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Biomedical subjects

A R Christlieb

Publications and source records attributed to A R Christlieb.

At least 19 recordsLinked to original sources
PubMed1994

Hypercholesterolemia--a determinant of renal function loss and deaths in IDDM patients with nephropathy.

The development of kidney disease in diabetes mellitus can be viewed as a two-stage process: (1) the development of proteinuria, and (2) its progression to chronic renal failure. Determinants of the latter were examined in 439 IDDM patients who had nephropathy and participated in the Diabetic Retinopathy Study. Using serum creatinine levels obtained during the follow-up period to assess the rate of loss of renal function, we found that only one-third of these patients experienced a rapid loss of function, while the others had slowly declining or unchanging renal function despite the presence of proteinuria and severe diabetic retinopathy. Among the many baseline variables examined, only elevated cholesterol and elevated systemic blood pressure were predictors of a rapid loss of renal function. Patients with this rapid loss of renal function also had the highest risk of death due to cardiovascular causes, as well as all causes. Once again, hypercholesterolemia was the major predictor of these deaths. In conclusion, efforts should be undertaken early to identify patients who are rapidly losing renal function so that interventions to modify systemic blood pressure and hypercholesterolemia may prevent or postpone the development of renal failure and death in patients with IDDM.

Death, Sudden, Cardiac↗
PubMed1992

Coronary artery disease is the major determinant of excess mortality in patients with insulin-dependent diabetes mellitus and persistent proteinuria.

The goal of this review was to assess the magnitude of coronary artery disease (CAD) mortality and its determinants in insulin-dependent diabetes mellitus (IDDM) patients with persistent proteinuria. By reanalyzing data from two previously published studies of patients with nephropathy, it was found that these patients had extremely high CAD mortality rates in comparison with IDDM patients without proteinuria, but only after the age of 35 yr. In addition, the risk of CAD death was associated with high serum cholesterol levels but was unrelated to systemic blood pressure, smoking habits, and obesity. Further studies of the determinants of CAD in patients with IDDM and proteinuria are urgently needed. Except for efforts to lower serum cholesterol, it is not known whether any other measure can be undertaken to reduce the extremely high mortality due to CAD that afflicts IDDM patients with persistent proteinuria, in particular those patients whose renal failure might have been "successfully" postponed by antihypertensive therapy.

Adult↗
PubMed1991

Evolving natural history of coronary artery disease in diabetes mellitus.

White diabetic patients are at high risk of developing coronary artery disease (CAD). The natural history of CAD in insulin-dependent (ID) and noninsulin-dependent (NID) diabetes mellitus (DM) is reviewed to gain insight into the mechanisms responsible for the development of premature or accelerated atherosclerosis in diabetic patients. In both IDDM and NIDDM, the risk of CAD increases with lengthening duration of diabetes; the risk, however, does not grow as a constant multiple of the nondiabetic risk of CAD, suggesting that the cumulative exposure to diabetes plays a significant role as a risk factor for CAD only in a subset of patients. This is consistent with the hypothesis that the diabetic milieu has an impact on the progression of atherosclerotic lesions but not on their initiation. This hypothesis is corroborated further by the observation that CAD does not occur in diabetic patients in populations with a low risk of CAD among nondiabetic patients. The component of the diabetic milieu responsible for promotion of atherosclerotic lesions is unknown. There is evidence, however, of a direct or indirect role of hyperinsulinemia in this process.

Adolescent↗
PubMed1991

Excess mortality associated with diuretic therapy in diabetes mellitus.

