Higher Homeostatic Model Assessment Research Articles

Effects of Life Style Modifications (Dietary and Exercise) on Insulin Resistance in Egyptian Men with Impaired Glucose Tolerance

Insulin resistance (IR) is considered one of the most serious chronic conditions. Although IR usually starts silently (euglycemic state), it can seriously lead to impaired glucose tolerance and the development of diabetes mellitus (DM) with other debilitating complications. The current study was conducted for four months to test the application of healthy dietary modification and/or regular programmed exercise on 120 Egyptian male subjects with high blood glucose levels, high insulin levels, and high homeostatic model assessment of insulin resistance (HOMA-IR). They were assigned into 4 groups. The first group received no intervention (control). The second group received healthy dietary intervention. The third group received regular exercise program. The fourth group received both healthy dietary intervention and regular exercise program. Along with blood glucose and insulin levels; weight and triglycerides (TG) levels were also assessed. Compared to the control group, the results showed significant reduction (p˂0.05) in both fasting and postprandial blood glucose and insulin levels as represented by HOMA-IR along with significant reduction (p˂0.05) in the other metabolic parameters assessed during the study in both dietary intervention alone and exercise intervention alone groups. The reduction was more significant (p˂0.05) in the group that received both healthy dietary and regular exercise intervention. In conclusion; IR could be avoided if either healthy dietary modification and/or regular programmed exercise are adopted.

Low-dose of phenolic rich extract from Annona squamosa Linn leaves ameliorates insulin sensitivity and reduces body weight gain in HF diet-induced obesity.

Obesity is associated with metabolic abnormalities that increase the risk and severity of several diseases. This study aimed to explore whether the aqueous extract of Annona squamosa Linn leaves (ASE) can ameliorate metabolic abnormalities associated with high fat (HF) diet-induced obesity. Forty-eight male Wistar rats were distributed among four treatment groups: a standard low-fat diet group, a HF diet group, and two HF diet groups with a daily oral dose of ASE (100 or 200 mg/kg body weights) administered for 9 weeks. Daily energy intake, body weight, blood glucose levels and glucose tolerance, and insulin tolerance were evaluated. At the end of the study, organs, and tissues were collected and weighed for analysis, and blood samples were collected to determine the serum insulin levels and serum liver enzymes. Total phenolic and flavonoid contents and 2,2-Diphenyl-1-picrylhydrazyl free radical antioxidant activity of the ASE were evaluated. Oral administration of the low dose of ASE to HF diet-fed rats significantly reduced the long-term food intake and body weight gain without altering adiposity compared with untreated HF diet-fed rats. This outcome was accompanied by a significant improvement in insulin sensitivity and a reduction in fasting blood glucose (FBG) levels measured at weeks 6 and 9 of the study. The high dose of ASE had a short-term effect on body weight gain and food and caloric intake, and in the long-term, it improved FBG levels measured at weeks 6 and 9 of the study. The high dose of ASE resulted in hyperinsulinemia and high homeostatic model assessment for insulin resistance (HOMA-IR) value compared to healthy rats. Total phenolic and flavonoid contents were 74.9 ± 0.491 mg of gallic acid equivalent and 20.0 ± 0.091 mg quercetin equivalent per g of ASE, respectively. The antioxidant activity of ASE expressed as half-maximal inhibitory concentration (IC50) value was 8.43 ± 0.825 mg/mL. These data suggest that ASE can safely and potently reduce the development of insulin resistance induced by HF diet feeding and lowering body weight gain in a dose-dependent manner.

ODP250 The Role of Urine Renal Injury Markers in Obese Children and Adolescents with Diabetes Mellitus

