Fasting Insulin Resistance Research Articles

Additive effects of Zamzam water in reducing fasting blood glucose and LDL-cholesterol in rats fed on a ketogenic diet

PurposeThe ketogenic diet (KD) has gained popularity due to its ability to improve type 2 diabetes, weight loss, antioxidant and anti-inflammatory activity. However, long-term use of the KD might not be safe due to its adverse effects. This study examined the effects of the KD alone or in combination with Zamzam water (holy water for Muslims) on glucose homeostasis, lipid parameters and oxidant-antioxidant variables in rats.Design/methodology/approachBased on the diet given for ten weeks, three groups of adult male Wistar rats were made (12 rats/group): (1) rats which fed on a chow diet and ordinary water, (2) rats which fed on KD and ordinary water and (3) rats which were given KD along with Zamzam. Fasting blood glucose (FBG), serum insulin, insulin resistance (HOMA-IR), LDL cholesterol, HDL cholesterol, superoxide dismutase and malondialdehyde were compared by one-way ANOVA followed by post-hoc Tukey’s HSD test among groups.FindingsRats which fed on KD and Zamzam water had significantly reduced FBG and LDL cholesterol compared to the rats which fed on a chow diet and ordinary water (p-values 0.001), and KD and ordinary water (p-value 0.004 and 0.006, respectively). Serum insulin, insulin resistance, HDL cholesterol, superoxide dismutase and malondialdehyde did not differ significantly.Originality/valueConsumption of KD along with Zamzam for ten weeks significantly reduces FBG and LDL cholesterol. KD alone does not decrease these parameters in ten weeks duration.

Association of muscle mass measured by D3-Creatine (D3Cr), sarcopenic obesity, and insulin-glucose homeostasis in postmenopausal women.

The D3-Creatine (D3Cr) dilution method is a direct and accurate measure of skeletal muscle mass. In this study, we examined the association of D3Cr muscle mass with measures of insulin-glucose homeostasis in community dwelling postmenopausal women. Additionally, we examined association of sarcopenic obesity, defined as low D3Cr muscle mass and high percent body fat, with fasting plasma glucose, insulin, hemoglobin A1c and insulin resistance. Insulin resistance was measured by the homeostatic measure of insulin resistance (HOMA-IR). This pilot study included 74 participants (mean age = 82.3 years) from the Women's Health Initiative-Buffalo site. The D3Cr method was initiated at a clinic visit and used to measure muscle mass via remote urine sample collection. Descriptive and graphical approaches and age-adjusted linear regression models were used to analyze study data. We examined muscle mass as an absolute value (kg) and scaled to body weight (D3Cr muscle mass/kg). There was an inverse relationship between skeletal muscle mass, and impaired insulin-glucose homeostasis. Women with low muscle mass had higher levels of insulin (uIU/mL; β = -0.40; 95% CI: -0.79, -0.01), fasting plasma glucose (mg/dL; β = -0.1; 95% CI: -0.2, 0.03), HbA1c (%; β = -2.30; 95% CI: -5.7, 1.1), and calculated homeostatic model of insulin resistance, HOMA-IR, (β = -1.49; 95% CI: -2.9, -0.1). Sarcopenic obesity was common in this population of women; 41% of participants were categorized as having low muscle mass and high percent body fat. Results demonstrate that D3Cr muscle mass is independently associated with measures of insulin-glucose homeostasis, but obesity is a stronger predictor of insulin resistance than muscle mass.

The clinical effect of probiotics on patients with non-alcoholic fatty liver disease: a meta-analysis

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. The present study explores the clinical efficacy of probiotics in the treatment of patients with NAFLD by conducting a systematic search of relevant databases. The RevMan 5.4 software was used to evaluate the effects of probiotics on liver function (i.e. alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT], lipid metabolism, blood glucose, inflammatory factors [e.g. tumor necrosis factor-α, TNF-α] and body mass index [BMI]) in patients with NAFLD. A total of 18 high-quality studies were included in the final meta-analysis. The results of the meta-analysis showed that the use of probiotics in the adjuvant treatment of patients with NAFLD improved liver function and reduced ALT levels (mean difference [MD]: −0.07; 95% confidence interval [CI]: −12.95, −7.19), AST levels (MD: −11.90; 95% CI: −16.55, −7.25) and GGT levels (MD: −8.61; 95% CI: −14.74, −2.48); additionally, the treatment effect was more obvious when the treatment time exceeded 12 weeks. Probiotic therapy reduced patients’ triglyceride levels (MD: −9.71; 95% CI: −18.39, −1.03) and total cholesterol levels (MD: −22.31; 95% CI: −25.41, −19.21). Probiotic treatment improved patients’ levels of fasting blood (MD: −8.22; 95% CI: −12.25, −4.20), insulin (MD: −2.68; 95% CI: −4.94, −0.41) and insulin resistance (MD: −0.72; 95% CI: −1.21, −0.24). Probiotic adjuvant therapy for patients with NAFLD reduced their BMI by approximately 1.67 (95% CI: −2.93, −0.41) and TNF-α levels. The adjuvant treatment of NAFLD with probiotics has a positive clinical effect, which is influenced by treatment time.

