INSULIN-RESISTANT GLUCOSE-METABOLISM IN PATIENTS WITH MICROVASCULAR ANGINA - SYNDROME-X

Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose c hallenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study was to examine whether patients with MA are insulin resistant. Nine patients with MA and seven control subjects were studied. All wer e sedentary and glucose-tolerant. Coronary arteriography was normal in all participants, and exercise-induced coronary ischemia was demonstr ated in all MA patients. A euglycemic. hyperinsulinemic clamp was perf ormed in combination with indirect calorimetry. Biopsy of vastus later alis muscle was taken in the basal state and after 4 hours of euglycem ia and hyperinsulinemia (2 mU . kg(-1). min(-1)). The fasting level of ''true'' serum insulin was significantly higher (43 +/- 6 v 22 +/- 3 pmol/L, P +/- .02) and the rate of insulin-stimulated glucose disposal to peripheral tissues was lower in patients with MA (13.4 +/- 1.0 v 1 8.2 +/- 1.4 mg . kg fat-free mass [FFM](-1). min(-1), P < .02) due to a decrease in nonoxidative glucose metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg . kg FFM(-1). min(-1), P < .02). No difference was found in glu cose or lipid oxidation rates between the two groups. In patients with MA, as well as in the pooled group of all participants, a positive co rrelation was demonstrated between the insulin-stimulated increment in fractional activity of skeletal muscle glycogen synthase (GS) and the increment in nonoxidative glucose metabolism after in vivo insulin ex posure (MA: r = .73, P = .03; all participants: r = .73, P = .005), in dicating a reduced in vivo activation of GS in MA patients. In conclus ion, (1) MA is part of the insulin resistance syndrome, and (2) the in sulin resistance is predominantly localized to the glycogen synthesis pathway in skeletal muscle tissue. Copyright (C) 1995 by W.B. Saunders Company