Homeostatic Model Of Insulin Resistance Research Articles

Investigating the Effects of Diet-Induced Prediabetes on Skeletal Muscle Strength in Male Sprague Dawley Rats.

Type 2 diabetes mellitus, a condition preceded by prediabetes, is documented to compromise skeletal muscle health, consequently affecting skeletal muscle structure, strength, and glucose homeostasis. A disturbance in skeletal muscle functional capacity has been demonstrated to induce insulin resistance and hyperglycemia. However, the modifications in skeletal muscle function in the prediabetic state are not well elucidated. Hence, this study investigated the effects of diet-induced prediabetes on skeletal muscle strength in a prediabetic model. Male Sprague Dawley rats were randomly assigned to one of the two groups (n = 6 per group; six prediabetic (PD) and six non-pre-diabetic (NPD)). The PD group (n = 6) was induced with prediabetes for 20 weeks. The diet that was used to induce prediabetes consisted of fats (30% Kcal/g), proteins (15% Kcal/g), and carbohydrates (55% Kcal/g). In addition to the diet, the experimental animals (n = 6) were supplied with drinking water that was supplemented with 15% fructose. The control group (n = 6) was allowed access to normal rat chow, consisting of 35% carbohydrates, 30% protein, 15% fats, and 20% other components, as well as ordinary tap water. At the end of week 20, the experimental animals were diagnosed with prediabetes using the American Diabetes Association (ADA) prediabetes impaired fasting blood glucose criteria (5.6-6.9 mmol/L). Upon prediabetes diagnosis, the animals were subjected to a four-limb grip strength test to assess skeletal muscle strength at week 20. After the grip strength test was conducted, the animals were euthanized for blood and tissue collection to analyze glycated hemoglobin (HbA1c), plasma insulin, and insulin resistance using the homeostatic model of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) concentration. Correlation analysis was performed to examine the associations of skeletal muscle strength with HOMA-IR, plasma glucose, HbA1c, and MDA concentration. The results demonstrated increased HbA1c, FBG, insulin, HOMA-IR, and MDA concentrations in the PD group compared to the NPD group. Grip strength was reduced in the PD group compared to the NPD group. Grip strength was negatively correlated with HbA1c, plasma glucose, HOMA-IR, and MDA concentration in the PD group. These observations suggest that diet-induced prediabetes compromises muscle function, which may contribute to increased levels of sedentary behavior during prediabetes progression, and this may contribute to the development of hyperglycemia in T2DM.

Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity.

Obesity-associated inflammation drives the development of insulin resistance and type 2 diabetes. We sought to identify associations of circulating regulatory T cells (Treg) with the degree of obesity (eg, body mass index Z-score [BMIz]), insulin resistance (homeostatic model of insulin resistance [HOMA-IR]), and glycemic control (HbA1c) in children and adolescents. We further sought to examine associations among bioenergetics of peripheral blood mononuclear cells (PBMCs) and CD4 T cells and BMIz, HOMA-IR, and HbA1c. A total of 65 children and adolescents between the ages 5 and 17 years were studied. HbA1c and fasting levels of plasma glucose and insulin were measured. We quantified circulating Tregs (CD3+CD4+CD25+CD127-FoxP3+) by flow cytometry, and measured mitochondrial respiration (oxygen consumption rate [OCR]) and glycolysis (extracellular acidification rate [ECAR]) in PBMCs and isolated CD4 T cells by Seahorse extracellular flux analysis. Tregs (% CD4) are negatively associated with BMIz but positively associated with HOMA-IR. In PBMCs, OCR/ECAR (a ratio of mitochondrial respiration to glycolysis) is positively associated with BMIz but negatively associated with HbA1c. In children, Tregs decrease as body mass index increases; however, the metabolic stress and inflammation associated with insulin resistance may induce a compensatory increase in Tregs. The degree of obesity is also associated with a shift away from glycolysis in PBMCs but as HbA1c declines, metabolism shifts back toward glycolysis. Comprehensive metabolic assessment of the immune system is needed to better understand the implications immune cell metabolic alterations in the progression from a healthy insulin-sensitive state toward glucose intolerance in children. This observational study was registered at the ClinicalTrials.gov (NCT03960333, https://clinicaltrials.gov/study/NCT03960333?term=NCT03960333&rank=1).