Gamma-glutamyl-leucine levels are causally associated with elevated cardio-metabolic risks.

Gamma-glutamyl dipeptides are bioactive peptides involved in inflammation, oxidative stress, and glucose regulation. Gamma-glutamyl-leucine (Gamma-Glu-Leu) has been extensively reported to be associated with the risk of cardio-metabolic diseases, such as obesity, metabolic syndrome, and type 2 diabetes. However, the causality remains to be uncovered. The aim of this study was to explore the causal-effect relationships between Gamma-Glu-Leu and metabolic risk. In this study, 1,289 subjects were included from a cross-sectional survey on metabolic syndrome (MetS) in eastern China. Serum Gamma-Glu-Leu levels were measured by untargeted metabolomics. Using linear regressions, a two-stage genome-wide association study (GWAS) for Gamma-Glu-Leu was conducted to seek its instrumental single nucleotide polymorphisms (SNPs). One-sample Mendelian randomization (MR) analyses were performed to evaluate the causality between Gamma-Glu-Leu and the metabolic risk. Four SNPs are associated with serum Gamma-Glu-Leu levels, including rs12476238, rs56146133, rs2479714, and rs12229654. Out of them, rs12476238 exhibits the strongest association (Beta = -0.38, S.E. = 0.07 in discovery stage, Beta = -0.29, S.E. = 0.14 in validation stage, combined P-value = 1.04 × 10-8). Each of the four SNPs has a nominal association with at least one metabolic risk factor. Both rs12229654 and rs56146133 are associated with body mass index, waist circumference (WC), the ratio of WC to hip circumference, blood pressure, and triglyceride (5 × 10-5 < P < 0.05). rs56146133 also has nominal associations with fasting insulin, glucose, and insulin resistance index (5 × 10-5 < P < 0.05). Using the four SNPs serving as the instrumental SNPs of Gamma-Glu-Leu, the MR analyses revealed that higher Gamma-Glu-Leu levels are causally associated with elevated risks of multiple cardio-metabolic factors except for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (P > 0.05). Four SNPs (rs12476238, rs56146133, rs2479714, and rs12229654) may regulate the levels of serum Gamma-Glu-Leu. Higher Gamma-Glu-Leu levels are causally linked to cardio-metabolic risks. Future prospective studies on Gamma-Glu-Leu are required to explain its role in metabolic disorders.

Epigenetic BET reader inhibitor apabetalone (RVX-208) counters proinflammatory aortic gene expression in a diet induced obesity mouse model and in human endothelial cells

Background and aimsObese patients are at risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). A lipid-rich diet promotes arterial changes by inducing hypertension, oxidative stress, and inflammation. Bromodomain and extraterminal (BET) proteins contribute to endothelial and immune cell activation in vitro and in atherosclerosis mouse models. We aim to determine if BET inhibition can reduce lipid-rich diet-induced vascular inflammation in mice. MethodsBody weight, serum glucose and lipid levels were measured in mice fed a high-fat diet (HFD) or low-fat diet (LFD) for 6 weeks and at study termination. BET inhibitors apabetalone and JQ1 were co-administered with the HFD for additional 16 weeks. Aortic gene expression was analyzed post necropsy by PCR, Nanostring nCounter® Inflammation Panel and bioinformatics pathway analysis. Transcription changes and BRD4 chromatin occupancy were analyzed in primary human endothelial cells in response to TNFα and apabetalone. ResultsHFD induced weight gain, visceral obesity, high fasting blood glucose, glucose intolerance and insulin resistance compared to LFD controls. HFD upregulated the aortic expression of 47 genes involved in inflammation, innate immunity, cytoskeleton and complement pathways. Apabetalone and JQ1 treatment reduced HFD-induced aortic expression of proinflammatory genes. Congruently, bioinformatics predicted enhanced signaling by TNFα in the HFD versus LFD aorta, which was countered by BETi treatment. TNFα-stimulated human endothelial cells had increased expression of HFD-sensitive genes and higher BRD4 chromatin occupancy, which was countered by apabetalone treatment. ConclusionsHFD induces vascular inflammation in mice through TNFα signaling. Apabetalone treatment reduces this proinflammatory phenotype, providing mechanistic insight into how BET inhibitors may reduce CVD risk in obese patients.