OBJECTIVE: To determine whether the high mortality among diabetic patients receiving treatment for hypertension can be explained by associated risk factors or must be attributed to a deleterious effect of antihypertensive treatment. DESIGN: Cohort analytic study with a median follow-up of 4.5 years. SETTING: Outpatients with diabetes and severe retinopathy who were enrolled in a multicenter, randomized clinical trial of laser treatment to prevent blindness had ophthalmologic examinations every 4 months and annual medical examinations that included measurement of blood pressure and recording of anti-hypertensive treatment. Only 5.5% of the patients were unavailable for follow-up. When a patient died, the circumstances surrounding the death were reviewed and classified by a mortality review committee. PARTICIPANTS: --There were 759 participants in the study; they were white, were aged 35 to 69 years, and had normal serum creatinine levels at the baseline examination. MEASUREMENTS AND MAIN RESULTS: --Patients were classified into five groups according to information recorded at the baseline and first annual follow-up examinations: normotensive (diastolic blood pressure less than 90 mm Hg), untreated hypertensive, hypertensive treated by diuretics alone, hypertensive treated by other agents alone, and hypertensive treated by both agents. Cardiovascular mortality was higher in patients treated for hypertension than in patients with untreated hypertension. The excess was primarily found in patients treated with diuretics alone, although that group had the lowest blood pressure with treatment. After adjusting for differences in risk factors, cardiovascular mortality was 3.8 times higher in patients treated with diuretics alone than in patients with untreated hypertension (P less than .001). CONCLUSIONS: --In individuals with diabetes, intervention with diuretics to reduce hypertension is associated with excess mortality. Until there is a clinical trial showing a beneficial effect of diuretic treatment in diabetic patients, there is urgent need to reconsider its continued usage in this population.

Adult↗
PubMed1990

Treatment selection considerations for the hypertensive diabetic patient.

Hypertension occurs with twice the frequency in the diabetic population as compared with the general nondiabetic population. Treatment of hypertension in diabetics can be complicated by diabetic complications and the potential for adverse effects from selected antihypertensive drugs. A rational approach to antihypertensive therapy in diabetics with or without concurrent diabetic complications incorporates a "stepped" approach to therapy that includes alternative step 1 agents (eg, angiotensin-converting enzyme inhibitors and calcium channel blockers) rather than traditional agents (eg, diuretics and beta-blockers). Evolving evidence with angiotensin-converting enzyme inhibitors reveals that they do not exacerbate complications of diabetes mellitus and also may arrest or slow the progression of diabetic nephropathy. Treatment algorithms for a stepped approach to the management of the hypertensive diabetic patient are proposed.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Acute myocardial infarction in diabetes mellitus and significance of congestive heart failure as a prognostic factor.

Diabetes mellitus has been associated with high mortality rates in patients with acute myocardial infarction (AMI). To better define prognosis in this population, the clinical course of 183 diabetics with AMI was studied. In-hospital mortality for all patients was 28% (52 of 183 patients). Mortality was significantly higher in patients with prior AMI than in patients without prior AMI (41 vs 18%, p less than 0.01) and was significantly higher in women than in men (37 vs 19%, p less than 0.01). The 2-fold increase in mortality among diabetic women was observed both in patients with and without prior AMI. The excess mortality among diabetic women was attributable to their increased risk for severe congestive heart failure (CHF) and cardiogenic shock. Death due to CHF occurred in 22% of all diabetic women with AMI compared with 6% of the diabetic men (p less than 0.01). Death resulting from complications other than CHF was similar for both sexes. There were no male-female differences in the history of prior AMI, systemic hypertension, obesity, nephropathy, frequency of Q-wave AMI, anterior AMI or peak creatine kinase levels to account for the high risk for CHF in diabetic women. It is therefore concluded that diabetic women with AMI are at increased risk for death due to CHF, and that this risk is not readily attributable to known conditions associated with CHF.

Adult↗
PubMed1988

Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus.

