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BACKGROUND: In circulating lymphocytes of individuals with insulin resistance and overt hyperglycaemia (NIDDM patients), alterations, affecting pyruvate dehydrogenase (PDH), the key enzyme in glucose oxidative breakdown, have been observed. They include below normal enzyme activity and, in vitro, no enzyme response to insulin at low physiological levels (5 µU/ml) as well as activation up to the basal values of controls with insulin at high physiological levels (50 µU/ml), instead of activation and inhibition respectively, as in controls. OBJECTIVE: To investigate whether these alterations characterize circulating lymphocytes of individuals with insulin resistance in whom derangements of glucose homeostasis are absent (obese subjects with normal glucose tolerance), or present but still controllable (nonobese and obese newly diagnosed NIDDM patients on an appropriate diet). SUBJECTS: Thirty obese subjects (BMI 36±3) responding normally to an oral glucose tolerance (OGT) test; 60 newly diagnosed NIDDM patients (30 nonobese, BMI 22±4 and 30 obese, BMI 38±2); 30 nonobese (BMI 21±5) and nondiabetic subjects, with no family history for NIDDM, served as controls. METHODS: Evaluation of PDH activity in circulating lymphocytes before and after exposure to insulin at 5 and 50 µU/ml, and of clinical parameters before and during an OGT test. RESULTS: 1) In circulating lymphocytes of obese nondiabetic subjects as well as obese and nonobese newly diagnosed NIDDM patients, PDH activity was significantly below normal. In vitro, enzyme response to insulin at 5 µU/ml was reduced in nonobese NIDDM patients with respect to controls, and absent in obese nondiabetic subjects and obese NIDDM patients. Enzyme response to insulin at 50 µU/ml was reversed in all individuals, which allowed enzyme activity to recover up to the basal level of controls. 2) In NIDDM patients and obese nondiabetic subjects, undergoing an OGT test, the area under the... [ABSTRACT FROM AUTHOR]

Insulin resistance and hyperinsulinemia are often considered intrinsic features of the polycystic ovary syndrome (PCOS). Nevertheless, conflicting results of insulin sensitivity and secretion have been obtained in the subgroup of normal-weight women with PCOS. Differences in body composition, ethnicity, and diet composition and a family history of metabolic diseases may act as confounding variables in women with PCOS. In the present study, insulin sensitivity and secretion were estimated by an iv glucose tolerance test (IVGTT), analyzed by minimal models, in 20 normal-weight healthy women with PCOS and no family history of type 2 diabetes mellitus and in 20 normally ovulating women, matched for age and body mass index. Insulin sensitivity [mean (95% confidence intervals); PCOS 4.0 (2.8-5.1) vs. controls 4.5 (3.5-5.4) 10(-4) min(-1)/microU.ml], and insulin secretion, expressed as the acute insulin response to glucose [PCOS 3.7 (3.3-4.2) vs. controls 3.7 (3.4-4.0) microU/ml] were similar in the two groups. The women with PCOS showed an increased proportion of total body fat (PCOS 29% vs. controls 27.2%; P < 0.01). They also showed decreased glucose effectiveness, i.e. the proportion of glucose uptake independent from insulin activity [PCOS 2.6 (2.1-3.0) vs. controls 3.8 (3.0-4.6) mg x 100 min(-1); P = 0.01]. The levels of insulin sensitivity and of glucose effectiveness did not correlate in either group. Whether the isolated finding of decreased glucose effectiveness could reflect an early stage in the development of the metabolic aberrations often associated with the syndrome remains to be clarified.