1. CHROMIUM SUPPLEMENTATION DECREASES INSULIN RESISTANCE AND TRUNK FAT Ellie Aghdassi, Ph.D., Irving E Salit, MD., Saira Mohammed, MSc.,Bianca M Arendt, Ph.D., and Johane P Allard, MD. The University Health Network, Toronto, Canada Role of Chromium (Cr) In Human Health Potentiates Insulin action  Glucose tolerance factor (GTF)  Lipid, Protein, Nucleic acid metabolism  Body composition Low Chromium is Associated With Abnormal Glucose Tolerance And Lipid Abnormalities (Woolliscroft 1977; Hopkins 1968; Anderson 1987; Riales 1981) Chromium: Mode Of Action  Increases insulin receptor number (Anderson 1987)  Activates receptor kinase ( required for phosphorylation of  -subunits) (Davis 1997)  Inhibits protein tyrosine phosphatase (Inhibits phosphorylation of  - subunits) (Imparl-Radosevich 1999)  I ncreases phosphorylation of the  -subunits of insulin receptor and thus increases insulin sensitivity Why Study Chromium in HIV? Frequent manifestations associated with ART are similar to low Cr status ( Abnormal glucose tolerance, Increased circulating insulin, Abnormal lipid profile, Alteration in body composition) HIV infection is associated with low levels of several micronutrients (Allard 1998, Baum 1995; Coodley 1991; Tang 1993; Abrams 1993) Low plasma chromium in HIV patients (Aghdassi et al, J Am Coll Nutr 2006) HYPOTHESIS In HIV-infected patients who have metabolic abnormalities, chromium supplementation improves insulin resistance and metabolic parameters Primary outcome: Change in insulin level Secondary outcomes: Changes in blood glycemia, HOMA, blood lipid profile and body composition (by DEXA scan) HOMA=homeostasis model assessment ={fasting blood glucose (mmol/L) x fasting blood insulin (mU/L)} / 22.5 BACKGROUND Screened HIV patients with at least one metabolic abnormality (n=110) Glucose > 6.1 mmol/l TG > 2 mmol/l Total cholesterol > 5.5 mmol/l HDL cholesterol < 0.9 mmol/l Body fat redistribution SUBJECTS & DESIGN Exclusion criteria -Cr-supplementation -Unstable drug regimen HIV patients with HOMA > 2.5 n=59 Randomized Chromium nicotinate (400 ug/d) (n=29) Placebo (di-calcium phosphate) (n=30) Completed n=25 Completed n=25 16 Weeks Subjects Characteristics RESULTS Ellie Aghdassi, Ph.D., RD. The University Health Network The Toronto General Hospital 200 Elizabeth Street, 10EN-242 Toronto, Ontario, M5G-2C4, Canada Tel: 416-340-4413 email:ellie.aghdassi@uhn.on.ca ABSTRACT Chromium (Cr) is an essential micronutrient; Cr deficiency has been reported to cause insulin resistance (IR), hyperglycemia and hyperlipidemia. Objectives: To investigate the effect of Cr supplementation on metabolic abnormalities, IR and body composition in people living with HIV (PLWH). Design: Randomized, double blind, placebo-controlled trial. Setting: Tertiary hospital clinic. Subjects: 59 HIV-positive subjects with evidence of body fat redistribution (BFR), elevated lipids or glucose and who were found to have IR based on the calculation of homeostasis model of assessment (HOMA). For inclusion, HOMA had to be> 2.5. Fifty subjects, 25 in each group completed the study. Intervention: Subjects were randomized to receive either 400 ug of Cr-nicotinate (Cr) or placebo (P) for a period of 16 weeks. Primary outcome: Change in fasting blood insulin. Other outcomes: Changes in fasting blood glucose, lipid profile and body composition. Results : Cr supplementation resulted in a significant decrease in blood insulin, blood triglycerides, HOMA, total body fat mass and trunk fat mass. Blood glucose, C-peptide, total cholesterol, LDL and HDL cholesterol and Hb A1c remained unchanged. Biochemical parameters did not change in the placebo group except for LDL cholesterol that increased significantly post supplementation with placebo. Body weight and medication profile remained stable throughout the study period for both groups. Conclusion: Chromium supplementation improved metabolic abnormalities, insulin resistance and body composition. The use of chromium supplements in conjunction with antiretroviral medications may be of benefit to PLWH and may decrease the medication- associated side effects such as insulin resistance and body fat redistribution. Chromium (n=29) Placebo (n=30) P-value Age (years)46.9 ± 1.450.9 ± 1.40.048 BMI (kg/m2)26.7 ± 0.826.2 ± 0.60.600 Gender (male/female)28/127/30.317 Smokers (%)20.7 %40.0 %0.107 CD4 (count/mm3)489 ± 55470 ± 480.794 Duration of HIV infection (years)11.1 ± 1.211.1 ± 1.00.965 Duration of ART (years) 8.1 ± 0.9 9.0 ± 0.90.471 Lipodystrophy score (Range: 1-32) 8.2 ± 1.4 8.3 ± 1.50.925 Presence of Body Fat Redistribution75.9%69.0%0.557 Undetectable Viral Load (<50 copies/ml)72.4 %63.0 %0.449 P=0.009 P=0.025  In HIV+ subjects with metabolic abnormalities chromium supplementation leads to:  ↓ insulin resistance  ↓ blood TG  ↓ total body fat mass  ↓ trunk fat mass  ↑ lean body mass  The effects of supplementation on insulin resistance was much more pronounced in patients with higher baseline insulin level  The effects on trunk fat mass was more pronounced in patients with BFR  Simple measurements such as fasting blood insulin, waist and hip circumference should be included in the routine assessment of the patients with metabolic abnormalities Results are expressed as Mean ± SEM or as proportion of patients. Comparison is done using Chi-square test for proportions and un-paired t-test for continuous variables. P<0.05 is considered statistically significant. Blood Biochemistry Body Composition P=0.038 P=0.033 Medication profile, body weight, did not change in the Cr-supplemented or the placebo group after 16 weeks. Results are reported as Mean ±SEM. Comparison is done using paired t-test between baseline and week 16 in each intervention group P=0.003 P=0.004 P=0.013 P=0.068 P=0.05 ChromiumPlacebo Comparison is done using Un-paired t-test between the chromium supplemented and the placebo group CONCLUSION Drop in insulin correlates with basal insulin level in Cr supplemented group R 2 =0.725 P=0.0001 Blood levels of glucose, Hb-A1c, C-peptide, total cholesterol and HDL cholesterol did not change in the Cr-supplemented or the placebo group after 16 weeks. # 936 Medications 1.0097% NRTI’s 0.87555.6%57.7%Protease Inhibitors 0.49444.4%53.8%NNRTI’s Lipid lowering27.6%30%0.838 Hypoglycemic10.3%13.3%0.723 Cardiovascular24.1%16.7%0.476 Antidepressant27.6 %34.5 %0.570