Homeostatic Model Of Insulin Resistance Research Articles

Metabolic Profile of Patients with Premature Ovarian Insufficiency.

Premature ovarian insufficiency (POI) is hypogonadism associated with amenorrhea, increased levels of gonadotropins, and hypoestrogenism. Deficiency of estrogens may contribute to higher risk of cardiovascular diseases and death. POI patients present several risk factors for the development of cardiovascular diseases (CVD): endothelial dysfunction, abnormal lipid profile, insulin resistance, and insulin action disturbances. Therefore, patients present a higher risk of developing metabolic syndrome. Materials and methods: Follicle stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol (E2), prolactin (PRL), testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid stimulating hormone (TSH), thyroxine (fT4), fasting serum glucose and insulin concentrations, homeostatic model for insulin resistance (HOMA-IR), and lipid profiles were assessed in 56 women (mean age: 30.7 ± 6.9) suffering from POI diagnosed according to European Society of Human Reproduction and Embryology (ESHRE) criteria and 68 healthy age-and-weight matched women (mean age: 27.3 ± 4.5). Results: After regression analysis with BMI and age correction, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) serum concentrations were found to be significantly higher in the POI group, when compared to healthy subjects, whilst triglycerides, glucose, insulin serum concentrations, HOMA-IR, as well as systolic (SBP) and diastolic blood pressure (DBP) did not differ significantly between both groups. A significant positive correlation was identified between TC and LDL-C levels, regardless of BMI and age, whilst SBP correlated only with serum glucose concentration. Additionally, FSH correlated positively with fasting serum glucose concentration after BMI and age correction. Conclusions: Certain metabolic parameters appeared to correlate with POI and these correlations persisted after correction for BMI and age. More research is required to determine the influence of absent ovulatory function on metabolic profiles in POI women. This information may additionally help in early identification of CVD risk factors in those patients.

Impact of short-term exercise training intensity on β-cell function in older obese adults with prediabetes.

The effect of work-matched exercise intensity on β-cell function is unknown in people with prediabetes before clinical weight loss. We determined if short-term moderate continuous (CONT) vs. high-intensity interval (INT) exercise increased β-cell function. Thirty-one subjects (age: 61.4 ± 2.5 yr; body mass index: 32.1 ± 1.0 kg/m2) with prediabetes [American Diabetes Association criteria, 75-g oral glucose tolerance test (OGTT)] were randomized to work-matched CONT (70% HRpeak) or INT (3 min 90% HRpeak and 3 min 50% HRpeak) exercise for 60 min/day over 2 wk. A 75-g 2-h OGTT was conducted after an overnight fast, and plasma glucose, insulin, C-peptide, and free fatty acids were determined for calculations of skeletal muscle [oral minimal model (OMM)], hepatic (homeostatic model of insulin resistance), and adipose (Adipose-IR) insulin sensitivity. β-Cell function was defined from glucose-stimulated insulin secretion (GSIS, deconvolution modeling) and the disposition index (DI). Glucagon-like polypeptide-1 [GLP-1(active)] and glucose-dependent insulinotropic polypeptide (GIP) were also measured during the OGTT, along with peak oxygen consumption and body composition. CONT and INT increased skeletal muscle- but not hepatic- or adipose-derived DI ( P < 0.05). Although both treatments tended to reduce fasting GLP-1(active) ( P = 0.08), early phase GLP-1(active) increased post-CONT and INT training ( P < 0.001). Interestingly, CONT exercise increased fasting GIP compared with decreases in INT ( P = 0.02). Early and total-phase skeletal muscle DI correlated with decreased total glucose area under the curve ( r = -0.52, P = 0.002 and r = -0.50, P = 0.003, respectively). Independent of intensity, short-term training increased pancreatic function adjusted to skeletal muscle in relation to improved glucose tolerance in adults with prediabetes. Exercise also uniquely affected GIP and GLP-1(active). Further work is needed to elucidate the dose-dependent mechanism(s) by which exercise impacts glycemia. NEW & NOTEWORTHY Exercise is cornerstone for reducing blood glucose, but whether high-intensity interval training is better than moderate continuous exercise is unclear in people with prediabetes before weight loss. We show that 2 wk of exercise training, independent of intensity, increased pancreatic function in relation to elevated glucagon-like polypeptide-1 secretion. Furthermore, β-cell function, but not insulin sensitivity, was also correlated with improved glucose tolerance. These data suggest that β-cell function is a strong predictor of glycemia regardless of exercise intensity.

