Pasquale J. Palumbo

Coronary atherosclerosis in diabetes mellitus: A population-based autopsy study

OBJECTIVES The study was conducted to test the hypothesis that the prevalence of coronary atherosclerosis is greater among diabetic than among nondiabetic individuals and is similar for diabetic individuals without clinical coronary artery disease (CAD) and nondiabetics with clinical CAD. BACKGROUND Persons with diabetes but without clinical CAD encounter cardiovascular mortality similar to nondiabetic individuals with clinical CAD. This excess mortality is not fully explained. We examined the association between diabetes and coronary atherosclerosis in a geographically defined autopsied population, while capitalizing on the autopsy rate and medical record linkage system available via the Rochester Epidemiology Project, which allows rigorous ascertainment of coronary atherosclerosis, clinical CAD, and diabetes. METHODS Using two measures, namely a global coronary score and high-grade stenoses, the prevalence of atherosclerosis was analyzed in a cohort of autopsied residents of Rochester, Minnesota, age 30 years or older at death, while stratifying on diabetes, clinical CAD diagnosis, age, and gender. RESULTS In this cohort, diabetes was associated with a higher prevalence of atherosclerosis. Among diabetic decedents without clinical CAD, almost three-fourths had high-grade coronary atherosclerosis and more than half had multivessel disease. Without diabetes, women had less atherosclerosis than men, but this female advantage was lost with diabetes. Among those without clinical CAD, diabetes was associated with a global coronary disease burden and a prevalence of high-grade atherosclerosis similar to that observed among nondiabetic subjects with clinical CAD. CONCLUSIONS These findings provide mechanistic insights into the excess risk of clinical CAD among diabetic individuals, thereby supporting the need for aggressive prevention of atherosclerosis in all diabetic individuals, irrespective of clinical CAD symptoms.

Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus.

Subsequent cancer incidence was determined in the population-based incidence cohort of Rochester, Minnesota, residents diagnosed with diabetes mellitus between 1945 and 1969. The relative risk of having cancer, excluding cervical and non-melanoma skin cancers, was not significantly increased following the diagnosis of diabetes mellitus. The potential biases of increased medical surveillance among diabetics and exacerbation of subclinical diabetes by occult malignancy did not appear to be important except in the case of subsequent pancreatic cancer.

Epidemiology of Persistent Proteinuria in Type II Diabetes Mellitus: Population-Based Study in Rochester, Minnesota

Clinical risk factors for nephropathy were assessed in a population-based study of Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort). The 1031 Rochester residents with non-insulin-dependent diabetes mellitus (NIDDM) were followed through their complete medical records in the community to 1 January 1982. The prevalence of persistent proteinuria was 8.2% at the diagnosis of NIDDM. Among those initially free of persistent proteinuria, the subsequent incidence was 15.3/1000 person-yr. Twenty years after the diagnosis of diabetes, the cumulative incidence of persistent proteinuria was 24.6%. A proportional hazards model identified the following risk factors for persistent proteinuria in NIDDM: elevated initial fasting blood glucose (P < .01); older age at onset of diabetes (P < .01); male gender (P = .05); and presence of macrovascular disease (P = .05), diabetic retinopathy (P = .05), or glycosuria (P = .07) at the diagnosis of diabetes. Separate analyses controlling for attained age indicated no association between duration of NIDDM and the incidence of persistent proteinuria. Stratified analysis of the two most significant risk factors (fasting blood glucose and age) indicated that hyperglycemia was a stronger risk factor for proteinuria in younger diabetic subjects, perhaps because of a competing risk of death in the elderly diabetic patient. In contrast to a recently described decreasing secular trend of proteinuria in Danish insulin-dependent diabetes mellitus patients, there was no decrease over the past 40 yr in proteinuria risk in this NIDDM incidence cohort.

