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OBJECTIVE: Insulin resistance may be a risk factor for diabetic microangiopathy, which may have a familial component. We carried out a family-based study to determine which components of the insulin resistance syndrome are associated with diabetic retinopathy and nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS: The Genesis France-Belgium Study is a multicenter binational study designed to investigate the genetic factors involved in the microvascular complications of type 1 diabetes using a family-based design. Probands were type 1 diabetic patients with diabetic retinopathy (classified as background, preproliferative, or proliferative) and possibly diabetic nephropathy (absent, incipient, established, or advanced). The insulin resistance score of their first-degree relatives was calculated according to their BMI and history of arterial hypertension, lipid disorders, and type 2 diabetes. RESULTS: The insulin resistance score of relatives was positively correlated with the albumin excretion rate (P = 0.0009) and fasting plasma glucose (P = 0.0003) and HbA(1c) (P < 0.0001) concentrations. This score was higher in the relatives of probands with than in those without diabetic nephropathy (P = 0.0370). Similarly, it was higher in relatives of subjects with proliferative diabetic retinopathy than in those of probands without, even after controlling for subjects with versus without diabetic nephropathy (P = 0.0379). However, the components of the insulin resistance score in relatives differed according to the severity of diabetic retinopathy or nephropathy in the probands. Obesity and history of arterial hypertension were most common in relatives of probands with proliferative diabetic retinopathy, whereas obesity and history of lipid disorders were most common in the relatives of probands with diabetic nephropathy. CONCLUSIONS: Familial insulin resistance segregates with diabetic complications: lipid disorders and obesity segregate with diabetic nephropathy, whereas arterial hypertension and obesity segregate with diabetic retinopathy.

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OBJECTIVE: To investigate whether a low dose of the angiotensin converting enzyme (ACE) inhibitor ramipril lowers cardiovascular and renal events in patients with type 2 diabetes who have microalbuminuria or proteinuria. DESIGN: Randomised, double blind, parallel group trial comparing ramipril (1.25 mg/day) with placebo (on top of usual treatment) for cardiovascular and renal outcomes for at least three years. SETTING: Multicentre, primary care study conducted mostly by general practitioners in 16 European and north African countries. PARTICIPANTS: 4912 patients with type 2 diabetes aged >50 years who use oral antidiabetic drugs and have persistent microalbuminuria or proteinuria (urinary albumin excretion > or = 20 mg/l in two consecutive samples), and serum creatinine < or = 150 micromol/l. MAIN OUTCOME MEASURES: The primary outcome measure was the combined incidence of cardiovascular death, non-fatal myocardial infarction, stroke, heart failure leading to hospital admission, and end stage renal failure. RESULTS: Participants were followed for 3 to 6 (median 4) years. There were 362 primary events among the 2443 participants taking ramipril (37.8 per 1000 patient years) and 377 events among the 2469 participants taking placebo (38.8 per 1000 patient years; hazard ratio 1.03 (95% confidence interval 0.89 to 1.20, P = 0.65)). None of the components of the primary outcome was reduced. Ramipril lowered systolic and diastolic blood pressures (by 2.43 and 1.06 mm Hg respectively after two years) and favoured regression from microalbuminuria (20-200 mg/l) or proteinuria (> 200mg/l) to normal level (< 20 mg/l) or microalbuminuria (P < 0.07) in 1868 participants who completed the study. CONCLUSIONS: Low dose (1.25 mg) ramipril once daily has no effect on cardiovascular and renal outcomes of patients with type 2 diabetes and albuminuria, despite a slight decrease in blood pressure and urinary albumin. The cardiovascular benefits of a daily higher dose (10 mg) ramipril observed elsewhere are not found with an eightfold lower daily dose.

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The investigations that can be performed in diabetes are not all of equal interest. Some are necessary and sufficient, others useless as their results are non-reproducible, and others still are of no therapeutic value. In order to complete the clinical assessment, the doctor must have at his disposal several simple tests, the results of which should lead to a modification of treatment. The diagnosis of diabetes rests on the level of the fasting glucose. The level of the glycosylated haemoglobin is the best investigation for an appreciation of the glycaemic control. At diagnosis and once a year thereafter, the measurement of the level of the total cholesterol and HDL, triglycerides, microalbuminuria, and creatinine, along with fundoscopy and a resting electrocardiogram are the necessary and sufficient investigations. Combined with the measurement of the arterial blood pressure and an assessment of tobacco use, these permit a good appreciation of the level of cardiovascular risk and the existence or not of complications.