Ameliorative potential of β-sitosterol and lupeol on high fat diet and streptozotocin -induced hepatorenal and cardiac complications via regulation of carbohydrate metabolic enzymes in diabetic rats

Introductionβ-Sitosterol is a plant-derived compound that shares structural similarities with cholesterol and is used to treat coronary artery disease, prostate cancer, breast cancer, and hypercholesterolemia etc. Lupeol is a natural pentacyclic triterpene, found in a variety of fruits, vegetables, and traditional Chinese medicines like Astragalusmembranaceus and AtractylodesmacrocephalaKoidz. Numerous pharmacological activities of lupeol have been investigated; they include applications as antioxidant, antiviral, antihypertensive, anti-inflammatory and antitumor agents.The current study wasaimed to examine the potential benefits of β-sitosterol and lupeol in reducing pathophysiological complications caused by high fat diet and streptozotocin by regulating the enzymes involved in the metabolism of carbohydrates in diabetic rats as there was no study on this aspect. MethodsMale albino wistar rats were given a high-fat diet for two weeks in order to cause diabetes in them. Following a two-week period, the animals were administered a low dosage of streptozotocin and maintained on an overnight fast. Using commercial diagnostic kits, we assessed plasma glucose and glycated hemoglobin (HbA1C). Plasma insulin level was assayed with the help of an ELISA kit and other assays were made biochemically. ResultsThe homeostatic model of insulin resistance, glucose 6-phosphatase, fructose 1,6-bisphosphatase, and blood glucose levels all significantly increased in the diabetic rats, while plasma insulin, hexokinase, glucose 6-phosphate dehydrogenase, and glycogen content significantly decreased.In addition, the hepatic (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) and renal (urea and creatinine) indicators in diabetic rats were raised, and their lipid profiles were disrupted. However, diabetic rats treated with lupeol and β-sitosterol significantly restored all these changed parameters to the levels close to normal. Furthermore, the treatment of lupeol and β sitosterol improved the liver, kidney and heart histology alteration to near normal and prevented the body weight loss. DiscussionBecause of its structural polymorphism, β-sitosterol appeared to be more effective than lupeol in all the parameters investigated and thus these results imply that β sitosterol is a more effective antidiabetic medication than lupeol.

Obesity contributes to telomere shortening in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial disorder and obesity occurs in 38% to 88% of these women. Although hyperandrogenism may contribute to telomere lengthening, increased body mass index (BMI) is associated with telomere erosion. We sought to compare leukocyte telomere length (LTL) in PCOS women with normal, overweight, and obese BMI. We evaluated the relationship between LTL and clinical variables of PCOS and inflammatory biomarkers independent of BMI. A total of 348 women (243 PCOS and 105 non-PCOS) were evaluated for anthropometric measures, total testosterone, androstenedione, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting insulin and glycemia, lipid profile, homocysteine, C-reactive protein (CRP) and homeostatic model of insulin resistance (HOMA-IR). LTL was measured by qPCR. The PCOS group presented higher weight, waist circumference, BMI, testosterone, LH, fasting insulin, FAI, and HOMA-IR, and lower E2, SHBG, and fasting glycemia measures compared with the non-PCOS. When stratified by BMI, LTL was increased in all subgroups in PCOS compared to non-PCOS. However, in the PCOS group, LTL was lower in overweight (P = 0.0187) and obese (P = 0.0018)compared to normal-weight women. The generalized linear model showed that BMI, androstenedione, homocysteine, and CRP were associated with telomere biology. Women with PCOS had longer LTL, however, overweight or obesity progressively contributes to telomere shortening and may affect reproductive outcomes of PCOS, while androstenedione may increase LTL.

Evaluating the association between longitudinal exposure to a PFAS mixture and adolescent cardiometabolic risk in the HOME Study.

Exposure to per- and polyfluoroalkyl substances (PFAS) throughout gestation and childhood may impact cardiometabolic risk. In 179 HOME Study participants (Cincinnati, OH; recruited 2003-2006), we used latent profile analysis to identify two distinct patterns of PFAS exposure from serum concentrations of four PFAS measured at birth and ages 3, 8, and 12 years. We assessed the homeostatic model of insulin resistance, triglycerides-to-high-density lipoprotein cholesterol ratio, leptin-to-adiponectin ratio, systolic blood pressure, visceral fat, and hemoglobin A1c levels at age 12 years. We used multivariable linear regression to assess the association of membership in the longitudinal PFAS mixture exposure group with a summary measure of overall cardiometabolic risk and individual components. One PFAS exposure profile (n = 66, 39%) had higher geometric means of all PFAS across all visits than the other. Although adjusted associations were null in the full sample, child sex modified the association of longitudinal PFAS mixture exposure group with overall cardiometabolic risk, leptin-to-adiponectin ratio, systolic blood pressure, and visceral fat (interaction term P values: 0.02-0.08). Females in the higher exposure group had higher cardiometabolic risk scores (ß = 0.43; 95% CI = -0.08, 0.94), systolic blood pressures (ß = 0.6; 95% CI = 0.1, 1.1), and visceral fat (ß = 0.44; 95% CI = -0.13, 1.01); males had lower cardiometabolic risk scores (ß = -0.52; 95% CI = -1.06, -0.06), leptin-to-adiponectin ratios (ß = -0.7; 95% CI = -1.29, -0.1), systolic blood pressures (ß = -0.14; 95% CI = -0.7, 0.41), and visceral fat (ß = -0.52; 95% CI = -0.84, -0.19). Exposure to this PFAS mixture throughout childhood may have sex-specific effects on adolescent cardiometabolic risk.

