Leptin and adipose tissue maldistribution in HIV-infected male patients with predominant fat loss treated with antiretroviral therapy.
BACKGROUND
Metabolic disturbances and fat maldistribution are main features of the antiretroviral-related lipodystrophy syndrome (LDS). Different phenotypes of fat distribution abnormalities can be observed: fat loss, fat accumulation, or a mixed pattern. In patients with predominant loss of fat, the roles of leptin, lipids, and glucose homeostasis disturbances have not yet been clearly established.


METHODS
The study comprised 34 HIV-infected male patients receiving antiretroviral treatment that included protease inhibitors. A lipoatrophic phenotype, defined as fat loss in face or extremities, both normal weight and waist:hip ratio, and absence of fat accumulation elsewhere, was present in all cases. Fat distribution disturbances were confirmed by abdominal and midthigh computed tomography-calculated adipose tissue content. Fasting plasma glucose, insulin, proinsulin, total leptin, testosterone, and lipid profiles were measured. After 2 hours, 75-g oral glucose tolerance test (OGTT), glucose, insulin, and proinsulin levels were also obtained. Insulin resistance was calculated using the homeostasis model assessment for insulin resistance (HOMA-r) method. Both healthy study subjects ( n = 385) and antiretroviral-naive HIV-positive patients ( n = 13) were used as controls.


RESULTS
Of these LDS patients, 5.8% showed diagnostic criteria for diabetes and 17.8% for impaired glucose tolerance. A lipid pattern characterized by high total cholesterol and high low density lipoprotein (LDL) plasma levels, hypertriglyceridemia, and normal high density lipoprotein (HDL) levels was observed. Fasting insulin and 2-hour post OGTT insulin levels, and insulin resistance index were significantly higher in LDS patients than in antiretroviral-naive HIV-positive patients. Plasma leptin levels were significantly lower in lipoatrophic patients than in healthy control individuals. Patients with LDS presented with significant midthigh fat reduction and visceral fat accumulation compared with findings in antiretroviral-naive HIV-positive patients. A significant correlation was found between plasma leptin levels and midthigh fat content.


CONCLUSIONS
Peripheral fat loss in extremities in LDS patients with lipoatrophic phenotype is also associated with low plasma leptin levels, visceral fat accumulation, and metabolic disturbances related to an increased cardiovascular risk. In LDS patients, plasma leptin levels could be a marker of subcutaneous adipose tissue content.
Estrada
Vicente
V
Department of Internal Medicine, Hospital Clínico San Carlos, Madrid, Spain.
Serrano-Ríos
Manuel
M
Martínez Larrad
Maria Teresa
MT
Villar
Noemi G P
NG
González López
Amparo
A
Téllez
Maria Jesus
MJ
Fernández
Cristina
C
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects*; D001823:Body Composition / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005215:Fasting; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D008060:Lipodystrophy / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood
D019380:Anti-HIV Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; D020738:Leptin; D011384:Proinsulin