Insulin-resistant glucose metabolism in patients with microvascular angina—syndrome X☆

Abstract 

Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, 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 were sedentary and glucose-tolerant. Coronary arteriography was normal in all participants, and exercise-induced coronary ischemia was demonstrated in all MA patients. A euglycemic, hyperinsulinemic clamp was performed in combination with indirect calorimetry. Biopsy of vastus lateralis muscle was taken in the basal state and after 4 hours of euglycemia 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 18.2 ± 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 glucose or lipid oxidation rates between the two groups. In patients with MA, as well as in the pooled group of all participants, a positive correlation 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 exposure (MA: r = .73, P = .03; all participants: r = .73, P = .005), indicating a reduced in vivo activation of GS in MA patients. In conclusion, (1) MA is part of the insulin resistance syndrome, and (2) the insulin resistance is predominantly localized to the glycogen synthesis pathway in skeletal muscle tissue.

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