Abstract 2231: Insulin and multi-system alterations in non-diabetic American adults: NHANES 1999-2016

Abstract Epidemiological evidence for a relationship between insulin resistance and cancer is emerging, and insulins' complex actions suggest that its dysregulation results in multisystem alterations. Using cross-sectional demographic and laboratory data from the continuous NHANES conducted from 1999-2016. we surveyed the range of multisystem alterations observed in normal (not diabetic or prediabetic) adult subjects in relation to variation in insulin and glucose levels. The homeostatic model of insulin resistance (HOMA-IR) was used as the key outcome measure of insulin resistance. We examined cardiovascular (BP), respiratory (FEV1, FVC), renal (BUN, creatinine), inflammatory (C-reactive protein, fibrinogen), lipid (triglycerides, LDL, HLD), hematologic (WBC, hemoglobin, cell counts), and nutritional (vitamin levels) factors in relation to HOMA-IR, C-peptide, Hgb1Ac and fasting glucose levels after adjustment for demographic (age, gender, smoking, alcohol, race, SES) and anthropometric (BMI) factors. Every system exhibited highly significant associations with insulin/glucose measures. Strong correlations (p &amp;lt; 0.0001, Pearson, accounting for sample weights) of HOMA-IR were observed with waist size, systolic and diastolic blood pressure, triglycerides, HDL (inverse), LDL and inflammatory markers: fibrinogen, C-reactive protein, ferritin. Measured serum levels of vitamin C, vitamin D, and folate (RBC), were inversely associated with HOMA-IR. The relationship for selected variables, to HOMA-IR quartiles is shown below. In a broad, representative sample of up to 9000 non-diabetic US subjects, we relate insulin resistance to adverse changes in anthropometric, cardiovascular, renal, metabolic, inflammatory and nutritional markers. Analyses accounting for NHANES sample design, confounding and potential interactions will be reported. Our preliminary results suggest that insulin resistance is linked to perturbations in normal function across numerous systems. HOMA-IR Quartiles, adjusted (95% CI)1st2nd3rd4thFerritin79.1(71-87)75.9 (70-82)82.3 (76-89)96.2 (82-110)BP (d)69.7 (69-71)71.8 (70-73)71.4 (70-73)73.2 (72-75)HDL60.8 (60-62)56.3 (56-57)54.1 (53-55)51.3 (50-52)WBC6.37 (6.3-6.5)6.44 (6.3-6.6)6.68 (6.5-6.8)6.96 (6.8-7.1) Citation Format: Neil E. Caporaso, Rena R. Jones, Lisa L. Kahle, Barry I. Graubard. Insulin and multi-system alterations in non-diabetic American adults: NHANES 1999-2016 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2231.

Insulin Resistance and Weight Loss in Obese Women with Polycystic Ovary Syndrome Treated with Liraglutide—Single Institution Experience

Background: Insulin resistance contributes to the pathogenesis of polycystic ovary syndrome (PCOS) in obese women, but its predictive value for weight loss with liraglutide treatment is unknown. Methods: Retrospective cohort study of 16 obese (BMI ≥30 kg/m2), nondiabetic women aged 18-42 with PCOS who were seen in a weight loss clinic between November 2014 and November 2016 and prescribed liraglutide (either 1.8 mg/day or 3.0 mg/day based on insurance coverage) and metformin. Maximum weight loss achieved from baseline until 2 to 13 months post-liraglutide initiation was compared. Spearman’s rank correlation was used to establish the relationship between pre-treatment Homeostatic Model for Insulin Resistance (HOMA-IR) and % weight loss. The University of Pennsylvania Institutional Review Board approved the study. Results: Overall median weight loss was 4.4 kg (-3.4% of initial weight). Median weight loss was -4.7 kg (-3.7%) in women treated with 3.0 mg daily (n=6) and -2.5 kg (-2.0%) in women treated with 1.8 mg (n=10). 6/16 (37.5%) of women experienced &amp;gt;5% weight loss: 2/6 women treated with 3.0 mg daily dosing, and 4/10 women treated with 1.8 mg daily. HOMA-IR at baseline was not associated strongly with % weight loss achieved for all subjects (rs= -0.31, p=0.24), or when stratified to examine those subjects receiving 3.0 mg daily (rs= -0.20; p=0.70) or 1.8 mg daily (rs= -0.36, p=0.31). Conclusions: In this small study, our findings suggest that insulin resistance at baseline does not strongly correlate with maximum weight loss achieved using liraglutide. Furthermore, our study suggests that liraglutide is an effective tool for weight loss. Overall, 37.5% of women achieved &amp;gt;5% weight loss from baseline, meeting the FDA’s categorical efficacy target for weight loss medications. Disclosure A. Crawford: None. L.G. Cooney: None. N. Jochym: None. A. Dokras: Consultant; Self; Fractyl Laboratories, Inc. A. Amaro: Consultant; Self; Novo Nordisk Inc., Andrew Technologies, LLC.

