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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.

We have evaluated the effect of metformin on haemorheology, lipid levels and insulin resistance in insulin-dependent diabetic patients over a 6-week period. Rheological parameters remained unaltered except for the whole blood clogging rate which decreased significantly. No effect on lipid levels was seen. The main effect of metformin was limited to daily insulin requirement and insulin units/kg bw. Bearing in mind the negative effects of high insulin levels, metformin could be useful in the prevention of atherogenesis in insulin-dependent diabetic patients.

Fasting plasma zinc levels were determined in 45 IDDM and in 40 NIDDM patients. Mean values were similar in both groups, but diabetic men showed a significantly higher plasma zinc (p less than 0.05) than diabetic women. In patients with diabetic nephropathy a lower zinc level was associated with decreased plasma albumin as compared to patients without complications (p less than 0.001). Neuropathy and macro-angiopathy were also associated with lower zincemia (p less than 0.05) but in the presence of normal albumin levels. In IDDM without nephropathy a significant positive correlation was found between plasma zinc and plasma glucose, albumin, branched chain amino acids and glutamine, while in NIDDM without nephropathy a significant positive correlation exists between plasma zinc and the amino acids glutamine, valine, histidine and lysine.

Twenty seven insulin-dependent (type I) diabetic patients (mean +/- SD; age: 30 y +/- 12; duration of diabetes 12 y +/- 2.5) were treated for at least 12 weeks with two regimens differing only in their fatty acid composition. The energy in the diabetic diet was contributed 50%-55% by carbohydrates, 15%-20% proteins and 30% by lipids. The diet high in poly-unsaturated-fatty-acids (PUFA) contained 61% PUFA and 17% of saturated fatty acids (SFA) while the diet low in PUFA was composed of only 4% PUFA and of 65% SFA. Group I followed the diet high in SFA for six weeks and then switched to the diet high in PUFA. Group II followed the diets in the reverse order. After six weeks of treatment with the high PUFA diet, total serum cholesterol decreased from 195 mg % +/- 11.1 mg % in group I and 179 mg% +/- 12.1 % in group II to 169 mg +/- 10.2 and 142 mg % +/- 8.1 respectively. This fall was mainly due to highly significant decrease in LDL-Cholesterol. VLDL-cholesterol and HDL-cholesterol in both groups remained almost unchanged. In group I a significant decrease in serum triglyceride from 88 mg % +/- 9.2 to 70 mg % +/- 10.9 was found after six weeks of treatment with the high PUFA diet. The atherogenic index decreased significantly in both groups. Six weeks of treatment with the high SFA diet reversed these results. Serum cholesterol increased mainly due to the highly significant increase in LDL-cholesterol, VLDL-cholesterol, HDL-cholesterol and triglycerides remaining unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

We have evaluated the effect of buflomedil on blood viscosity in insulin-dependent diabetic patients. At the start several rheological parameters were disturbed in these patients. After 3 months of treatment with buflomedil, blood viscosity was significantly decreased at low (P less than 0.05) and high (P less than 0.05) shear rates. The decrease in whole blood viscosity was due to a significant decrease (P less than 0.05) in plasma viscosity, which could be attributed to a significant (P less than 0.01) fall in plasma fibrinogen. There was no effect on erythrocyte deformability as assessed by erythrocyte viscosity measurements. We conclude that treatment with buflomedil improved but did not normalize some rheological parameters in insulin-dependent diabetic patients.

Fifteen insulin-dependent diabetes mellitus (IDDM) patients with minor diabetic complications underwent an intensified conventional insulin treatment (ICIT) program consisting of multiple daily insulin injections with an insulin pen. Blood viscosity parameters were measured before the start, after 6 weeks, 1 and 2 years with a Contraves LS30 viscosimeter. At the start several rheological parameters were disturbed in the diabetic subjects. Mean total hemoglobin A1 (HbA1) significantly (at least P less than 0.05) decreased while the plasma free insulin level significantly increased (at least P less than 0.05) under ICIT. During the first 6 weeks hematocrit (P less than 0.01), plasma (P less than 0.05), whole blood (P less than 0.05) and erythrocyte (P less than 0.01) viscosities significantly decreased but they increased again at 1 year of ICIT. Only plasma viscosity (P less than 0.05) remained below the starting value after 1 and 2 years. Normalization of the blood sugar level improved plasma and whole blood viscosity by an insulin-induced dilution phenomenon after 6 weeks. The persisting decrease in plasma viscosity was accompanied by a significant alteration of the plasma protein profile. These findings suggest that metabolic status influences blood rheology in IDDM patients but by different mechanisms on a short- or long-term basis.

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.