E. Rillaerts

Relationship of Body Fat Distribution Pattern to Atherogenic Risk Factors in NIDDM: Preliminary Results

Because recent knowledge indicates that the distribution of fat deposits in men may be a better predictor of cardiovascular disease than the degree of obesity alone, some risk factors for atherosclerosis were evaluated in 51 middle-aged men with non-insulin-dependent diabetes mellitus. Abdominal adiposity (waist/hip ratio, WHR) was related to parameters of metabolic control, lipid parameters, and known vascular complications in three different groups. In groups with abdominal obesity, mean annual hemoglobin A1 was significantly (P < .01) higher than in patients without an abdominal fat distribution. Atherogenic index was significantly increased in the group with the highest WHR and highdensity lipoprotein cholesterol (HDL-chol) levels were significantly decreased in both groups with upper-body fat distribution. The frequency of peripheral vascular disease, coronary ischemic heart disease, and hypertension was most prominent in diabetic subjects with an abdominal fat mass distribution. A highly significant (P < .001) correlation was present between WHR and HDL-chol and WHR and the total-cholesterol/ HDL-chol ratio; this significant correlation remains after correction for body mass index. A similar correlation could be found between WHR and systolic and diastolic blood pressures. These results demonstrate an association of excess abdominal fat, even without manifest obesity, with worse diabetes metabolic control, cardiovascular complications, and blood lipid levels actually considered to play an important role in atherogenesis.

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 (ω6FAs) were isocalorically exchanged with ω3FAs (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 >5. Total cholesterol did not change, but HDL-chol (P < .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 < .05). There was a small (∼2%) but significant (P < .05) decrease of whole-blood viscosity at low shear rate because of a similarly small (∼2%) decrease (P < .05) of plasma viscosity. Erythrocyte viscosity values and the erythrocyte transit time, measured with the St. Georges filtrometer, remained unchanged during fish oil intake. Four weeks after stopping the ω3FA administration, the triglyceride level was again increased (P < .05) and was even higher than the starting value (P < .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.

Effects of metformin on haemorheology, lipid parameters and insulin resistance in insulin-dependent diabetic patients (IDDM)

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.

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 (∼16%) than at the high (∼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.

Blood rheology during an intensified conventional insulin treatment (ICIT) in insulin-dependent diabetes

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.

Effect of weight reduction on blood viscosity parameters in obese women

Obesity has been shown to be associated with disturbed hemorheological parameters. We investigated whether these abnormalities could be reversed by weight reduction. Therefore we evaluated blood viscosity parameters of 20 obese women before and after weight loss, achieved after 6 months of a hypocaloric diet (1000 kcal/day)

Effect of oral antidiabetic drug withdrawal in type 2 diabetes.

Oral hypoglycaemic agents were withdrawn in 22 Type 2 diabetic patients to establish whether long‐term use of these products is really necessary. Discontinuation of the drugs resulted in significant increases of HbA1 (8.1 ± 1.1 to 11.3 ± 2.4%) and fasting (9.1 ± 2.1 to 13.6 ± 4.0 mmol l‐1) and postprandial (12.3 ± 3.0 to 18.7 ± 5.7 mmol l‐1) plasma glucose levels after 12 weeks (all p < 0.01). This was associated with a reduction of fasting (12.4 ± 6.2 to 8.0±3.4 mU l‐1) and postprandial (35.7 ± 13.2 to 19.3 ± 13.4 mU l‐1) serum insulin concentrations, and fasting (0.8 ± 0.4 to 0.5 ± 0.2 nmol l‐1) and postprandial (1.8 ± 0.6 to 1.0 ± 0.5 nmol l‐1) serum C‐peptide concentrations (all p < 0.01). Only one patient did not show metabolic deterioration after drug withdrawal. In multivariate analysis no significant correlations could be found between measures of baseline diabetic control and the deterioration after drug withdrawal.

The influence of buflomedil on blood viscosity parameters in insulin-dependent diabetic patients: a preliminary study

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.

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.

Blood Viscosity Parameters in Coronary Heart Disease: Effect of Fish Oil Supplementation

We have evaluated blood viscosity parameters in 20 men suffering from coronary heart disease (CHD) and in 15 control subjects. Whole blood viscosity at a standardized haematocrit of 45% was significantly increased in the CHD-patients, both at low (p less than 0.001) and high (p less than 0.05) shear rate. The increased whole blood viscosity in these patients was explained by an increased plasma viscosity (p less than 0.01), while the erythrocyte suspension viscosity values at a standardized haematocrit of 70%, reflecting erythrocyte deformability, were within the normal range. We have studied the effects of a daily supplementation of 1.5 g omega-3 polyunsaturated fatty acids on blood viscosity in the CHD patients. After 6 weeks of treatment whole blood viscosity, at low and high shear rate, and plasma viscosity were significantly improved (all p less than 0.05), although not normalized. There was no effect of the fish oil on erythrocyte deformability.