Eishi Miki

The Role of Circulating Glucose and Triglyceride Concentrations and Their Interactions with Other “Risk Factors” as Determinants of Arterial Disease in Nine Diabetic Population Samples from the WHO Multinational Study

In 9 of the 14 national samples of diabetic patients assembled for the WHO Multinational Study of Vascular Disease in Diabetes additional laboratory data made it possible to relate manifestations of macrovascular disease to blood glucose concentrations as well as to diabetes duration and to other potential determinants. In five of the samples, serum triglyceride concentrations were also measured and were included in simple and multivariate analyses. Ischemic heart disease defined from Minnesota-coded EKGs and standardized WHO questionnaires was more strongly associated with serum triglyceride concentrations than with serum cholesterol concentrations, an association less notable in non-insulin-dependent diabetic patients. Ischemic heart disease was not related to the single fasting plasma glucose estimated for this study. Stroke and amputation were much more strongly related to the known duration of diabetes than was ischemic heart disease, and they were both related to blood glucose concentration measured at the time of study. Despite major variation in arterial disease prevalence rates between collaborating centers, risk for diabetic women appeared to equal that for diabetic men. The major variation in arterial disease prevalence between national groups could be accounted for only in part by the risk factors studied. Other factors, genetic or more likely environmental, are likely to contribute to the variation in arterial disease susceptibility and, if definable, may be potentially preventable.

The appearance of retinopathy and progression to proliferative retinopathy: the WHO multinational study of vascular disease in diabetes

Abstract.Aims/hypothesis: We aimed to estimate incidences of any retinopathy and proliferative diabetic retinopathy (PDR) by direct ophthalmoscopy and relate them to baseline risk factors in re-examined diabetic survivors from 10 centres of the WHO Multinational Study of Vascular Disease in Diabetes. Methods: After a mean follow-up of 8.4 years (11.7 years in Oklahoma), 2877 (71.6 %) survivors were resubmitted to standardised direct ophthalmoscopy as at baseline. The presence of any retinopathy and PDR were recorded at each centre and their incidence estimated in those without retinopathy and PDR at baseline. The independent associations of these incidences with baseline risk factors are expressed as odds ratios derived from multiple logistic regression analyses, within individual centres (which included fasting plasma glucose in 8 and triglyceride in 5) and in pooled data. Results: Of the 4662 original patients, 465 (10.4 %) of those without and 77 (43.0 %) of those with baseline PDR had died (p < 0.001). Any retinopathy was newly reported at follow-up in 47.7 % and PDR in 9.7 % of those free of them at baseline, with reported incidences varying substantially among centres. Incident retinopathy appeared earlier in the known course of diabetes but incidence rates rose more slowly with duration in patients with Type II (non-insulin-dependent) diabetes mellitus than in those with Type I (insulin-dependent) diabetes mellitus. In pooled data and in some individual centres, any retinopathy incidence gave significantly positive odds ratios with age, diabetes duration, systolic pressure, plasma cholesterol, BMI, insulin treatment and proteinuria, and with fasting plasma glucose in the centres where it was measured. Positive odds ratios for PDR were similarly obtained for age, duration, insulin treatment, cholesterol, proteinuria and fasting glycaemia. Smoking status odds ratios were negative for both outcomes. Conclusion/interpretation: Incidence of ophthalmoscopically ascertained any retinopathy varied about twofold and of PDR about threefold among centres. Although, in part attributable to differences between observers, variation in incidence in all centres and in some cases within centres was associated with a number of baseline risk factors. Such associations are not likely due to observer variation or selection biases and emerged despite the imprecision of clinical ophthalmoscopy. Improved detection and control of these risk factors should reduce the impact of diabetic retinopathy and its consequences. [Diabetologia (2001) 44 [Suppl 2]: S 22–S 30]

Relation of the Course of Retinopathy to Control of Diabetes, Age, and Therapeutic Agents in Diabetic Japanese Patients

