Erythrocyte sorbitol dehydrogenase activity in diabetic patients.

An increased polyol-pathway activity is implicated in the pathogenesis of some diabetic complications. Little is known about the sorbitol-dehydrogenase (SDH) activity in diabetic patients, although cataract is described in diabetes as well as in SDH deficiency. Therefore, we studied SDH activity and the relation with complications and with sorbitol accumulation in erythrocytes from 96 type 1 diabetics and 29 age- and sex-matched healthy subjects. When comparing these groups erythrocyte sorbitol (ERY-SOR) was significantly (P < 0.001) increased in the diabetic patients, but no difference in SDH could be demonstrated. In the diabetic patients ERY-SOR was predominantly related to the glycaemia (r = 0.37; P < 0.001). The SDH activity correlated with HbA1 (r = 0.20; P < 0.03). In diabetic patients with severe nephropathy the ERY-SOR value is no longer different from the control value. It was concluded that, in poor metabolic control the SDH activity is increased, which counteracts but does not prevent the sorbitol accumulation nor the genesis of complications. In patients with macroalbuminuria the ERY-SOR decreases to the normal range. Since SDH activity is similar in type 1 diabetics and controls the decreased ERY-SOR in this complication might be due to other metabolic pathways.

Effect of omega-3 fatty acids in diet of type I diabetic subjects on lipid values and hemorheological parameters.

Twelve type I (insulin-dependent) diabetic subjects in stable metabolic control for at least 3 mo received a controlled diet containing 50% carbohydrate, 35% fat, and 15% protein. Calorie intake varied from 1800 to 2200 calories, depending on individual needs. Part of the polyunsaturated omega-6 fatty acids (omega 6FAs) were isocalorically exchanged with omega 3FAs (2.7 g/day provided by fish oil concentrates) for 10 wk. Subject selection was based on the fact that the atherogenic index (total cholesterol/high-density lipoprotein cholesterol [HDL-chol]) remained greater than 5. Total cholesterol did not change, but HDL-chol (P less than .05) increased significantly, and the mean +/- SD atherogenic index decreased from 5.9 +/- 1.1 to 5.1 +/- 1.3. Plasma triglyceride levels also decreased (P less than .05). There was a small (approximately 2%) but significant (P less than .05) decrease of whole-blood viscosity at low shear rate because of a similarly small (approximately 2% decrease (P less than .05) of plasma viscosity. Erythrocyte viscosity values and the erythrocyte transit time, measured with the St. George's filtrometer, remained unchanged during fish oil intake. Four weeks after stopping the omega 3FA administration, the triglyceride level was again increased (P less than .05) and was even higher than the starting value (P less than .05). Plasma and whole-blood viscosity also increased to the starting levels, demonstrating that lipid alterations are accompanied with blood viscosity changes in the presence of a stable metabolic control.

Hypertension in obese and non-obese non-insulin dependent diabetics a matter of regional adiposity?

There is growing evidence that differences in fat distribution can be predictive for differences in the prevalence of metabolic disturbances, cardio-vascular disease, stroke and death, independent of commonly used indices of obesity. This study evaluates regional body fat distribution as a possible main reason for hypertension in obese and non-obese type II diabetics. 42% of normal weight diabetics with abdominal obesity are hypertensive versus 47% of obese diabetics; only 5% hypertension could be found when a lower body segment fat distribution is present. A significant (p less than 0.001) correlation exists between fat mass topography and both systolic (r = 0.49) and diastolic (r = 0.49) blood pressure. This correlation remains true after correction for body mass index and percent glycosylated hemoglobin. These results suggest that localization of fat in the upper body segment should be considered as a additive risk for hypertension.

Effect of statil (ICI 128436) on erythrocyte viscosity in vitro.

The hypothesis that sorbitol accumulation could contribute to a reduced erythrocyte deformability in diabetes was investigated. Erythrocyte sorbitol and erythrocyte viscosity at high and low shear rates were studied in 20 insulin-dependent diabetic (IDDM) and 20 matched control subjects. An increased erythrocyte sorbitol and an increased low-shear erythrocyte viscosity were found in the IDDM patients, but there was no significant correlation (r = .11, NS) between the parameters. Incubation (3 h, 37 degrees C) in a Krebs buffer containing 33.3 mM glucose resulted in a significant sorbitol accumulation, but erythrocyte viscosity was not affected. Despite this fact, addition of 1 mM statil (ICI 128436) in the 5.5- and 33.3-mM glucose media not only prevented erythrocyte sorbitol accumulation but also improved erythrocyte viscosity in diabetic and control subjects. The effect was more pronounced at the low (approximately 16%) than at the high (approximately 2%) shear rate. The effect on erythrocyte viscosity disappeared by washing the erythrocytes after incubation, although erythrocyte sorbitol remained different. Our results suggest that sorbitol accumulation does not contribute to an increased erythrocyte viscosity in diabetes, and statil shows a positive effect on erythrocyte viscosity independent of its aldose reductase-inhibiting property.