Changes In Homeostasis Model Assessment Of Insulin Resistance Research Articles

Vitamin D supplementation on prediabetic adults with vitamin D deficiency: a double-blind placebo-controlled randomized clinical trial

Hypovitaminosis D (<20 ng/mL) is thought to increase insulin resistance and meta-inflammation contributing to the pathogenesis of diabetes mellitus (DM). Correcting vitamin D deficiency in people with prediabetes might halt its progression to DM. The aim of this study was to examine the effect of vitamin D supplementation on insulin resistance, glycemic status, and inflammation in prediabetic adults with vitamin D deficiency. This doubleblind randomized placebo-controlled trial was done among 27 newly detected prediabetic adults with hypovitaminosis D randomly assigned to 60,000 IU of vitamin D weekly for eight weeks followed by monthly for the next four months or placebo along with lifestyle modification in both groups [vitamin D (n= 14) vs. Placebo (n=13). They were comparable in terms of sex, age and borlymass index. Glycemic status, fasting plasma glucose (FPG) and Hemoglobin A1C (HbA1C), insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) and inflammatory marker high sensitivity C reactive protein (hs-CRP) were measured at baseline and after six months of intervention. Vitamin D levels (ng/mL) increased in both groups from baseline (vitamin D vs. placebo: 12.2±5.9 vs. 3.9±3.5, mean±SD). FPG (mmol/L) significantly decreased in the Vitamin D group (before vs. after: 5.9±0.6 vs. 5.5±0.7, P=0.016, mean±SD), whereas HbA1C (%) and hs- CRP (mg/L) significantly increased in the placebo group (before vs. after- HbA1C: 5.8±0.3 vs. 6.0±0.4, P<0.001; hs-CRP: 5.0±4.4 vs. 5.6±4.9, P=0.039, mean±SD). Percent changes in glycemic status, HOMA-IR, and hs-CRP were statistically similar between the groups. Our study failed to demonstrate the positive effects of vitamin D supplementation on reducing glucose, insulin resistance, or inflammatory marker in prediabetic adult patients with hypovitaminosis D. BSMMU J 2022; 15(3): 167-174

Very Low-Carbohydrate High-Fat Diet Improves Risk Markers for Cardiometabolic Health More Than Exercise in Men and Women With Overfat Constitution: Secondary Analysis of a Randomized Controlled Clinical Trial

PurposeThis randomized controlled parallel-group study examined the effects of a very low-carbohydrate high-fat (VLCHF) diet and high-intensity interval training (HIIT) program over 12-weeks on cardiometabolic risk factors in individuals with overfat constitution.MethodsNinety-one participants out of 109 completed the study. The participants were randomly allocated to the HIIT (N = 22), VLCHF (N = 25), VLCHF+HIIT (N = 25), or control (N = 19) groups for 12 weeks. Fasting plasma samples were collected before the intervention and after 4 and 12 weeks. The analyzed outcomes included complete blood count, glucose, insulin, glycated hemoglobin, triglycerides (TG), cholesterol, high- and low-density lipoprotein (HDL-C and LDL-C), lipoprotein(a), adiponectin (Adpn), leptin (Lep), tumor necrosis factor α (TNF-α), other interleukins (hs-IL-6, IL-1β, and IL-10), and IL-1RA. The homeostasis model assessment of insulin resistance (HOMA-IR), Adpn/Lep ratio, TG/HDL-C ratio, and TyG index were calculated and analyzed. Blood pressure was measured before the intervention, after 4, 8, and 12 weeks (ClinicalTrials.gov: NCT03934476).ResultsAbsolute changes in HOMA-IR, Adpn/Lep ratio, LDL-C, and diastolic blood pressure after 12 weeks differed by study groups (p < 0.05). The most pronounced changes were revealed in the VLCHF (ΔM [95% CI]; HOMA-IR: −0.75 [−1.13; −0.55]; Adpn/Lep: 9.34 [6.33; 37.39]; LDL-C: 0.06 [−0.12; 0.50] mmol/l) and VLCHF+HIIT (HOMA-IR: −0.44 [−1.14; 0.12]; Adpn/Lep: 4.26 [2.24; 13.16]; LDL-C: 0.25 [−0.04; 0.50] mmol/l) groups.ConclusionsA 12-week VLCHF diet intervention in individuals with overfat constitution is effective for favorable changes in HOMA-IR (compared to HIIT), Adpn/Lep ratio, and diastolic blood pressure. HIIT, or HIIT combined with the VLCHF diet, had no additional benefits for the analyzed variables. No adverse side effects were observed.