Insulin-like growth factor-1 and cognition in normoglycemia, prediabetes, and type 2 diabetes mellitus

BackgroundThe relationship between insulin-like growth factor-1 (IGF-1) and cognition has been studied in healthy individuals, but not extensively with regards to insulin resistance and type 2 diabetes mellitus (T2DM). In this retrospective observational study, we investigated relationships of IGF-1 with memory and executive function across people with normoglycemia, prediabetes, and T2DM. MethodsData from the Midlife in the United States (MIDUS) study were used. Episodic memory and executive function were assessed using the Brief Test of Adult Cognition by Telephone approximately 21.42 ± 12.10 months prior to measuring IGF-1 levels from a fasting blood sample. Normoglycemia was identified as individuals without a physician diagnosis of diabetes and glycated hemoglobin (HbA1c) ≤5.6%. Prediabetes was identified as those without a physician diagnosis of diabetes and HbA1c between 5.7%−6.4%. T2DM was identified as anyone with a physician diagnosis of diabetes, or HbA1c ≥6.5%, or anyone using an oral hypoglycemic medication. The associations were assessed using linear regressions controlling for age, sex, education, body mass index, C-reactive protein, HbA1c or homeostatic model of insulin resistance, MIDUS wave, exercise, smoking status, sleep quality, alcohol intake, oral hypoglycemic use, and insulin use. ResultsThe study included 1400 participants, which consisted of 583 normoglycemic (48.4% female, mean age 51.0 ± 12.2 years), 512 prediabetes (58.4% female, mean age 57.3 ± 11.8 years), and 305 T2DM participants (53.8% female, mean age 57.6 ± 11.5 years). Peripheral IGF-1 concentrations were lower (F2,1397 = 28.29, p < 0.001) in people with prediabetes or T2DM, vs. normoglycemia. Participants with prediabetes or T2DM had lower episodic memory (F2,1397 = 9.21, p < 0.001) and executive function (F2,1397 = 20.29, p < 0.001) composite z-scores than people with normoglycemia. Higher IGF-1 concentrations were associated with better executive performance in individuals with prediabetes (β = 0.115 [0.028, 0.202], p = 0.010), but not in individuals with normoglycemia or T2DM. An interaction between IGF-1 and sex in predicting executive function was observed in the prediabetes group (β = −0.344, p = 0.042), where the relationship was weaker in females (β = 0.106 [−0.012, 0.224], p = 0.077) than males (β = 0.251 [0.123, 0.380], p < 0.001). No associations were seen between IGF-1 and memory. ConclusionThe results suggest that peripheral IGF-1 concentrations may be related to executive function, and that the relationship may be sex-specific and dependent on diabetes status.

Associations between insulin‐like growth factor‐1 and executive function in normoglycemia, prediabetes, and type 2 diabetes mellitus

AbstractBackgroundThe relationship between insulin‐like growth factor‐1 (IGF‐1) and cognition has been studied in healthy individuals, yet the results have been inconclusive. The aim of this study was to determine whether the association between IGF‐1 and executive function differs in individuals with normoglycemia, prediabetes, and type 2 diabetes mellitus (T2DM).MethodThe Midlife in the United States (MIDUS) study used the Brief Test of Adult Cognition by Telephone (BTACT) to assess cognitive function. A composite z‐score for executive function was created from the following tests: Digits backward span, category fluency, number series, backward counting, and Stop and Go Switch Task (SGST). IGF‐1 levels were measured from fasting blood samples using an immunochemiluminescent assay. Normoglycemia was defined as individuals without a physician diagnosis of diabetes and glycated hemoglobin (HbA1c) &lt; 5.6%. Prediabetes was defined as those without a physician diagnosis of diabetes and HbA1c between 5.7%‐6.4%. T2DM was defined as anyone with a physician diagnosis of diabetes, or HbA1c ≥6.5%, or use of oral hypoglycemic medication. Multiple imputation was used to handle missing covariate data. A linear regression model controlling for demographic factors, homeostatic model of insulin resistance (HOMA‐IR), C‐reactive protein (CRP) levels, exercise, smoking, sleep disturbance, alcohol intake and medication use, was used to determine the cross‐sectional association between IGF‐1 and executive function across subgroups.ResultThe MIDUS dataset included 447 normoglycemia (47.0% female, mean age 53.4±9.6), 467 prediabetes (57.4% female, mean age 56.8±10.6), and 271 T2DM participants (53.1% female, mean age 57.5±9.8). In participants with prediabetes, IGF‐1 levels were associated with better executive function (β = 0.126, p = 0.007), particularly in males (β = 0.258, p&lt;0.001). This association was absent in individuals with normoglycemia or T2DM. Compared to males with prediabetes, the opposite trend was observed in males with T2DM (β = ‐0.181, p = 0.062).ConclusionThe findings of this study suggest that the association between IGF‐1 and executive function may be influenced by insulin resistance or T2DM. Gaining a better understanding of why the associations differ in T2DM compared to prediabetes may explain the inconsistency observed in the literature and help elucidate the mechanism behind cognitive decline in T2DM.

