Overweight HIV patients with abdominal fat distribution treated with protease inhibitors are at high risk for abnormalities in glucose metabolism - a reason for glycemic control.
ABSTRACT In HIV patients, disorders in glucose metabolism seem to be side effects of highly active antiretroviral therapy (HAART) which may be favoured by obesity, abdominal fat accumulation and familial disposition for diabetes mellitus (DM). The aim of our study was to identify patients at high risk for abnormalities in glucose metabolism taking into account HAART, familial disposition for DM and anthropometric parameters.
Plasma glucose, insulin, c-peptide and insulin resistance (homeostasis model assessment, HOMA) were determined in 44 HIV patients [16 without HAART, 19 with protease inhibitors (PI), 9 without PI (non-PI)] and in 11 healthy subjects. Glucose tolerance was determined by standard procedures. Body mass index (BMI), triceps skin fold thickness and waist circumference were measured and the waist-to-hip-ratio was calculated. Familial disposition for DM was assessed by questionnaire.
Impaired fasting glucose was observed in 28% of HAART-treated patients (21% with PI, 7% non-PI), in 13% of HAART-naive but none in healthy controls. 58% of PI, 44% of non-PI, 38% of HAART-naive and none of healthy controls had a HOMA-index > 2.5 which indicates insulin resistance. HAART-treated patients had significantly higher fasting glucose levels (PI: 97 +/- 11 mg/dL, p = 0.048; non-PI: 109 +/- 58 mg/dL, p = 0.009) compared to healthy controls (72 +/- 8 mg/dL). HOMA-Index was higher in PI treated patients (3.74 +/- 3.08) than in HIV negative controls (0.95 +/- 0.28, p = 0.018). The duration of HAART (p = 0.045), overweight and familial disposition for DM (p = 0.017) significantly affected fasting glucose among PI users. Waist circumference affected c-peptide (p = 0.046) concentration in these patients.
HIV patients on long-term PI therapy with overweight and familial disposition for DM are at high risk to develop abnormalities of glucose metabolism. Thus, measurements of HOMA-Index, BMI and waist circumference should be routinely done especially in PI medicated patients.
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ABSTRACT: Metabolic complications of HIV pose challenges for health maintenance among young adults who acquired HIV in early childhood. Between July 2004 and July 2009, we evaluated 47 HIV-infected subjects who acquired HIV in early life. Participants completed glucose tolerance testing; insulin, lipid, urine albumin, and creatinine determinations; and dual-energy x-ray absorptiometry scans. Longitudinal data were available for 39 subjects; duration of follow-up was 26.4 ± 16.8 months. At baseline, participants were 17.1 ± 3.9 years old; and duration of antiretroviral therapy was 12.7 ± 3.4 years. CD4 count was 658 ± 374 cells per cubic millimeter, and 55% had undetectable viral load. Impaired glucose tolerance was present in 15%; 33% had insulin resistance (homeostasis model assessment of insulin resistance >4.0). Furthermore, 52% had triglycerides of at least 150 mg/dL, 36% had high-density lipoprotein cholesterol less than 40 mg/dL, 18% had low-density lipoprotein cholesterol of at least 130 mg/dL, and 25% had total cholesterol of at least 200 mg/dL. Microalbuminuria was present in 15% of participants and was inversely correlated with CD4% (P = .001). During follow-up, more than one third remained insulin resistant; lipid parameters tended to improve. There were significant increases in body mass index (P = .0002), percentage leg fat (P = .008), and percentage trunk fat (P = .002). Impaired glucose tolerance, insulin resistance, dyslipidemia, and microalbuminuria are common among young adults with HIV. Long-term exposure to therapy may translate into substantial persistent metabolic risk.Metabolism: clinical and experimental 10/2010; 60(6):874-80. · 2.59 Impact Factor
Article: HIV protease inhibitors and obesity.[show abstract] [hide abstract]
ABSTRACT: To review the current scientific literature and recent clinical trials on HIV protease inhibitors and their potential role in the pathogenesis of lipodystrophy and metabolic disorders. HIV protease inhibitor treatment may affect the normal stimulatory effect of insulin on glucose and fat storage. Further, chronic inflammation from HIV infection and protease inhibitor treatment trigger cellular homeostatic stress responses with adverse effects on intermediary metabolism. The physiologic outcome is such that total adipocyte storage capacity is decreased, and the remaining adipocytes resist further fat storage. This process leads to a pathologic cycle of lipodystrophy and lipotoxicity, a proatherogenic lipid profile, and a clinical phenotype of increased central body fat distribution similar to the metabolic syndrome. Protease inhibitors are a key component of antiretroviral therapy and have dramatically improved the life expectancy of HIV-infected individuals. However, they are also associated with abnormalities in glucose/lipid metabolism and body fat distribution. Further studies are needed to better define the pathogenesis of protease inhibitor-associated metabolic and body fat changes and their potential treatment.Current opinion in endocrinology, diabetes, and obesity 10/2010; 17(5):478-85.