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.