Engaging Hispanic Adolescents with Type 2 Diabetes or Obesity in Personalized Exercise

The prevalence of obesity in Hispanic youth (21.9%; Ogden and Flegal, 2015) is the highest of all racial and ethnic groups, increasing their odds for the development of type 2 diabetes (T2D). The purpose of this secondary analysis of a larger trial of a 16-week personalized exercise intervention was to examine differences in exercise adherence and baseline perceptions of benefits and barriers to exercise, exercise self-efficacy and family support to exercise in Hispanic adolescents diagnosed with T2D or obesity. Changes in body mass index, waist circumference, glycosylated hemoglobin (HbA1c), homeostatic model for insulin resistance (HOMA-IR), lipid profile, cardiorespiratory fitness, blood pressure and perception of health were also examined following the intervention. There were 21 adolescents enrolled in the study, 13 with T2D (3 males, 10 females) and 8 who were obese (3 males, 5 females). The personalized programs were based upon individual adolescent choices to promote moderate to vigorous activity (MVPA) and included gym memberships, dance videos, biking, basketball, softball and walking. Adolescents wore the ActigraphTM accelerometer (model GT1M, Pensacola, FL) for tracking exercise throughout the intervention. The completion rate was 88% vs. 59% (67% overall) for obese vs. T2D, with obese adolescents engaging in higher duration of MVPA compared to those with T2D (mean 46.4 ± 33.8 vs. 36.3 ± 16.0 min/day, NS). Perceptions of family support for exercise were associated with benefits of exercise (r = .50, p = .021); barriers to exercise were associated with less MVPA (r = - .56, p = .017). Barriers were significantly higher in those with T2D (p = .01). Despite not meeting recommended activity guidelines, perceptions of health improved for all completing the intervention (p = .01). Future efforts for engaging Hispanic adolescents in regular exercise are warranted to delay the onset of T2D and the development of poor outcomes particularly for those already diagnosed with T2D. Disclosure M.S. Faulkner: None. S. Michaliszyn: None.

Impact of the No-Carrageenan Diet on Glucose Tolerance and Insulin Resistance in Adults with Prediabetes

Previous animal and cell-based studies indicated that exposure to the common food additive carrageenan impaired glucose tolerance and increased insulin resistance. Carrageenan is widely used in processed foods to improve solubility, but predictably causes inflammation, which contributes to insulin resistance by inhibition of insulin signaling. To test if removal of carrageenan from the diet could reduce insulin resistance, we initiated a double-blinded, controlled feeding study in individuals with prediabetes, defined by Hemoglobin A1c values of 5.7%-6.4%. All procedures were approved by the University of Illinois at Chicago IRB. Participants were provided study diets for 12 weeks, which either contained or did not contain carrageenan, and had similar composition of protein, carbohydrate, and fat. An additional group was comprised of individuals who participated in study tests, but ate their usual diet. Subjects on study diets picked up their food weekly at UIC and had blood tests, including 2h glucose tolerance tests performed at entry, 6, and 12 weeks. Inflammatory parameters, including fecal calprotectin, were measured at entry and conclusion. Preliminary study results from 17 participants indicate that the carrageenan-free diet was associated with significant decline in hemoglobin A1c (p=0.004, unpaired t-test, two-tailed), HOMA-IR (homeostatic model for insulin resistance) score (p=0.0064), insulin resistance (p=0.02), and leukocyte phospho-serine IRS-1 (p=0.003) and NF-kappaB, compared to study participants on the control study diet or their regular diet. Study findings indicate significant decline in insulin resistance by removal of carrageenan from the diet. Additional studies of inflammatory parameters, immune cell subsets, and fecal microbiome are pending. Disclosure J.K. Tobacman: None.

Utility of Fibroscan in Screening Overweight and Obese Children at Risk for Nonalcoholic Fatty Liver Disease