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OBJECTIVE: The DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study allowed investigators to analyze factors leading to the development of congestive heart failure (CHF) in type 2 diabetic patients with abnormal urinary albumin concentration. RESEARCH DESIGN AND METHODS: Type 2 diabetic subjects of both sexes aged >or=50 years who had a urinary albumin concentration >or=20 mg/l were randomly allocated to 1.25 mg/day ramipril or placebo in addition to their usual treatment and treated for 3-6 years in a double-blind fashion. Major outcomes including hospitalization for CHF were recorded during the follow-up. RESULTS: Of the 4912 included patients, 187 developed CHF during the study. There was no significant difference in the incidence of CHF between the two treatment groups. Using a multivariate analysis, independent risk factors for the occurrence of CHF were age, history of cardiovascular disease, baseline urinary albumin concentration, baseline HbA(1c), and smoking habits. A total of 68 of the 187 patients (36.4%) died during the 12 +/- 11-month period after the first hospitalization for CHF, whereas the annual mortality rate of the population who did not develop CHF was 3.2%. CONCLUSIONS: Presence of atherosclerotic disease, baseline urinary albumin concentration, and HbA(1c) level were indicators for further development of CHF. Occurrence of CHF is a major prognostic turn in a diabetic patient's life.

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Estimates and projections suggest an epidemic expansion of diabetes incidence and prevalence in Europe. To evaluate trends in type 1 and type 2 diabetes in seven European countries (Finland, Denmark, the UK, Germany, France, Spain, and Italy), a variety of information is available, including population-based studies on small or large cohorts of subjects representative of the general population in a particular country, European co-operative studies, and sales figures for insulin and oral hypoglycemic agents that allow extrapolation of the number of pharmacologically treated diabetic patients. The incidence of type 1 diabetes in young people is increasing in most European countries, as is its prevalence in all age groups. Type 2 diabetes is the major contributor to the epidemic rise in diabetes. From 1995 to 1999, the prevalence of type 2 diabetes increased considerably, particularly in the UK, Germany, and France. Costs of ambulatory and in-hospital diabetic care (including antidiabetic, antihypertensive, and hypolipidemic agents) have increased even more rapidly than has the number of affected patients. Diabetes trends in Europe are alarming; health care professionals involved in diabetes care must be made aware of these detrimental trends, and health care delivery to patients with diabetes must be improved.

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BACKGROUND: In selected young patients with type 1 diabetes mellitus and end-stage renal failure, simultaneous pancreas and kidney (SPK) transplantation is the treatment of choice. We conducted a retrospective, case-controlled study to compare the function, survival and pathology of renal allografts after SPK and kidney-alone (KA) transplantations. METHODS: We studied 26 consecutive SPK patients and 67 KA controls matched for time of transplantation. Renal function was assessed by routine evaluation of serum creatinine and its course by the 1/serum creatinine vs time curve. Histologic evaluation of early biopsies (0-3 months post-transplantation, n=63), intermediate biopsies (3 months-1 year, n=75) and late biopsies (after 1 year, n=35) were performed by two independent reviewers. RESULTS: SPK and KA recipients differed significantly with regard to donor and recipient age, time on the waiting list, HLA sensitization, renal cold ischaemia time (CIT) and the incidence of delayed graft function. Acute rejection was more frequent after SPK than KA (54 vs 27%; P=0.01), despite higher trough levels of calcineurin inhibitors. After SPK and KA, actuarial patient and renal allograft survival and renal function were comparable at 1 and 4 years. Severe chronic lesions, especially vascular lesions, and calcineurin-inhibitor nephrotoxicity were more frequent in intermediate and late biopsies in the SPK group. CONCLUSIONS: We confirmed that patient and graft survival is comparable between SPK and KA recipients. Despite the use of optimal organs and shorter CIT in SPK, renal graft function was not different in the two groups. Histologic chronic lesions were more severe in SPK than in KA recipients. This might be caused by acute rejection episodes or be due to more severe nephrotoxicity after SPK, because of higher doses of calcineurin inhibitors, or higher sensitivity to calcineurin-inhibitor nephrotoxicity.

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