1984. Effects of Semaglutide on Adipose Tissue in HIV-Associated Lipohypertrophy

Abstract Background Lipohypertrophy (central adipose tissue (AT) accumulation) is a common and significant problem in people with HIV (PWH). Pathogenesis remains elusive; yet, AT abnormalities are key drivers of cardiometabolic co-morbidities in HIV. We aimed to assess effects of semaglutide, a glucagon-like peptide-1 receptor agonist, on AT in PWH with lipohypertrophy. Methods We conducted a randomized, double-blinded, placebo-controlled trial of virologically-suppressed, non-diabetic PWH ≥ 18 years of age on stable antiretroviral therapy (ART) with body mass index (BMI) ≥ 25 kg/m2, increased waist circumference/waist-to-hip ratio, and subjective increased abdominal girth after ART initiation. Participants were randomized 1:1 to 32 weeks semaglutide (8-week titration + 24 weeks 1.0 mg weekly subcutaneous injection) or matching placebo. Computed tomography and whole-body dual-energy X-ray absorptiometry were used to measure area/density in abdominal AT [total (TAT), visceral (TAT), and subcutaneous (SAT)] and body composition [lean body mass (LBM), limb/trunk/total body fat (TBF)], resp. Semaglutide effects were estimated using generalized estimating equations or simultaneous quantile regressions on outcome variables. Results 108 participants were enrolled (N = 54 semaglutide: median age = 52 years, 70% male, 61% Black, 83% integrase inhibitor). Groups were well-matched at baseline. In unadjusted models, semaglutide group had greater reductions (P &amp;lt; 0.05) in BMI, homeostatic model of insulin resistance (HOMA-IR), trunk fat, TBF (at quantile ≥ 75th), TAT, and SAT with trends (P &amp;lt; 0.1) for limb fat and VAT (Fig 1/Table 1). Semaglutide effects remained significant for BMI, HOMA-IR, trunk fat, TAT, and VAT after adjusting for age, sex, CD4, and ART duration (Table 2); caloric intake was also significant at ≤ 50th quantile. No differences were seen in LBM, AT density, or VAT/TAT ratio. Semaglutide was well-tolerated; serious adverse events were rare. Conclusion Semaglutide significantly decreased central fat in PWH with lipohypertrophy, primarily driven by reductions in VAT. Semaglutide may offer an effective treatment to decrease visceral adiposity and reduce co-morbidity risk. Further investigation is needed to determine mechanisms by which reductions in visceral adiposity occur. Disclosures Grace A. McComsey, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support

Association of Physical Inactivity with MRI Markers of Brain Aging: Assessing Mediation by Cardiometabolic and Epigenetic Factors.

Cardiometabolic risk factors and epigenetic patterns, increased in physically inactive individuals, are associated with an accelerated brain aging process. To determine whether cardiometabolic risk factors and epigenetic patterns mediate the association of physical inactivity with unfavorable brain morphology. We included dementia and stroke free participants from the Framingham Heart Study Third Generation and Offspring cohorts who had accelerometery and brain MRI data (n = 2,507, 53.9% women, mean age 53.9 years). We examined mediation by the 2017-revised Framingham Stroke Risk Profile (FSRP, using weights for age, cardiovascular disease, atrial fibrillation, diabetes and smoking status, antihypertension medications, and systolic blood pressure) and the homeostatic model of insulin resistance (HOMA-IR) in models of the association of physical inactivity with brain aging, adjusting for age, age-squared, sex, accelerometer wear time, cohort, time from exam-to-MRI, and season. We similarly assessed mediation by an epigenetic age-prediction algorithm, GrimAge, in a smaller sample of participants who had DNA methylation data (n = 1,418). FSRP and HOMA-IR explained 8.3-20.5% of associations of higher moderate-to-vigorous physical activity (MVPA), higher steps, and lower sedentary time with higher brain volume. Additionally, FSRP and GrimAge explained 10.3-22.0% of associations of physical inactivity with lower white matter diffusivity and FSRP explained 19.7% of the association of MVPA with lower free water accumulation. Our results suggest that cardiometabolic risk factors and epigenetic patterns partially mediate the associations of physical inactivity with lower brain volume, higher white matter diffusivity, and aggregation of free water in the extracellular compartments of the brain.