Is there any difference in insulin resistance status between cases of benign and malignant ovarian neoplasms? A study on surrogate markers of insulin resistance in Indonesian non-diabetic women.

The association between insulin resistance (IR) and ovarian neoplasm is little known. The present study attempted to investigate the difference in clinicopathological characteristics, metabolic parameters, and IR prevalence between benign and malignant ovarian neoplasms. The cross-sectional study involved 52 non-diabetic women with benign (n=27) and malignant (n=25) diagnoses in a tertiary hospital in Indonesia. Fasting insulin level (FIL), homeostatic model assessment of IR and β-cell dysfunction (HOMA-IR and HOMA-β), fasting IR index (FIRI), and quantitative insulin sensitivity check index (QUICKI) were used as surrogate markers to evaluate IR. Parametric and nonparametric statistical tests were employed to analyze the different parameters between the two groups. Pearson or Spearman's rank test assessed the correlation between markers and clinical variables. Results revealed that patients with benign neoplasms were younger than those with malignant neoplasms (38.63 vs. 47.40 years; P=0.003) and had a higher median body mass index (BMI) than their counterparts (22.98 vs. 18.61 kg/m2; P=0.014). Different characteristics between benign and malignant neoplasm cases were found in menopausal status, ovary side affected, systolic blood pressure, and BMI classes. Endometrial cysts and mucinous carcinoma were the most often diagnosed benign and malignant neoplasms. Malignant neoplasms had a lower median HOMA-β score than benign neoplasms (49.33 vs. 75.79; P=0.011), indicating more severe β-cell dysfunction. No significant difference was observed in the prevalence of IR between benign and malignant ovarian neoplasms for the following values of each marker: FIL (25.9% vs. 12.0%), HOMA-IR (37.0% vs. 28.0%), FIRI (51.9% vs. 48.0%) and QUICKI (81.5% vs. 92.0%). The indicators of FIL, HOMA-IR, HOMA-β, FIRI, and QUICKI correlated with each other and confirmed the reliability of these surrogate markers for measuring IR status in ovarian neoplasms. In brief, benign ovarian neoplasms tended to have more IR when compared with malignant ovarian neoplasms. However, this difference was not statistically significant.

Diabetes and the Prostate: Elevated Fasting Glucose, Insulin Resistance and Higher Levels of Adrenal Steroids in Prostate Cancer.

Although epidemiological studies suggest a lower prostate cancer incidence rate in patients with type 2 diabetes, cancer survival is markedly reduced. Underlying mechanisms that connect the two diseases are still unclear. Potential links between type 2 diabetes and prostate cancer are hallmarks of the metabolic syndrome, such as hyperglycemia and dyslipidemia. Therefore, we explored the systemic metabolism of 103 prostate cancer patients with newly diagnosed and yet untreated prostate cancer compared to 107 healthy controls, who were carefully matched for age and BMI. Here, we report that patients with prostate cancer display higher fasting blood glucose levels and insulin resistance, without changes in insulin secretion. With respect to lipid metabolism, serum triglyceride levels were lower in patients with prostate cancer. In addition, we report increased adrenal steroid biosynthesis in these patients. Our results indicate that higher fasting glucose levels in patients with prostate cancer may be explained at least in part by insulin resistance, due to the enhanced synthesis of adrenal steroids.

Resveratrol impacts health in patients with diabetes mellitus and other metabolic conditions

Background Resveratrol is a polyphenol with many properties, including activity against glycation, oxidative stress, inflammation, neurodegeneration, carcinogenesis and aging. It appears to be a promising compound for the prevention and treatment of metabolic diseases. The aim of this review is to summarize the results of the latest clinical trials that concern effects of resveratrol in diabetes mellitus type 1 and 2 and its complications - diabetic foot ulcers, diabetic nephropathy and non-alcoholic fatty liver disease. Aim of the study Based on in vitro studies and animal models, it has been observed that resveratrol reverses the factors causing premature death: obesity, hypertension, and hyperlipidemia. Because of its anti-inflammatory, antioxidant, cardioprotective and blood lowering glucose effects, it appears to be a promising compound for the treatment of metabolic conditions. The review presents different clinical trials concerning the efficiency of resveratrol supplementation in patients with diabetes mellitus and metabolic syndrome and their complications. Most studies focused on assessing the effect of resveratrol supplementation as an adjunctive treatment of diabetes mellitus type 2 and in this group of patients it gave the best results causing reduction of fasting glucose levels, fasting insulin concentration, insulin resistance and improvement of insulin sensitivity and lipid profiles. Conclusions Resveratrol remains a potential drug in the treatment of metabolic diseases like diabetes mellitus. However, the results of the conducted trials are inconscient. More research is needed to confirm the effectiveness of resveratrol supplementation in treating diabetes, its complications and other metabolic conditions.