Abstract Backgrounds Diabetic children especially who are obese lead to poor glycemic control thus are at higher risk for early microvascular complications. Renal tubulointerstitial markers play integral role in the evaluation of diabetic nephropathy and various biomarkers have been proposed. Yet, their role in obese pediatric population is uncertain. The aim of this study is to investigate renal injury markers in children with diabetes mellitus (DM) in relation with obesity and determine their role for early predictor of diabetic complications. Methods Fifty-three children and adolescents diagnosed with either type 1 or 2 DM and 44 controls aged 7-18 years were included. Clinical and laboratory characteristics including renal injury markers among subjects were compared with respective to body mass index (BMI), presence and type of DM. Results Urine neutrophil gelatinase associated lipocalin and kidney injury molecule-1 were lower whereas beta-2 microglobulin and n-acetylglucosamine (NAG) concentrations were higher in controls compared to diabetic children. None of renal injury markers showed significant difference between normoweight and obese children. In multiple regression analyses, urine NAG was associated with HbA1c and the presence of DM while high homeostatic model assessment of insulin resistance was identified as a risk factor of for increased urine NAG in type 2 diabetic children. Conclusion Urine NAG could be a marker associated not only with diabetic nephropathy, but also with insulin resistance regardless of BMI. Presentation: No date and time listed

Multidimensional sleep clusters and cardiometabolic risk factors in adolescents: Results from the GINIplus and LISA studies

BACKGROUND AND AIM Evidence of an association between sleep duration and body mass index is vast, but other sleep characteristics might also be relevant for cardiometabolic health. We aimed to identify sleep clusters based on multidimensional sleep characteristics, and to determine their associations with cardiometabolic risk markers in adolescents. METHODS A total of 1096 participants of the GINIplus and LISA birth cohorts, wearing accelerometers for one week during the 15-year follow-up, were included. K-means cluster analysis was performed based on twelve sleep characteristics including daily average and day-to-day variability, respectively, of total sleep time (TST), sleep efficiency, sleep-onset latency, sleep onset timing, time awake per hour after sleep onset, number of awakenings per hour. Cardiometabolic markers were dichotomized based on established cut-offs or sex-specific percentiles, including high fat mass index, prehypertension, high triglycerides, low high-density lipoprotein cholesterol, high C-reactive protein, and high homeostatic model assessment of insulin resistance (HOMA-IR). Cross-sectional, logistic regression models were run adjusting for potential confounders. RESULTS Five sleep clusters were identified: good sleep (n=391; average TST 7.7 hours), late but high-efficient sleep (n=224; 6.9 hours), irregular sleep (n=101; 6.9 hours), difficulty staying asleep (n=298; 6.8 hours), and difficulty falling asleep (n=82; 6.9 hours). Compared with "good sleep”, the "irregular sleep” cluster was associated with higher odds of high triglycerides (odds ratio (OR) = 2.43, 95% confidence interval (CI) =1.29-4.60). Moreover, the "difficulty falling asleep” cluster was associated with increased odds of high HOMA-IR (OR=3.09, 95%CI=1.25-7.65). The "late but high-efficient sleep” and "difficulty staying asleep” clusters were not significantly associated with cardiometabolic markers. CONCLUSIONS Clusters describing "difficulty falling asleep” and "irregular sleep” patterns were associated with high insulin resistance and high triglycerides, respectively, in adolescents. Improving sleep quality and quantity in different sleep dimensions might benefit adolescents’ cardiometabolic health. KEYWORDS Sleep, cardiometabolic markers, adolescents, cluster analysis, accelerometry

Predictors of early and sustained virological response of viral hepatitis C.

Due to complex interplay between host and viral factors, pathogenesis of chronic hepatitis C (CHC) is considered a challenging issue. Infection with hepatitis C virus (HCV) is not confined only to liver but can induce disturbances in many other organs and systems. Our primary aim for this study was to evaluate biological response rates and sustained virological response (SVR) in patients diagnosed with CHC, treated with Interferon-alpha (IFN-α), Pegylated (PEG)–IFN-α2a or -α2b plus Ribavirin. The second aim of the study was the identification of predictive factors for a favorable response to antiviral therapy in patients diagnosed with CHC. We enrolled in this study 210 patients diagnosed with CHC who have accomplished all inclusion and exclusion criteria, treated with PEG–IFN plus Ribavirin. Patients’ recovery progress has been evaluated by determining: age, gender; biochemical tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST); serological assays – detect anti-HCV antibody and molecular assays – detect, quantify and/or characterize hepatitis C viral load (ribonucleic acid) (HCV-RNA); liver histopathological (HP) examination. According to their response to treatment, they were classified into responders (n=145) and non-responders (n=65). Liver biopsies were histopathologically evaluated for necroinflammatory grade and fibrosis stage according to the modified Ishak and Metavir scoring systems for chronic hepatitis. Demographic, laboratory, and HP results were introduced in statistical analysis. These parameters were included in area under curve (AUC) analysis in order to estimate their degree of influence on getting early virological response (EVR) and SVR. Our study demonstrates that factors connected to treatment failure in CHC are linked to older age, high hepatitis C viral load, and impaired glucose tolerance at beginning of treatment [high fasting glucose and insulin, high homeostatic model assessment of insulin resistance (HOMA-IR) index] and also to liver histology features (high fibrosis score, liver steatosis, iron infiltration, and more or less high necroinflammatory activity). Analyzing results of our study shows that HOMA-IR index, serum insulin levels, baseline HCV-RNA, baseline mean blood glucose and HP score like Ishak fibrosis score, steatosis score and liver iron score may have a predictive value for obtaining an EVR in patients diagnosed with CHC.