Effect of Curcumin towards Metabolic Disturbance Parameters in Patient with PCOS: A Systematic Review and Meta-Analysis of Clinical and Preclinical Randomized Controlled Trials

Objective: Polycystic Ovarian Syndrome (PCOS) is a gynecologic and endocrine disorder with metabolic disturbances and infertility as the most common long-term consequences. Curcumin comes up as one of the alternative herbal remedies in PCOS treatment options. This study aimed to investigate the therapeutic effect of curcumin on metabolic disturbance parameters in PCOS patients and PCOS-modeled rats. Method: A systematic search of eligible studies was done using PubMed, Google Scholar, EBSCO-Host, and ProQuest according to the PRISMA 2009 guideline. We further assessed for risk of bias using SYRCLE’s risk of bias tool for preclinical studies and The Cochrane risk of bias assessment tool for the clinical studies. We used Review Manager (version 5.4) with random effect model to obtain a pooled mean difference with 95% CIs. Results: Five preclinical studies and three clinical studies were selected and pooled. The significant decrease in the level of Fasting Plasma Glucose (FPG), Fasting Insulin (FI), lipid profile, and Homeostatic Model of Insulin Resistance (HOMA-IR) value, and a significant increase in Quantitative Insulin-Sensitivity Check Index (QUICKI) value found in preclinical studies. The result for clinical studies showed a significantly decreased HOMA-IR values (SMD=-0.36, p=0.001), FPG level (SMD=-3.32, p=0.0001), Serum Insulin level (SMD=-1.47, p=0.002), and increased QUICKI value (SMD=0.01, p=0.006). Conclusion: Curcumin offers a substantial effect on metabolic disturbance parameters in PCOS patients and could be an alternative promising treatment for PCOS patients in the future.

Short-term effect of plant-based Nordic diet versus carbohydrate-restricted diet on glucose levels in gestational diabetes – the eMOM pilot study

BackgroundThe optimal nutritional treatment for gestational diabetes (GDM) is still a matter of debate. With increasing rates of GDM and potential negative consequences for the health of mother and child, the best treatment should be established. The Nordic diet with emphasis on plant-based protein show promising health outcomes in other populations but has yet to be investigated in GDM population. The aim of this study, which is part of the “Effect of plant-based Nordic diet versus carbohydrate-restricted diet on glucose levels in gestational diabetes” (eMOM) pilot study was to compare the short-term effects of healthy Nordic diet (HND) and the currently recommended moderate restriction of carbohydrates diet (MCRD) on glucose and lipid metabolism in women with GDM.MethodsThis was a randomized crossover where each of the diet interventions (HND and MCRD) were consumed for 3 days with a 3-day wash-out period in between. In total, 42 pregnant women diagnosed with GDM (< 29 + 0 gestational week) were randomized. Glucose data was collected by continuous glucose monitors (CGM, Freestyle Libre®, Abbott, USA) worn for 14 days, and participants gave blood samples before and after diet interventions. The primary outcome was time spent in glucose target range (TIR, < 7.8 mmol/L). TIR, 3-day mean tissue glucose as well as changes in fasting glucose, homeostatic model of insulin resistance (HOMA-IR) and blood lipids were analyzed with paired samples statistical analyses.ResultsThirty-six women with complete 14 days CGM data were analyzed. Both diet interventions produced a high degree of TIR (99% SD 1.8), without a difference between the diets (p = 0.727). The 3-day mean glucose was significantly lower in HND than in MCRD (p = 0,049). Fasting insulin (p = 0,034), insulin resistance (p = 0,030), total and LDL cholesterol (p = 0,023 and 0,008) reduced more in the MCRD diet than the HND. NS differences in any other measure of CGM or blood tests.ConclusionsHND and MCRD did not differ in terms of their short-term effect on TIR. A larger study with sufficient power is needed to confirm the differences in short-term mean glucose, insulin resistance and lipid metabolism.Trial registrationRegistered in clinicaltrials.gov (21/09/2018, NCT03681054).

1101-P: Glycemia after Pediatric Bariatric Surgery—Outcomes and Predictors

Background: Metabolic and bariatric surgery (MBS) is a safe and efficacious treatment for children and adolescents with severe forms of obesity. However, there are few data on the effects of pre-surgical fasting insulin homeostasis measures on post-surgical weight loss or glycemia. Methods: We analyzed data from n=216/242 individuals with ≥ Class 2 obesity prospectively enrolled in the multi-center, Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study for up to eight years. Individuals who had type 1 diabetes, a gastric band procedure, or lacked baseline data for insulin homeostasis measurements were excluded, leaving 216 individuals for analysis. Body composition was assessed through bioelectrical impedance measurements. An analysis of fasting markers of insulin homeostasis using homeostatic model of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), or HOMA-β and outcomes following MBS was performed. Results: Our cohort had a baseline mean age of 16.5 years, BMI of 52.7 kg/m2, and was 75.4% female. At 8-year follow up, participants had a mean BMI of 43.0 kg/m2. Pre-surgical measures of insulin homeostasis did not predict change in BMI or fat mass over eight years. However, larger improvements in HbA1c were positively associated with younger baseline age, higher baseline HOMA-IR and HOMA-β, and lower baseline HbA1c. Conclusion: Baseline markers of insulin homeostasis were not significantly associated with weight loss outcomes, but did predict glycemia 8 years after MBS. Disclosure S.Sisley: Speaker's Bureau; Rhythm Pharmaceuticals, Inc. A.S.Shah: None. K.J.Nadeau: None. M.M.Kelsey: Other Relationship; Boehringer Ingelheim Inc., Janssen Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc., Lilly. T.Gu: None. M.Michalsky: Advisory Panel; Lilly, Other Relationship; Intuitive Surgical, Stock/Shareholder; Intuitive Surgical. T.M.Jenkins: None. T.Inge: None. Funding National Institutes of Health (U01DK072493); U.S. Department of Agriculture-Agricultural Research Service (3092-5100-065)