Effect of acupuncture and metformin on insulin sensitivity in women with polycystic ovary syndrome and insulin resistance: a three-armed randomized controlled trial.

STUDY QUESTIONDoes acupuncture improve insulin sensitivity more effectively than metformin or sham acupuncture in women with polycystic ovary syndrome (PCOS) and insulin resistance (IR)?SUMMARY ANSWERAmong women with PCOS and IR, acupuncture was not more effective than metformin or sham acupuncture in improving insulin sensitivity.WHAT IS KNOWN ALREADYUncontrolled trials have shown that acupuncture improved insulin sensitivity with fewer side effects compared with metformin in women with PCOS and IR. However, data from randomized trials between acupuncture and metformin or sham acupuncture are lacking.STUDY DESIGN, SIZE, DURATIONThis was a three-armed randomized controlled trial enrolling a total of 342 women with PCOS and IR from three hospitals between November 2015 and February 2018, with a 3-month follow-up until October 2018.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen aged from 18 to 40 years with PCOS and homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.14 were randomly assigned (n = 114 per group) to receive true acupuncture plus placebo (true acupuncture), metformin plus sham acupuncture (metformin, 0.5 g three times daily) or sham acupuncture plus placebo (sham acupuncture) for 4 months, with an additional 3-month follow-up. True or sham acupuncture was given three times per week, and 0.5 g metformin or placebo was given three times daily. The primary outcome was change in HOMA-IR from baseline to 4 months after baseline visit. Secondary outcomes included changes in the glucose AUC during an oral glucose tolerance test, BMI and side effects at 4 months after baseline visit.MAIN RESULTS AND THE ROLE OF CHANCEAfter 4 months of treatment, the changes of HOMA-IR were –0.5 (decreased 14.7%) in the true acupuncture group, –1.0 (decreased 25.0%) in the metformin group and –0.3 (decreased 8.6%) in the sham acupuncture group, when compared with baseline. True acupuncture is not as effective as metformin in improving HOMA-IR at 4 months after baseline visit (difference, 0.6; 95% CI, 0.1–1.1). No significant difference was found in change in HOMA-IR between true and sham acupuncture groups at 4 months after baseline visit (difference, –0.2; 95% CI, –0.7 to 0.3). During the 4 months of treatment, gastrointestinal side effects were more frequent in the metformin group, including diarrhea, nausea, loss of appetite, fatigue, vomiting and stomach discomfort (31.6%, 13.2%, 11.4%, 8.8%, 14.0% and 8.8%, respectively). Bruising was more common in the true acupuncture group (14.9%).LIMITATIONS, REASONS FOR CAUTIONThis study might have underestimated the sample size in the true acupuncture group with 4 months of treatment to enable detection of statistically significant changes in HOMA-IR with fixed acupuncture (i.e. a non-personalized protocol). Participants who withdrew because of pregnancy did not have further blood tests and this can introduce bias.WIDER IMPLICATIONS OF THE FINDINGSTrue acupuncture did not improve insulin sensitivity as effectively as metformin in women with PCOS and IR, but it is better than metformin in improving glucose metabolism (which might reduce the risk of type 2 diabetes) and has less side effects. Metformin had a higher incidence of gastrointestinal adverse effects than acupuncture groups, and thus acupuncture might be a non-pharmacological treatment with low risk for women with PCOS. Further studies are needed to evaluate the effect of acupuncture combined with metformin on insulin sensitivity in these women.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by grants 2017A020213004 and 2014A020221060 from the Science and Technology Planning Project of Guangdong Province. The authors have no conflicts of interest.TRIAL REGISTRATION NUMBERClinicaltrials.gov number: NCT02491333.TRIAL REGISTRATION DATE8 July 2015.DATE OF FIRST PATIENT’S ENROLLMENT11 November 2015.

Electrolyzed hydrogen-rich water for oxidative stress suppression and improvement of insulin resistance: a multicenter prospective double-blind randomized control trial.