Study Objective: Nonalcoholic fatty liver disease (NAFLD) is associated with elevated risk for metabolic syndrome, type 2 diabetes, cardiovascular disease and cirrhosis. Available diagnostic tools (plasma aminotransferases and liver ultrasound) have low sensitivity. This study screened a broad population of children from an endocrine clinic with a combination of imaging tools and biomarkers previously used only in children with known liver disease. We hypothesized that Fibroscan (an ultrasound based imaging tool for hepatic fibrosis) would correlate well with MR-elastography (MRE) and be a useful adjunct in combination with known biomarkers of fatty liver disease to screen for advanced cases of NAFLD. Methods: Overweight patients were recruited from pediatric and endocrinology clinics. They underwent liver 1H magnetic resonance spectroscopy, magnetic resonance elastography, liver Fibroscan, and fasting lab studies. Plasma biomarkers analyzed included hemoglobin A1c, lipid panel, AST and ALT levels, cytokeratin 18 and homeostatic model of insulin resistance. Results: Twenty seven patients were recruited and analyzed. NAFLD was present in 30% of patients based on ≥5.5% intrahepatic triglyceride content (liver fat) on 1H-MRS. Five patients (19%) showed fibrosis based on Fibroscan ≥7%, however, only one case was confirmed to have fibrosis on MRE. Two patients with positive Fibroscan were unable to undergo MRE. Metabolic markers including A1c and HOMA-IR were worse in NAFLD vs. no NAFLD patients, but only triglycerides and ALT reached statistical significance. Conclusions: Fibroscan is useful to eliminate fibrosis, but a positive fibroscan must be further evaluated as many false positives occurred. In combination with triglycerides and ALT, this tool may be useful to stratify those patients most at risk for severe NAFLD and those patients requiring evaluation by pediatric gastroenterologists, biopsy, and more intensive intervention. Disclosure K.A. Dayton: None. F. Bril: None. K. Cusi: Consultant; Self; Janssen Global Services, LLC., Eli Lilly and Company. Research Support; Self; Cirius Therapeutics. Other Relationship; Self; Nordic Bioscience. Research Support; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc.. Other Relationship; Self; Quest Diagnostics. Research Support; Self; Zydus Pharmaceuticals (USA) Inc.. Other Relationship; Self; OWL metabolomics, Echosens. Research Support; Self; Janssen Global Services, LLC.. Consultant; Self; Tobira Therapeutics, Pfizer Inc..

The possible antidiabetic effects of vitamin D receptors agonist in rat model of type 2 diabetes.

Vitamin D3 deficiency was found to be tightly linked to many health problems including metabolic syndrome, cancer, cardiovascular diseases, and type 2 diabetes mellitus. In our study, we tested the possible antidiabetic effects of one of vitamin D3 analogs, alfacalcidol, solely or in a combination with metformin on type 2 diabetic rats. Type 2 diabetic model rats were induced by feeding high-fat diet for 4weeks followed by intraperitoneal injection of streptozotocin. In addition to the control group, the diabetic rats were divided into four groups: untreated, metformin-treated, alfacalcidol-treated, and combination-treated group (metformin + alfacalcidol) for 4weeks. The level of fasting blood glucose, fasting serum insulin, homeostatic model of insulin resistance, serum lipid profile, liver enzymes, calcium, phosphorus, and 25-hydroxyvitamin D3 were also determined. Besides, sterol regulatory element binding protein-1c (SREBP-1c) and vitamin D receptors (VDR) gene expression at mRNA and protein levels were evaluated. The level of significance was fixed at P ≤ 0.05 for all statistical tests. Alfacalcidol, solely or combined with metformin, significantly ameliorated glucose homeostasis and lipid profile parameters (P < 0.001) with a neutral effect on calcium and phosphorus levels. Significant downregulation of mRNA expression of SREBP-1c in the liver, white as well as brown adipose tissues (P < 0.001) and different patterns of mRNA expression of VDR gene in pancreas and white adipose tissue were observed in rats treated with alfacalcidol solely or in combination with metformin. Vitamin D3 analogs can modulate glucose parameters and lipid metabolism in a diabetic rat model and it provides additional protective effects when combined with metformin.

Insulin resistance is associated with depression risk in polycystic ovary syndrome

To test the hypothesis that insulin resistance is associated with depression risk in polycystic ovary syndrome (PCOS). Secondary analysis of data from a multicenter randomized trial. Multicenter university-based clinical practices. Seven hundred thirty-eight women with PCOS by modified Rotterdam criteria seeking pregnancy enrolled in a randomized clinical trial comparing clomiphene citrate versus letrozole. The Primary Care Evaluation of Mental Disorders Patient Health Questionnaire was self-administered to identify depression using a validated algorithm at enrollment. Demographic and anthropometric data were collected, and serum assays were performed. Insulin resistance was estimated using the homeostatic model of insulin resistance (HOMA-IR), with a cutoff of >2.2 considered abnormal. Demographic, endocrine, and metabolic parameters associated with depression. In a univariate logistic regression analysis, elevated HOMA-IR was associated with 2.3-fold increased odds of depression (odds ratio [OR] = 2.32; 95% confidence interval [CI], 1.28-4.21). This association remained significant after controlling for age andbody mass index (adjusted OR [aOR] = 2.23; 95% CI, 1.11-4.46) and in a model including additional potential confounders (aOR = 2.03; 95% CI, 1.00-4.16). Insulin resistance has a strong and independent association with depression in PCOS and may serve as a physiologic mediator. Our findings corroborate a growing body of evidence linking insulin resistance to depressed mood. The association between insulin resistance and depressed mood warrants further investigation to elucidate mechanisms and identify potential therapeutic targets.