Effect of Yijinjing combined with elastic band exercise on muscle mass and function in middle-aged and elderly patients with prediabetes: A randomized controlled trial.

This study investigated the effect of Yijinjing combined with elastic band exercise on muscle mass and muscle function in patients with prediabetes. This study was a randomized controlled trial designed in parallel (Chinese Clinical Trial Registry: ChiCTR2000039049). Participants with prediabetes (n = 47) were randomly divided into control (n = 21, 63.5 ± 4.7 years,16 females) and exercise (n = 26, 62.0 ± 5.0 years, 20 females) groups. The former maintained their original lifestyle, and the latter received Yijinjing combined with elastic band exercise five times a week for 6 months. All the outcome measures were assessed immediately at baseline, after 3- and 6-month intervention. After 6-month of the exercise, the body weight, body mass index, leg fat mass, gynoid fat mass, and total body fat mass in exercise group were significantly decreased compared with those at baseline (p < 0.05). Compared with those at baseline, total lean mass decreased at 3 and 6 months in both groups. The total muscle mass loss in the exercise group was always less than that in control group at all time periods, but the difference was not statistically significant. Handgrip strength, gait speed, reaction time, leg power, eye-closed and single-legged standing, and sit-and-reach were significantly improved for the exercise group at 3 and 6 months (p < 0.05). Gait speed and reaction time between both groups at 3 and 6 months were significant different (p < 0.05), and leg power at 6 months (p < 0.05). Compared with baseline, the reaction time of control group at six months was significantly improved (p < 0.05), and no other significant changes were observed. Compared with those at baseline, fasting plasma glucose, 2-h post-meal plasma glucose, fasting insulin, total cholesterol, and insulin resistance index in exercise group gradually decreased, and growth hormone was gradually increased with significance at 6 months (p < 0.05). 25-hydroxyvitamin D gradually and significantly increased in both groups at 3 and 6 months (p < 0.05). But two groups' testosterone levels weren't significant change. Yijinjing combined with elastic band exercise can substantially reduce the body weight and body fat content of middle-aged and elderly patients with Prediabetes, improve muscle function and growth hormone secretion, and delay muscle mass reduction and diabetes development. [http://www.chictr.org.cn/showproj.aspx?proj=62753], identifier [ChiCTR2000039049].

Impact of anthocyanin component and metabolite of Saskatoon berry on gut microbiome and relationship with fecal short chain fatty acids in diet-induced insulin resistant mice

Previous studies demonstrated that oral administration of Saskatoon berry powder (SBp) reduced fasting plasma glucose (FPG), insulin resistance, lipids, and inflammatory markers in diet-induced insulin resistant rodents. Mechanism for the beneficial effects of SB remains unclear. The present study examined the effects of high fat-high sucrose (HFHS) diet supplemented with or without 5% SBp, cyanidin-3-glucoside (C3G, an anthocyanin rich in SBp) at a dosage of C3G in 5% SBp, or equimolar concentration of protocatechuic acid (PCA, a relatively stable metabolite of C3G) for 11 weeks on FPG, cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), circulatory inflammatory markers, fecal microbiota, and short chain fatty acids in mice. HFHS diet significantly enhanced FPG, insulin, HOMA-IR, lipids and inflammatory markers, but reduced the abundance of fecal Bacteroidetes, Muribaculaceae and propionate compared to low fat diet. Supplementation of SBp, C3G or PCA significantly attenuated HFHS diet induced metabolic and inflammatory markers, and increased the abundances of fecal Muribaculaceae and propionate compared to HFHS diet alone. The abundances of fecal Muribaculaceae negatively correlated with FPG, lipids, HOMA-IR and inflammatory markers in the mice. The abundances of fecal propionate positively correlated with fecal Muribaculaceae and negatively correlated with the metabolic and inflammatory markers. The findings suggest that C3G in SBp and PCA contribute to the metabolic and anti-inflammatory effect of SBp in mice. The increases in fecal Muribaculaceae and propionate may play important regulatory roles in the anti-diabetic and anti-inflammatory benefits of SBp, C3G, and PCA in mice.

