c-peptide and Acquired-Immunodeficiency-Syndrome

Protease inhibitor-based highly active antiretroviral therapy (PI-HAART) has been implicated in dyslipidemia, peripheral insulin resistance, and abnormal adipose tissue deposition in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome, or AIDS. In vitro evidence indicates that some PIs reduce adipocyte lipoprotein (LPL) and hepatic lipase (HL) expression and activities. We examined whether LPL and HL activities are reduced in HIV-infected patients with dyslipidemia. Fasting serum lipids, glucoregulatory hormones, and postheparin LPL and HL activities, as well as whole body and regional adiposity, were measured in 19 HIV-seronegative controls, 9 HIV+ patients naive to all anti-HIV medications, 9 HIV+ patients naive to PIs, 9 HIV+ patients with prior PI experience but not currently receiving PIs, and 47 HIV+ patients receiving PI-HAART. The PI-HAART group had low LPL and HL activities. However, multiple linear regression analysis indicated that low postheparin LPL activity contributed only partially to HIV-dyslipidemia. Central adiposity and high C-peptide levels (an indicator of high insulin secretion) were stronger predictors of HIV-dyslipidemia. Low LPL and HL activities, by themselves, were insufficient to explain HIV-dyslipidemia because the PI-naive group had low LPL and HL activities but had normal adiposity, C-peptide levels, and serum lipid and lipoprotein levels. HDL-cholesterol was lower in PI-HAART and PI-naive groups than seronegative controls and was directly associated with LPL activity. These findings suggest that HIV-dyslipidemia is mediated primarily by factors that influence triglyceride and lipoprotein synthesis (e.g., central adiposity and hyperinsulinemia) and mediated only partially by factors that influence triglyceride clearance (e.g., lipase activity).

Topics: Acquired Immunodeficiency Syndrome; Adipose Tissue; Adult; Antiretroviral Therapy, Highly Active; Body Composition; C-Peptide; Cross-Sectional Studies; Female; Humans; Hyperlipidemias; Lipoprotein Lipase; Male; Predictive Value of Tests; Triglycerides; Viscera

Lipolysis is higher in patients with acquired immunodeficiency syndrome (AIDS) than in healthy control subjects. To evaluate whether this increase in lipolysis is related to increased beta-adrenergic sensitivity, we compared the lipolytic response to epinephrine (approximately 15 ng x kg(-1) x min(-1)) of six AIDS patients with that of six matched control subjects. Lipolysis was measured by infusion of [2H2]glycerol and [2H2]palmitate. The baseline rates of appearance of palmitate (2.06 +/- 0.21 compared with 1.45 +/- 0.07 micromol x kg(-1) x min(-1)) and glycerol (2.35 +/- 0.16 compared with 1.35 +/- 0.06 micromol x kg(-1) x min(-1)) were higher in AIDS patients (P < 0.05). The absolute increase in lipolysis, an indicator of the responsiveness to epinephrine, was not different between groups for the rate of appearance of palmitate (86 +/- 14 compared with 75 +/- 7 micromol x L(-1) x min(-1)) or glycerol (79 +/- 13 compared with 59 +/- 6 micromol x L(-1) x min(-1)). Plasma concentrations of epinephrine were not different between groups. Lipolysis was higher whereas the lipolytic response to epinephrine was normal in AIDS patients. Increased lipolytic sensitivity to catecholamines is not the cause of increased lipolysis in AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; C-Peptide; Epinephrine; Glycerol; Humans; Hydrocortisone; Insulin; Lipolysis; Male; Middle Aged; Norepinephrine; Palmitic Acid; Thyroid Hormones

To describe a glucose abnormality in AIDS that is characterized by transient NIDDM followed by hyperinsulinemic normoglycemia.. A 36-yr-old Hispanic man with AIDS was on long-standing aerosolized pentamidine therapy in 1986. He received a course of intravenous pentamidine 5 mo before the onset of diabetes. Nonketotic hyperglycemia responded to sulfonylurea, which had to be discontinued 3 mo later because of normoglycemia.. Diabetes diagnosis was made by three separate fasting blood glucose values of 16.2, 18.1, and 29.9 mM, and HbA1C of 10.1% (normal 4.2-5.9). The patient became euglycemic 5 mo after diagnosis while on no treatment. An oral glucose tolerance test was then normal, and C-peptide stimulation showed supra-normal response.. Transient severe NIDDM in this case could not be linked to acute stress. Pentamidine, in a progressively increasing cumulative dose, is one possible, albeit unusual, etiology because the diabetes was not permanent. After diabetes remission, the data suggest residual insulin resistance that is unusual in HIV-positive patients. Diverse glucose abnormalities exist in AIDS. Awareness of their presentation is clinically helpful.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Glucagon; Glucose Tolerance Test; Glyburide; Humans; Insulin; Male; Pentamidine; Proinsulin