Contribution of 20-year body mass index and waist circumference history to poor cardiometabolic health in overweight/obese and normal weight adults: A cohort study

Background and aimsWe investigated the associations of 20-year body mass index (BMI) and waist circumference (WC) histories with risk of being 1) metabolically unhealthy overweight/obese (MUOO) vs metabolically healthy overweight/obese (MHOO) and 2) metabolically unhealthy normal weight (MUNW) vs metabolically healthy normal weight (MHNW). Methods and resultsParticipants comprised 3018 adults (2280 males; 738 females) with BMI and WC measured, every ~5 years, in 1991–1994, 1997–1999, 2002–2004, 2007–2009, and 2012–2013. Mean age in 2012–2013 was 69.3 years, with a range of 59.7–82.2 years. Duration was defined as the number of times a person was overweight/obese (or centrally obese) across the 5 visits, severity as each person's mean BMI (or WC), and variability as the within-person standard deviation of BMI (or WC). At the 2013–2013 visit, participants were categorised based on their weight (overweight/obese or normal weight; body mass index (BMI) ≥25 kg/m2) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol, high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance). Logistic regression was used to estimate associations with the risk of being MUNW (reference MHNW) and MUOO (reference MHOO) at the last visit. BMI and WC severity were each related to increased risk of being unhealthy, with estimates being stronger among normal weight than overweight/obese adults. The estimates for variability exposures became null upon adjustment for severity. Individuals who were overweight/obese at all 5 time points had a 1.60 (0.96–2.67) times higher risk of being MUOO than MHOO compared to those who were only overweight/obese at one (i.e., the last) time point. The corresponding estimate for central obesity was 4.20 (2.88–6.12). Greater duration was also related to higher risk of MUNW than MHNW. ConclusionBeing overweight/obese yet healthy seems to be partially attributable to lower exposure to adiposity across 20 years of adulthood. The results highlight the importance of maintaining optimum and stable BMI and WC, both in adults who become and do not become overweight/obese.

Glucose tolerance in a cohort of Egyptian children after kidney transplantation

BackgroundPost- transplantation diabetes mellitus (PTDM) in children is a serious metabolic complication that can endanger both graft and patient survival. These complications can be partially reduced by early diagnosis & prompt treatment of impaired glucose tolerance. The aim of this study was to assess glucose tolerance & insulin resistance among a cohort of kidney transplanted children. MethodsThirty consecutive pediatric kidney transplant recipients were subjected to basal evaluation of plasma glucose and insulin then underwent oral glucose tolerance test (OGTT). ResultsAbnormal glucose metabolism was detected in 7 (23.3%) patients; 3 (10%) patients with PTDM; 3 (10%) patients with impaired fasting glucose (IFG) and 1 (3.3%) patient with IFG and impaired glucose tolerance (IGT). Four (13.3%) patients had high Homeostatic model assessment of insulin resistance (HOMA-IR). Patients with abnormal glucose metabolism had significantly higher tacrolimus trough levels and higher maintainence steroid doses (p values = 0.003,0.026). Significant positive correlation existed between pre-transplantation glucose level and post-transplantation fasting glucose (p = 0.001, r = 0.69), glucose at 120 min (p = 0.018, r = 0.429) and HOMA-IR (p = 0.008, r = 0.47). ConclusionAbnormalities in glucose metabolism (IFG, IGT &PTDM) are frequent in Egyptian pediatric kidney transplant recipients. OGTT is the gold standard for assessment of abnormalities in glucose metabolism.

