S Okada

Factors Related to Aortic Pulse-Wave Velocity in Patients with Non-Insulin-Dependent Diabetes Mellitus

The factors that influence the severity of large vessel pathology in patients with non-insulin-dependent diabetes mellitus (NIDDM) were investigated in 154 randomly selected patients. Measurements of aortic pulse-wave velocity were used to quantify the severity of large vessel pathology. The results showed that of the 20 variables considered, age, systolic blood pressure, duration of disease and serum creatinine were all significantly correlated with pulse-wave velocity. Multiple regression analysis with pulse-wave velocity as the criterion variable showed that age, systolic and diastolic blood pressures were all significant explanatory variables, with age carrying the greatest weight. The findings suggest that controlling blood pressure is most important as a means of containing large vessel pathology in patients with NIDDM.

Effects of chronic, urea-induced osmotic diuresis on kidney weight and function in rats

SummaryTo study the effects of chronic osmotic diuresis which were not associated with hyperglycaemia on the rat kidney, osmotic diuresis was induced by i. v. infusion of urea. A 5 mol/l urea solution was continuously infused at a rate of 100 ml · kg−1 · day−1 on the basis of body weight on day 0. Duration of infusion was 2, 6, 10 or 14 days. Control rats received continuously infused Ringers solution. Urea-treated groups developed osmotic diuresis (urine flow = about 0.04 ml · min −1 · 100 g body weight−1) comparable to that in rats with experimental diabetes mellitus induced by i. v. streptozotocin (55 mg/kg), however urea-induced osmotic diuresis was not associated with blood glucose level increases. Compared with their controls, rats receiving urea for 2–14 days had markedly increased kidney weight. Rats receiving urea for 10 days showed greatest kidney weight increase, 0.565 ± 0.044 g/100 g body weight (mean ± SD), representing a 53% increase compared with the control (0.369 ± 0.034 g/100 g body weight). Kidney weight was associated with increases in kidney protein content. In contrast, none of control kidney weight values differed significantly from day 0 values (=normal rats; 0.387 ± 0.028 g/100 g body weight). Creatinine clearance values in urea-treated groups were also higher than those in controls. The maximum value, 0.65 ± 0.17.ml · min−1 · 100 g body weight−1, was recorded in the 14-day group and was significantly higher than the corresponding control value (0.34 ± 0.07 ml · min−1 · 100 g body weight−1) (p <0.001). Urea clearance values were also significantly higher in urea-treated groups than in respective controls. This study suggests that osmotic diuresis may induce renal hypertrophy/hyperplasia and glomerular hyperfiltration immediately after development of diabetes.

Factors related to stress in patients with non-insulin-dependent diabetes mellitus

Stress was assessed using State-Trait Anxiety Inventory scores in 40 non-insulin-dependent diabetes mellitus (NIDDM) patients, and the results were compared with those for 40 sex- and age-matched healthy controls. Fludiazepam was administered to the patients for 12 weeks and stress was reassessed. The Manifest Anxiety Scale score correlated with Trait (r = 0.548, P <0.0001) and State (r = 0.474, P < 0.0001) scores, validating the latter as measurements of stress. Both Trait (43.4 vs 35.8, P < 0.001) and State (41.6 vs 33.8, P < 0.001) scores were significantly higher in NIDDM patients than in healthy controls. Administration of an anxiolytic, fludiazepam (0.25 mg, three times daily, orally) for 12 weeks lowered Trait score (43.5 to 36.9, 0.0001), State score (41.6 to 35.8, P < 0.0002), glycosylated haemoglobin (8.4 to 7.3%, P < 0.0001), systolic blood pressure (151.2 to 143.4 mmHg, P < 0.0017) and diastolic blood pressure (84.2 to 77.7 mmHg, P < 0.0018). Multiple regression analysis revealed that the significant explanatory variables for the change in State score during anxiolytic administration were the changes in total cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein B: A1 and glycosylated haemoglobin (R 2 = 0.3224, P < 0.0022). The results indicate that stress is detected at a higher frequency in patients with NIDDM than in healthy controls, and that blood glucose and lipid metabolic factors are significant explanatory variables for this stress. This stress is correlated with glucose metabolism and blood pressure and, moreover, these factors could all be proved concomitantly by the administration of an anxiolytic.