Exploring interindividual differences in fasting and postprandial insulin sensitivity adaptations in response to sprint interval exercise training

ABSTRACT Previous studies have concluded that wide variance in changes in insulin sensitivity markers following exercise training demonstrates heterogeneity in individual trainability. However, these studies frequently don’t account for technical, biological, and random within-subject measurement error. We used the standard deviation of individual responses (SDIR) to determine whether interindividual variability in trainability exists for fasting and postprandial insulin sensitivity outcomes following low-volume sprint interval training (SIT). We pooled data from 63 untrained participants who completed 6 weeks of SIT (n = 49; VO2max: 35 (7) mL⋅kg−1⋅min−1) or acted as no-intervention controls (n = 14; VO2max: 34 (6) mL⋅kg−1⋅min−1). Fasting and oral glucose tolerance test (OGTT)-derived measures of insulin sensitivity were measured pre- and post-intervention. SDIR values were positive and exceeded a small effect size threshold for changes in fasting glucose (SDIR = 0.27 [95%CI 0.07,0.38] mmol⋅L−1), 2-h OGTT glucose (SDIR = 0.89 [0.22,1.23] mmol⋅L−1), glucose area-under-the-curve (SDIR = 66.4 [−81.5,124.3] mmol⋅L−1⋅120min−1) and The Cederholm Index (SDIR = 7.2 [−16.0,19.0] mg⋅l2⋅mmol−1⋅mU−1⋅min−1), suggesting meaningful individual responses to SIT, whilst SDIR values were negative for fasting insulin, fasting insulin resistance and insulin AUC. For all variables, the 95% CIs were wide and/or crossed zero, highlighting uncertainty about the existence of true interindividual differences in exercise trainability. Only 2–22% of participants could be classified as responders or non-responders with more than 95% certainty. Our findings demonstrate it cannot be assumed that variation in changes in insulin sensitivity following SIT is attributable to inherent differences in trainability, and reiterate the importance of accounting for technical, biological, and random error when examining heterogeneity in health-related training adaptations. Highlights This study tested whether true interindividual variability exists for changes in insulin sensitivity and glyceamic control following 6-weeks of low volume sprint interval training (SIT). The high level of technical, biological, and random error associated with repeated measurements of insulin sensitivity and glycaemic control, means we can neither confidently conclude that there is evidence of true interindividual differences in the trainability of these outcomes following SIT, nor confidently identify responders or non-responders for such parameters. Researchers contrasting responders vs. non-responders for a given parameter, either to understand mechanisms of adaptation and/or develop physiological/genetic/epigenetic predictors of response, need to be aware that identification of responders and non-responders with sufficient certainty may not be achievable for parameters with a high level of technical, biological, and random error.

Zinc normalizes hepatic lipid handling via modulation of ADA/XO/UA pathway and caspase 3 signaling in highly active antiretroviral therapy-treated Wistar rats

BackgroundAlthough highly active antiretroviral therapy (HAART) is effective in the management of HIV, it has been reported to induce hepatic injury and non-alcoholic fatty liver (NAFLD). However, there is a lack of data on the roles of the adenosine deaminase (ADA)/xanthine oxidase (XO)/uric acid (UA) pathway and caspase 3 signaling in HAART-induced NAFLD. Also, whether or not zinc confers protection against HAART-induced NAFLD is not known. AimThis study evaluated the involvement of the ADA/XO/UA pathway and caspase 3 signaling in HAART-induced hepatic lipid accumulation. It also evaluated the possible protective effect of zinc in HAART-induced hepatic lipid accumulation and injury. MethodsThirty two male Wistar rats (n = 8/group) were assigned into four groups namely; vehicle-treated (p.o), zinc-treated (3 mg/kg/day of elemental zinc; p.o), HAART-treated (a cocktail of 52.9 mg/kg of Efavirenz, 26.48 mg/kg of Lamivudine, and 26.48 mg/kg of Tenofovir; p.o), and HAART + zinc-treated groups. The treatment lasted for 8 weeks. ResultsHAART administration led to increased body weight and hepatic weight, but unaltered hepatic organo-somatic index. HAART exposure also resulted in impaired glucose homeostasis, evidenced by increased fasting blood glucose, hyperinsulinemia, and insulin resistance (IR), increased plasma and hepatic cholesterol and triglycerides, and impaired hepatic function as depicted by elevated hepatic injury markers and reduced glycogen synthase activity and glycogen content. These findings were accompanied by increased plasma and hepatic ADA and XO activities, UA and malondialdehyde levels, inflammatory markers, and caspase 3 activities. However, HAART suppressed plasma and hepatic antioxidant defenses. Furthermore, HAART distorted hepatic histoarchitecture and reduced hepatic sinusoidal diameter. Co-administration of zinc with HAART normalized HAART-induced alterations. ConclusionsThese findings showed that downregulation of the ADA/XO/UA pathway and caspase 3 signalings may rescue the liver from HAART-induced lipid accumulation and injury.

Impact of Germinated Brown Rice and Brown Rice on Metabolism, Inflammation, and Gut Microbiome in High Fat Diet-Induced Insulin Resistant Mice.