P0894OBESITY IMPAIRS THE ACUTE RESPONSE TO AN ORAL PHOSPHATE CHALLENGE

Abstract Background and Aims T Obesity is an increasing health problem world-wide. People who are overweight or obese are at greater risk of developing chronic diseases including cardiovascular disease (CVD). Factors associated with dysregulated phosphate metabolism have been linked to the presence of vascular calcification in people with type 2 diabetes (T2D) with normal kidney function. Insulin resistance and abdominal obesity are associated with increased circulating levels of phosphaturic hormones including fibroblast growth factor 23 (FGF-23) and parathyroid hormone (PTH). Abnormalities in phosphate regulation may not be reflected in single circulating measurements of serum phosphate, but can be revealed by the acute circulating and mineral response to an oral challenge of phosphate. The aim of this study was to determine if obesity and insulin resistance impact the acute capacity to excrete an oral phosphate challenge. Method Community-dwelling people (N=78) free of T2D and symptomatic CVD (∼10 males and ∼10 females from each decade between 40 and 80 years) with normal kidney function were recruited from Kingston, Ontario, Canada. Following a 12-hour fast, participants consumed a 1250 mg phosphate drink (sodium phosphate) where blood and urine were collected at baseline, 1, 2 and 3 hours following the oral challenge. Participants with a high-risk metabolic profile characterized by an elevated waist-to-height ratio (WHtR) (> 0.58) were matched by age and sex to participants with a low risk WHtR (<0.5). Results The results reveal a significant impact of obesity on phosphate excretion in response to an oral phosphate challenge. There was an association between WHtR ratio and the level of iFGF-23 (R=-0.34 p<0.01) but not PTH. After adjustment for age and sex, WHtR ratio was inversely correlated with urinary phosphate excretion in response to the phosphate challenge (R=-0.29, p=0.02) and the change in fractional excretion of phosphate (r=-0.34, p=0.007). From the larger cohort, an age- and sex- matched subset was selected for 12 high risk and 12 low risk metabolic profiles with WHtR of 0.66±0.02 and 0.46±0.01, respectively. Kidney function was the same between the two groups (eGFR 92.3±13.1 versus 95.8±13.6 ml/min/1.73m2 respectively) but high risk participants had significantly higher homeostatic model assessment of insulin resistance (HOMA-IR) (1.61±0.81 versus 0.68±0.3, p<0.01). Participants with a high risk metabolic profile had a greater increase in serum phosphate from baseline (29% increase in the area under the curve, p=0.04) and a significantly blunted increase in the fractional excretion of phosphate in response to the oral phosphate challenge (35% reduction in area under the curve [AUC], p=0.03) compared to the matched low risk profile participants. Conclusion Overweight/obese individuals demonstrate impaired response to an oral phosphate challenge, whereby phosphate excretion was impaired and there was increased exposure to new circulating phosphate. An impaired acute phosphate response may contribute to the initiation or propagation of vascular calcification. Dysregulated phosphate homeostasis may be an under-recognized cardiovascular risk factor in obese people that could be modified by diet and weight loss. Whether insulin enhances renal phosphate reabsorption requires further study.

<p>Adiposity Indicators as Cardio-Metabolic Risk Predictors in Adults from Country with High Burden of Obesity</p>

