Relation of weight gain and weight loss on subsequent diabetes risk in overweight adults.

STUDY OBJECTIVE: To determine whether long term weight gain and weight loss are associated with subsequent risk of type 2 diabetes in overweight, non-diabetic adults. DESIGN: Prospective cohort. Baseline overweight was defined as BMI>/=27.3 for women and BMI>/=27. 8 for men. Annual weight change (kg/year) over 10 years was calculated using measured weight at subjects' baseline and first follow up examinations. In the 10 years after measurement of weight change, incident cases of diabetes were ascertained by self report, hospital discharge records, and death certificates. SETTING: Community. PARTICIPANTS: 1929 overweight, non-diabetic adults. MAIN RESULTS: Incident diabetes was ascertained in 251 subjects. Age adjusted cumulative incidence increased from 9.6% for BMI<29 to 26. 2% for BMI>/=37. Annual weight change over 10 years was higher in subjects who become diabetic compared with those who did not for all BMI<35. Relative to overweight people with stable weight, each kg of weight gained annually over 10 years was associated with a 49% increase in risk of developing diabetes in the subsequent 10 years. Each kg of weight lost annually over 10 years was associated with a 33% lower risk of diabetes in the subsequent 10 years. CONCLUSIONS: Weight gain was associated with substantially increased risk of diabetes among overweight adults, and even modest weight loss was associated with significantly reduced diabetes risk. Minor weight reductions may have major beneficial effects on subsequent diabetes risk in overweight adults at high risk of developing diabetes.

Diabetes mellitus and nontraumatic lower extremity amputation in black and white Americans: the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, 1971-1992.

BACKGROUND: The comparative long-term risk of non-traumatic lower extremity amputation (LEA) in black and white Americans, 2 groups with strikingly different rates of diabetes mellitus, is not known. OBJECTIVE: To examine the 20-year incidence of LEA in relation to race and diabetes mellitus. METHODS: The 14 407 subjects in the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study were observed prospectively between 1971 and 1992. Prevalent diabetes mellitus was ascertained at the baseline examination, and incident diabetes mellitus, during follow-up. Lower extremity amputation was ascertained from hospital discharge records. Cox regression analysis was used to estimate associations between race, diabetes mellitus, and risk of first LEA. RESULTS: During the study period, 158 LEAs occurred among 108 subjects. While black subjects constituted 15.2% of the cohort, they represented 27.8% of the subjects with amputation (P = .002). The 20-year age-adjusted rate ratio of first LEAs for black subjects-white subjects was 2.14. Regression analyses confirmed the importance of diabetes mellitus as a key LEA risk factor. The association between prevalent diabetes mellitus and LEA risk was substantially higher (relative risk [RR], 7.19; 95% confidence interval [CI], 4.61-11.22) than that for incident diabetes mellitus (RR, 3.15 [CI, 1.84-5.37]), highlighting the importance of diabetes mellitus duration on LEA risk. While preliminary analyses adjusted for age and diabetes indicated a significant association between race and LEA risk (RR, 1.93 [95% CI, 1.26-2.96]), the effect of race diminished (RR, 1.49 [95% CI, 0.95-2.34]) following adjustment for education, hypertension, and smoking. CONCLUSIONS: Although black subjects experienced higher age- and diabetes mellitus-adjusted rates of amputation than their white counterparts, a combination of social and environmental factors may account for the apparent ethnic difference. More research into nonbiological factors associated with LEA may reduce the occurrence of these procedures in both black and white individuals.

Differential effects of BMI on diabetes risk among black and white Americans.

OBJECTIVE: To determine whether the associations of BMI and fat distribution with diabetes risk are modified by race. RESEARCH DESIGN AND METHODS: Data from the National Health and Nutrition Examination Survey, Epidemiologic Follow-up Study (1971-1992), were used to investigate potential interactions of BMI and fat distribution with race. Incident diabetes was defined by self-report of physician-diagnosed diabetes, hospital and nursing home discharge records, and death certificates. RESULTS: Among the 1,531 black and 9,852 white subjects who were nondiabetic at baseline, 1,139 (10.0%) developed diabetes during 20 years of follow-up. Although the cumulative risk of diabetes increased with baseline BMI in all four race-sex groups, the sex-specific odds ratios (ORs) for black:white subjects decreased with increasing BMI. In particular, for BMI of 22 kg/m2, the OR of diabetes for black:white individuals was 1.87 and 1.76 (P < 0.01) for men and women, respectively; for BMI of 32 kg/m2, the OR decreased to 0.99 and 1.20 (NS) for men and women, respectively. Skinfold ratio was also associated with increased diabetes risk in all race-sex groups, but did not modify the association between race and diabetes. CONCLUSIONS: These findings suggest that the effect of BMI on diabetes risk is different for black and white Americans, with a larger risk for blacks than whites at low BMI and an equivalent risk for both groups at high BMI. A lower degree of visceral adiposity among blacks at higher BMI or a greater impact of visceral adiposity among blacks at low BMI may help explain the interaction of race and BMI on diabetes risk.