Electrolyzed hydrogen-rich water (EHW) is known to have suppressive effects on oxidative stress (OS). However, its benefit in type 2 diabetes mellitus (T2DM) remains unclear. This study aimed to investigate the effect of EHW on T2DM. This was a multicenter, prospective, double-blind, randomized controlled trial of 50 patients with T2DM who were assigned to the EHW or filtered water (FW) groups. The primary endpoint was changes in insulin resistance (IR) evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). OS markers such as urinary 8-hydroxy-2'-deoxyguanosine excretion (8-OHdG), plasma diacron-reactive oxygen metabolites (d-ROM), and plasma biological antioxidant potential (BAP) and other clinical data, including serum lactate concentration (lactate), were evaluated. There were no significant differences in the changes in HOMA-IR between the EHW and FW groups. However, lactate levels decreased significantly in the EHW group, and this decrease was significantly correlated with a reduction in HOMA-IR, fasting plasma glucose, and fasting plasma insulin level. Serum lactate level also significantly correlated to decreased insulin bolus secretion after 90min with glucose loading in the EHW subjects with HOMA-IR > 1.73. No EHW treatment-related adverse effects were observed. There were no significant effect of EHW in the change in HOMA-IR in this study; larger-scale and longer-term study are needed to verify the effects of EHW in T2DM patients. The online version contains supplementary material available at 10.1007/s13340-021-00524-3.

Effect of moderate-intensity seated exercise on the management of metabolic outcomes in hypertensive individuals with or without exercise habits

BackgroundWe aimed to evaluate the effect of moderate-intensity seated exercise on metabolic outcomes in hypertensive individuals with or without exercise habits. MethodsForty-two hypertensive individuals volunteered for this study and were classified into 3 groups by their habits and place for moderate-intensity exercise prior to this study: NONE (<2 days/week or no exercise; n = 13), HOME (≥30 min/day and ≥2 days/week at home; n = 15), and GYM (≥30 min/day and ≥2 days/week at a hospital gym; n = 14). They performed their daily activities as usual and seated exercise (stepping and stepping with trunk rotation; a range of 11–13 on the Borg rating of perceived exertion scale) for at least 15 min/day and at least 3 days/week for 12 weeks. ResultsThirty-five participants (age: 67.7 ± 5.9 years) completed the study, and there was no difference among the 3 groups regarding weekly exercise. The homeostasis model assessment of insulin resistance (HOMA-IR) value in the NONE group was significantly higher than that in the GYM group at baseline (p < 0.05), but it decreased significantly after 12 weeks (from 2.2 ± 0.8 to 1.7 ± 0.7, p < 0.05). Changes in HOMA-IR in the NONE group after 12 weeks was greater than that in the HOME and GYM groups (both p < 0.01). The HOME and GYM groups showed no significant changes in any of the variables. ConclusionModerate-intensity seated exercise may be an effective strategy to improve insulin resistance in hypertensive individuals without exercise habits.

Impact of 3-year changes in fasting insulin and insulin resistance indices on incident hypertension: Tehran lipid and glucose study

BackgroundTo examine the association between changes in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and insulin-glucose ratio (IGR) levels, over approximately 3 years with incident hypertension.MethodsA total of 2814 Iranian participants (1123 men) without hypertension and known diabetes at baseline and the first examination were followed for a median of 6.32 years. The associations between quartiles of changes in fasting insulin and IR indices with incident hypertension were assessed using multivariate Cox proportional hazard regression analyses with first quartile as reference. The models were adjusted for baseline values of insulin or each IR index, and age, sex, smoking, physical activity, educational levels, marital status, history of cardiovascular diseases, baseline levels of systolic and diastolic blood pressures, estimated glomerular filtration rate, triglycerides, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose (only for insulin change) and both body mass index (BMI) per se, and its change. Akaike’s information criteria (AIC) was applied as indicator for goodness of fit of each predictive model. The discrimination ability of models was calculated using the Harrell’s C statistic.ResultsDuring the study, 594 incident cases of hypertension (253 men) were identified. The 4th quartile of changes in insulin, HOMA-IR, and IGR showed hazard ratios (95% confidence interval) of 1.31 (1.01–1.69), 1.18 (0.92–1.52), and 1.53 (1.18–1.98) for hypertension, respectively, in fully-adjusted models. Changes in fasting insulin levels and IR indices showed significant increasing trends for incident hypertension, moving from 1st to 4th quartiles (all P-values < 0.05). Focusing on model fitness, no superiority was found between changes in fasting insulin, HOMA-IR, and IGR to predict incident hypertension. The discriminatory powers of changes in fasting insulin and IR indices as assessed by C index were similar (i.e. about 80%).ConclusionChanges in fasting insulin and IR indices were significantly associated with developing hypertension among normotensive population even after considering BMI changes.