The effects of high-load and low-load resistance training on insulin resistance, lipids and inflammation in coronary artery disease patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Javna agencija za raziskovalno dejavnost Republike Slovenije. Background Prevalence of diabetes and dysmetabolism is high in patients with coronary artery disease (CAD), therefore, the combination of resistance training (RT) and aerobic training (AT) is advised to provide optimal control of insulin metabolism, dyslipidaemia, and inflammation. Since previous studies examined only the effects of low load (LL) to moderate load resistance training (RT) (&amp;lt;60% of one repetition maximum [1-RM]), the effects of high load (HL) RT remains to be investigated. Purpose This study aimed to examine the effects of HL-RT and LL-RT combined with AT in comparison to solely AT on insulin resistance, lipids, and inflammation in patients with CAD. Methods Seventy-nine patients with CAD were randomised to combined AT and LL-RT (30%-40% of 1-RM), combined AT and HL-RT (70%-80% of 1-RM) or AT alone (50%-80% of peak power output). The study was completed by 59 patients, with [mean (SD)] age = 61 (8) years, height = 172.1 (8.4) cm, weight = 85.47 (15.43) kg and left ventricular ejection fraction = 53 (9) %. Patients in all three groups performed the same progressive AT consisted of 3-5 min of work-load interval cycling separated by 2 min of unloaded cycling progressing from 50% to 80% maximal workload achieved at baseline cardiopulmonary exercise test. In RT groups, the training load progressed from 70% of 1-RM (6–11 reps/set) to 80% of 1-RM (6–8 reps/set) in HL-RT group and from 35% of 1-RM (12–22 reps/set) to 40% of 1-RM (12–16 reps/set) in LL-RT group in the first seven weeks of the intervention. After 1-RM re-evaluation, training load progressed from 70% 1-RM (11 reps/set) to 80% 1-RM (6–8 reps/set) in HL-RT group, and from 35% 1-RM (22 reps/set) to 40% 1-RM (12–16 reps/set) in LL-RT group. We collected blood samples after overnight fast (≥10 hours) at baseline (prior to first training session) and post-training (prior to last training session) for analysis of glucose, insulin, homeostatic model of insulin resistance, total cholesterol, triglycerides, HDL and LDL cholesterol and C-reactive protein levels. Results Two-way analysis of variance showed only significant time effect on total cholesterol and LDL cholesterol (both p &amp;lt; 0.001) and C-reactive protein (p = 0.017), while there was no significant effect of time x group interaction on any of the blood biomarkers. When compared with baseline, total cholesterol and LDL levels were significantly lower after AT (total cholesterol: -0.4 mmol/l, p = 0.013; LDL: -0.4 mmol/l, p = 0.006) and HL-RT (total cholesterol: -0.5 mmol/l, p = 0.002; LDL: -0.5 mol/l, p = 0.002). In addition, there was a borderline decrease in triglycerides (AT group: -0.18 mmol/l, p = 0.053), glucose (LL-group: -0.6 mmol/l, p = 0.065) and C-reactive protein (HL-RT group: -0.9 mmol/l, p = 0.069) levels. Conclusions The combination of AT and RT, regardless of the RT load, was not superior to AT alone in improvement of insulin and lipids metabolism, and inflammation in patients with CAD.

Relationship between measures of adiposity, blood pressure and arterial stiffness in adolescents. The MACISTE study.

Children and adolescents with adiposity excess are at increased risk of future cardiovascular (CV) disease. Fat accumulation promotes the development of elevated blood pressure (BP) and arterial stiffness, two main determinants of CV risk which are strongly inter-related. We aimed at investigating whether the association between overweight and arterial stiffness, taken at different arterial segments, is mediated by increased BP or is BP-independent. Three hundred and twenty-two Italian healthy adolescents (mean age 16.9±1.4 years, 12% with overweight) attending the "G. Donatelli" High School in Terni, Italy, underwent measurement of arterial stiffness by arterial tonometry (aortic stiffness) and semiautomatical detection of pressure-volume ratio of the common carotid (carotid stiffness). The mediator effect of BP was tested for each anthropometric or biochemical measure of fat excess related to arterial stiffness. Both carotid and aortic stiffness showed positive correlations with body mass index, waist, hip, and neck circumferences (NC). Only carotid stiffness, but not aortic stiffness, was associated with serum markers of fat accumulation and metabolic impairment such as insulin, homeostatic model of insulin resistance (HOMA-IR), serum gamma-glutamyl transferase (sGGT) and uric acid. The association with NC was stronger for carotid than for aortic stiffness (Fisher z -to- R 2.07, P = 0.04), and independent from BP. In healthy adolescents, fat accumulation is associated with arterial stiffness. The degree of this association differs by arterial segments, since carotid stiffness is more strongly associated to adipose tissue excess than aortic stiffness and shows a BP-independent association with NC whereas aortic stiffness does not.