Influence of prostaglandin E1 on heavy proteinuria in slightly azotaemic diabetics.

Treatment of non-insulin-dependent diabetes mellitus patients with nephropathy of the nephrotic type using 40 μg prostaglandin E1 given intravenously twice daily for 4 weeks reduced the urinary protein concentration. Prostaglandin E1 also increased the total serum protein and serum albumin concentrations, and reduced creatinine clearance and plasma renin activity following frusemide loading. Treatment with the prostaglandin did not, however, significantly affect the blood urea nitrogen and the serum creatinine concentration. It is concluded that prostaglandin E1 has overt effects on diabetic nephropathy.

Relationship between Cardiac Autonomic Neuropathy and Diabetic Microangiopathies and Macro Angiopathy in Patients with Non-Insulin-Dependent Diabetes Mellitus

The relationship between cardiac autonomic neuropathy and diabetic microangiopathies and macroangiopathy was investigated in 103 patients with non-insulin-dependent diabetes mellitus. Cardiac autonomic nerve function was assessed by determining the uptake of [123I]metaiodobenzyl-guanidine into the myocardium. Cardioparasympathetic nerve function was assessed by comparing electrocardiographically the expiratory and inspiratory respiratory rate (RR) interval ratios, during a period of deep breathing, and the coefficients of variation of the RR intervals. Nerve conduction velocity measurements were used to assess diabetic somatic neuropathy, and measurement of pulse-wave velocity provided an indication of the extent of aortic sclerosis. The only correlations between the parameters of cardiac autonomic neuropathy and parameters of diabetic microangiopathies and macroangiopathy were between the expiratory to inspiratory RR interval ratio and both the conduction velocity of the tibial nerve and pulse-wave velocity, and between the heart to lung ratio (cardiac autonomic nerve function) and nephropathy. These correlations may have occurred by chance; alternatively they may indicate a difference in the onset mechanisms of cardiac parasympathetic and sympathetic neuropathies in diabetics.

Improvement of Stress Reduces Glycosylated Haemoglobin Levels in Patients with Type 2 Diabetes

The effects of reducing stress on glucose metabolism in diabetics were evaluated in 20 patients with type 2 diabetes (10 of each sex) who were given an anxiolytic (fludiazepam) for 12 weeks. Patients were tested 4 weeks before the start of anxiolytic treatment (A), immediately before the first dose (B), and before the end of the study period (C) using the State-Trait Anxiety Index and glycosylated haemoglobin levels. There were no significant differences between the trait or state anxiety scores or the glycosylated haemoglobin levels at times A and B before treatment. However, for all three measurements, the values at time C, after treatment, showed significant improvements, compared with those at both times A and B (P < 0.05). The improvement in the trait anxiety score was weakly correlated with the decrease in the glycosylated haemoglobin level (r = 0.426, P < 0.01). No correlation was seen between state anxiety scores and glycosylated haemoglobin levels. The results suggest that suppressing anxiety in patients with type 2 diabetes reduces glycosylated haemoglobin levels.

Effect of Prostaglandin E1 on Renal Haemodynamics in a Patient with Diabetic Nephropathy

A 66-year old male with severe hyperglycaemia due to previously uncontrolled diabetes mellitus was also suffering from arteriosclerosis obliterans and diabetic nephropathy. The patient was treated with 16 IU/day insulin zinc suspension. In addition, an intravenous infusion of 80 μg/day prostaglandin E1 was given for 28 days in an attempt to improve the arteriosclerosis obliterans and diabetic nephropathy. Treatment resulted in a reduction in fasting blood glucose but no decline in urinary protein. Prostaglandin E1 treatment, however, produced an improvement in renal haemodynamics assessed by renography.