The constituents of germinated brown rice (GBR), brown rice (BRR), and white rice (WHR) and their impact on metabolism, inflammation, and gut microbiota in high fat (HF) diet-fed mice were examined. The contents of total fiber and γ-aminobutyric acid in BRR and GBR were higher than that in WHR (p < 0.05). Male C57 BL/6J mice received HF diet+26 g% of WHR, BRR, or GBR for 12 weeks. BRR and GBR comparably reduced HF diet-induced increases in fasting plasma glucose, lipids, insulin resistance, and inflammatory markers compared to WHR (p < 0.01). The abundance of fecal Bacteroidetes in mice fed HF+GBR or HF+BRR was higher than in HF+WHR-fed mice (p < 0.05). The abundance of fecal Lactobacillus gasseri in GBR-fed mice was greater than that in WHR- or BRR-fed mice (p < 0.05). The results indicated that GBR or BRR attenuated hyperglycemia, insulin resistance, and inflammation in mice. HF+GBR, but not HF+BRR, increased a probiotic bacteria in the gut.

Interaction between MTNR1B polymorphisms and lifestyle intervention on pregnancy outcomes

Abstract Background Interactions between polymorphisms of the melatonin receptor 1B gene (MTNR1B) and lifestyle intervention for gestational diabetes have been described. Whether these are specific for physical activity or healthy eating intervention is unknown. Objectives To assess the interaction between MTNR1B rs10830962 and rs10830963 polymorphisms and lifestyle interventions during pregnancy. Methods Women with a BMI of ≥ 29 kg/m2 (n = 436) received counseling on healthy eating (HE), physical activity (PA) or both. The control group received usual care. The analysis had a factorial design with comparison of HE versus no HE and PA versus no PA. Maternal outcomes at 24-28 weeks were gestational weight gain (GWG), maternal fasting glucose, insulin, insulin resistance (HOMA-IR), and development of GDM. Interaction between receiving either HE or PA intervention and genotypes of both rs10830962 and rs10830963 was assessed using multilevel regression analysis. Results GDM risk was increased in women homozygous for the G allele of rs10830962 or rs10830963 (OR 2.60 [95% CI 1.34, 5.06] and 2.83 [1.24, 6.47], respectively). Significant interactions between rs10830962 and interventions were found: In women homozygous for the G allele, but not in the other genotypes, the PA intervention reduced maternal fasting insulin (beta -0.16 [95%CI -0.33, 0.02], p = 0.08) and HOMA-IR (-0.17 [-0.35, 0.01], p = 0.06). In heterozygous women, HE intervention had no effect, whereas in women homozygous for the C allele, HE intervention reduced GWG (-1.6 kg [-2.4, -0.8]). Discussion In women homozygous for the risk allele of MTNR1B rs10830962, GDM risk was increased and PA intervention might be more beneficial than HE intervention for reducing maternal insulin resistance. Key messages

Effects of vitamin D on insulin resistance and fasting blood glucose in pregnant women with insufficient or deficient vitamin D: a randomized, placebo-controlled trial

BackgroundGestational diabetes is one of the most common metabolic disorders during pregnancy. Some studies have reported the effect of vitamin D deficiency on the incidence of this disorder. Therefore, the purpose of the present study was to determine the effect of vitamin D supplementation on fasting blood glucose (FBG) levels, fasting blood insulin (FBI) levels and insulin resistance index (HOMA-IR) (primary outcomes) and symptoms of depression, musculoskeletal pain, frequency of gestational diabetes and the frequency of abortion (secondary outcomes).MethodsIn this triple-blind randomized controlled trial, 88 pregnant women at 8–10 weeks of pregnancy who had the vitamin D of less than 30 ng/ml were randomly assigned to the vitamin D group (n = 44) and control group (n = 44) using block randomization. The vitamin D group received 4,000 units of vitamin D tablets daily and the control group received placebo tablets for 18 weeks. Independent t-test, Mann-Whitney U and ANCOVA tests were used to analyze the data.ResultsAfter the intervention, there was no statistically significant difference between the two groups in terms of FBG (P = 0.850), FBI (P = 0.353), HOMA-IR (P = 0.632), mean score of depressive symptoms (P = 0.505), frequency of gestational diabetes (P = 0.187) and frequency of abortion (P = 1.000) and there was only a difference in terms of serum vitamin D level (P = 0.016) and musculoskeletal pain including knee pain (P = 0.025), ankle pain (P < 0.001) and leg pain (P < 0.001).ConclusionVitamin D could improve the musculoskeletal pain in pregnant women but couldn’t decrease FBG, FBI, HOMA-IR, depression symptoms score, incidence of GDM and abortion.Trial registration:Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N59. Date of registration: 4/11/2020. URL: https://en.irct.ir/user/trial/50973/view; Date of first registration: 21/11/2020.

