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Download Update on Lipodystrophy
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Metabolic Complications of HIV Dr Lou Haenel, Jr Endocrinology 12/10 Terminology Lipodystrophy Lipoatrophy Lipohypertrophy HIV HAART (Highly Active Anti-Retroviral Therapy) Facial lipoatrophy Buffalo Hump Peripheral Lipoatrophy Body-Fat Abnormalities Reported in 40-50% of ambulatory HIVinfected patients Preliminary case definition by DEXA and CT imaging not ready for widespread clinical practice Central fat accumulation tends to be visceral in location Location Visceral (Hepatic, Omental) Buffalo hump Breasts Facial Neck Extremities Etiology HIV – Direct virus mediated effect Protease Inhibitor Nucleoside analogue reversetranscriptase inhibitors Nonnucleoside reverse transcriptase inhibitors Cytokine mediated effect (Adipocytokine) Pathogenesis Inhibiting sterol regulatory enhancerbinding protein 1 (SREBP1) mediated activation of retinoid X and PPARλ Disruption of adipogenesis Inhibit mitochondrial DNA polymerase alpha (DNA replication) TNFα receptor alteration Clinical Implications Physical changes Hypertriglyceridemia Low HDL cholesterol Modest increases in LDL cholesterol Increased diastolic BP Increased Metabolic syndrome profile Increased cardiovascular risk Update on Lipodystrophy Dr. Louis C. Haenel, IV Endocrinology UMDNJ-SOM Volunteer Faculty Dyslipidemia Cholesterol elevation seen in 27% pts on combination tx (>240 mg/dl) Triglyceride elevation seen in 40% pts (>200 mg/dl) HDL <35 mg/dl seen in 27% Dyslipidemia ↑ small, dense LDL 2 ↑ apolipoprotein B More atherogenic profile ↑ free fatty acid levels ↓ clearance of VLDL . Carbohydrate Metabolism Impaired glucose tolerance seen in more than 35% of HIV infected pts compared to 5% in age and BMI matched controls DM was 3.1X as likely to develop in HIV pts treated with combination therapy vs control population Pathogenesis ↑ circulating free fatty acids Accumulation of intramyocellular lipids Low level of adiponectin Reduced pparα activity which leads to reducing glucose transport mediated via Glut4 transporter Reduce Beta cell insulin secretion Assessment Before initiating HIV therapy, patients should be tested for fasting blood glucose and cholesterol levels Rechecked several weeks after change in therapy and yearly Oral glucose tolerance test Cardiovascular Disease Diabetes Mellitus is considered a coronary risk equivalent Established risk factors Hypertension is seen at higher rates in patients in HAART therapy than for agematched controls PI therapy may promote atherosclerosis by ↑ CD-36 dependent cholesterol ester accumulation in macrophages Risk Factor Modification Dyslipidemia Hypertension Insulin resistance Sedentary lifestyle Weight Family history Tobacco Treatment of Lipodystrophy Change in HAART therapy Exercise Metformin Thiazolidinediones Leptin Recombinant Growth Hormone therapy Recombinant testosterone therapy Oral testosterone therapy Treatment of Metabolic Syndrome Diet Exercise Metformin Thiazolidinediones Additional diabetes mellitus treatment strategies Treatment of Hypertension Ace inhibitor therapy Angiotensin receptor blocker therapy Hydrochlorothiazide Beta blocker therapy Treatment of Dyslipidemia Fibric Acid derivatives (Tricor, Lopid) Cholesterol absorption inhibitors (Zetia) Thiazolidinediones Statin therapy Pravachol Crestor Beware of Lescol, Zocor, Mevacor Improvement of Appearance Surgery Liposuction Injectable agents Polylactic acid (promotes collagen formation)
