LIPOPROTEIN ABNORMALITIES IN NON-INSULIN-DEPENDENT DIABETIC-PATIENTS WITH IMPAIRED EXTRAHEPATIC INSULIN SENSITIVITY, HYPERTENSION, AND MICROALBUMINURIA

We investigated whether specific lipoprotein abnormalities are present in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension and/or microalbuminuria. Fifteen normotensive normoalbuminuric (H-M-), 32 hypertensive normoalbuminuric (H+M-), and 22 hypertensive microalbuminuric (H+M+) NIDDM patients and 20 sex-, age-, and weight-matched nondiabetic control subjects were studied. Lipoprotein size was measured by nondenaturing polyacrylamide gradient gel electrophoresis; insulin sensitivity was assessed by using a euglycemic hyperinsulinemic clamp and [6,6(2)H]glucose tracer infusion for simultaneous measurement of hepatic glucose output and whole-body glucose utilization. Total plasma and very-low-density lipoprotein cholesterol were higher in H+M+ than in control subjects (5.84+/-0.98 versus 4.97+/-0.98 and 0.57+/-0.54 Versus 0.26+/-0.21 mmol/L, mean+/-SD, P<.05). Plasma triglycerides were higher in H+M+ than in either control or H-M- subjects (2.17+/-1.32 versus 1.18+/-0.67 and 1.30+/-0.59 mmol/L, respectively; P<.05). The mean low-density lipoprotein diameter was 27.2+/-0.8 in control, 26.7+/-0.8 in H-M-, 26.5+/-0.8 nm in H+M- (P<.05 versus control subjects), and 26.0+/-0.8 nm in H+M+ subjects (P<.05 Versus control subjects). The mean cholesterol level of the large high-density lipoprotein particles was lower in H+M- and H+M+ (0.37+/-0.14 and 0.36+/-0.16 mmol/L) than in control and H-M- (0.54+/-0.41 and 0.54+/-0.27 mmol/L, P<.05) subjects. Whereas hepatic glucose output was less inhibited in all diabetic patients than in control subjects, whole-body glucose disposal was lower in H+M+ (97+/-13 mg/m(2) per minute, mean+/-SEM, P<.05) and H+M- (69+/-12 mg/m(2) per minute, P<.05) but not in H-M- (277/-38 mg/m(2) per minute) NIDDM patients than in control subjects (263+/-45 mg/m(2) per minute). Hypertension (without or with microalbuminuria) appears to be associated with small low-density lipoprotein particles and low high-density lipoprotein cholesterol(2), while microalbuminuria (with hypertension) is associated with elevated triglycerides in NIDDM patients. Moreover, in NIDDM patients the presence of hypertension with or without microaIbuminuria is associated with impaired extrahepatic insulin sensitivity. The atherogenic lipoprotein pattern might partially explain why NIDDM patients with microalbuminuria and hypertension are prone to cardiovascular diseases.