Insulin Treatment, Endogenous Insulin Concentration, and ECG Abnormalities in Diabetic Pima Indians Cross-Sectional and Prospective Analyses QUAN ZHI LIU, WILLIAM C. KNOWLER, ROBERT G. NELSON, MOHAMMED F. SAAD, MARIE A. CHARLES, IRVING M. LIEBOW, PETER H. BENNETT, AND DAVID J. PETTITT The prevalence and incidence of CHD, defined by ECG abnormalities according to the Tecumseh criteria for Minnesota Codes, were determined in Pima Indians >25 yr of age. In a cross-sectional analysis, the age-sex-adjusted prevalence (± SE) of ECG abnormalities was higher in 1454 NIDDM patients (6.86 ± 0.65%) than in 1696 nondiabetic subjects (3.23 ± 0.63%; prevalence rate ratio = 2.12; 95% Cl 1.39-3.25). In a prospective analysis, the age-sex-adjusted incidence (± SE) of ECG abnormalities was higher in 824 NIDDM patients (12.77 ±1.67) than in 935 nondiabetic subjects (5.93 ± 1.43 cases/1000 person-yr; incidence rate ratio = 2.15; 95% Cl 1.26-3.69). The prevalence of ECG abnormalities in insulin-treated NIDDM patients was significantly higher than in NIDDM patients not treated with insulin (age-sex-adjusted OR = 2.83; 95% Cl 1.84-4.33); and this association persisted when adjusted for other factors such as sBP, BMI, duration of diabetes, serum cholesterol concentration, and oral hypoglycemic agents (OR = 2.12; 95% Cl 1.34-3.37). In the prospective analysis, the incidence of ECG abnormalities in NIDDM patients treated with insulin was higher than in those NIDDM patients not treated with insulin, but, when controlled for age, sex, duration of diabetes, and oral hypoglycemic agents in a proportional-hazards model, the relationship with insulin treatment was not statistically significant From the Diabetes and Arthritis Epidemiology Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes, and Digestive and Kidney Diseases (NIDDK); and the Department of Biostatistics and Epidemiology, the Cleveland Clinic Foundation, Phoenix, AZ. Address correspondence and reprint requests to Dr. William C. Knowler, Diabetes and Arthritis Epidemiology Section, NIDDK, 1550 East Indian School Road, Phoenix, AZ 85014. Received for publication 22 January 1991 and accepted in revised form 25 March 1992. NIDDK, National Institute of Diabetes, Digestive and Kidney Diseases; CHD, coronary heart disease; NIDDM, non-insulin-dependent diabetes mel- litus; Cl, confidence interval; OR, odds ratio; sBP, systolic blood pressure; BMI, body mass index; BP, blood pressure; GTT, glucose tolerance test; IGT, impaired glucose tolerance; CVD, cardiovascular disease; WHO, World Health Organization; df, degree of freedom; IDDM, insulin-dependent diabe- tes mellitus. (incidence rate ratio = 1.36; 95% Cl 0.80-2.31). This suggests that insulin treatment may be a marker of more severe diabetes, and that factors associated with clinical indications for insulin treatment, rather than insulin treatment per se, are related causally to CHD. On the other hand, endogenous fasting and 2-h postload serum insulin concentrations were not associated with ECG abnormalities among 761 NIDDM patients not treated with insulin nor among 1226 nondiabetic subjects. Furthermore, in the prospective study, neither endogenous fasting nor 2-h postload serum insulin was associated with the subsequent development of ECG abnormalities in NIDDM patients or nondiabetic subjects. Diabetes 41:1141-50,1992 C HD is more common in people with diabetes than in those without (1-9). Many studies have attempted to identify differences in CHD risk factors between diabetic and nondiabetic peo- ple, but the underlying mechanism for the effect of diabetes on CHD remains unclear (1-3,5,8,10,11). Hy- perinsulinemia may contribute to atherogenesis and may be partly responsible for the higher rate of CHD in NIDDM (8,12-17). However, data on hyperinsulinemia as a risk factor for CHD in diabetic patients are inconsistent and contradictory because of confounding by other potential cardiovascular risk factors, such as obesity and high BP (7,11,13,14,18). The Pima Indians of the Gila River Indian Community in southern Arizona have the world's highest reported prev- alence and incidence of NIDDM (19) and an unusually high frequency of obesity (20). Fatal CHD, uncommon in Pima Indians, occurs almost exclusively in those with NIDDM (21). However, the prevalence of ECG abnormal- ities is low in this population (22-23). The purpose of this study is to determine the prevalence and incidence of ECG abnormalities and to identify factors, including DIABETES, VOL. 41, SEPTEMBER 1992 1141 Downloaded from http://diabetesjournals.org/diabetes/article-pdf/41/9/1141/359767/41-9-1141.pdf by guest on 04 November 2022