Only one third of patients with juvenile-onset insulin-dependent diabetes seem to be susceptible to diabetic nephropathy. To test whether this susceptibility is related to a predisposition to hypertension, we investigated the association of nephropathy with markers of risk for hypertension. We randomly selected 89 patients with insulin-dependent diabetes from a roster of children and adolescents who were seen between 1968 and 1972 at about the time the diagnosis was made. These 89 patients were recalled for examination, as young adults, in 1986 and 1987. Patients with nephropathy (cases, n = 33) were compared with controls without nephropathy (n = 56). Having a parent with hypertension tripled the risk of nephropathy (odds ratio, 3.7; 95 percent confidence interval, 1.4 to 10.1). Moreover, cases had significantly higher values for maximal velocity of lithium-sodium countertransport in red cells than controls (mean maximal velocity +/- SE, 0.51 +/- 0.04 vs. 0.38 +/- 0.02 mmol per liter of cells per hour; P less than 0.05). The excess risk associated with both these indicators of a predisposition to hypertension was evident principally in patients with poor glycemic control during their first decade of diabetes; the odds ratios were 4.5 (95 percent confidence interval, 1.1 to 18.7) for patients with a parental history of hypertension and 7.7 (95 percent confidence interval, 1.8 to 33.8) for patients with a maximal velocity of lithium-sodium countertransport greater than or equal to 0.35 mmol per liter of cells per hour. We conclude that the risk of renal disease in patients with juvenile-onset insulin-dependent diabetes is associated with a genetic predisposition to hypertension. Predisposition to hypertension appears to increase susceptibility for renal disease principally in patients with poor glycemic control.

Adult↗
PubMed1987

Systemic hypertension, diabetes mellitus and the kidney.

Diabetic nephropathy is manifested by albuminuria, hypertension and progressive loss of renal function. Only one-third of patients with insulin-dependent diabetes mellitus of juvenile onset develop nephropathy and the risk of nephropathy does not increase with increasing duration of diabetes. Hypertension occurs almost exclusively in patients with nephropathy. Therefore, there is a subset of patients at risk for both nephropathy and hypertension. It is important to identify the patients destined to develop nephropathy, to define the pathophysiology responsible for the nephropathy in this subset of patients and to develop programs to interrupt the pathophysiology early in its course and hopefully prevent the progression to end-stage renal failure. Potential markers to identify patients who will develop nephropathy include a family history of hypertension, increased glomerular filtration rate and renal mass and presence of significant microalbuminuria. Studies are needed to evaluate various classes of drugs for their efficacy in altering the pathophysiologic hemodynamic changes leading to nephropathy.

Albuminuria↗
PubMed1987

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

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.

Adolescent↗
PubMed1985

The changing natural history of nephropathy in type I diabetes.

Events in the natural history of diabetic nephropathy (including the onset of persistent proteinuria and end-stage renal failure) were studied in a cohort of 292 patients with juvenile-onset type I diabetes who were followed for 20 to 40 years. The risk of persistent proteinuria increased rapidly between the fifth and 15th years of diabetes and declined thereafter. This pattern suggests that susceptibility to this complication was limited to a subset of patients and was exhausted over time. Patients with the most frequent severe hyperglycemia (the highest quartile) during the first 15 years of diabetes had a risk of persistent proteinuria that was four and a half times higher than that for those with the least frequent hyperglycemia (the lowest quartile). Patients whose diabetes was diagnosed in the 1930s had twice the risk of persistent proteinuria as those in whom the condition was diagnosed in later decades. Once persistent proteinuria appeared, progression to renal failure almost always followed. Half reached this stage within 10 years, and the interval for progression did not vary according to sex, frequency of hyperglycemia, or calendar year of diagnosis of diabetes. This period, however, was significantly shorter (eight versus 14 years) for patients whose diabetes was diagnosed after puberty than for those who were younger at onset. In conclusion, the development of diabetic nephropathy consists of at least two stages. The onset of proteinuria, although related to the level of exposure to hyperglycemia, appears to be influenced by genetic and/or environmental factors. The second stage, progression to renal failure, seems to be influenced by processes related to maturation or aging.

Adolescent↗
PubMed1985

Hypertension, orthostatic hypotension and the microvascular complications of diabetes.

