SummaryThe activities of hepatic and lipoprotein lipase and the levels of lipo-and apoproteins were compared in two groups of normoglycaemic men representing the highest (n = 18) and lowest (n = 15) fasting insulin quintiles of first degree male relatives of non-insulin-dependent diabetic patients. The high insulin group representing insulin-resistant individuals had significantly lower post-heparin plasma lipoprotein lipase activity than the low insulin group (14.2 + 4.0 vs 20 + 5.8 ~mol NEFA-m1-1 9 h -1, p < 0.001); hepatic lipase activity did not differ between the two groups (24.2 + 11 vs 18.0 _+ 5.3 ~mol NEFA-ml -~ . h -1, NS). The lipoprotein lipase/hepatic lipase ratio in the high insulin group was decreased by 66 % as compared to the low insulin group (0.75 + 0.57 vs 1.25 +_ 0.65, p < 0.01). In the high insulin group both total and VLDL triglycerides were higher than in the low insulin group (1.61 + 0.57 vs 0.86 + 0.26 mmol/1, p < 0.001 and 1.00 + 0.47 vs 0.36 + 0.16 mmol/1, p < 0.001, respectively) whereas HDL cholesterol and HDL 2 cholesterol were lower (1.20 + 0.30 vs 1.43 + 0.22 mmol/1, p<0.05 and 0.49+0.21 vs 0.71+0.17mmol/1, p < 0.05, respectively). Total cholesterol, LDL cholesterol or HDL 3 cholesterol did not differ between the two groups. The mean particle size of LDL was smaller in the high insulin group than in the low insulin group (258 + 7 vs 265 + 6 A, p < 0.05). We propose that the changes of lipoprotein lipase and lipoprotein lipase/hepatic lipase ratio cluster with insulin resistance and provide a possible mechanism to explain the lowering of HDL cholesterol and elevation of triglyceride concentrations observed in insulin-resistant subjects. [Diabetologia (1995) rides and lowering of HDL-cholesterol, is an inherent feature in this cluster of metabolic abnormalities which also include insulin resistance, hyperinsulinism, central obesity, impaired glucose tolerance or non-insulin-dependent diabetes mellitus (NIDDM) and hypertension. Recently, the preponderance of small dense LDL has been linked with this constellation [4,5]. The lipoprotein pattern has been termed as the atherogenic lipoprotein phenotype and it is associated with excess risk of coronary heart disease [6, 7].A major challenge is to define the causal sequence between dyslipidaemia and insulin resistance. Several studies have demonstrated that fasting insulin is related to high trigtyceride levels [8][9][10][11]. Substantial evidence indicates that hypertriglyceridaemia is indeed

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Hypertension and non-insulin-dependent diabetes mellitus (NIDDM) are characterized by a strong genetic component and impaired ability to store glucose as glycogen in skeletal muscle. Impaired insulin activation and altered genetic control of muscle glycogen synthase, the rate-limiting enzyme for glucose storage in skeletal muscle, could provide an explanation for this insulin resistance. We examined whether there is an association between the glycogen synthase gene (Xba I polymorphism) and hypertension in 304 nondiabetic subjects. We examined glucose tolerance with an oral glucose tolerance test and glucose storage in skeletal muscle with the euglycemic insulin clamp technique in combination with indirect calorimetry. The Xba I A2 allele of the glycogen synthase gene was enriched in subjects with hypertension and a family history of NIDDM (48%) compared with normotensive subjects without a family history of NIDDM (6%, P < .0001). The presence of the A2 versus the A1 allele was associated with decreased rates of insulin-stimulated glucose storage in hypertensive subjects (11.2 +/- 2.3 versus 16.9 +/- 2.6 mumol/kg lean body mass per minute, P = .029) but not in normotensive subjects (28.0 +/- 4.6 versus 29.6 +/- 3.7 mumol/kg lean body mass per minute). In conclusion, Xba I polymorphism of the glycogen synthase gene identifies a subgroup of hypertensive subjects with a family history of NIDDM. The data suggest that a locus in the glycogen synthase gene region on chromosome 19 may serve as a "thrifty gene," increasing susceptibility for insulin resistance when exposed to other environmental or genetic factors.