Preoperative predictors of cost in Medicare-age patients undergoing coronary artery bypass grafting.

BACKGROUND: Identification of preoperative factors that contribute to the cost of coronary artery bypass grafting could aid in predicting the procedure's expense. In this study, 30 sociodemographic and clinical preoperative factors were examined with "survival analysis" techniques to determine characteristics related to total hospital cost. METHODS: Characteristics of all patients age 65 or older undergoing isolated coronary artery bypass grafting from July 1993 to April 1995 (n = 757) were recorded. Software was developed within the hospital's Transitions Systems, Inc, database to calculate the outcome variable of total cost. Nonparametric methods were used for the univariate analysis of the data, and the Cox proportional hazards model was used for the multivariable analysis, censoring 25 patients who died in the hospital. RESULTS: Median hospital cost from the day of the operation until discharge was $15,198. Median length of stay after the operation was 6 days. Multivariable analysis revealed that age, preoperative renal failure, history of cerebrovascular accident, low ejection fraction, and surgical urgency were independent predictors of total cost. CONCLUSIONS: This study, using an accurate representation of true hospital cost and a modeling technique that accounts for the confounding effect of in-hospital death on cost, provides a template for analysis of cost in other patient groups.

Evidence that apolipoprotein(a) phenotype is a risk factor for coronary artery disease in men < 55 years of age.

Whereas the importance of plasma lipoprotein(a) [Lp(a)] levels as a risk factor for premature coronary artery disease (CAD) is certain, it is not clear if the apolipoprotein(a) [apo(a)] phenotype plays an additional and independent role. To investigate the possible effect of apo(a) phenotype on premature CAD (in patients < 55 years of age), plasma Lp(a) concentrations, the apo(a) phenotypes, and their relation with many recognized CAD risk factors were examined in 96 non-diabetic male patients with angiographically defined CAD and in 83 age-matched male control subjects with no angiographic evidence of CAD. Results demonstrate that patients with premature CAD are characterized by higher Lp(a) levels (24 +/- 21 vs 17 +/- 15 mg/dl, p < 0.01) and a higher frequency of S2 phenotype (32% vs 15%, p < 0.01). Patients with an S2 phenotype exhibited significantly higher plasma Lp(a) concentrations than control subjects with the same isoform (37 +/- 22 vs 22 +/- 17 mg/dl, p < 0.05). A significant correlation was found between apo B and Lp(a) levels in patients with an S2 phenotype. In addition, patients had a low frequency of S1 and S4, and a high frequency of double-band phenotypes of apo(a). Multivariate analysis did not demonstrate an independent role for apo(a) phenotype as a risk factor for premature CAD. In conclusion, CAD patients < 55 years of age have a very different pattern of apo(a) phenotypes than subjects with no angiographic evidence of CAD; this study confirms the hypothesis that apo(a) phenotype may play an additional role in the etiology of premature CAD.

Different determinants of neovascularization on the optic disc and on the retina in patients with severe nonproliferative diabetic retinopathy.

Almost all patients with type I and many with type II diabetes develop proliferative retinopathy. This entity consists of two components: new blood vessels on the optic disc (NVD), which frequently lead to visual loss, and new blood vessels elsewhere on the retina (NVE), which do not pose such a serious threat to vision. This study examined determinants of neovascularization specifically on the optic disc in eyes with severe nonproliferative retinopathy. The study eyes were under surveillance as the untreated control eyes of participants in the Diabetic Retinopathy Study. During the 5-year follow-up period, NVE developed in almost all of the eyes, whereas the cumulative incidence of NVD in these same eyes was 64% and varied according to several factors. The risk of NVD in a study eye was increased if the contralateral treated eye had NVD rather than NVE or severe nonproliferative retinopathy (odds ratio [OR], 6.1; P < .0001). It was also increased if the study eye had, at the baseline examination, soft exudates and intraretinal microvascular abnormalities (OR, 5.7; P = .002) or soft exudates alone (OR, 4.0; P = .04). Nephropathy and poor glycemic control were each associated with a two-fold increase in risk but neither was statistically significant. Eyes of individuals over 40 years of age were protected from the development of NVD (OR, 0.5; P < .05). The findings of this study support the hypothesis that, in patients with diabetes, the development of NVD is determined by different factors than the development of NVE.

Severity of coronary artery disease in young patients with insulin-dependent diabetes mellitus.

