Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes
TL;DR: 36 patients with insulin-dependent diabetes mellitus who had 'Albustix'-negative urine but raised urinary albumin excretion were randomly assigned to either remaining on conventional insulin treatment or continuous subcutaneous insulin infusion and followed up for 2 years.
About: This article is published in The Lancet.The article was published on 1986-12-06. It has received 455 citations till now. The article focuses on the topics: Excretion & Albuminuria.
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TL;DR: Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
Abstract: Background Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. Methods A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. Results In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. Conclusions Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
21,148 citations
TL;DR: In conclusion, intensive glycemic control by multiple insulin injection therapy can delay the onset and the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese patients with NIDDM.
2,927 citations
TL;DR: Albuminuria in Type 1 (insulin-dependent) diabetes is not only an indication of renal disease, but a new, independent riskmarker of proliferative retinopathy and macroangiopathy.
Abstract: Albuminuria in Type 1 (insulin-dependent) diabetes is not only an indication of renal disease, but a new, independent risk-marker of proliferative retinopathy and macroangiopathy. The coincidence of generalised vascular dysfunction and albuminuria, advanced mesangial expansion, proliferative retinopathy, and severe macroangiopathy suggests a common cause of albuminuria and the severe renal and extrarenal complications associated with it. Enzymes involved in the metabolism of anionic components of the extracellular matrix (e.g. heparan sulphate proteoglycan) vulnerable to hyperglycaemia, seem to constitute the primary cause of albuminuria and the associated complications. Genetic polymorphism of such enzymes is possibly the main reason for variation in susceptibility.
1,294 citations
TL;DR: Retinopathy is so characteristic of diabetes that its presence has been incorporated into the nosologic definition of NIDDM, while lower levels of hyperglycemia that are of sufficient magnitude to be associated with retinopathy are classified as NID DM.
Abstract: Diabetes mellitus is a disease of metabolic dysregulation, most notably abnormal glucose metabolism, accompanied by characteristic long-term complications. The complications that are specific to diabetes include retinopathy, nephropathy, and neuropathy. Patients with all forms of diabetes of sufficient duration, including insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), are vulnerable to these complications, which cause serious morbidity (Table 1 and Table 2). Retinopathy is so characteristic of diabetes that its presence has been incorporated into the nosologic definition of NIDDM. Only hyperglycemia of sufficient magnitude to be associated with retinopathy is classified as NIDDM, while lower levels of hyperglycemia that are . . .
1,254 citations
TL;DR: Long-term intensified insulin treatment, as compared with standard treatment, retards the development of microvascular complications in patients with insulin-dependent diabetes mellitus.
Abstract: Background A cause-and-effect relation between blood glucose concentrations and microvascular complications in patients with insulin-dependent diabetes mellitus has not been established. Methods We randomly assigned 102 patients with insulin-dependent diabetes mellitus, nonproliferative retinopathy, normal serum creatinine concentrations, and unsatisfactory blood glucose control to intensified insulin treatment (48 patients) or standard insulin treatment (54 patients). We then evaluated them for microvascular complications after 18 months and 3, 5, and 7.5 years. Results Mean (±SD) glycosylated hemoglobin values were reduced from 9.5 ±1.3 percent to 7.1 ±0.7 percent in the group receiving intensified treatment and from 9.4 ±1.4 percent to 8.5 ±0.7 percent in the group receiving standard treatment (P = 0.001). In 12 of the patients receiving intensified treatment (27 percent of those included in the analysis) and 27 of those receiving standard treatment (52 percent), serious retinopathy requiring photocoag...
1,221 citations
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TL;DR: By standardizing the technical conditions of the experiment it is possible to use this principle for the immunochemical determination of antigens, and the lower limit of the method was found to correspond to 0·0025 μg of antigen, and to an antigen concentrations of 1·25 μg per ml.
8,937 citations
TL;DR: It was found that the system of phenol and 4-amino phenazone is well suited to the determination of glucose and the development of phosphatase is described.
Abstract: the oxygen acceptors originally used were 0 tolidine, benzidine and o-dianisidine. It has since been established that these three substances are carcinogens and many alternative oxygen acceptors have been suggested. Any dye showing oxidation-reduction properties or any dye formed by oxidation, such as those used in colour photography, are potentially useful but it is obviously advantageous to use reagents which have high stability. For manual work on blood a two-solution technique is desirable, one solution being used to precipitate the protein and the other to develop the colour. The development of such a method will now be described. In the determination of phosphatase, use is made of the fact that phenol in the presence of an oxidising reagent gives a purple colour with 4-amino phenazone. The possibility that the H.Oz released in the reaction of glucose oxidase with glucose could act as the oxidising agent was investigated and it was found that the system of phenol and 4-amino phenazone is well suited to the determination of glucose. By suitable adjustment of conditions the colour develops completely in 10 minutes, being stable thereafter for at least 30 minutes. Using a single-solution phosphotungstic acid precipitant containing phenol to precipitate blood protein the only other solution required is one containing glucose oxidase, peroxidase and 4-amino phenazone. These solutions contain azide as preservative; azide has no effect on the rate of colour development. In the micro and macro automated methods, the two solutions required are a diluent containing 4-amino phenazone and a colour reagent containing glucose oxidase, peroxidase and phenol.
4,548 citations
TL;DR: Elevated levels of microalbuminuria strongly predict the development of clinical diabetic nephropathy, and these levels of AER are potentially reversible, and their detection and treatment may prevent diabetic renal disease.
1,665 citations
TL;DR: It is concluded that microalbuminuria predicts the development of diabetic nephropathy and that elevated glomerular filtration rates and increased blood pressure may also contribute to this progression.
Abstract: We studied whether microalbuminuria (urinary albumin excretion rates of 15 to 150 micrograms per minute) would predict the development of increased proteinuria in Type I diabetes. We also studied the influence of glomerular filtration rate, renal blood flow, and blood pressure on the later development of proteinuria. Forty-four patients who had had Type I diabetes for at least seven years and who had albumin excretion rates below 150 micrograms per minute were studied from 1969 to 1976, and 43 were restudied in 1983. Of the 14 who initially had albumin excretion rates at or above 15 micrograms per minute, 12 had clinically detectable proteinuria (over 500 mg of protein per 24 hours) or an albumin excretion rate above 150 micrograms per minute at the later examination. Of the 29 who initially had albumin excretion rates below 15 micrograms per minute, none had clinically detectable proteinuria at the later examination, although four had microalbuminuria. Those whose condition progressed to clinically overt proteinuria had elevated glomerular filtration rates and higher blood pressures at the initial examination than did those in whom proteinuria did not develop. Renal blood flow was not elevated in these patients. We conclude that microalbuminuria predicts the development of diabetic nephropathy and that elevated glomerular filtration rates and increased blood pressure may also contribute to this progression.
1,605 citations
TL;DR: The effect of early aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in ten insulin-dependent diabetics and the glomerular filtration rate decreased significantly and the urinary albumin excretion rate and arterial blood pressure rose significantly.
910 citations