[Guide for the young diabetic. 10th lesson. 1 month in 12 or vacation sojourns for young diabetics].
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Biomedical subjects
Publications and source records attributed to H Dorchy.
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To determine whether protein excretion during exercise is an earlier sign of renal dysfunction in diabetic adolescents than the basal measurements, urinary creatinine, total proteins, albumin, and beta 2-microglobulin were studied before, immediately after, and 30 min after exercise until exhaustion on a bicycle ergometer in a group of 21 adolescent diabetic boys (Albustix negative) and in a comparable control group. Among the 21 diabetic subjects, 11 had an incipient retinopathy diagnosed by fluorescein angiography. Urinary output of creatinine was similar in diabetic and in nondiabetic groups, and did not vary during exercise. At rest, the urinary output of total proteins, albumin, and beta 2-microglobulin was significantly higher in diabetic subjects than in controls. These data suggest that the subclinical proteinuria of diabetes is of mixed origin, being both glomerular and tubular. An exercise test leading to exhaustion did not give any additional information other than the basal excretion. There was no difference between diabetic subjects with early retinal vascular changes and those free from all retinopathy.
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Recently, we have documented an abnormal in vivo complement metabolism in Type 1 diabetic children treated with monocomponent porcine insulin Monotard MC and its correction after switch-over to human insulin Protaphane HM. This prompted us to investigate the ability of different kinds of insulin preparations to induce complement activation in vitro. Freshly collected serum samples from healthy blood donors were incubated with commercial rapid and intermediate or long-acting (by protamine sulphate (PS) or zinc) insulin preparations for 2 hours at 37 degrees C. The C3d content of the supernatants was measured by turbidimetry as a marker of C3 complement fraction consumption. Only long-acting preparations of insulins without protamine sulphate were associated with highly significant increased levels of C3d, whatever the source of insulin, animal or human. Moreover, addition of exogenous protamine sulphate was able to inhibit the C3 conversion. This effect was dose-dependent and peaked at the concentration of commercial NPH insulin preparations. The mechanism by which protamine sulphate inhibits complement activation in vitro could be related to its ability to interfere with the physical nature of the solid surfaces presented by the insulin crystals. Indeed, insulin crystals were rapidly cleared (< 5 min) in the incubated serum when small doses of protamine sulphate were added. The complement activating capacity of long-acting insulin without protamine was dose dependent, equivalent to the known complement activator Zymosan, and abolished in the presence of EDTA. In conclusion, the present study has documented the ability of some protracted insulin preparations to activate the complement system in vitro if they are devoided of protamine sulphate. On the other hand, short-acting and NPH insulins are not complement activators.
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Insulin detemir (Levemir) is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid. Insulin detemir is 98-99% albumin bound in plasma. It has a more predictable glucose-lowering effect than NPH insulin or insulin glargin. There is a dose-response relationship, but at the dose of 0.4 units/ kg (an average normal dose), the duration of action reaches nearly 24 h. Therefore, detemir, most often injected once per day at bedtime, seems to be the ideal basal insulin in the basal-prandial therapy for type 1 diabetic patients. The boli of insulin, in order to cover the meals, may be done with a rapid acting human insulin and/or a fast acting analogue. In comparison with NPH insulin, detemir has been shown to reduce the risk of (severe) hypoglycaemias, particularly nocturnal (up to 50%). Fasting hyperglycaemia is often lower, but it is not necessarily true for glycated haemoglobin. In addition, detemir has been associated with less weight gain than NPH insulin. Detemir is well tolerated and no specific safety concerns have been raised.