Effect of plasma leptin on insulin resistance - Leptin

Nutrition Research Newsletter, May, 2003

The association between obesity and type 2 diabetes has been well known for decades. Obesity-induced insulin resistance and hyperinsulinemia may play a certain role in this relationship, insulin resistance is a metabolic state in which physiological concentrations of insulin produce a less than normal biological response. A dipose tissue may play a role in insulin resistance worsening among obese subjects. The adipocyte, the primary site of energy storage, secretes a surplus of polypeptides, such as plasma leptin and tumor necrosis factor-alpha (TNF-alpha), which consist of a complex network of endocrine, autocrine, and paracrine signals that may be associated with the development of obesity, insulin resistance, and diabetes later in life.

A recent Taiwanese study evaluated the association of plasma leptin, circulating nonesterified fatty acid (NEFA) and TNF-alpha levels in relation to obesity-mediated insulin resistance status among normal-weight and overweight children. According to Chu et al., this could help us better understand the possible mechanisms of obesity-mediated insulin resistance among obese children.

A total of 1032 children were included in this study. The researchers measured body weight and height in all of the subjects. Plasma insulin and leptin levels were measured by radioimmunoassay, while plasma NEFA levels and TNFR1 levels were measured by enzymatic acyl-coenzyme A synthase-acyl-coenzyme A oxidase spectrophotometric methods and enzyme-linked immunosorbent assay, respectively. The insulin resistance index (IRI) was calculated using a homeostasis model assessment and insulin-resistance syndrome (IRS) summary score was calculated by adding the quartile ranks from the distribution of systolic BP, serum triglyceride, high-density lipoprotein-cholesterol (inverse) and insulin levels.

Overweight children had higher BP, plasma leptin, and insulin levels and higher IRI and IRS than normal-weight children. Plasma leptin and TNFR1 were positively correlated with insulin levels, IRI and IRS. In multivariate regression analyses, TNFR1 was positively associated with insulin level and IRI in girls; NEFA was positively associated only with IRS. Plasma leptin levels were significantly positively associated with insulin levels, IRI and IRS, even after adjusting for BMI and other potential confounding variables.

The results show that plasma leptin levels may be a more useful independent marker of plasma insulin levels, insulin resistance status and IRS, even after adjusting for body fatness and other confounders among school children in Taiwan. The macronutrients may be associated with the development of obesity and insulin resistance in humans. One of the study limitations is that it did not have an appropriate questionnaire to measure dietary information, which may limit the results that evaluate the possible mechanisms of dietary factors on insulin resistance status among children. Further studies are needed, which can continue to help us better understand the possible mechanisms of developing insulin resistance in obese children.

Nain-Feng Chu, Jin-Biou Chang and Shih-Ming Shieh. Plasma leptin, fatty acids, and tumor necrosis factor-receptor and insulin resistance in children. Obesity Reesearch 11(4): 532-540 (April 2003) [Address correspondence to Dr. Nain-Feng Chu, Department of Community Medicine, Tri-Service General Hospital, National Defense Medical Center, PO Box 90048-509, Nei-Hu, Taipei, Taiwan, R.O.C. E-mail: chuepi@ndmctsgh.edu.tw]