Follow-up results of the progression of diabetic retinopathy in 364 patients who attended the Diabetes Clinic of the Third Department of Internal Medicine (University of Tokyo) regularly for more than two years were analyzed in relation to their degree of control, age and therapeutic agents. Ophthalmologic examinations were performed by two ophthalmologists without referring to other data. In 289 untreated cases, retinopathy at the initial visit was more frequent and more severe when known duration of diabetes was longer and initial fasting blood sugar was higher. The degree of control was judged by fasting blood sugar values determined frequently and regularly. Progression of retinopathy was significantly more frequent in the fair and poor control groups than in the good control group. In older age groups, progression, especially occurrence of new lesions, was more frequent. Sulfonylurea did not appear inferior to insulin so long as an acceptable degree of control was maintained.

FREQUENCY, DEGREE, AND PROGRESSION WITH TIME OF PROTEINURIA IN DIABETIC PATIENTS

Abstract The frequency of proteinuria in 333 Summary patients attending a diabetes clinic regularly for at least four years was analysed. Frequency of + + or more proteinuria at the initial visit increased from 4·0% in a subgroup with known duration of diabetes of less than one year, to 16·4% when known duration exceeded ten years. Among the groups which, on the basis of repeated fasting blood-sugar measurement, were judged as achieving good control during follow-up, the frequency of progression of proteinuria was low and was unrelated to the pretreatment fasting blood-sugar.

The incidence of visual impairment and its determinants in the WHO multinational study of vascular disease in diabetes

Abstract.Aims/hypothesis: Incidence of severe visual impairment and the ultimate prevalence of all grades of impairment were estimated in the 10 centres of the WHO Multinational Study of Vascular Disease in Diabetes (WHO MSVDD) participating in the follow-up. Methods: Visual function was ascertained at follow-up in 2994 (77.9 %) of the 3845 eligible participating survivors of the 4709 originally recruited for the WHO MSVDD using the same baseline enquiry method. The associations between incident severe visual impairment, follow-up prevalence of all grades of impairment and baseline risk factors were examined by univariate and stepwise multiple logistic regression analysis. Results: Overall, 8.4 year incidence of severe visual impairment was 1.94 % and showed statistically significant univariate correlations with age at diagnosis, diabetes duration, systolic blood pressure, fasting blood glucose and cholesterol, insulin treatment and strongly with baseline retinopathy. Baseline retinopathy, systolic pressure and cholesterol were statistically significant in multivariable analysis. Differences between centres (0.3 % to 3.45 %) were not significant. Ultimate prevalence of all grades of impairment differed between centres and within almost all of them was correlated in multivariable analysis with baseline retinopathy and proteinuria. Conclusion/interpretation: Comparisons of incident severe visual impairment between centres are restricted by selective mortality, low incidence rates and relatively small numbers in each centre but before retinopathy, baseline systolic pressure and cholesterol predicted severe visual impairment. Follow-up prevalence of all degrees of impairment varied among centres and were associated with prior retinopathy and renal disease at baseline. [Diabetologia (2001) 44 [Suppl 2]: S 31–S 36]

Demonstration of anti-“a-component” antibody — A possible means to differentiate patients with auto-antibodies to endogenous insulin from insulin-treated patients

SummaryThe presence of anti-“a-component” antibody was examined in sera of 4 groups of patients with or without anti-insulin antibody, using 125 I-a-component and the polyethylene glycol precipitation method. 125I-a-component crossreacted with insulin antibody. This cross-reactivity was abolished after preincubation of these sera with monocomponent insulin. The specific anti-“a-component” antibody could be estimated in this procedure. After preincubation with monocomponent insulin, significant binding of 125I-a-component was demonstrated in sera of most patients treated with ordinary commercial insulin, but not in sera of 2 hypoglycemic patients suspected of an insulin autoimmune syndrome. Some cases treated with commercial insulin for less than one year and all cases treated with monocomponent insulin for 7–10 months did not have significant anti-“a-component” antibody. The test for the presence of anti-“a-component” antibody is not definitive but if positive it differentiates “auto-antibodies” from the antibodies produced by injections of commercial insulin.