BackgroundIn Qatar more than 70% 0f the adults are overweight and obese. Different adiposity assessment methods have been proposed to identify individuals at cardio-metabolic risk.PurposeThis study aimed to compare anthropometric indicators with Dual-energy X-ray absorptiometry (DXA) –derived adiposity indicators in predicting cardio-metabolic risk among Qatari adults.Patients and MethodsA random sample of five hundred and fifty-eight (558) healthy Qatari adults (men and women) aged 20 to 50 years was obtained from Qatar Biobank survey data. Anthropometric data (weight, height, and waist circumference), the DXA-derived data, and cardio-metabolic (CM) risk parameters were analyzed. A Spearman partial correlation coefficient, Receiver Operating Characteristics (ROC) curve and an area under curve (AUC) were used to assess the predicting ability of adiposity indicators for CM risk factors.ResultsAdiposity indices (anthropometric and DXA) were significantly correlated with most of the CM indicators (r= −0.292 to 0.486, p< 0.001). The AUC of waist to height ratio (WHtR) was significantly higher than that of body mass index (BMI) and waist circumference (WC) in the prediction of low high density lipoprotein (HDL) (AUC=0.65, AUC=0.59; AUC=0.64), high low density lipoprotein (LDL) (AUC=0.67; AUC=0.62; AUC=0.66), high cholesterol (AUC=0.66; AUC=0.63; AUC=0.63), and high Homeostatic Model Assessment- (HOMA) (AUC= 0.81; AUC= 0.78; AUC=0.78). Among DXA- parameters, trunk fat had the highest AUCs for total cholesterol (AUC= 0.64, CI=0.56, 0.73), triglycerides and glucose index (TyG) (AUC=0.69, CI=0.64, 0.74), and HOMA (AUC=0.78, CI= 0.73, 0.84).ConclusionResults of the present study show that adiposity indicators (WC and WHtR) are clinically valuable tools to identify individuals at risk of CVD compared to DXA–derived parameters, while DXA can provide more accurate estimates.

The high homeostatic model assessment of insulin resistance as risk factor for acne vulgaris

Background: Acne vulgaris (AV) is a common chronic skin disease involving blockage and or inflammation of pilosebaceous glands which usually affects teenagers and young adults. Elevated sebaceous gland secretion, Propionibacterium acne colonization and inflammation, high androgen effects, and follicular hyperproliferation are the main pathogenic factors of AV. IGF-1 and insulin were studied to stimulate sebaceous lipogenesis. In the skin, besides inducing lipid production in human sebocytes IGF-1 also induces keratinocyte proliferation in vitro and in vivo. HOMA-IR is an examination to determine insulin activity in the basal state.Objective: To prove that high HOMA-IR value is a risk factor for the occurrence of acne vulgaris.Methods: This study is a case control analytic study by comparing HOMA-IR in subjects with AV (case group) and non AV (control group). AV is diagnosed based on clinical predilection. Insulin testing was carried out by the immulite 2000 device through the immunochemiluminescent method.Results: Mean HOMA-IR of case group is 2.63 ± 0.29 meanwhile in the control group was 1.71 ± 0.26 (p &lt;0.001). Subjects with high HOMA-IR had 4.8 times higher risk to experience AV compared to patients with normal HOMA-IR values (p &lt;0.001; 95% IK 2,765-8,332). Conclusion: HOMA-IR values in acne patients were higher than controls. A high HOMA-IR value is an AV risk factor.

The high homeostatic model assessment of insulin resistance as risk factor for acne vulgaris

Background: Acne vulgaris (AV) is a common chronic skin disease involving blockage and or inflammation of pilosebaceous glands which usually affects teenagers and young adults. Elevated sebaceous gland secretion, Propionibacterium acne colonization and inflammation, high androgen effects, and follicular hyperproliferation are the main pathogenic factors of AV. IGF-1 and insulin were studied to stimulate sebaceous lipogenesis. In the skin, besides inducing lipid production in human sebocytes IGF-1 also induces keratinocyte proliferation in vitro and in vivo. HOMA-IR is an examination to determine insulin activity in the basal state.&#x0D; Objective: To prove that high HOMA-IR value is a risk factor for the occurrence of acne vulgaris.&#x0D; Methods: This study is a case control analytic study by comparing HOMA-IR in subjects with AV (case group) and non AV (control group). AV is diagnosed based on clinical predilection. Insulin testing was carried out by the immulite 2000 device through the immunochemiluminescent method.&#x0D; Results: Mean HOMA-IR of case group is 2.63 ± 0.29 meanwhile in the control group was 1.71 ± 0.26 (p &lt;0.001). Subjects with high HOMA-IR had 4.8 times higher risk to experience AV compared to patients with normal HOMA-IR values (p &lt;0.001; 95% CI 2.765-8.332).&#x0D; Conclusion: HOMA-IR values in acne patients were higher than controls. A high HOMA-IR value is an AV risk factor.