Serum C3 and C4 levels and complement-dependent antibody-mediated cytotoxic activity of islet cell surface antibody in Type 1 (insulin-dependent) diabetic children

SummaryThe role of complement in the pathogenesis of diabetes was studied in 31 Type 1 (insulin-dependent) diabetic children by assaying serum islet cell surface antibody, C3, C4 and serum complement-dependent antibody-mediated cytotoxicity. Nine of 21 islet cell surface antibody-positive children were within 5 months of disease onset and showed significantly lower serum C3 and C4 levels than either 1 year later or the remainder of the islet cell surface antibody-positive children at 6–12 months after disease onset. The overall trend of all islet cell surface antibody-positive diabetic children within 1 year of disease onset was toward increased serum C3 and C4 levels as the disease progressed. Serum C4 concentration and complement-dependent antibody-mediated cytotoxicity which showed an initial negative correlation were uncorrelated 1 year later. Four children who were initially strongly islet cell surface antibody-positive but negative 1 year later also exhibited significantly higher (p<0.05) mean serum C4levels after 1 year. There was a significant decrease in complement-dependent antibody-mediated cytotoxicity when sera from the diabetic children were treated with either ethylene glycol tetra-acetic acid or ethylene diamine tetra-acetic acid. These data strongly suggest that complement-dependent antibody-mediated cytotoxicity induced by the classical complement pathway involving an islet cell surface antibody may play an important role in the pathogenesis of Type 1 diabetes.

The Effect of an α-Glucosidase Inhibitor and Insulin on Glucose Metabolism and Lipid Profiles in Non-Insulin-Dependent Diabetes Mellitus

Studies were carried out to assess various ways of improving glycaemic control and lipid profiles of patients with non-insulin-dependent diabetes mellitus (NIDDM) in whom glucose metabolism was poor. Part or all of the dose of the sulphonylurea that had been used to treat patients in Group 1 (n = 8) was replaced by an α-glucosidase inhibitor. Symptoms related to hypoglycaemia disappeared and the postprandial blood glucose level was significantly increased (P < 0.043) but serum lipid levels were not significantly altered and the mean glycosylated haemoglobin level was unchanged. In Group 2 (n = 10) patients, a large part of the insulin dose was replaced by an α-glucosidase inhibitor. Hypoglycaemia-related symptoms disappeared but there were no significant changes in lipid profiles, postprandial blood glucose or glycosylated haemoglobin levels. The third group of patients (n = 9) had been treated with insulin alone and were given additional α-glucosidase inhibitor without changing their insulin dose. This did not significantly change their lipid profiles, postprandial blood glucose or glycosylated haemoglobin levels. In Group 4 (n = 9) the addition of an α-glucosidase inhibitor to the initial sulphonylurea did not produce any significant changes in mean postprandial blood glucose or glycosylated haemoglobin levels. The results for individual patients indicated that the glycosylated haemoglobin levels had improved after the change of treatment only in those patients whose connective peptide immunoreactivity was > 6.0 ng/ml.

Effect of an α-Glucosidase Inhibitor Combined with Sulphonylurea Treatment on Glucose Metabolism in Patients with Non-Insulin-Dependent Diabetes Mellitus

Ten patients with non-insulin-dependent diabetes mellitus who were being treated with a sulphonylureal compound but whose glucose metabolism needed further improvement were given a combination of their usual sulphonylurea treatment and an α-glucosidase inhibitor. Treatment with the α-glucosidase inhibitor (0.6 mg/day), in addition to glibenclamide (7.5 mg/day in two patients; 5.0 mg/day in four; 2.5 mg/day in one) or tolbutamide (500 mg/day in three patients) for 4 weeks, improved hyperglycaemia after meals from 237 – 247 mg/dl to 192 mg/dl, and reduced glycosylated haemoglobin levels from 8.5 – 8.6% to 7.9% without causing hypoglycaemia.