To study the effects of improved control of blood glucose on markers of renal glomerular and tubular function, we initially determined, by radioimmunoassay technics, urinary excretion rates of albumin and beta2 microglobulin in 17 nondiabetic subjects and in 43 insulin-dependent, clinically nonproteinuric diabetic patients. Duration of diabetes ranged from six months to 39 years, and the patients were studied while receiving conventional therapy. Mean urinary albumin excretion was significantly elevated in the diabetics, but beta2-microglobulin excretion rates were not different from those of the controls, suggesting that the increased albumin excretion was due to increased transglomerular loss of albumin. Seven patients with long-term diabetes (duration of six to 33 years), selected because of elevated albumin excretion, were studied before and during a continuous, subcutaneous insulin infusion for a period of one to three days. Urinary albumin excretion was significantly reduced during the insulin infusion, but mean beta2-microglobulin excretion did not change. Strict control of blood glucose, even in the short term, may reverse a functional renal abnormality in long-duration, insulin-dependent diabetes.

The APPENDIX section contains a complete list of centers that participated in the EURODIAB IDDM Complications Study.Abbreviations: AER, albumin excretion rate; CHD, coronary heart disease; CV, coefficient of variation. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Relationship Between Plasma Sialic Acid Concentration and Microvascular and Macrovascular Complications in Type 1 DiabetesThe EURODIAB Complications StudyOBJECTIVE -To test the hypothesis that an increased plasma concentration of sialic acid, a marker of the acute-phase response, is related to the presence of diabetic micro-and macrovascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS -We investigated the relationship betweenplasma sialic acid concentration and nephropathy, retinopathy, neuropathy, and coronary heart disease (CHD) in a cross-sectional survey of 1,369 people with type 1 diabetes. Subjects were participants in the EURODIAB IDDM Complications Study, which involved 31 centers in 16 European countries.RESULTS -There was a significantly increasing trend of plasma sialic acid with severity of retinopathy (P Ͻ 0.001 in men) and with degree of urinary albumin excretion (P Ͻ 0.001 men, P Ͻ 0.01 women). Plasma sialic acid correlated with increasing plasma creatinine concentration (P Ͻ 0.009 men, P Ͻ 0.0002 women), and men with neuropathy had a higher plasma sialic acid concentration than those without (P Ͻ 0.006). There was no significant correlation between plasma sialic acid and CHD in either sex. Elevated plasma sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbA 1c , plasma triglyceride and cholesterol concentrations, waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women). In multiple logistic regression analysis, plasma sialic acid was independently related to proliferative retinopathy and urinary albumin excretion rate in men.CONCLUSIONS -We conclude that an elevated plasma sialic concentration is strongly related to the presence of microvascular complications in type 1 diabetes, especially retinopathy and nephropathy. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.

Low-volume, dual-rate, continuous subcutaneous insulin infusion (CSII) creates long periods of nearnormalization of blood glucose and major intermediary metabolites in most insulin-requiring diabetic patients. The technology and strategy of the system are discussed. We have observed encouraging clinical and fluorescein angiographic improvement in severe diabetic retinopathy after 3 mo of outpatient CSII; in the kidney, glomerular capillary permeability (microalbuminuria) is reduced or normalized in long-standing diabetic patients after a few days of CSII-induced strict control. Reduction in insulin dose during CSII treatment of newly diagnosed ketonuric diabetic patients may indicate improved B-cell function in this group. Although CSII must remain a research tool, undertaken only under close medical supervision, it is increasingly likely that the technique affords the conditions for testing the hypothesis that metabolic near-normalization of diabetes slows, arrests, or reverses the course of the microvascular disease associated with the syndrome, DIABETES CARE 3. -290-300, MARCH-APRIL 1980.

No abstract

Continuous delivery of drugs from portable and implantable pumps offers several advantages over intermittent therapy, including control and maintenance of blood levels of the drug within a narrow therapeutic range, and increased predictability of response. Clinical applications are discussed in the areas of diabetes mellitus, infertility and delayed puberty, iron overload, anticoagulation, analgesia, prevention of premature labour, cardiac arrhythmias, dissolution of gallstones and anticancer therapy.

Diabetologia (1986) 29: 823 -Letters to the Editor 4) Logistic regression analysis is appropriate, as BMI was entered into the equation as a categorical variable, in three categories, where the rate in the two extreme ones is compared to the middle one. 5) Our questionnaire referred to all types of habitual activity, including work time as well as at leisure time. The rate of persons involved in any type of sport was minimal. "High" physical activity was defined as activity score in the highest tertile of the study group. The score consisted of the weekly number of hours spent in moderate activity (heavy activity was not reported by any of the 502 individuals constituting the subsample interviewed for dietary intake and physical activity) + half of the hours spent in light activity defined according to the Committee on Dietary Allowances [2]. Using this crude measure, and accounting for age, BMI and total caloric intake, the risk for Type 2 diabetes for "highly" active individuals of both sexes was 0.67 with 90% confidence limits 0.4%0.96 (p = 0.04) [3]. This was validated by significantly lower insulin response in the "highly" active individuals in all sex and BMI categories (unpublished data).Yours sincerely M. Modan, A. Karasik and H. Halkin rum C-peptide in Type 1 diabetic patients and their siblings. We found in this study that DR4+ diabetic patients showed better preservation of their C-peptide blood concentrations than diabetic patients with other HLA types. It is difficult to reconcile these findings with the Ludvigsson et al. [1] results showing that DR3 + diabetic patients have a milder disease. Both our study [2] (not prospective) and the Ludvigsson et al. study [11 (based on questionnaire data and multicenter) have weaknesses. Thus, this subject needs independent confirmation.The observation by Ludvigsson et al.[1] that 15patients were DR4-, DR3 -, DR2+, presumably mostly from France, is of considerable interest. We have recently shown that there is a third HLArelated susceptibility axis for diabetes (in addition to the DR3 -and DR4related axes) defined by homozygous typing cells (Dw) and restriction fragment length polymorphisms which is part of Dtl2-LD-MN2 as well as DRI-Dwl haplotypes [3]. Those 15 patients presumably carried one or both of these haplotypes.Yours sincerely, J. Barbosa References 1. ModanM, KarasikA, HalkinH, FuchsZ, LuskyA, ShitritA, Mo-danB (1986) Effect of past and concurrent body mass index on prevalence of glucose intolerance and Type 2 (non-insulin-dependent) diabetes and on insulin response: the Israel study of glucose intolerance obesity and hypertension. Diabetologia 29: 82-89 2. Committee on Dietary Allowances Food and Nutrition Board (1980) Recommended dietary allowances, 9th revised edn. National Academy of Sciences, p 24 3. ModanM, Lubin F, ShitritA, LuskyA (1986) Habitual diet, physical activity, body mass index and glucose intolerance. The Israel GOH Study,, Diabetes 35 [Suppl 1]: 74A

No abstract