Effects of probiotic yogurt on glycemic indexes and endothelial dysfunction markers in patients with metabolic syndrome.

The relationship between gut microflora and metabolic syndrome components such as obesity, low-grade chronic systemic inflammation, dyslipidemia, and altered glucose metabolism is now acknowledged. The aim of this study was to assess the effects of probiotic yogurt on glycemic indexes and endothelial dysfunction markers in patients with metabolic syndrome. This was a randomized, double-blind, placebo-controlled clinical trial of 44 patients with metabolic syndrome (22 men and 22 women), who were 20 to 65 y of age. The patients were assigned to either a treatment or control group and consumed 300g/d of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 or a regular yogurt for 2 mo, respectively. Each group contained 22 participants. Fasting blood glucose and serum insulin was performed to derive homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity (Quicki), and HOMA of β-cell function (HOMA- β). In addition, markers of vascular cell adhesion molecule cell (VCAM)-1, intercellular adhesion molecule cell (ICAM)-1, and plasminogen activator inhibitor (PAI)-1 were measured to evaluate endothelial function at the beginning and at the end of the study. Consumption of probiotic yogurt resulted in a significant reduction in the level of blood glucose and VCAM-1. Significant changes in PAI-1, VCAM-1, insulin, HOMA-IR, and Quicki were observed in the probiotic yogurt group after intervention compared with baseline. Consumption of probiotic yogurt improved fasting blood glucose and partly modified serum endothelial function markers. These results suggest that regular intake of probiotic yogurt may exert positive effects on the treatment of metabolic syndrome.

Hormonal and Metabolic Effects of Coenzyme Q10 and/or Vitamin E in Patients With Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. The hormonal and metabolic effects of coenzyme Q10 (CoQ10) and/or vitamin E in patients with PCOS have not been studied, to our knowledge. To evaluate the effects of CoQ10 and/or vitamin E on glucose homeostasis parameters and reproductive hormones in women with PCOS. Randomized, double-blind, placebo-controlled clinical trial among 86 women with PCOS. CoQ10 or vitamin E or combination for 8 weeks. Glucose homeostasis parameters and sex hormone concentrations. After adjustment for potential confounders, supplementation with CoQ10 alone or in combination with vitamin E, compared with placebo, had significant effects on fasting blood sugar (FBS); vitamin E's effect on FBS was not significant. A significant reduction in homeostasis model assessment of insulin resistance (HOMA-IR) was observed in the CoQ10 and combined groups. CoQ10, vitamin E, and cosupplementation led to decreased serum total testosterone levels (P < 0.001) compared with those of the placebo group. CoQ10 supplementation in combination with vitamin E significantly improved in sex hormone-binding globulin (SHBG) levels compared with other groups (P = 0.008). Linear regression analysis revealed that changes in FBS, insulin, and HOMA-IR were predictors of change in free androgen index (P < 0.05). CoQ10 with or without vitamin E supplementation among women with PCOS had beneficial effects on serum FBS and insulin levels, as well as HOMA-IR and total testosterone levels. However, only cosupplementation affected SHBG concentrations.

Short-Term Impact of Laparoscopic Sleeve Gastrectomy on Serum Cartonectin and Vaspin Levels in Obese Subjects.