The Genetic Basis for the Increased Prevalence of Metabolic Syndrome among Post-Traumatic Stress Disorder Patients.

Post-traumatic stress disorder (PTSD) is a highly debilitating psychiatric disorder that can be triggered by exposure to extreme trauma. Even if PTSD is primarily a psychiatric condition, it is also characterized by adverse somatic comorbidities. One illness commonly co-occurring with PTSD is Metabolic syndrome (MetS), which is defined by a set of health risk/resilience factors including obesity, elevated blood pressure, lower high-density lipoprotein cholesterol, higher low-density lipoprotein cholesterol, higher triglycerides, higher fasting blood glucose and insulin resistance. Here, phenotypic association between PTSD and components of MetS are tested on a military veteran cohort comprising chronic PTSD presentation (n = 310, 47% cases, 83% male). Consistent with previous observations, we found significant phenotypic correlation between the various components of MetS and PTSD severity scores. To examine if this observed symptom correlations stem from a shared genetic background, we conducted genetic correlation analysis using summary statistics data from large-scale genetic studies. Our results show robust positive genetic correlation between PTSD and MetS (rg[SE] = 0.33 [0.056], p = 4.74E-09), and obesity-related components of MetS (rg = 0.25, SE = 0.05, p = 6.4E-08). Prioritizing genomic regions with larger local genetic correlation implicate three significant loci. Overall, these findings show significant genetic overlap between PTSD and MetS, which may in part account for the markedly increased occurrence of MetS among PTSD patients.

In-utero HIV exposure and cardiometabolic health among children 5-8 years: findings from a prospective birth cohort in South Africa.

To evaluate if in-utero HIV exposure is associated with adverse cardiometabolic health outcomes at 5-8 years of age. Prospective cohort study. We enrolled a random sample of HIV-exposed but uninfected (HEU) and HIV-unexposed children from the Drakenstein Child Health study, a longitudinal birth cohort study in Cape Town, South Africa, in a cardiometabolic health pilot study. Outcomes were assessed by trained study staff and included: anthropometry, body composition and size, blood pressure, fasting plasma glucose, HbA1c, lipids, and insulin resistance using HOMA-IR. We used multivariable linear and log-binomial regression to estimate associations between HIV-exposure and cardiometabolic outcomes, adjusted for child age, sex, height, body size, and maternal factors as appropriate. We included 260 children (HEU n = 100, HIV-unexposed n = 160). HEU children had older mothers (median age 30 vs. 26 years), with minimal differences in gestational age and size at birth by HIV-exposure status. In multivariable analyses, HEU children had lower weight-for-age (mean difference -0.35, 95% confidence interval -0.66, -0.05), and height-for-age (mean difference -0.29, 95% confidence interval -0.56, -0.03; z-scores). There were no differences in adiposity, impaired glucose metabolism, or lipid levels by HIV-exposure status. Overall, 12% of children had blood pressure more than 90th percentile, with no differences by HIV-exposure status. Overall, there were few differences in cardiometabolic outcomes between HEU and HIV-unexposed children in this South African cohort. Although these findings are reassuring, monitoring of cardiometabolic health is important as HEU and HIV-unexposed children enter adolescence and cardiometabolic risk trajectories become established.

The impact of ethnicity and intra-pancreatic fat on the postprandial metabolome response to whey protein in overweight Asian Chinese and European Caucasian women with prediabetes.

The "Thin on the Outside Fat on the Inside" TOFI_Asia study found Asian Chinese to be more susceptible to Type 2 Diabetes (T2D) compared to European Caucasians matched for gender and body mass index (BMI). This was influenced by degree of visceral adipose deposition and ectopic fat accumulation in key organs, including liver and pancreas, leading to altered fasting plasma glucose, insulin resistance, and differences in plasma lipid and metabolite profiles. It remains unclear how intra-pancreatic fat deposition (IPFD) impacts TOFI phenotype-related T2D risk factors associated with Asian Chinese. Cow's milk whey protein isolate (WPI) is an insulin secretagogue which can suppress hyperglycemia in prediabetes. In this dietary intervention, we used untargeted metabolomics to characterize the postprandial WPI response in 24 overweight women with prediabetes. Participants were classified by ethnicity (Asian Chinese, n=12; European Caucasian, n=12) and IPFD (low IPFD < 4.66%, n=10; high IPFD ≥ 4.66%, n=10). Using a cross-over design participants were randomized to consume three WPI beverages on separate occasions; 0g (water control), 12.5g (low protein, LP) and 50g (high protein, HP), consumed when fasted. An exclusion pipeline for isolating metabolites with temporal (T0-240mins) WPI responses was implemented, and a support vector machine-recursive feature elimination (SVM-RFE) algorithm was used to model relevant metabolites by ethnicity and IPFD classes. Metabolic network analysis identified glycine as a central hub in both ethnicity and IPFD WPI response networks. A depletion of glycine relative to WPI concentration was detected in Chinese and high IPFD participants independent of BMI. Urea cycle metabolites were highly represented among the ethnicity WPI metabolome model, implicating a dysregulation in ammonia and nitrogen metabolism among Chinese participants. Uric acid and purine synthesis pathways were enriched within the high IPFD cohort's WPI metabolome response, implicating adipogenesis and insulin resistance pathways. In conclusion, the discrimination of ethnicity from WPI metabolome profiles was a stronger prediction model than IPFD in overweight women with prediabetes. Each models' discriminatory metabolites enriched different metabolic pathways that help to further characterize prediabetes in Asian Chinese women and women with increased IPFD, independently.