Cardiovascular events remain a leading cause of morbidity and mortality in patients with juvenile-onset, insulin-dependent diabetes mellitus. To examine the extent and severity of the atherosclerotic lesions underlying this excess morbidity and mortality, clinical and angiographic findings were examined in 32 patients with insulin-dependent diabetes and in 31 nondiabetic patients, matched for age and symptoms, undergoing elective cardiac catheterization for evaluation of coronary artery disease. With respect to the individuals without diabetes, patients with insulin-dependent diabetes were significantly more likely to have severe narrowings, to have them in all three major coronary arteries, and to have them in distal segments. Severe narrowing of multiple vessels was significantly more common in men than in women and in individuals with hypercholesterolemia. We conclude that the high risk of cardiovascular events observed in young patients with insulin-dependent diabetes is secondary to advanced atherosclerotic lesions in coronary arteries. Involvement of distal segments of coronary arteries make these patients frequently unsuitable for bypass grafts.

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.

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.

Prevalence of retinopathy in diabetic subjects from out-patient clinics in Lombardy (Italy), and associated risk factors. A multicentre epidemiologic study.

There is little information on the prevalence of diabetic complications in Italy. For this reason, a multicentre population-based study was carried out in 1983-1985 in 12 representative out-patient clinics for the treatment of diabetes in the Lombardy region. Out of a total population of 17,704 patients 1160 diabetic subjects were randomly selected within strata based on their duration of disease (less than or equal to 5; 6-10; 11-20; greater than 20 years). Eight hundred and thirty-eight responders were examined using standardised protocols. The estimated prevalences (adjusted for duration of disease) for the total population involved in the study were 29.7% and 7.6% for background and proliferative retinopathy respectively. The overall standardised rates were higher in insulin-dependent diabetes mellitus (IDDM) (53.6%) than in non-insulin-dependent diabetes mellitus (NIDDM) (34.7%) for both background (41.1%, 28.4% respectively) and proliferative (12.5%, 6.2% respectively) retinopathy, and increased with the duration of disease. The analysis of the relationship between diabetic retinopathy and the calculated risk factors did not show any association with hypertension or metabolic control, except for post-prandial blood glucose in subjects with durations 6-10 and greater than 20 years; an association with azotaemia was found in subjects with durations less than or equal to 5 and 11-20 years. Diabetic retinopathy appeared to be independently associated with the type of treatment and not with the type of diabetes, metabolic control, or hypertension.

Impact of blood pressure on diabetic retinopathy.

Although an elevated blood pressure has been proposed as one of the major risk factors for the development and acceleration of diabetic retinopathy, demonstration of an unequivocal association between high blood pressure and retinopathy is lacking. Recent epidemiologic, cross-sectional studies indicated a close relationship between elevated systolic blood pressure and diabetic retinopathy, particularly in NIDDM subjects. In IDDM patients, the association with diastolic blood pressure was more pronounced. In the few prospective studies with sufficient number of individuals and acceptable documentation of retinal changes, in addition to poor metabolic control elevated blood pressure emerged as one of the best predictors of the development of severe deterioration of diabetic eye disease. In the Joslin study the risk of progression to severe forms of diabetic retinopathy increased exponentially with hemoglobin A1c and was dramatically different in patients with diastolic blood pressure below versus above 70 mmHg. It was hypothesized that a very low diastolic blood pressure is associated with some mechanisms which are protective against progression of eye lesions. Treatment and adequate control of hypertension is strongly recommended in all diabetic patients, the optimal level of blood pressure reduction, however, is yet to be determined.

First degree family history of diabetes and risk factors for cardiovascular disease in non-diabetic subjects in the National Telephone Company: a metabolic survey.

The effect of first degree family history of diabetes on known risk factors for cardiovascular disease was evaluated in 4989 non-diabetic employees of the Italian Telephone Company. Family history of diabetes was present in 759 subjects (476 males and 283 females); in these subjects body mass index, diastolic blood pressure, blood glucose levels (fasting and one and two-hour post-load), triglyceride and cholesterol levels were significantly higher than in age and sex-matched controls. In different age groups (less than 30, 31-40, 41-50, greater than 50 years) the effect of first degree family history of diabetes was evaluated after stratification by sex. In males with first degree family history of diabetes, this effect was strongest in the under 30 age group: body mass indices, systolic and diastolic blood pressures, fasting and two-hour post-load blood glucose levels, triglyceride and cholesterol levels were all significantly higher than in subjects with negative family history of diabetes. These differences between subjects with negative and positive family histories declined with age and disappeared in subjects over 50. In females the effect of familial diabetes was weaker and delayed for body mass index and one hour blood glucose, appearing only in subjects over 30. Multiple logistic analysis indicated that only body mass index and one-hour blood glucose levels were independently associated with positive family history of diabetes. The differences observed between males and females in the youngest age group were also confirmed by this analysis. These data may indicate a multifactorial genetic link leading to increased cardiovascular morbidity in subjects with diabetes.