Effect of one time high dose "stoss therapy" of vitamin D on glucose homeostasis in high risk obese adolescents.

To study the effect of using a one time high dose "stoss therapy" of vitamin D2 (ergocalciferol: VD2) on indices of insulin sensitivity {whole body sensitivity index: WBISI} and secretion {insulinogenic index: IGI} measured during an oral glucose tolerance test (OGTT) in obese adolescents with VDD (25 OHD; serum metabolite of vit D: < 30 ng/dL). In a randomized placebo controlled cross over design 20 obese adolescents with vitamin D deficiency (VDD) had baseline OGTT. Arm A received one time high dose 300,000 IU of ergocalciferol and Arm B received placebo. After 6 weeks the adolescents were reassigned to Arm A if they were in Arm B and vice versa. 25OHD, calcium, parathyroid hormone, comprehensive metabolic panel, urine calcium creatinine ratio were measured at each study visit. OGTTs to assess indices of sensitivity and secretion were done at baseline, 6 weeks and 12 weeks respectively. Adolescents were obese and insulin resistant (mean ± SD: mean age = 15.1 ± 1.9 years; BMI: 32.7 ± 9.8; homeostatic model of insulin resistance: HOMA-IR: 4.2 ± 2.8). Stoss therapy with VD2 increased 25OHD from baseline (16.7 ± 2.9 to 19.5 ± 4.5; p = 0.0029) when compared to the placebo. WBISI (2.8 ± 1.9) showed a trend towards improvement in Rx group (p = 0.0577) after adjustment for covariates. IGI (3 ± 2.2) showed an improvement in both Rx and placebo groups. Our study demonstrated that using a high dose of VD2 (300,000 IU) did not have any beneficial effect on insulin sensitivity (whole body sensitivity index {WBISI}) and secretory indices (insulinogenic index {IGI}) in obese adolescents. High dose "stoss therapy" of VD2 did not appear to have any beneficial effect on glucose homeostasis on obese adolescents.

Fasting and post-glucose load measures of insulin resistance and risk of incident atrial fibrillation: The Cardiovascular Health Study

Background and aimsExisting literature in individuals without diabetes has not demonstrated a relationship between IR and incident AF; however, data are limited and only fasting glucose measures of IR were assessed. We evaluated the relationship of both fasting and post-glucose load IR measures with the development of atrial fibrillation in nondiabetic older adults. Methods and resultsAmong Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged 65 years or older enrolled in two waves (1989–1990 and 1992–1993), those without prevalent AF or diabetes and with IR measures at baseline were followed for the development of AF, identified by follow-up visit electrocardiograms, hospital discharge diagnosis coding, or Medicare claims data, through 2014. Fasting IR was determined by the homeostatic model of insulin resistance (HOMA-IR) and post-glucose load IR was determined by the Gutt index. Cox proportional hazards models were used to determine the association of IR with risk of AF. Analyses included 3601 participants (41% men) with a mean age of 73 years. Over a median follow-up of 12.3 years, 1443 (40%) developed AF. After multivariate adjustment, neither HOMA-IR nor the Gutt index was associated with risk of developing AF [hazard ratios (95% confidence intervals): 0.96 (0.90, 1.03) for 1-SD increase in HOMA-IR and 1.03 (0.97, 1.10) for 1-SD decrease in the Gutt index]. ConclusionsWe found no evidence of an association between either fasting or post-glucose load IR measures and incident AF.

Abdominal obesity adversely affects bone mass in children.

AIMTo determine the effect of childhood obesity and insulin resistance on bone health.METHODSWe conducted a cross sectional study in pubertal adolescents and young adults 13-20 years old who were either overweight/obese or normal weight. Participants were Tanner 3 or above for pubertal stage, and had fasting blood work done to measure glucose, insulin, C-reactive protein and lipid levels. Homeostatic model of insulin resistance (HOMA-IR) was calculated using the formula (Fasting Blood Glucose *Insulin/405). Body composition and bone mineral density were measured using dual energy X-ray absorptiometry (DXA; Hologic QDR 4500, Waltham, MA, United Kingdom).RESULTSPercent trunk fat was associated inversely with whole body bone mineral content (BMC), whereas HOMA-IR was associated positively with whole body BMC.CONCLUSIONOur results suggest that abdominal adiposity may have an adverse effect on whole body bone parameters and that this effect is not mediated by insulin resistance.

