Background Renal function declines progressively in patients who have diabetic nephropathy, and the decline may be slowed by antihypertensive drugs The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy Methods We performed a randomized, controlled trial comparing captopril with placebo in patients with insulin-dependent diabetes mellitus in whom urinary protein excretion was > or = 500 mg per day and the serum creatinine concentration was Results Two hundred seven patients received captopril, and 202 placebo Serum creatinine concentrations doubled in 25 patients in the captopril group, as compared with 43 patients in the placebo group (P = 0007) The associated reductions in risk of a doubling of the serum creatinine concentration were 48 percent in the captopril group as a whole, 76 percent in the subgroup with a baseline serum creatinine concentration of 20 mg per deciliter (177 mumol per liter), 55 percent in the subgroup with a concentration of 15 mg per deciliter (133 mumol per liter), and 17 percent in the subgroup with a concentration of 10 mg per deciliter (884 mumol per liter) The mean (+/- SD) rate of decline in creatinine clearance was 11 +/- 21 percent per year in the captopril group and 17 +/- 20 percent per year in the placebo group (P = 003) Among the patients whose base-line serum creatinine concentration was > or = 15 mg per deciliter, creatinine clearance declined at a rate of 23 +/- 25 percent per year in the captopril group and at a rate of 37 +/- 25 percent per year in the placebo group (P = 001) Captopril treatment was associated with a 50 percent reduction in the risk of the combined end points of death, dialysis, and transplantation that was independent of the small disparity in blood pressure between the groups Conclusions Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone

The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The collaborative study group

BACKGROUND Intensive diabetes therapy aimed at achieving near normoglycemia reduces the risk of microvascular and neurologic complications of type 1 diabetes. We studied whether the use of intensive therapy as compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the long-term incidence of cardiovascular disease. METHODS The DCCT randomly assigned 1441 patients with type 1 diabetes to intensive or conventional therapy, treating them for a mean of 6.5 years between 1983 and 1993. Ninety-three percent were subsequently followed until February 1, 2005, during the observational Epidemiology of Diabetes Interventions and Complications study. Cardiovascular disease (defined as nonfatal myocardial infarction, stroke, death from cardiovascular disease, confirmed angina, or the need for coronary-artery revascularization) was assessed with standardized measures and classified by an independent committee. RESULTS During the mean 17 years of follow-up, 46 cardiovascular disease events occurred in 31 patients who had received intensive treatment in the DCCT, as compared with 98 events in 52 patients who had received conventional treatment. Intensive treatment reduced the risk of any cardiovascular disease event by 42 percent (95 percent confidence interval, 9 to 63 percent; P=0.02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57 percent (95 percent confidence interval, 12 to 79 percent; P=0.02). The decrease in glycosylated hemoglobin values during the DCCT was significantly associated with most of the positive effects of intensive treatment on the risk of cardiovascular disease. Microalbuminuria and albuminuria were associated with a significant increase in the risk of cardiovascular disease, but differences between treatment groups remained significant (P< or =0.05) after adjusting for these factors. CONCLUSIONS Intensive diabetes therapy has long-term beneficial effects on the risk of cardiovascular disease in patients with type 1 diabetes.

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Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes.

Background Renal function declines progressively in patients who have diabetic nephropathy, and the decline may be slowed by antihypertensive drugs. The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy. Methods We performed a randomized, controlled trial comparing captopril with placebo in patients with insulin-dependent diabetes mellitus in whom urinary protein excretion was ≥ 500 mg per day and the serum creatinine concentration was ≤ 2.5 mg per deciliter (221 μmol per liter). Blood-pressure goals were defined to achieve control during a median follow-up of three years. The primary end point was a doubling of the base-line serum creatinine concentration. Results Two hundred seven patients received captopril, and 202 placebo. Serum creatinine concentrations doubled in 25 patients in the captopril group, as compared with 43 patients in the placebo group (P =0.007). The associated reductions in risk...

https://www.nejm.org/doi/pdf/10.1056/NEJM199311113292004

The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy.

Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair 2009–2011 [§§][1]

Sidney C. Smith, Jr, MD, FACC, FAHA, Past Chair 2006–2008 [§§][1]

Cynthia D. Adams, MSN, APRN-BC, FAHA[§§][1]

Nancy M

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

This review provides the reader with the up-to-date evidence-based basis for prescribing exercise as medicine in the treatment of 26 different diseases: psychiatric diseases (depression, anxiety, stress, schizophrenia); neurological diseases (dementia, Parkinson's disease, multiple sclerosis); metabolic diseases (obesity, hyperlipidemia, metabolic syndrome, polycystic ovarian syndrome, type 2 diabetes, type 1 diabetes); cardiovascular diseases (hypertension, coronary heart disease, heart failure, cerebral apoplexy, and claudication intermittent); pulmonary diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis); musculo-skeletal disorders (osteoarthritis, osteoporosis, back pain, rheumatoid arthritis); and cancer. The effect of exercise therapy on disease pathogenesis and symptoms are given and the possible mechanisms of action are discussed. We have interpreted the scientific literature and for each disease, we provide the reader with our best advice regarding the optimal type and dose for prescription of exercise.

/pdf/exercise-as-medicine-evidence-for-prescribing-exercise-as-4ap89k53ch.pdf

Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases

The risk of premature coronary artery disease (CAD) and its determinants were investigated in a cohort of 292 patients with juvenile-onset, insulin-dependent diabetes mellitus (IDDM) who were followed for 20 to 40 years. Although patients with juvenile-onset IDDM had an extremely high risk of premature CAD, the earliest deaths due to CAD did not occur until late in the third decade of life. After age 30 years, the mortality rate due to CAD increased rapidly, equally in men and women, and particularly among persons with renal complications. By age 55 years the cumulative mortality rate due to CAD was 35 +/- 5%. This was far higher than the corresponding rate for nondiabetic persons in the Framingham Heart Study, 8% for men and 4% for women. Angina and acute nonfatal myocardial infarction followed a similar pattern, as did asymptomatic CAD detected by stress test, so that their combined prevalence rate was 33% among survivors aged 45 to 59 years. Age at onset of IDDM and the presence of eye complications did not contribute to risk of premature CAD. This pattern suggests that juvenile-onset diabetes and its renal complications are modifiers of the natural history of atherosclerosis in that although they profoundly accelerate progression of early atherosclerotic lesions to very severe CAD, they may not contribute to initiation of atherosclerosis.

Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus.

The prevalence of hypertension in various age groups of diabetics and its role as a risk factor in juvenileonset insulin-dependent diabetics followed for 40 yr after diagnosis was evaluated. The results show clearly that hypertension is more prevalent in diabetics of any age after age 24 yr than in the general population. In this type of diabetes, although death due to renal disease occurs earlier than that due to coronary heart disease, both causes of death are significantly related to hypertension. Those patients with an onset of diabetes 13 yr of age or younger can expect to live longer following the diagnosis of diabetes mellitus than those with an onset after 13 yr of age, perhaps because hypertension appears at about the same age in both groups. Case/control analysis of the data shows that survivors have significantly less hypertension than those dying of renal or cardiac disease. Furthermore, the close temporal relationship between the onset of hypertension and the onset of proteinuria in patients with either renal or coronary deaths suggests that the hypertension in these patients is renal in origin. Two other risk factors, smoking and serum lipids, were evaluated in this population. From the data thus far accumulated, neither smoking nor lipids appear to influence mortality significantly. We conclude that hypertension is the major additive risk factor for mortality in juvenile-onset insulin-dependent diabetics.

R F Bradley

Papers

Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus.

Hypertension: The Major Risk Factor in Juvenile-onset Insulin-dependent Diabetics