Cartonectin is a potent anti-inflammatory adipokine that might be implicated in metabolism and energy storage. Our objective was to evaluate the influence of weight reduction following laparoscopic sleeve gastrectomy (LSG) on serum cartonectin and vaspin levels. Thirty-two individuals (29 female and 3 male) with morbid obesity underwent LSG. Anthropometric indices, lipid profile, fasting serum concentrations of glucose, insulin, vaspin, and cartonectin were measured prior and 3months after LSG. Insulin sensitivity was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). Following LSG, circulating cartonectin level increased significantly while serum vaspin was significantly decreased. The percentage change of serum cartonectin level correlated negatively with the percentage changes in body mass index, waist circumference, and waist-hip ratio and positively with percentage changes in LDL-C, triglycerides, and HOMA-IR after adjustment for age and sex. Moreover, the changes in vaspin concentration positively correlated with the changes in insulin level and HOMA-IR after adjustment for age and sex. In a multiple stepwise linear regression model, the changes in waist circumference explained 13% variability of changes in cartonectin level while the changes in HOMA-IR and LDL-C were responsible for 31% of the variability in changes of vaspin level. LSG-induced weight loss rapidly increases serum cartonectin level and decreases the serum vaspin level in morbidly obese subjects. The changes in cartonictin level seem to be influenced by the changes of waist circumference while the changes of HOMA-IR and LDL-C might be determinant factors of the changes in vaspin level.

Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial

ObjectiveAlterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and...

The Effect of Vitamin D Supplementation on the Glycemic Status and the Percentage of Body Fat Mass in Adults with Prediabetes: A Randomized Clinical Trial

Background: Low serum levels of vitamin D are supposed to contribute to the incidence of diabetes; therefore, vitamin D supplementation may reduce the incidence of diabetes in individuals with prediabetes. Objectives: The aim of this current study was to examine the effect of vitamin D supplementation on the glycemic status and percentage of body fat mass in adults with prediabetes. Methods: In a 3-month randomized placebo-controlled supplementation trial, 120 eligible subjects were randomly assigned in a vitamin D or placebo group. They were stratified according to the percentage of body fat mass into four blocks to receive 1000 IU/daily vitamin D or an identical placebo tablet respectively, for 3 months. The study was conducted from January to March of 2016 in Urmia in the North West of Iran. Participants were adults aged 18 to 70 with prediabetes. The fasting blood sugar (FBS), glycated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), serum 25(OH)D levels, and percentage of body fat mass were assessed before and after the intervention. Results: The comparison of changes from baseline between two groups showed a significant inverse association between the changes in serum 25(OH)D and changes in FBS (-4.64 ± 11.38 compared with -2.11 ± 9.15 for placebo; P = 0.03), HOMA-IR (-0.73 ± 4.2 compared with 0.44 ± 4.4 for placebo, P = 0.01) and serum insulin (-1.98 ± 15.25 compared with 2.47 ± 15.85 for placebo; P = 0.007) but not in the percentage of body fat mass (-0.28 ± 0.77 compared with -0.39 ± 2.82 for placebo; P = 0.39). Conclusions: The study demonstrated that 1000 IU vitamin D supplementation for 3 months can decrease the insulin resistance in individuals with prediabetes; however, it has no significant effect on body fat mass percentage.

Abstract 47: Weight-loss Diets, Adiponectin, and Changes of Cardiometabolic Risk in the 2-year Pounds Lost Trial

Background: Evidence suggests that the beneficial effects of weight-loss diet interventions on improvement in cardiovascular risk factors may be partly through modulating secretion of adiponectin from adipose tissue. However, it remains unclear whether the long-term weight-loss diets change adiponectin levels; and how such changes, if exist, affect cardiometabolic risk. Objectives: To investigate effects of weight-loss diets with different compositions of macronutrients on long-term changes of circulating adiponectin concentrations and cardiometabolic risk factors, as well as dietary interactions with variation in the adiponectin gene. Methods: In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, 811 overweight or obese adults were randomly assigned to 1 of 4 diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the 4 diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The current analysis was restricted to participants who had baseline plasma adiponectin measurement (n=768). Circulating adiponectin and cardiometabolic outcomes were repeatedly measured at baseline, 6 months, and 2 years. We genotyped single-nucleotide polymorphism rs266171 in the adiponectin gene. Linear mixed models were used to compare changes in adiponectin concentrations across diet groups over the intervention and predict trajectory of changes in cardiometabolic risk factors. Results: Circulating adiponectin concentrations significantly increased over 2 years, similarly in 4 weight-loss diet intervention groups. Change of plasma adiponectin was significantly associated with decreases in weight, waist circumference, triglycerides, fasting insulin, and insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA-IR), and increase in HDL cholesterol, after adjusting for age, gender, ethnicity, follow-up time, diet group, and baseline level of respective outcome trait. The associations remained similar after further controlling for concurrent weight change. In addition, we observed significant interactions between rs266717 genotype and dietary fat on changes in fasting insulin and HOMA-IR (P for interaction=0.03 for both) at 6 months with adjustment for covariates. Participants who are homozygous for T allele of rs266717 had more reductions in fasting insulin and HOMA-IR than those with other genotypes in response to the high-fat diet, but such differences were not observed in the low-fat diet group. Conclusions: Regardless of macronutrient compositions, weight-loss diets beneficially increased circulating adiponectin, which was related to improvement of cardiometabolic profiles. Dietary fat intakes modified the effect of adiponectin variant rs266717 on improvement of insulin resistance.