Eating and Lifestyle Habits in Underweight Patients with Insulin Resistance.

In recent years, there has been a significant increase in the prevalence of insulin resistance (IR) which has become a global health problem. Obesity is the typical clinical presentation of IR. The connection between underweight and IR is less known. The study aimed to investigate the characteristics of eating habits in underweight and obese patients with IR. After the obtained results, propose suitable dietary instructions specific to 2 subject groups. The task was to determine the difference in the nutritional status of underweight and obese patients with proven IR. The questionnaire was designed to collect data on diet and eating habits. The research included 60 subjects of both sexes between the ages of 20 and 60. Inclusion criteria for entering the study were: proven obesity (BMI ≥ 30), underweight (BMI≤18,5) and confirmed IR by assessment of the homeostatic model for insulin resistance (HOMA IR-2). BMI, waist-to-hip ratio (WHR), and visceral fat area (VFA) were calculated using the bioelectrical impedance. Data on dietary habits was collected using a questionnaire that included general patient data, physical activity, lifestyle and eating habits. Descriptive statistical methods were used to process and analyse the obtained data. The average BMI in obese subjects was 34.32 kg/m2, and in underweight subjects, 17.26 kg/m2. There are statistically significant differences between BMI, WHR and VFA. The mean value of HOMA-IR in the obese patients was 2.87 and in the underweight, 2.45. Underweight subjects have a statistically significant (p<0.05) tendency to lose weight, consume milk and milk products, prefer lean meat, and drink more alcohol. Obese subjects are significantly (p<0.05) less physically active, more prone to insomnia, tend to gain weight, enjoy food, consume fewer fruits and vegetables and more carbohydrate food, do not follow clinical nutritional guidelines, and mostly eat in a social setting. Both groups rarely practiced mindful eating. Consumption of highly processed food and sweets is common in both groups. There are statistically significant differences in the dietary and lifestyle habits of underweight and obese patients diagnosed with IR. It is necessary to educate healthcare workers and the general population about the importance of nutrition for preventing IR, regardless of body weight.

Association between integrase strand transfer inhibitor use with insulin resistance and incident diabetes mellitus in persons living with HIV: a systematic review and meta-analysis

Whether integrase strand transfer inhibitors (INSTIs) are associated with a higher risk of incident type 2 diabetes mellitus (DM) than other antiretroviral therapies (ART) needs to be established.MEDLINE, Embase, Web...

Obesity and metabolic dysfunction correlate with background parenchymal enhancement in premenopausal women.

This study tested the hypothesis that obesity and metabolic abnormalities correlate with background parenchymal enhancement (BPE), the volume and intensity of enhancing fibroglandular breast tissue on dynamic contrast-enhanced magnetic resonance imaging. Participants included 59 premenopausal women at high risk of breast cancer. Obesity was defined as BMI ≥ 30 kg/m2 . Metabolic parameters included dual-energy x-ray absorptiometry-quantified body composition, plasma biomarkers of insulin resistance, adipokines, inflammation, lipids, and urinary sex hormones. BPE was assessed using computerized algorithms on dynamic contrast-enhanced magnetic resonance imaging. BMI was positively correlated with BPE (r=0.69; p < 0.001); participants with obesity had higher BPE than those without obesity (404.9 ± 189.6 vs. 261.8 ± 143.8cm2 ; Δ: 143.1cm2 [95% CI: 49.5-236.7]; p=0.003). Total body fat mass (r=0.68; p < 0.001), body fat percentage (r=0.64; p < 0.001), visceral adipose tissue area (r=0.65; p < 0.001), subcutaneous adipose tissue area (r=0.60; p < 0.001), insulin (r=0.59; p < 0.001), glucose (r=0.35; p=0.011), homeostatic model of insulin resistance (r=0.62; p < 0.001), and leptin (r=0.60; p < 0.001) were positively correlated with BPE. Adiponectin (r=-0.44; p < 0.001) was negatively correlated with BPE. Plasma biomarkers of inflammation and lipids and urinary sex hormones were not correlated with BPE. In premenopausal women at high risk of breast cancer, increased BPE is associated with obesity, insulin resistance, leptin, and adiponectin.

Effect of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D and Homeostatic Model of Insulin Resistance Levels in Healthy Pregnancy: A Systematic Review and Meta-Analysis.