Contribution of insulin resistance to decreased baroreceptor sensitivity & cardiometabolic risks in pre-obesity & obesity.

Background & objectives:Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well studied. This study was conducted to assess the difference in cardiovascular (CV) risk profile in IR and non-IR (NIR) conditions, and contribution of IR to cardiometabolic risks in pre-obese and obese individuals.Methods:Basal CV, blood pressure variability, autonomic function test and cardiometabolic parameters were recorded in pre-obese (n=86) and obese (n=77) individuals during 2012 and 2015. The association of altered cardiometabolic parameters with homeostatic model for IR (HOMA-IR) in pre-obese and obese groups and with baroreceptor sensitivity (BRS) in IR and NIR groups was calculated by appropriate statistical analysis.Results:Decreased BRS, a known CV risk and cardiometabolic parameters were significant in IR (pre-obese and obese) group compared to the NIR group. Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activities was observed in individuals with IR. There was no significant difference in the level of independent contribution of HOMA-IR to cardiometabolic parameters in pre-obese and obese groups. Adiponectin and inflammatory markers had an independent contribution to BRS in IR group.Interpretation & conclusions:Findings of the present study demonstrated that the intensity of cardiometabolic derangements and CV risk were comparable between IR, pre-obese and obese individuals. Pro-inflammatory state, dyslipidaemia and hypoadiponectinaemia might contribute to CV risk in these individuals with IR. IR could possibly be the link between altered metabolic profile and increased CV risks in these individuals independent of the adiposity status.

Insulin resistance and cognitive test performance in elderly adults: National health and nutrition examination survey (NHANES)

ObjectivesTo examine the relationship between homeostatic model of insulin resistance (HOMA-IR) and cognitive test performance among population≥60years in a national database. HypothesisHigher insulin resistance is associated with lower cognitive test performance score in the population≥60years. ParticipantsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999–2000 and 2001–2002. MeasurementsCognitive test performance was measured by the Digit Symbol Substitution (DSS) exercise score. The main independent variable was the homeostasis model assessment of insulin resistance (HOMA-IR). We used bivariate analysis and generalized linear model adjusting for age, gender, race, education, body mass index, and systolic and diastolic blood pressures; total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride levels; and physical activity, diabetes mellitus, stroke, and congestive heart failure. STATA 14 was used to analyze the data taking into consideration the design, strata and weight. ResultsOf the 1028 participants, 44% were male and 85% were white. The mean age was 70.0±0.28 (SE) years. Their average HOMA-IR was 3.6±0.14 and they had a mean of 49.2±0.8 correct DSS score in the cognitive test. Adjusting for the confounding variables, HOMA-IR was associated with decline in DSS score (B=−0.30, 95% confidence interval=−0.54 and −0.05, p=0.01). The model explained 44% of the variability of the DSS score (R2=0.44). Significant predictors of decline in DSS score were age, gender, race, and education (p=0.01). ConclusionInsulin resistance as measured by HOMA-IR was independently associated with lower cognitive test performance score among elderly participants aged ≥60years. Longitudinal studies are needed to test the mechanism and the causal relationship.

Effect of Pericardial Fat Volume and Density on Markers of Insulin Resistance and Inflammation in Patients With Human Immunodeficiency Virus Infection

Treated human immunodeficiency virus (HIV) infection is characterized by ectopic fat deposition, a persistent inflammatory state, and increased cardiometabolic risk. In this secondary analysis of a placebo controlled trial of rosuvastatin among 147 HIV+ subjects (median age 46; 78% men) on stable antiretroviral therapy, we aimed to evaluate longitudinal associations between computed tomography (CT) measures of pericardial fat (PCF) volume and density, insulin resistance, and inflammation. We measured PCF volume and density (mean attenuation in Hounsfield units) by noncontrast gated CT at baseline and week 96. Homeostatic model of insulin resistance was calculated from fasting insulin and glucose at entry, 24, 48, and 96 weeks. At baseline, insulin resistance correlated positively with PCF volume and negatively with density. Similarly divergent correlations of volume and density were observed with waist:hip ratio, nadir CD4+ count, and duration of antiretroviral therapy. In a linear mixed model, PCF density was associated with insulin resistance independent of PCF volume, body mass index, metabolic syndrome, and biomarkers of immune activation and systemic inflammation; however, baseline PCF measures were not associated with longitudinal changes in insulin resistance. Soluble CD163, a marker of monocyte activation, positively correlated with PCF volume and was associated with insulin resistance in linear models. Statin treatment assignment did not affect PCF volume or density change (both p > 0.8). In conclusion, the quantity and quality (i.e., radiodensity) of PCF are differentially related to insulin resistance and inflammation in patients with treated HIV infection.