Synergistic association of changes in serum uric acid and triglycerides with changes in insulin resistance after walking exercise in community-dwelling older women

ABSTRACTIntroduction: Serum uric acid (SUA) and triglyceride (TG) levels are strongly correlated with insulin resistance; however, the association after a walking exercise program in community-dwelling older women has not been investigated. Methods: The present study included 100 postmenopausal women (mean ± standard deviation, 68 ± 7 years) from a rural village in Japan. The Nordic walking program of 120 min per week was performed for 12 weeks. Before and after the intervention, SUA, TG, various relevant factors and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. Results and conclusions: Multivariate linear regression analysis showed that baseline TG and γ-glutamyltransferase (GGT) were significantly associated with baseline HOMA-IR. After the 12-week training program, changes in TG, SUA and GGT were significantly associated with changes in HOMA-IR. In addition to their direct associations, we observed a synergistic association between changes in TG and SUA and changes in HOMA-IR. Participants were divided into three groups (tertiles) according to changes in TG and SUA. The tertiles of changes in SUA correlated significantly with changes in HOMA-IR in participants in the tertile with the greatest decrease in TG (r = 0.525, p = 0.001), but not in the other two tertiles of change in TG (r = 0.049, p = 0.699). There was a significant interaction between SUA and TG for changes in HOMA-IR (β = 0.281, p = 0.005). These results suggest that changes in TG and SUA are synergistic factors associated with changes in insulin resistance after a 12-week walking exercise program in community-dwelling older women.

Comparison of spironolactone and spironolactone plus metformin in the treatment of polycystic ovary syndrome

The aim of this study was to evaluate and compare the effects of spironolactone and spironolactone plus metformin treatments on body mass index (BMI), hirsutism score, hormone levels, and insulin resistance in women with polycystic ovary syndrome (PCOS). Thirty-seven patients with PCOS were randomly assigned to receive spironolactone 100 mg/d (spironolactone group, 18 patients) or spironolactone 100 mg/d plus metformin 2000 mg/d (combination group, 19 patients) for 12 months. BMI, modified Ferriman–Gallway score (FGS), serum levels of regarding hormones, and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed before and after the treatments. Six patients in the spironolactone group and four patients in the combination group reported inter-menstrual vaginal bleeding during treatments. In hirsutism scores, the spironolactone therapy resulted in 25.2% reduction, while combination therapy resulted in 28.3% reduction (p > 0.05, between groups). When the groups were compared in terms of percent changes in BMI, FGS, HOMA-IR, and hormone values other than free testosterone, no significant difference was noted. In the present study, FGSs were significantly decreased in both groups; however, combination therapy was not more effective than spironolactone alone in terms of BMI, FGS, hormone levels, or insulin resistance.

Co-existence of insulin resistance and high concentrations of circulating oxidized LDL lipids

Introduction. Insulin metabolism has been previously linked to oxidized low-density lipoproteins (ox-LDL), but corroborating intervention studies are lacking. We investigated whether changes in ox-LDL levels are accompanied by changes in insulin sensitivity in a 32-month life-style intervention study.Materials and methods. A 2-month weight reduction was followed by 6-month diet and exercise counselling and a 2-year follow-up period. Men of 35–50 years of age, BMI ≥ 30 kg/m2, and waist circumference > 100 cm were recruited via newspapers in the city of Tampere, Finland. Of the 90 men meeting the inclusion criteria, 67 (76%) completed the study. Ox-LDL was estimated as the presence of oxidized lipids in LDL. Homeostasis model assessment of insulin resistance (HOMA-IR), ox-LDL, and ratio of ox-LDL and high-density lipoprotein cholesterol (ox-LDL/HDL-c) were used as the main outcome measures.Results. The detected changes in HOMA-IR were strikingly similar to those in ox-LDL and ox-LDL/HDL-c. Compared to the first HOMA-IR quartile, the fourth quartile had 23%–51% higher concentrations in ox-LDL and ox-LDL/HDL-c at all time points (P < 0.05 for all).Conclusion. This weight reduction intervention study adds evidence to support the connection between insulin metabolism and oxidized LDL, possibly contributing to the higher incidence of atherosclerotic cardiovascular diseases among diabetic patients.