Clinical study: obesity, diabetes, and heart diseaseCoronary atherosclerosis in diabetes mellitus: A population-based autopsy study☆

OBJECTIVES The study was conducted to test the hypothesis that the prevalence of coronary atherosclerosis is greater among diabetic than among nondiabetic individuals and is similar for diabetic individuals without clinical coronary artery disease (CAD) and nondiabetics with clinical CAD. BACKGROUND Persons with diabetes but without clinical CAD encounter cardiovascular mortality similar to nondiabetic individuals with clinical CAD. This excess mortality is not fully explained. We examined the association between diabetes and coronary atherosclerosis in a geographically defined autopsied population, while capitalizing on the autopsy rate and medical record linkage system available via the Rochester Epidemiology Project, which allows rigorous ascertainment of coronary atherosclerosis, clinical CAD, and diabetes. METHODS Using two measures, namely a global coronary score and high-grade stenoses, the prevalence of atherosclerosis was analyzed in a cohort of autopsied residents of Rochester, Minnesota, age 30 years or older at death, while stratifying on diabetes, clinical CAD diagnosis, age, and gender. RESULTS In this cohort, diabetes was associated with a higher prevalence of atherosclerosis. Among diabetic decedents without clinical CAD, almost three-fourths had high-grade coronary atherosclerosis and more than half had multivessel disease. Without diabetes, women had less atherosclerosis than men, but this female advantage was lost with diabetes. Among those without clinical CAD, diabetes was associated with a global coronary disease burden and a prevalence of high-grade atherosclerosis similar to that observed among nondiabetic subjects with clinical CAD. CONCLUSIONS These findings provide mechanistic insights into the excess risk of clinical CAD among diabetic individuals, thereby supporting the need for aggressive prevention of atherosclerosis in all diabetic individuals, irrespective of clinical CAD symptoms.

Diabetes Mellitus: Incidence, Prevalence, Survivorship, and Causes of Death in Rochester, Minnesota, 1945–1970

The incidence and prevalence of diabetes mellitus in residents of Rochester, Minnesota, for 25 years (1945 to 1970) were determined from available medical records. The over-all incidence rate for diabetes is 133 new cases per 100,000 population per year (age-adjusted to 1970 U.S. white population). The rate increased with age for both men and women and was higher among men over 30 years of age. The average annual incidence rates per five-year period for juvenile-onset diabetes mellitus were low and variable and showed little change. Polyuria, polydipsia, glycosuria, lean habitus, loss of weight, and high levels of fasting hyperglycemia at initial diagnosis occurred more frequently in younger than in older patients. The peak incidence in 1960 through 1964 and the decrease in the following five years may be a reflection of the introduction of the AutoAnalyzer method for blood glucose in 1958. The average annual incidence rates for 1955 through 1959 and 1965 through 1969 were essentially the same. The over-all prevalence for diabetes mellitus is 1.6 per cent, with a higher rate among men than among women over 40 years of age; among school children the rate is 0.1 per cent. Survivorship in the diabetic population is lower than that in the general population. The leading cause of death was coronary heart disease, the death rate from it being higher than for the general population.

Chronic Renal Failure in Non-Insulin-Dependent Diabetes Mellitus: A Population-Based Study in Rochester, Minnesota

STUDY OBJECTIVE To identify the incidence of clinically defined chronic renal failure by clinical type of diabetes in a community diabetic incidence cohort, and to evaluate the relation between persistent proteinuria and chronic renal failure in non-insulin-dependent diabetes mellitus. DESIGN Retrospective incidence cohort study. SETTING Population-based in Rochester, Minnesota. PATIENTS Residents of Rochester, Minnesota, with diabetes initially diagnosed between 1945 and 1979 who had follow-up to 1984 for clinically defined chronic renal failure. MEASUREMENTS AND MAIN RESULTS Among 1832 persons with non-insulin-dependent diabetes who were initially free of chronic renal failure, 25 developed chronic renal failure (incidence, 133 per 100,000 person-years: CI, 86 to 196). The subsequent incidence of chronic renal failure among 136 insulin-dependent diabetic Rochester residents, three of whom developed chronic renal failure, was 170 per 100,000 person-years (CI, 35 to 497). After adjusting for potential confounding factors, we found that the risk for chronic renal failure associated with the presence of persistent proteinuria at the time of the diagnosis of non-insulin-dependent diabetes was increased 12-fold (hazard ratio, 12.1; CI, 4.3 to 34.0). When persistent proteinuria developed after the diagnosis of non-insulin-dependent diabetes mellitus, the cumulative risk for chronic renal failure 10 years after the diagnosis of persistent proteinuria was 11%. CONCLUSIONS These population-based data suggest that most cases of chronic renal failure in diabetes occur in persons with non-insulin-dependent diabetes. These data also identify the increased risk for chronic renal failure among persons with non-insulin-dependent diabetes mellitus who have persistent proteinuria present at or developing after the diagnosis of non-insulin-dependent diabetes mellitus, such data may be useful for directing interventions to prevent or delay the development of chronic renal failure.

