Glycemic status and soluble tumor necrosis factor receptor levels in relation to plasma leptin concentrations among normal weight and overweight US men

Abstract

OBJECTIVE: Leptin, an adipocyte-derived protein product of the obesity (ob) gene, is a multifunctional polypeptide associated with the development of obesity-related disorders in humans. There is considerable inter-individual variation in plasma leptin even among subjects with comparable obesity levels, which suggests that factors other than adipose mass may be involved in the regulation of leptin expression andaor production. The purpose of this study was to evaluate the potential role of glycemic status and adipose-derived cytokines in regulating plasma leptin levels among normal and overweight men. DESIGN: Cross-sectional study. SUBJECTS AND MEASUREMENTS: We measured plasma leptin, insulin, c-peptide and plasma soluble tumor necrosis factor receptor (sTNF-R) concentrations in 178 men. The subjects were selected from the Health Professionals Followup Study (HPFS), and aged 47 ± 64 y in 1994, were free of cardiovascular disease, diabetes mellitus, malignant neoplasms, and had provided a fasting blood sample and a detailed lifestyle questionnaire. RESULTS: Men in the highest quintile of plasma leptin (mean 12.7 ngaml) weighed more, were less physically active and had higher circulating insulin, c-peptide, sTNF-R1 and sTNF-R2 concentrations than men in the lowest quintile (mean 2.8 ngaml). We found a signi®cant correlation between plasma insulin, c-peptide, glycosylated hemoglobin (HbA1c), and sTNF-R1 on leptin concentrations (with Spearman correlation coef®cients ranging from 0.17 to 0.48 and all P`0.05). Only HbA1c and sTNF-R1 were independently and positively associated with plasma leptin after further adjusting for body mass index and other metabolic parameters of interest. Interestingly, these observed associations were limited to men with a BMI !25 kgam 2 . CONCLUSION: Our results suggest that glucose homeostasis and the activity of the TNF system may modulate leptin secretion and production among overweight men. Glucose homeostasis and TNF-a a is important in metabolic disorders related to hyperleptinemia.

Inflammatory Markers and Risk of Developing Type 2 Diabetes in Women

“…Interestingly, the positive association between TNF-␣R2 was more evident in nonobese than obese women. This result is consistent with previous findings that TNF-␣R2 was more strongly correlated with leptin, insulin, and C-peptide among normal weight than overweight subjects (41).…”

Circulating TNF Receptors 1 and 2 Predict ESRD in Type 2 Diabetes

“…18 In contrast to this study, the patients in our other study were young, had normal renal function, did not have proteinuria, and were not obese. Although some reports demonstrated that TNFRs may be related to those clinical characteristics, 20 our two studies indicate that the concentrations of TNFR1 and TNFR2 are not markedly influenced by these clinical covariates. Moreover, they are a stable patient characteristic as demonstrated in our other work.…”

Insulin, Insulin-like Growth Factor-I, Endogenous Estradiol, and Risk of Colorectal Cancer in Postmenopausal Women

“…C-peptide is often used in such settings because C-peptide levels are thought to be less variable than insulin. C-peptide levels do, however, substantially increase postprandially (11), and there is an imperfect correlation of C-peptide and insulin even when measured in fasting specimens (12). Therefore, although recent prospective studies of C-peptide have provided important data, their findings have been inconsistent (13)(14)(15)(16)(17), and direct measurement of insulin, the putative carcinogenic agent, may provide a more accurate estimation of the relation of hyperinsulinemia with colorectal cancer.…”