Intakes and sources of dietary sugars and their association with metabolic and inflammatory markers

SummaryBackground & aimsAssociations of dietary sugars with metabolic and inflammatory markers may vary according to the source of the sugars. The aim of this study was to examine the association of dietary sugars from different sources [beverages (liquids), foods (solids), extrinsic (free) or intrinsic (non-free)] with metabolic and inflammatory markers.MethodsPopulation-based cross-sectional study of adults in the East of England (n = 9678). Sugar intakes were estimated using food frequency questionnaires. Fasting glycated haemoglobin, glucose, insulin, and C-Reactive Protein (CRP) were measured and indices of metabolic risk were derived (homeostatic model of insulin resistance, HOMA-IR and metabolic risk z-score).ResultsIn multiple linear regression analyses adjusted for potential confounders including BMI and TEI, sugars from liquids were positively associated with ln-CRP [b-coefficient (95%CI), 0.14 (0.05,0.22) per 10%TEI] and metabolic risk z-score [0.13 (0.07,0.18)]. Free sugars were positively associated with ln-HOMA-IR [0.05 (0.03,0.08)] and metabolic risk z-score [0.09 (0.06,0.12)]. Sugars from solids were not associated with any outcome. Among major dietary contributors to intakes (g/d), sugars in fruit, vegetables, dairy products/egg dishes, cakes/biscuits/confectionary and squash/juice drinks were not associated, but sugar added to tea, coffee, cereal was significantly positively associated with all outcomes. Sugars in 100% juice [0.16 (0.06,0.25) per 10%TEI] and other non-alcoholic beverages [0.13 (0.03,0.23)] were positively associated with metabolic risk z-score.ConclusionHigher intakes of sugars from non-alcoholic beverages and sugar added to tea, coffee, cereal were associated with glycaemia and inflammatory markers. Sugars from solids were not associated, irrespective of whether they were intrinsic or extrinsic. Positive associations of free sugars were largely explained by contribution of beverages to intake.

Effects of KDT501 on Metabolic Parameters in Insulin-Resistant Prediabetic Humans.

Context:KDT501 is an isohumulone drug that has demonstrated beneficial effects on metabolic parameters in mice.Objective:This study was intended to examine potential improvements in metabolism in humans.Design and Setting:Changes in carbohydrate and lipid metabolism, along with inflammatory markers, were evaluated in prediabetic humans in a clinical research center.Participants:Nine obese patients participated. All had prediabetes or normal glucose tolerance plus three features of metabolic syndrome.Intervention:All participants were treated with escalating doses of KDT501 to a maximum dose of 1000 mg every 12 hours for a total of 28 days.Outcome Measures:Changes in carbohydrate metabolism were measured with oral glucose tolerance, homeostatic model of insulin resistance, and euglycemic clamp; changes in plasma lipids and response to a lipid tolerance test; and changes in plasma inflammatory markers.Results:The drug was well tolerated. After KDT501 treatment, plasma triglycerides were reduced at 4 hours during a lipid tolerance test. Furthermore, plasma adiponectin and high-molecular-weight adiponectin increased significantly, and plasma tumor necrosis factor-α decreased significantly. There were no significant changes in oral glucose tolerance test results or insulin sensitivity measures.Conclusions:Despite the small sample size and the short duration of therapy, KDT501 administration reduced measures of systemic inflammation and improved postmeal plasma triglyceride levels, which may be beneficial in participants with insulin resistance or metabolic syndrome.

Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial.