Do worse baseline risk factors explain the association of healthy obesity with increased mortality risk? Whitehall II Study

ObjectiveTo describe 20-year risk factor trajectories according to initial weight/health status and investigate the extent to which baseline differences explain greater mortality among metabolically healthy obese (MHO) individuals than healthy non-obese individuals.MethodsThe sample comprised 6529 participants in the Whitehall II study who were measured serially between 1991–1994 and 2012–2013. Baseline weight (non-obese or obese; body mass index (BMI) ≥30 kg/m2) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance (HOMA-IR)) were defined. The relationships of baseline weight/health status with 20-year trajectories summarizing ~25,000 observations of systolic and diastolic blood pressures, HDL-C, triglycerides, glucose, and HOMA-IR were investigated using multilevel models. Relationships of baseline weight/health status with all-cause mortality up until July 2015 were investigated using Cox proportional hazards regression.ResultsTrajectories tended to be consistently worse for the MHO group compared to the healthy non-obese group (e.g., glucose by 0.21 (95% CI 0.09, 0.33; p < 0.001) mmol/L at 20-years of follow-up). Consequently, the MHO group had a greater risk of mortality (hazard ratio 2.11 (1.24, 3.58; p = 0.006)) when the referent group comprised a random sample of healthy non-obese individuals. This estimate, however, attenuated (1.34 (0.85, 2.13; p = 0.209)) when the referent group was matched to the MHO group on baseline risk factors.ConclusionsWorse baseline risk factors may explain any difference in mortality risk between obese and non-obese groups both labelled as healthy, further challenging the concept of MHO.

Insulin resistance causes inflammation in adipose tissue.

Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa.

Glucose metabolism before and after radioiodine therapy of a patient with Graves' disease: Assessment by continuous glucose monitoring.

Hyperthyroidism causes impaired glucose tolerance, insulin resistance (IR) and insulin secretion. However, the glucose variability affected by thyroid dysfunction remains unclear. Glucose variability was assessed by continuous glucose monitoring (CGM) in a non-diabetic patient with Graves' disease (GD), to the best of our knowledge, for the first time. A 28-year-old man with GD, who had been taking methimazole for 4 years, was treated with radioiodine on August 17th 2016. Although the patient exhibited normal glycated hemoglobin (HbA1c; 5.3%) and blood glucose values during the oral glucose tolerance test (OGTT; fasting and 120 min blood glucose were 5.38 and 6.39 mmol/l, respectively) before radioiodine therapy, CGM exhibited high 24 h mean glucose and nocturnal hyperglycemia. An increased fasting insulin level, suppressed levels of blood glucagon and high homeostatic model assessment of IR were also observed. The disordered glucose metabolism improved as soon as the patient's thyroid function turned to hypothyroidism 4 months after radioiodine therapy. The glucose intolerance in patients with hyperthyroidism, missed by the OGTT and HbA1c tests, may be more common than anticipated.

Regional Patterns of Pulsatility Index and Wall Shear Stress Across Cerebral Circulation of Adolescents with High Insulin Resistance