Metabolic response to 6-week aerobic exercise training and dieting in previously sedentary overweight and obese pre-menopausal women: A randomized trial

BackgroundThe aim of this study was to compare 6 weeks short-term moderate intensity aerobic exercise and dieting on serum metabolomics and cardio-metabolic risk factors in pre-menopausal women. MethodsNinety previously inactive overweight and obese (BMI 25–35 kg/m2) women (age 41.5 ± 7.6 years) were randomized to either a 6-week Nordic walking exercise program (EX, n = 45) or dietary counseling group (DI, n = 45). Body composition, serum glucose, insulin and lipids were measured. Serum low-molecular-weight metabolites and lipid constituents were analyzed by nuclear magnetic resonance spectroscopy. Measurements were done at baseline and 7 days after the last training session. ResultsSix weeks aerobic exercise program yielded reductions in serum free fatty acids (−34.7%, 95% confidence interval (CI), −50 to −18, p < 0.001), glucose (−9.6%, 95%CI, −15 to −4, p < 0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) (−28.7%, 95%CI, −48 to −10, p = 0.005) without changes in body weight or fat mass. Diet counseling resulted in loss of body weight (1.5%, 95%CI, −2.3 to −0.7, p = 0.001) but no changes in free fatty acids, fasting glucose, or HOMA-IR were found. ConclusionOur results indicate that small weight loss does not produce measurable health benefits, whereas short-term regular aerobic exercise can improve glucose and lipid metabolism even in the absence of weight loss in previously sedentary overweight and obese women.

Genetic Determinant for Amino Acid Metabolites and Changes in Body Weight and Insulin Resistance in Response to Weight-Loss Diets

Background— Circulating branched-chain amino acids and aromatic amino acids were recently related to insulin resistance and diabetes mellitus in prospective cohorts. We tested the effects of a genetic determinant of branched-chain amino acid/aromatic amino acid ratio on changes in body weight and insulin resistance in a 2-year diet intervention trial. Methods and Results— We genotyped the branched-chain amino acid/aromatic amino acid ratio—associated variant rs1440581 near the PPM1K gene in 734 overweight or obese adults who were assigned to 1 of 4 diets varying in macronutrient content. At 6 months, dietary fat significantly modified genetic effects on changes in weight, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) after adjustment for the confounders (all P for interaction ≤0.006). Further adjustment for weight change did not appreciably change the interactions for fasting insulin and HOMA-IR. In the high-fat diet group, the C allele was related to less weight loss and smaller decreases in serum insulin and HOMA-IR (all P ≤ 0.02 in an additive pattern), whereas an opposite genotype effect on changes in insulin and HOMA-IR was observed in the low-fat diet group ( P =0.02 and P =0.04, respectively). At 2 years, the gene-diet interactions remained significant for weight loss ( P =0.008) but became null for changes in serum insulin and HOMA-IR resulting from weight regain. Conclusions— Individuals carrying the C allele of the branched-chain amino acid/aromatic amino acid ratio—associated variant rs1440581 may benefit less in weight loss and improvement of insulin sensitivity than those without this allele when undertaking an energy-restricted high-fat diet. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00072995.

Colesevelam Plus Rosuvastatin 5 mg/Day Versus Rosuvastatin 10 mg/Day Alone on Markers of Insulin Resistance in Patients with Hypercholesterolemia and Impaired Fasting Glucose

