S Tanokuchi

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.

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.

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.

Factors Related to the Development and Progression of Diabetic Retinopathy in Patients with Type 2 Diabetes

This study was intended to clarify the factors associated with the development and progression of diabetic retinopathy in patients with Type 2 diabetes. A total of 107 patients with Type 2 diabetes underwent fundoscopic examination by an ophthalmologist, and the factors that might be associated with the severity of retinopathy were investigated. Analysis of variance and the χ 2 test were performed to determine whether 22 separate factors were associated with the severity of diabetic retinopathy. There were significant associations between retinopathy and duration of disease, systolic blood pressure, urinary albumin index, and blood urea nitrogen. Multiple regression analysis with retinopathy as the criterion variable and 20 other factors as explanatory variables revealed that, of those explanatory variables showing statistical significance, the strongest associations were with duration of disease and type of diabetic therapy, in that order. The χ2 test also revealed significant associations between retinopathy and both the type of diabetic therapy and the use of anti-hypertensive therapy. The results suggest that the duration of illness and the type of diabetic therapy are strongly related to the development and progression of retinopathy in patients with Type 2 diabetes. These findings suggest that insulin deficiency in patients with Type 2 diabetes should be corrected as early and as vigorously as possible, and that modification of daily activities to achieve a more nearly non-diabetic state should be instituted first, with supplementary drug therapy added as required.

Influence of Prostaglandin E1 on Slight Proteinuria in Non-Azotaemic Diabetics

In an investigation into the effect of prostaglandin E1 on proteinuria in nephrotic diabetic nephropathy, five patients were treated with 40 μg prostaglandin E1 administered intravenously over 2 h twice daily for 4 weeks. The following parameters were compared before and after treatment: protein excretion in urine; total serum protein concentration; serum albumin concentration; creatinine clearance; blood urea nitrogen; and serum creatinine content. A further five patients with nephropathy resulting from non-insulin-dependent diabetes mellitus were selected as controls. Analysis of the results using Students t-test showed no significant change in any of the parameters before and after treatment.