Diabetic retinopathy and control of diabetes with special reference to blood glucose levels

Data concerning diabetic retinopathy were collected prospectively in the Diabetes Clinic of the Third Department of Internal Medicine, University of Tokyo, from the beginning of the Clinic in 1957 until 1985. These data are analyzed here. The prevalence and severity of the retinopathy at the initial visit was strongly related to the duration of diabetes before examination. Pretreatment fasting blood glucose levels were also significantly related. During follow-up, the incidence of retinopathy was most strongly influenced by the degree of control of blood glucose, followed by other factors like blood pressure, age at diagnosis, etc. The effectiveness of sulfonylurea on retinopathy was not inferior to insulin so long as good control was obtained. It was deduced from the analysis of the chain of events that dot hemorrhage is the initial component of diabetic retinopathy, followed by hard exudate, blot hemorrhage, soft exudate and proliferative retinopathy. A six-year fluorescein angiography follow-up of well-controlled non-insulin dependent cases with mild retinopathy showed that microaneurysms disappear rapidly during the first year and more slowly thereafter. The avascular areas once formed seem to progress despite the degree of control exerted here. The other Japanese results are discussed.

Prevalence of Major Vascular Complications at the Initial Visit Among Japanese Diabetic Patients

The frequencies of retinopathy, proteinuria, hypertension, and electrocardiographic (ECG) abnormalities in 2025 diabetic subjects new to our clinic in Tokyo were analyzed in relation to status at initial visit with respect to age, estimated duration of diabetes, and fasting blood glucose. Frequency and severity of retinopathy increased markedly with duration of diabetes. A relationship was found between retinopathy at first visit and level of blood glucose at that time. Proteinuria also clearly increased with duration; its frequency was generally higher in older age groups. Frequency of hypertension increased with age up to 60 yr, but there was no association between prevalence of hypertension and duration of diabetes. ECG abnormalities also increased with age, although serious abnormalities were rare even in older subjects. Hypertension and ECG abnormalities were not more common in those with higher initial blood glucose values, and the frequencies of these aberrations did not increase with the duration of diabetes. ECG abnormalities were more common among hypertensives, especially in younger age groups. Despite the clear effect of degree and duration of hyperglycemia on microvascular complications, there was no evidence of a direct effect of hyperglycemia on macrovascular abnormalities in this study.

Accelerated oligosaccharide absorption and altered serum metabolites during oral glucose tolerance test in young Japanese with impaired glucose tolerance

Impaired glucose tolerance (IGT) is a subtype of prediabetes, a condition having high risk for development to diabetes mellitus, but its pathophysiology is not fully understood. In the present study, we examined metabolic changes in IGT by using two types (D‐glucose [Glc] and partial hydrolysate of starch [PHS]) of oral glucose tolerance tests (OGTTs), with emphasis on serum incretins and metabolites.

The production and characteristics of anti-insulin, anti-a-component and anti-proinsulin antibodies in patients treated with monocomponent or conventional insulin

SummaryHighly purified pork monocomponent insulin produced less anti-insulin antibody than conventional insulins in diabetic patients. The smaller amount of anti-insulin antibody produced by MC insulin bound pork insulin more strongly than beef insulin in both displacement and direct binding studies of125I-insulin. On the contrary, anti-insulin antibody which was produced by conventional insulins (beef insulin or mixture of pork and beef insulin) bound beef insulin more strongly. No significant anti-a-component and anti-proinsulin antibodies were detected in diabetics treated with highly purified monocomponent pork insulin about two years, compared to significant production of these antibodies in diabetics treated with conventional insulins. These results suggest that the species difference of the insulin molecule itself plays a significant role for the production of anti-insulin antibody, as the impurities do, in insulin-treated diabetic patients. The production of anti-insulin and anti-a-component antibodies decreased clearly after switching to highly purified monocomponent from conventional insulin. No effect of the switching on insulin requirement was found; however, better control of diabetes was accomplished in relation to the level of fasting blood sugar.