Statin use has been associated with adverse effects on insulin sensitivity and the development of new-onset diabetes. Colesevelam exhibits favorable effects on glucose metabolism. It is not known whether the combination of colesevelam plus low-dose statin has different effects on insulin resistance versus higher-dose statin in patients with impaired fasting glucose (IFG) and hypercholesterolemia. This was a prospective randomized open-label blinded end point (PROBE) study. Forty patients with hypercholesterolemia and IFG were randomized to receive rosuvastatin 5 mg/day plus colesevelam 3.75 g/day (RC, n=20) or rosuvastatin 10 mg (R, n=20) for 3 months. The primary end point was the difference in the change of homeostasis model assessment of insulin resistance (HOMA-IR) index between the groups. HOMA-IR index significantly decreased in the RC group (-32%, P=0.04 vs. baseline) but nonsignificantly increased (+15%, P=NS) in the R group. Insulin levels decreased in the RC group (-26%, P=NS) but increased in the R group (+15%, P=NS). Both changes in HOMA-IR and insulin differed significantly between groups (both p<0.05). Glucose levels decreased in the RC group (-5%, P=NS), whereas they remained unaltered in the R group. Similar reductions in low-density lipoprotein cholesterol were observed in both groups (-45%; P<0.001 vs. baseline). Triglycerides remained unchanged in the RC group but decreased in the R group (-24%, P<0.001 vs. baseline and P=0.02 vs. RC group). The combination of colesevelam with rosuvastatin 5 mg/day may be associated with favorable effects on markers of insulin resistance compared with rosuvastatin 10 mg/day in patients with hypercholesterolemia and IFG. Whether this is associated with less new-onset diabetes remains unknown.

Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial

Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that is increased in obesity and established type 2 diabetes. We assessed whether GDF-15 can predict future insulin resistance and impaired glucose control in obese nondiabetic individuals. Plasma GDF-15 concentrations were measured with an automated electrochemiluminescent immunoassay at baseline and after 4 years in 496 obese nondiabetic individuals (52% men, median age 48 years, median body mass index (BMI) 37.6 kg/m(2)) enrolled in the XENical in the prevention of Diabetes in Obese subjects (XENDOS) trial. The median GDF-15 concentration at baseline was 869 ng/l (interquartile range 723-1064 ng/l). GDF-15 was related to body weight, BMI, waist-to-hip ratio, and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) (all P < 0.01). Changes in GDF-15 from baseline to 4 years were related to changes in body weight, BMI, waist-to-hip ratio, and HOMA-IR (all P < 0.05). Baseline GDF-15 was associated with the risk to have prediabetes or diabetes at 4 years by univariate analysis (odds ratio (OR) FOR 1 unit increase in ln GDF-15, 3.2; 95% confidence interval (CI): 1.7-6.1; P<0.001), and after multivariate adjustment for age, gender, treatment allocation (orlistat vs placebo), BMI, waist-to-hip ratio, and glucose control at baseline (OR 2.2; 95% CI: 1.1-4.7; P=0.026). Similarly, baseline GDF-15 was independently associated with HOMA-IR at 4 years (P=0.024). This first longitudinal study of GDF-15 in a large cohort of obese individuals indicates that GDF-15 is related to abdominal obesity and insulin resistance and independently associated with future insulin resistance and abnormal glucose control.

The association between pentraxin 3 and insulin resistance in obese children at baseline and after physical activity intervention

BackgroundThe role of pentraxin-3 (PTX3) in the development of insulin resistance is still not clear. We aimed to test 1) whether circulating PTX3 levels are associated with insulin resistance and 2) whether changes in PTX3 levels after the physical activity are associated with changes in insulin resistance. MethodsFifty-seven overweight or obese children (39 boys, 18 girls; age: 12.04±0.82y, BMI: 26.5±1.2kg/m2) participated in the study. All participants were housed together and their amount of physical activity (1823.5±1.34kcal/day) and food intake (1882±68.8kcal/day) were tightly controlled. ResultsCirculating PTX3 levels at baseline were negatively associated with fasting insulin (r=−.336, p=0.012) and homeostasis model assessment of insulin resistance (HOMA-IR) (r=−.334, p=0.014) even after adjustment for BMI and Tanner stage. The degree of change in PTX3 levels notably associated with changes in fasting insulin (r=−.280, p=0.035) and HOMA-IR (r=−.281, p=.034) in response to the physical activity intervention. Subgroup analysis further indicates that HOMA-IR was improved more in subjects whose PTX3 levels were increased compared with subjects who PTX3 levels were decreased (HOMA-IR delta: −2.33±1.3 vs −1.46±0.70, p=0.004). ConclusionPTX3 is negatively associated with insulin resistance and associated with changes in insulin resistance induced by physical activity in overweight and obese children.