BackgroundInsulin resistance (IR) is associated with altered arterial stiffness, blood flow, and shear stress patterns in the peripheral circulation of middle‐aged and older diabetic and non‐diabetic hypertensive populations. Both altered blood flow and shear stress patterns may contribute to the elevated risk of cerebrovascular disease in IR populations. The aim of this study was to determine if adolescents (12–18yrs) with high IR (indexed as High Homeostatic Model Assessment of IR, HOMA‐IR) display early signs of cerebrovascular dysfunction. We hypothesized that young adolescents with a high HOMA‐IR would exhibit increased stiffness and decreased shear patterns in cerebral conduit arteries.Methods2 healthy controls (17±3) and 3 IR subjects (14±1) underwent a single 4D Flow MRI scan (scan time ~ 5min, no contrast given) to quantify cerebral blood flow (CBF), pulsatility index (PI) and wall shear stress (WSS) in extracranial and intracranial conduit arteries. 11 arteries were analyzed: middle cerebral (MCA) x2, anterior cerebral (ACA) x2, posterior cerebral (PCA) x2, vertebral (VA) x2, internal carotid (ICA) x2, and basilar. PI was calculated for each artery as [(CBFmax − CBFmin)/CBFmean]. WSS was measured by segmenting the vascular tree from PC angiograms and calculating the velocity gradient at the vessel wall using 4D flow MRI data over ~3 voxel. Due to voxel limitations, the PCA value is exploratory. Total CBF was calculated as the sum of both ICA and both VA. Significance was determined using a two‐tail Welch's t‐test.ResultsIndividuals with IR displayed higher HOMA‐IR (IR 5.3±0.2, Ctrl, 3.3±0.3, p=0.02), BMI (kg•m2; IR 28±2, Ctrl 19±4, p=0.03) and fasting insulin (μU/mL; IR 25±4, Ctrl 13±0, p=0.04), but fasting glucose was not different (mg/dL; IR 79±4, Ctrl 93±5, p=0.07). PI was not different between groups among the 11 conduit arteries. However, there was a trend for higher PI in the IR group in the left PCA and right VA. Resting WSS did not differ between Ctrl and IR among the 11 conduit arteries. Similarly, total resting CBF was not different between Ctrl and IR (mL/min; IR 811±115, Ctrl 735±79, p=0.64).ConclusionPI or WSS were similar in 11 conduit arteries of cerebral circulation in adolescent controls compared to IR. These data indicate IR does not cause measurable arterial stiffening or altered total cerebral blood flow patterns. Therefore, the pathogenic arterial characteristics observed in middle‐aged adults with IR may be linked to the duration and/or severity of IR in association with other known vascular pathological processes linked to aging.Support or Funding InformationThis research was made possible by the National Science Foundation Grant #HRD‐1500138 (UW‐Madison WiscAMP‐BD program) and UW Graduate School Pilot Funding.

IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV‐coinfected patients

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate(®) assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n=65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P=0.024), as well as the subgroups of patients with significant fibrosis (P=0.047) and infected with HCV genotype 3 (P=0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR)=2.02; P=0.034), in patients with significant fibrosis (aOR=2.86; P=0.039) and HCV genotype 3 patients (aOR=4.89; P=0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.

Lipodystrophy and Inflammation Predict Later Grip Strength in HIV-Infected Men: The MACS Body Composition Substudy

Body fat changes in HIV-infected persons are associated with increased systemic inflammation and increased mortality. It is unknown whether lipodystrophy is also associated with declines in physical function. Between 2001 and 2003, 33 HIV-infected men with evidence of lipodystrophy (LIPO⁺), 23 HIV-infected men without lipodystrophy (LIPO⁻), and 33 seronegative men were recruited from the Multicenter AIDS Cohort Study (MACS) for the Body Composition substudy. Visceral adipose tissue (VAT) was assessed by quantitative computed tomography. Lean body mass (LBM) and extremity fat were measured by dual-energy x-ray absorptiometry. Insulin resistance was estimated by Homeostatic Model Assessment (HOMA). Serum interleukin (IL)-6, soluble tumor necrosis factor (TNF)-α receptors I and II (sTNFRI and sTNFRII), and highly sensitive C-reactive protein (hs-CRP) concentrations were quantified from archived serum samples. These measurements were correlated with grip strength measured in 2007 using linear regression. At the substudy visit, the LIPO⁺ group had higher HOMA, sTNFRI, sTNFRII, and IL-6 levels than the LIPO⁻ group. In 2007, the LIPO⁺ group had lower median grip strength than the LIPO⁻ group (34.4 vs. 42.7 kg, p=0.002). Multivariable analysis of HIV⁺ men showed older age, lower LBM, higher sTNFRII concentrations, and LIPO⁺ status [adjusted mean difference -4.9 kg (p=0.045)] at the substudy visit were independently associated with lower subsequent grip strength. Inflammation, lower LBM, and lipodystrophy in HIV-infected men were associated with lower subsequent grip strength. These findings suggest that inflammation may contribute to declines in functional performance, independent of age.

