory genes in response to metabolic stressors. The aim of this study was to investigate adipose tissue depot-specific DNA methylation differences in the glucocorticoid receptor (GR) and its co-chaperone, FK506-binding protein 51 kDa (FKBP5), both key modulators of the HPA axis.MethodsAbdominal subcutaneous adipose tissue (ASAT) and gluteal subcutaneous adipose tissue (GSAT) biopsies were obtained from a sample of 27 obese and 27 normal weight urban-dwelling South African women. DNA methylation and gene expression were measured by pyrosequencing and quantitative real-time PCR, respectively. Spearman’s correlation coefficients, orthogonal partial least-squares discriminant analysis and multivariable linear regression were performed to evaluate the associations between DNA methylation, messenger RNA (mRNA) expression and key indices of obesity and metabolic dysfunction.ResultsTwo CpG dinucleotides within intron 7 of FKBP5 were hypermethylated in both ASAT and GSAT in obese compared to normal weight women, while no differences in GR methylation were observed. Higher percentage methylation of the two FKBP5 CpG sites correlated with adiposity (body mass index and waist circumference), insulin resistance (homeostasis model for insulin resistance, fasting insulin and plasma adipokines) and systemic inflammation (c-reactive protein) in both adipose depots. GR and FKBP5 mRNA levels were lower in GSAT, but not ASAT, of obese compared to normal weight women. Moreover, FKBP5 mRNA levels were inversely correlated with DNA methylation and positively associated with adiposity, metabolic and inflammatory parameters.ConclusionsThese findings associate dysregulated FKBP5 methylation and mRNA expression with obesity and insulin resistance in South African women. Additional studies are required to assess the longitudinal association of FKBP5 with obesity and associated co-morbidities in large population-based samples.Graphical abstract