Prevalences of hypertension and orthostatic hypotension and their relationship to the microvascular complications of diabetes were assessed in 702 individuals aged 18-74 years, who had been selected as a representative sample of surviving patients with diabetes diagnosed at the Joslin Clinic between 1939 and 1965. In diabetes of short, long and very long duration, hypertension was 1.7, 1.9 and 2.1 times more frequent, respectively, than in the white U.S. population, regardless of gender. The excess frequency of hypertension in short duration diabetes suggests that some etiologic factor is shared by both conditions, while the magnification of the excess with increasing duration could be explained by an effect of diabetes on the kidney. Hypertension without accompanying proteinuria was not associated with retinopathy. Orthostatic hypotension was observed in 12% of the males and 13% of the females. The magnitude of the fall in systolic blood pressure was correlated with age, postprandial blood glucose, supine diastolic blood pressure, and the presence of retinopathy. Patients with proliferative retinopathy had the largest fall in systolic blood pressure.

Adult↗
PubMed1984

Amyloid deposition in serosal membranes. Its occurrence with cardiac tamponade, bilateral ureteral obstruction, and gastrointestinal bleeding.

Widely dispersed amyloid deposition of the serosa occurring in a patient produced impairment of cardiac, renal, and gastrointestinal integrity by encasement. This patient survived the acute complications of both cardiac tamponade and bilateral ureteral obstruction due to amyloid. This case demonstrates the utility of resorting to aggressive life-support mechanisms despite an apparently systemic spread of amyloid disease in selected cases.

Amyloid↗
PubMed1982

Retinal vascular reactivity to norepinephrine and angiotensin II in normals and diabetics.

Retinal arterial vasoconstriction induced by an infusion of angiotensin II or norepinephrine was investigated in eight normal controls (N), nine diabetics without retinopathy (DNR), and 10 diabetics with retinopathy (DR) by color fundus photographs taken before and after the infusions. Image analysis was done by a semiautomated computerized microdensitometer using a videoscanner. Normal controls and diabetics without retinopathy had a significant reduction in diameter compared with diabetics with retinopathy, who failed to constrict arterioles in response to either vasopressor. The mechanism of this phenomenon is unclear. Semiautomated computerized microdensitometry is reproducible and appears to be a sensitive technique to evaluate the vascular reactivity of the retinal vasculature.

Adult↗
PubMed1981

Predictability of surgical cure of renovascular hypertension.

Seventy-five patients with renal artery stenosis were studied; 50 patients had unilateral lesions and 25 had bilateral lesions. Divided renal vein renins and peripheral renins were collected under strict salt intake, drug intake, and postural conditions. Divided renal vein renin ratios and a scoring system that included peripheral renin and affected and contralateral renal secretion of renin were applied to each patient and compared in each to the patient's ultimate surgical result. Both methods, if positive, are highly predictive of cure in patients with renal artery disease. Both methods are plagued by significant false-negative rates, 20% for renal vein ratio, 33% for the scoring system in patients with unilateral stenosis, and 35% and 48%, respectively, in patients with bilateral renal artery stenosis. For these reasons, surgical selection should be based on evaluation of a combination of the clinical presentation, angiographic findings, and renin data.

Adult↗
PubMed1979

Renal artery stenosis in hypertensive diabetics.

The incidence of atherosclerotic renal artery stenosis was compared in consecutive renal angiography of 28 hypertensive diabetics and 104 hypertensive non-diabetics. Mean age and sex distribution were comparable. Angiographic evidence of atherosclerotic renal artery stenosis was present in 10 diabetics (36 per cent) and 50 non-diabetics (48 per cent). Stenosis was considered hemodynamically significant if the renal vein renin ratio of the involved to uninvolved side was 1.4:1.0 or more. A renal vein renin ratio equal to or more than 1.4 was observed in 4 of 7 diabetics (57 per cent) and 31 of 47 non-diabetics (67 per cent). Fibromuscular hyperplasia was not seen in diabetics but was present in 12 per cent of the non-diabetics. Hypertension was treated surgically and improved in 2 of 3 diabetics (67 per cent) and in 17 of 19 non-diabetics (89 per cent) with angiographic and hemodynamic evidence of renal artery stenosis. In this series the incidence of atherosclerotic renal artery stenosis of physiologic consequence was not significantly different in hypertensive diabetics when compared to hypertensive non-diabetics.

Adult↗