Res. 2003;11:1048 -1054. Objective: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. Research Methods and Procedures: Twenty-four insulinresistant obese subjects with varying degrees of glucose tolerance completed a 6-month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor-␣ (TNF-␣), interleukin-6 (IL-6)] and highly sensitive C-reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. Results: Participants had a 6.9 Ϯ 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 Ϯ 3 vs. 23.6 Ϯ 3 ng/mL, p ϭ 0.01) and IL-6 (2.75 Ϯ 1.51 vs. 2.3 Ϯ 0.91 pg/mL, p ϭ 0.012). TNF-␣ levels tended to decrease (2.3 Ϯ 0.2 vs. 1.9 Ϯ 0.1 pg/mL, p ϭ 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r ϭ 0.464, p Ͻ 0.05) and with changes in highly sensitive C-reactive protein (r ϭ 0.466, p Ͻ 0.05). Discussion: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL-6 and a tendency toward a decrease in circulating TNF-␣, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.

Insulin resistance is the core metabolic abnormality in type 2 diabetes. Its high prevalence and its association with dyslipidemia, hypertension, hyperinsulinemia, and high coronary and cerebrovascular mortality put it in the forefront as the plausible target for aggressive intervention. Measurements of insulin sensitivity provide clinicians and clinical researchers with invaluable instruments to objectively evaluate the efficiency of both current and potentially useful interventional tools. Although several methods had been developed and validated to evaluate insulin sensitivity, none of these methods can be universally used in all patients. Nonetheless, a method suitable for use in clinical or basic research may not necessarily be a practical method for use in clinical practice or for epidemiologic research. We reviewed the currently used methods for assessment of insulin sensitivity. For each method, we summarized its procedure, normal value, cut-off value for defining insulin resistance, advantages and limitations, validity, accuracy for each patient population, and suitability for use in clinical practice and in research settings. The methods reviewed include fasting plasma insulin, homeostatic model assessment, quantitative insulin sensitivity check index, glucose-to-insulin ratio, continuous infusion of glucose with model assessment, indices based on oral glucose tolerance test, insulin tolerance test, and the so called "gold standard" methods, the hyperinsulinemic euglycemic clamp and the frequently sampled-intravenous glucose tolerance test.

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