Our aim was to investigate the effects and prevalence of nonresponders (NR) to high-intensity interval training (HIIT) and resistance training (RT) in women with insulin resistance on cardiometabolic health parameters. Sedentary overweight/obese insulin-resistant women (age = 33.5 ± 6.5 yr; body mass index = 29.9 ± 3.7 kg/m2) were randomly assigned to a triweekly HIIT program (HIIT; n = 18) or resistance training (RT; n = 17). Anthropometry (body mass, fat mass, muscle mass, waist circumference, and skinfold thickness), cardiovascular (blood pressure), metabolic [fasting glucose, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR)], as well as muscle strength, and endurance performance covariables were measured before and after 12 wk in both intervention groups. The interindividual variability to exercise training of the subjects was categorized as responders and NR using as cut points two times the typical error of measurement in mean outcomes. After intervention, significant reduction in waist circumference, skinfold thicknesses, fat mass, blood pressure, fasting glucose, insulin, and HOMA-IR (P < 0.05) were identified to HIIT and RT group, respectively. Both HIIT and RT groups exhibited a significant decrease in the endurance performance, whereas only RT exhibited increased muscle strength. Significant differences in the NR prevalence between the HIIT and RT groups were identified for a decrease in fat mass (HIIT 33.3% vs. RT 70.5%; P = 0.028), muscle mass (HIIT 100% vs. RT 52.9%; P = 0.001), and tricipital skinfold (HIIT 5.5% vs. RT 29.4%; P < 0.041). For diastolic blood pressure, significant differences were observed in the NR prevalence between the HIIT and RT groups (55.5% vs. 94.1; P = 0.009). However, there were no differences in the NR prevalence between HIIT and RT for decreasing fasting glucose. Twelve weeks of HIIT and RT have similar effects and NR prevalence to improve glucose control variables; however, there is different NR prevalence in other anthropometric, cardiovascular, strength, and endurance performance measurements in insulin-resistant women. These findings were displayed with a similar time investment per week of 114 vs. 108 min, respectively, to HIIT and RT.NEW & NOTEWORTHY The effects and prevalence of nonresponders (NR) to improve glucose control variables have predominately been reported by endurance training. A uniqueness of the present study was to examine the NR prevalence in women with insulin resistance after high-intensity interval (HIIT) and resistance training (RT). This study demonstrates that 12 wk of HIIT and RT have similar effects and NR prevalence to improve glucose control variables. However, significantly different NR prevalence were observed in other anthropometric, cardiovascular, strength, and endurance performance measurements.

Abstract 12159: Metabolite Profiles Are Associated With Metabolically Unhealthy Obesity in Children and Adolescents

Background: Metabolite profiling has been used to identify mechanisms of cardiometabolic disease (CMD). Whether metabolites can identify metabolic healthy obesity (MHO) versus unhealthy obesity (MUO) remains unclear. Hypothesis: We hypothesized that specific metabolite profiles would be associated with adverse cardiometabolic phenotypes in non-diabetic overweight/obese youth. Methods: We performed untargeted metabolomics (81 polar metabolites) in 90 overweight/obese youth (age 15.5±4.8 years, 54% female, BMI 33.8±10.0 kg/m 2 ), and used principal components analysis to identify metabolite clusters. Metabolically unhealthy obesity (MUO) was defined as one of the following: homeostatic model of insulin resistance (HOMA-IR) ≥ 3.16, hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg), triglycerides ≥ 150 mg/dl, HDL &lt;40 mg/dl or glucose ≥100. We used logistic regression to estimate the association between metabolite clusters and MUO. Results: Five principal components (PC) accounted for 61.9% variance in polar metabolites. Polar PC2 contained aromatic amino acids (phenylalanine, tyrosine), branched-chain amino acids (e.g., leucine, valine, isoleucine), and their downstream metabolites (e.g., glutamine) and was associated with MUO (odds ratio OR=1.92, 95% confidence interval CI 1.06-3.48, P=0.03). Conclusions: We identified patterns of metabolites previously implicated in diabetes risk in adults (e.g., branched chain and aromatic amino acids) associated with CMD phenotypes in overweight/obese youth. Common metabolic pathways contribute to heterogeneity in cardiometabolic health in pediatric obesity as in adults.

Raising threshold for diagnosis of polycystic ovary syndrome excludes population of patients with metabolic risk

To characterize the population of patients excluded from a diagnosis of polycystic ovary syndrome (PCOS) when follicle number criteria are increased to 25 per ovary as suggested by the Androgen Excess and Polycystic Ovary Syndrome Society's recent task force. Cross-sectional study. Tertiary academic center. A total of 259 women with PCOS according to Rotterdam criteria who were systematically examined from 2007 to 2015, with 1,100 ovulatory women participating in the Ovarian Aging (OVA) Study as controls. Anthropometric measurements, serum testing, ultrasonic imaging, and comprehensive dermatologic exams. Body mass index (BMI), waist to hip ratio (WHR), serum cholesterol, fasting glucose and insulin, follicle count per ovary, biochemical hyperandrogenemia, and hirsutism. Forty-seven of 259 women meeting the Rotterdam criteria (18.1%) were excluded from a diagnosis of PCOS when the follicle number criteria was increased to 25. These women had clinical evidence of hyperandrogenism (68.1%) and biochemical hyperandrogenemia (44.7%), although fewer reported oligoanovulation (26.8%). The excluded women had elevated total cholesterol, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR) when compared with controls despite controlling for age and BMI. The women excluded from the PCOS diagnosis by raising the threshold of follicle number per ovary to ≥25 continue to show evidence of metabolic risk.