Incidence of Diabetes Mellitus by Clinical Type

The incidence of diabetes mellitus by clinical type was determined for the community of Rochester, Minnesota, 1945–69. Overall adjusted incidence rates per 100,000 person-years were 8.4 for IDDM, 80.1 for obese NIDDM, 45.6 for nonobese NIDDM, and 3.6 for secondary diabetes, using our definitions. Strict use of National Diabetes Data Group criteria would have reduced the apparent incidence of all diabetes by about 20% through the deletion of NIDDM cases. The National Diabetes Data Group classification improved the clinical homogeneity of IDDM patients compared with “juvenile-onset” diabetes but had little effect on NIDDM relative to “maturity-onset” diabetes, since essentially the same patients were included in both groups. Separation of NIDDM into obese and nonobese subcategories accomplished little in the way of defining two more homogeneous subgroups.

Hyperlipidemia in Patients With Primary and Secondary Hypothyroidism

Hypothyroidism is associated with an increased risk of coronary artery disease. This observation may in part be related to the lipid abnormalities in patients with this condition. The lipid profiles of 268 patients with primary hypothyroidism and 27 with secondary hypothyroidism, who were examined in the Thyroid Clinic at the Mayo Clinic during a 1-year period, were reviewed. Hyperlipidemia was commonly associated with both primary and secondary hypothyroidism. The lipid values decreased with treatment of hypothyroidism. Type IIa hyperlipidemia was the most common lipid abnormality in patients with primary hypothyroidism, whereas type IIb was the most common in those with secondary hypothyroidism. Total/high-density lipoprotein cholesterol and low-density lipoprotein/high-density lipoprotein cholesterol ratios were increased in both male and female patients with primary and secondary hypothyroidism, and they decreased with restitution of the euthyroid state, although this decrease achieved statistical significance only in female patients. Significant associations with total thyroxine were noted for total cholesterol and triglycerides and with thyroid-stimulating hormone (thyrotropin) for total cholesterol and low-density lipoprotein cholesterol. Thus, both primary and secondary hypothyroidism are commonly associated with an atherogenic lipid profile, which improves with replacement of thyroid hormone. Even after restitution of the euthyroid state, however, the lipid profile remains atherogenic in male patients. In comparison with primary hypothyroidism, the lipid profile is more atherogenic in secondary hypothyroidism because of the lower high-density lipoprotein cholesterol levels associated with this condition.

Incidence and Prevalence of Clinical Peripheral Vascular Disease in a Population-based Cohort of Diabetic Patients

Clinical peripheral vascular disease (PVD) was studied in an incidence cohort of 1073 residents of Rochester, Minnesota, who were found to have diabetes mellitus in the period 1945–69. About 8%; of patients already had clinical evidence of PVD at the time of diagnosis of diabetes. The proportion increased with the age at which diabetes was discovered. Among those unaffected initially, the incidence of subsequent PVD was slightly greater for men, 21.3 per 1000 person-years, than for women, 17.6 per 1000, and it increased both with age and duration of diabetes. The cumulative incidence of subsequent PVD was estimated to be 15%; at 10 yr and 45% at 20 yr after the diagnosis of diabetes. The age-adjusted prevalence of residents with diabetes and a history of PVD was 3.3 per 1000 population 30 yr of age or over on 1 January 1970.

Incidence of Diabetic Retinopathy and Blindness: A Population-based Study in Rochester, Minnesota

Among the 1135 Rochester residents discovered to have diabetes in the period 1945–69, the prevalence of retinopathy was 2.6% at the time of initial diagnosis. Among those free of retinopathy at diagnosis of diabetes, the subsequent incidence of any retinopathy was 17.4 per 1000 person-years and for proliferative retinopathy alone was 1.6 per 1000 person-years, based on 12,000 person-years of follow-up. The incidence rate of retinopathy was almost three times greater among residents with insulin-dependent (IDDM) than with non-insulin-dependent diabetes (NIDDM); however, the actual number of retinopathy cases was over four times greater among the more numerous residents with NIDDM. By 20 yr after diagnosis of diabetes, the cumulative incidence of retinopathy approached 70% among IDDM subjects and was 30% and 36%, respectively, among the obese and nonobese NIDDM residents. The epidemiologic patterns for proliferative retinopathy were qualitatively similar to those for nonproliferative retinopathy. The risk of blindness was greater among those with proliferative than with nonproliferative retinopathy but was substantial even for those without retinopathy. Most blindness was caused by factors other than isolated diabetic retinopathy.