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.

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 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.

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 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 less than 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 less than 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.

Blood viscosity in human obesity: relation to glucose tolerance and insulin status.

Obesity is known to be associated with an elevated risk for cardiovascular disease. Rheological disturbances could be factors contributing to these vascular complications. Therefore we have evaluated blood viscosity parameters in 128 obese (BMI greater than 28 kg/m2) adults and in 90 non-obese healthy subjects. Whole blood, plasma and erythrocyte viscosity values were determined with a Contraves LS30 viscosimeter. Plasma and whole blood viscosity were significantly (all P less than 0.001) increased in the obese subjects. The increased low shear erythrocyte viscosity suggested a diminished erythrocyte deformability in obesity. The rheological abnormalities were present even in the absence of impaired glucose tolerance, diabetes, hypertension or hyperlipidaemia. In the obese group the rheological parameters showed significant correlations (at least P less than 0.05) with BMI, insulin or C-peptide area during an oral glucose tolerance test and plasma lipids. Our findings demonstrate that obesity per se may be associated with abnormal blood viscosity properties.

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.

Rapid method for the analysis of red blood cell fatty acids by reversed-phase high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for a rapid qualitative and quantitative analysis of p-bromophenacyl esters of red blood cell fatty acids in humans. Both free and bound fatty acids, extracted with hexane-2-propanol (3:2) from packed red blood cells were derivatized with p-bromophenacyl bromide and analysed. Ten identical samples taken from a mixed pool of packed red blood cells from healthy subjects were analysed on two different columns. The fatty acid p-bromophenacyl esters were analysed on a 10 RP-18 column with methanol-acetonitrile-0.01 M ammonium formate as mobile phase and also on a 10 RP-8 column with acetonitrile-0.01 M ammonium formate as mobile phase. The two methods gave analogous results except in total analysis time: that on a 10 RP-8 column is ca. 40% shorter. Furthermore, a quantitative analysis of a standard solution to evaluate the extraction procedure in the absence or in the presence of the red blood cell core indicated a significant difference when the core is present.

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.

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 less than .01) higher than in patients without an abdominal fat distribution. Atherogenic index was significantly increased in the group with the highest WHR and high-density 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 less than .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.

Erythrocyte sorbitol content in diabetic patients: relation to metabolic control.

Since intracellular sorbitol is considered a factor perhaps involved in the pathogenesis of some diabetic complications, erythrocyte sorbitol content was measured in diabetics (IDDM and NIDDM) and in a control group and its relation with metabolic control was investigated. The erythrocyte sorbitol content was significantly increased in diabetic population (p less than 0.001) as compared to the controls. In newly diagnosed IDDMs the erythrocyte sorbitol content changed in parallel with the blood sugar level indicating that the accumulation can be reversed in erythrocytes. In a cross-sectional study a significant positive correlation existed in IDDMs between the concentration of red cell sorbitol and the plasma glucose concentration (r = 0.45; p less than 0.001). Also the HbA1 values correlated (r = 0.44; p less than 0.001) with the erythrocyte sorbitol content. In NIDDMs no correlation with metabolic control could be demonstrated.

Luminometric measurement of ATP concentrations in human semen.

A positive correlation is found between the ATP concentration and the sperm motility characteristics. So ATP measurement may contribute to a better selection of patients; in vases of asthenospermia, a differential diagnosis between ultrastructural abnormalities and problems related to energy supply is possible without the expensive electron microscopy.

[Effects of the relative enrichment of polyunsaturated fatty acids in insulin-dependent diabetic patients]. / Effets d'un enrichissement relatif en acides gras poly-insaturés chez des sujets diabétiques insulinodépendants.

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)

Plasma zinc levels in diabetes mellitus: relation to plasma albumin and amino acids.

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.