Effects of Exercise Training on Inflammatory and Cardiometabolic Risk Biomarkers in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The interaction between type 2 diabetes mellitus (T2DM) and cardiometabolic morbidity and mortality stems from the progressive nature of inflammation underpinning both diseases. Exercise training is considered an effective treatment strategy for T2DM and cardiometabolic diseases. The current systematic review and meta-analysis investigated the effects of exercise training on inflammatory and cardiometabolic risk biomarkers in patients with T2DM. Electronic databases (PubMed/Medline, Embase, Cochrane Library, CINAHL, Google Scholar, Scopus, and Web of Science) were searched for randomized controlled trials (RCTs) from inception to January 2022. We used random effects models to estimate weighted mean differences with 95% confidence intervals. Twenty-five RCTs were included (N = 1257 participants; mean age = 52years). Included studies had moderate to good overall methodological quality (TESTEX = 9 (range 7-13). Meta-analysis indicated that exercise training significantly increased adiponectin and decreased fasting insulin, homeostatic model assessment for insulin resistance, tumor necrosis factor-α, interleukin-6, and C-reactive protein (ps ≤ 0.05). Subgroup analysis by type of training indicated that aerobic exercise had the most consistent beneficial effects as compared to other types of exercise training; however, there was high heterogeneity among studies. Different types of exercise training increase adiponectin levels and decrease pro-inflammatory cytokines such as TNF-α, IL-6, and CRP, as well as fasting insulin and insulin resistance markers in patients with T2DM. However, these effects were not beneficial for more commonly measured cardiometabolic risk factors (i.e., lipid profiles). Additional relevant clinical trials are required to confirm these results. This systematic review and meta-analysis was prospectively registered in the PROSPERO database (CRD42022307396).

Cross-sectional and longitudinal associations of urinary zinc with glucose-insulin homeostasis traits and type 2 diabetes: Exploring the potential roles of systemic inflammation and oxidative damage in Chinese urban adults

The link between zinc exposure and glucose metabolism or the development of type 2 diabetes (T2D) is controversial, and underlying mechanisms are unclear. This study aimed to explore the associations of zinc exposure with glucose-insulin homeostasis traits and the long-term effects of zinc on the development of T2D, and further to estimate the potential roles of inflammation and oxidative damage in such relationships. We investigated 3890 urban adults from the Wuhan-Zhuhai cohort, and followed up every three years. Mixed linear model was applied to estimate dose-response associations between urinary zinc and glycemia traits [fasting plasma insulin (FPI), fasting plasma glucose (FPG), insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and β-cell dysfunction (homeostasis model assessment of β-cell function, HOMA-B)], as well as zinc and biomarkers for systemic inflammation (C-reactive protein) and oxidative damage (8-isoprostane and 8-hydroxy-2′-deoxyguanosine). Logistic regression model and Cox regression model were conducted to evaluate the relationships between urinary zinc and prevalence and incidence of T2D, respectively. We further performed mediation analysis to assess the roles of inflammation and oxidative damage biomarkers in above associations. At baseline, we observed significant dose-response relationships of elevated urinary zinc with increased FPI, FPG, HOMA-IR, and T2D prevalence and decreased HOMA-B, and such associations could be strengthened by increased C-reactive protein, 8-isoprostane, and 8-hydroxy-2′-deoxyguanosine. Elevated C-reactive protein significantly mediated 9.09% and 17.67% of the zinc-related FPG and HOMA-IR increments, respectively. In longitudinal analysis, a significantly positive association between urinary zinc and T2D incidence was observed among subjects with persistent high urinary zinc levels when compared with those with persistent low zinc levels. Our results suggested that high levels of zinc exposure adversely affected on glucose-insulin homeostasis and further contributed to increased risk of T2D cross-sectionally and longitudinally. Moreover, inflammatory response might play an important role in zinc-related glucose metabolic disorder.