Progressive insulin resistance is a physiological condition during pregnancy that can lead to gestational diabetes. Given the association between low blood vitamin D levels and insulin resistance, the present meta-analysis evaluated the effect of vitamin D supplementation on serum 25-hydroxyvitamin D (25[OH]D) and the homeostatic model of insulin resistance (HOMA-IR) levels in non-diabetic pregnant women. A comprehensive literature search was conducted using electronic databases and gateways such as Cochrane Library, Medline, Google Scholar, Science Direct, Web of Sciences, Embase, and Scopus. Articles up to 2020 in both English and Persian were included in the study. The effect of vitamin D supplementation on 25(OH)D and HOMA-IR was determined based on the differences in mean changes from baseline to post-intervention. Weighted mean and 95% confidence intervals (CI) were pooled using a random-effects model. Data were analyzed using STATA software. Four studies, including six trials with 380 participants, reported that vitamin D supplementation increased 25(OH)D (mean change: 13.72, 95% CI: 7.28-20.17) and decreased HOMA-IR (mean change: 1.46, 95% CI: 0.56-2.37) levels compared with the placebo group. A high weekly dose of vitamin D further reduced HOMA-IR levels (adjusted R2=77.99, I2 residuals=80.49%, P=0.047). There was no significant association between the dose of vitamin D and 25(OH)D (P=0.974). Intervention duration was not associated with an increase in 25(OH)D (P=0.102), nor with a decrease in HOMA-IR (P=0.623). Vitamin D supplementation increased 25(OH)D and decreased HOMA-IR levels in non-diabetic pregnant women. Vitamin D in high doses further reduced HOMA-IR, but did not affect 25(OH)D concentrations.

Eating and Lifestyle Habits in Underweight Patients with Insulin Resistance

Background: In recent years, there has been a significant increase in the prevalence of insulin resistance (IR) which has become a global health problem. Obesity is the typical clinical presentation of IR. The connection between underweight and IR is less known. Objective: The study aimed to investigate the characteristics of eating habits in underweight and obese patients with IR. After the obtained results, propose suitable dietary instructions specific to 2 subject groups. The task was to determine the difference in the nutritional status of underweight and obese patients with proven IR. The questionnaire was designed to collect data on diet and eating habits. Methods: The research included 60 subjects of both sexes between the ages of 20 and 60. Inclusion criteria for entering the study were: proven obesity (BMI ≥ 30), underweight (BMI≤18,5) and confirmed IR by assessment of the homeostatic model for insulin resistance (HOMA IR-2). BMI, waist-to-hip ratio (WHR), and visceral fat area (VFA) were calculated using the bioelectrical impedance. Data on dietary habits was collected using a questionnaire that included general patient data, physical activity, lifestyle and eating habits. Descriptive statistical methods were used to process and analyse the obtained data. Results: The average BMI in obese subjects was 34.32 kg/m2, and in underweight subjects, 17.26 kg/m2. There are statistically significant differences between BMI, WHR and VFA. The mean value of HOMA-IR in the obese patients was 2.87 and in the underweight, 2.45. Underweight subjects have a statistically significant (p&lt;0.05) tendency to lose weight, consume milk and milk products, prefer lean meat, and drink more alcohol. Obese subjects are significantly (p&lt;0.05) less physically active, more prone to insomnia, tend to gain weight, enjoy food, consume fewer fruits and vegetables and more carbohydrate food, do not follow clinical nutritional guidelines, and mostly eat in a social setting. Both groups rarely practiced mindful eating. Consumption of highly processed food and sweets is common in both groups. Conclusion: There are statistically significant differences in the dietary and lifestyle habits of underweight and obese patients diagnosed with IR. It is necessary to educate healthcare workers and the general population about the importance of nutrition for preventing IR, regardless of body weight.

Assessment of serum levels of vitamin D and tissue levels of vitamin D receptors in acanthosis nigricans

Background Acanthosis nigricans (AN) is a skin disorder characterized by symmetrical, thickened, dark plaques comprising hyperkeratosis and acanthosis. Vitamin D (VD) plays an important role in the regulation of skin proliferation and differentiation, and mediates its action by binding to specific vitamin D receptors (VDR) in the nuclei of target cells. Objective To measure the serum levels of VD and tissue levels of VDR in a group of Egyptian patients with AN in comparison to healthy controls, in order to shed more light on the possible relation between VD, VDR, and AN. Patients and methods This study included 25 AN patients and 25 age-matched and sex-matched healthy controls. Blood samples and skin biopsies were taken from all participants for the evaluation of serum VD, glucose, insulin, and tissue VDR levels. Results Serum VD and tissue VDR were significantly lower (P<0.001 for both), while serum insulin and homeostatic model for insulin resistance were significantly higher (P<0.001 and P=0.002, respectively) in patients than controls. Patients had a more deficient pattern of VD status than controls (P<0.001). There was a statistically significant positive correlation between serum VD and tissue VDR in patients (r=0.632, P=0.001). Conclusion The present study suggests a possible role for low serum VD and tissue VDR levels in causing AN, in genetically predisposed individuals.