Insulin Resistance as a Predictor of Gains in Body Fat, Weight, and Abdominal Fat in Nondiabetic Women: A Prospective Study

The purpose was to determine the relationship between insulin resistance (IR) and risk of gaining body fat percentage (BF%), body weight, and abdominal fat over 18 months. A prospective cohort study was conducted using a sample of 226 women. IR was assessed using fasting blood insulin and glucose levels to calculate homeostatic model assessment (HOMA). Participants were divided into High (4th quartile) Moderate (2nd and 3rd quartiles), and Low (1st quartile) HOMA categories. BF% was estimated using plethysmography (Bod Pod), weight was measured in a standard swimsuit, and abdominal fat was indexed using the average of two circumferences taken at the umbilicus. Participants wore accelerometers and completed weighed food logs for 7 consecutive days to control for the effect of physical activity (PA) and energy intake, respectively. On average, women in the High HOMA group decreased in BF% (-0.48 ± 3.60), whereas those in the Moderate (0.40 ± 3.66) and Low HOMA (1.17 ± 3.15) groups gained BF% (F = 5.4, P = 0.0211). Changes in body weight showed a similar dose-response relationship (F = 4.7, P = 0.0317). However, baseline IR was not predictive of changes in abdominal fat (F = 0.8, P = 0.3635). Controlling for several covariates had little effect on gains in BF% and weight, but adjusting for initial BF% and/or initial weight nullified changes in BF% and weight across the IR groups. In conclusion, women with High HOMA tend to gain significantly less BF% and weight than women with low or moderate HOMA. The decreased risk appears unrelated to several covariates, except initial BF% and weight levels, which seem to play key roles in the relationships.

Prevalence of insulin resistance in a young adult population. Relationship with weight status

AimTo estimate the prevalence of insulin resistance using both the Homeostatic Model Assessment (HOMA) index and basal insulinemia, and to analyze its relationship to overweight, as measured by body mass index (BMI) and waist circumference (WC). Patients and methodsA series of 118 non-diabetic young adults aged 18 and 19years attending a primary care health center were studied. They were contacted by telephone, and their BMI, WC, HOMA and basal insulinemia were measured, among other parameters. ResultsHOMA values ≥P90 (HOMA ≥3.15) were found in 9.3% of the sample (50% in the obesity group). Insulinemia ≥P90 (16.9) was found in 11%. Based on BMI, 17.8% were overweight (26.5% of men, 11.6% of women), and 6.8% were obese (6.1% of men, 7.2% of women). Based on WC, 5.71% were obese when waist was measured at the midpoint and 15.38%, when measured at the iliac crest. HOMA was found to be significantly correlated to weight increase, BMI, WC, systolic blood pressure, triglycerides, and blood glucose, while correlation was only found between insulinemia and increased WC and decreased high lipoprotein cholesterol (HDL) levels. ConclusionIn this young adult sample, increased BMI and WC were associated to increased insulin resistance. High HOMA values were found in 9.3% of subjects.

Prevalencia de resistencia a insulina en una población de jóvenes adultos. Relación con el estado ponderal

AimTo estimate the prevalence of insulin resistance using both the Homeostatic Model Assessment (HOMA) index and basal insulinemia, and to analyze its relationship to overweight, as measured by body mass index (BMI) and waist circumference (WC). Patients and methodsA series of 118 non-diabetic young adults aged 18 and 19 years attending a primary care health center were studied. They were contacted by telephone, and their BMI, WC, HOMA and basal insulinemia were measured, among other parameters. ResultsHOMA values ≥ P90 (HOMA ≥3.15) were found in 9.3% of the sample (50% in the obesity group). Insulinemia ≥ P90 (16,9) was found in 11%. Based on BMI, 17.8% were overweight (26.5% of men, 11.6% of women), and 6.8% were obese (6.1% of men, 7.2% of women). Based on WC, 5.71% were obese when waist was measured at the midpoint and 15.38%, when measured at the iliac crest. HOMA was found to be significantly correlated to weight increase, BMI, WC, systolic blood pressure, triglycerides, and blood glucose, while correlation was only found between insulinemia and increased WC and decreased high lipoprotein cholesterol (HDL) levels. ConclusionIn this young adult sample, increased BMI and WC were associated to increased insulin resistance. High HOMA values were found in 9.3% of subjects.