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February 6, 1991, Vol 265, No. 5 >
ARTICLE | February 6, 1991

Why Is Diabetes Mellitus a Stronger Risk Factor for Fatal Ischemic Heart Disease in Women Than in Men?: Title and subTitle BreakThe Rancho Bernardo Study FREE

Elizabeth L. Barrett-Connor, MD; Barbara A. Cohn, PhD; Deborah L. Wingard, PhD; Sharon L. Edelstein, MSc
[+] Author Affiliations

Reprint requests to the Department of Community and Family Medicine, M-007, University of California, San Diego, La Jolla, CA 92093-0607 (Dr Barrett-Connor).


JAMA. 1991;265(5):627-631. doi:10.1001/jama.1991.03460050081025
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References

We report here the 14-year sex-specific effect of non—insulin-dependent diabetes mellitus on the risk of fatal ischemic heart disease in a geographically defined population of men and women aged 40 through 79 years. There were 207 men and 127 women who had diabetes at baseline based on medical history or fasting hyperglycemia. They were compared with 2137 adults who had fasting euglycemia and a negative personal and family history of diabetes. The relative hazard of ischemic heart disease death in diabetics vs nondiabetics was 1.8 in men and 3.3 in women, after adjusting for age, and 1.9 and 3.3, respectively, after adjusting for age, systolic blood pressure, cholesterol, body mass index, and cigarette smoking using the Cox regression model. The sex difference in the independent contribution of diabetes to fatal heart disease was largely explained by the persistently more favorable survival rate of women (than men) without diabetes.

(JAMA. 1991;265:627-631)

REFERENCES

1 +
Wingard DL.  The sex differential in morbidity, mortality, and lifestyle . Annu Rev Public Health. 1984;;5:433-458.
2 +
Barrett-Connor E, Orchard T.  Diabetes and heart disease . In: Harris MI, Hamman RF, eds. Diabetes in America . Bethesda, Md: National Institutes of Health;1985;:1-41. NIH Publication 85-1468.
3 +
Pyöräla K, Laakso M.  Macrovascular disease in diabetes mellitus . In: Mann JI, Pyöräla K, Teuscher A, eds. Diabetes in Epidemiological Perspective . New York, NY: Churchill Livingstone Inc; 1983;:183-264.
4 +
Barrett-Connor E, Wingard DL.  Sex differential in ischemic heart disease mortality in diabetics . Am J Epidemiol. 1983;;118:489-496.
5 +
Criqui M, Barrett-Connor E, Austin M.  Differences between respondents and nonrespondents in a population-based cardiovascular disease study . Am J Epidemiol. 1978;;108:367-372.
6 +
Austin MA, Criqui MH, Barrett-Connor E, Holdbrook MJ.  The effect of response bias on the odds ratio . Am J Epidemiol. 1981;;114:137-143.
7 +
The International Classification of Diseases, Ninth Revision, Clinical Modification: ICD-9-CM . 2nd ed. Washington, DC: US Dept of Health and Human Services, Public Health Service; 1980;.
8 +
Cox DR.  Regression models and life tables (with discussion) . J R Stat Soc. 1972;;8:187-220.
9 +
Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data . New York, NY: John Wiley & Sons Inc; 1980;.
10 +
Barrett-Connor E.  The prevalence of diabetes mellitus in an adult community as determined by history or fasting hyperglycemia . Am J Epidemiol. 1980;;111:705-712.
11 +
Barrett-Connor E, Criqui MH, Klauber MR, Holdbrook MJ.  Diabetes and hypertension in a community of older adults . Am J Epidemiol. 1981;;113:276-284.
12 +
Barrett-Connor E, Grundy SM, Holdbrook MJ.  Plasma lipids and diabetes mellitus in an adult community . Am J Epidemiol. 1982;;115:657-663.
13 +
Wingard DL, Sinsheimer P, Barrett-Connor EL, McPhillips JB.  Community-based study of prevalence of NIDDM in older adults . Diabetes Care . 1990;;13( (suppl 2) ):3-8.
14 +
Harris MI, Hadden WC, Knowler WC, et al.  Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in US population aged 20-74 years . Diabetes. 1987;;36:523-534.
15 +
Blunt BA, Barrett-Connor E, Wingard DL.  Evaluation of fasting plasma glucose as a screening test for diabetes mellitus in older Americans: Rancho Bernardo study . Presented at the 50th Scientific Sessions Meeting, American Diabetes Association; June 17,1990 ; Atlanta, Ga.
16 +
Barrett-Connor E.  Factors associated with the distribution of fasting plasma glucose in an adult community . Am J Epidemiol. 1980;;112:518-523.
17 +
Eaker ED, Castelli WP.  Coronary heart disease and its risk factors among women in the Framingham Study . In: Baker ED, Packard B, Wenger NK, Clarkson TB, Tyroler HA, eds. Coronary Heart Disease in Women . New York, NY: Haymarket Doyma Inc; 1987;:122-130.
18 +
Kleinman JC, Donahue RP, Harris MI, et al.  Mortality among diabetics in a national sample . Am J Epidemiol. 1988;;128:389-401.
19 +
Pan W-H, Cedres LB, Liu K, et al.  Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease mortality in men and women . Am J Epidemiol. 1986;;123: 504-516.
20 +
Diabetes Drafting Group.  Prevalence of small vessel and large vessel disease in diabetic patients from 14 centres: the WHO multinational study of vascular disease in diabetics . Diabetologia. 1985;;28:615-640.
21 +
Robertson WB, Strong JP.  Atherosclerosis in persons with hypertension and diabetes mellitus . Lab Invest. 1968;;18:538-551.
22 +
Walden CE, Knopp RH, Wahl PW, et al.  Sex differences in the effect of diabetes mellitus on lipoprotein triglyceride and cholesterol concentrations . N Engl J Med. 1984;;311:953-959.
23 +
Barrett-Connor E, Witztum JL, HoldbrookM.  A community study of high-density lipoproteins in adult non—insulin-dependent diabetics . Am J Epidemiol. 1983;;117:186-192.
24 +
Nelson RG, Sievers ML, Knowler WC, et al.  Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non—insulin-dependent diabetes . Circulation . 1990;;81: 987-995.
25 +
Gordon DJ, Probstfield JL, Garrison RJ, et al.  High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies . Circulation . 1989;;79:8-15.
26 +
Crouse JR III.  Gender, lipoproteins, diet, and cardiovascular risk: sauce for the goose may not be sauce for the gander . Lancet . 1989;;2:318-320.
27 +
Barrett-Connor E, Wingard DL, Criqui MH, Suarez L.  Is borderline fasting hyperglycemia a risk factor for cardiovascular death? J Chron Dis. 1984;;37:773-779.
28 +
Kissebah AH, Vydelingum N, Murray R, et al.  Relation of body fat distribution to metabolic complications of obesity . J Clin Endocrinol Metab. 1982;;54:254-260.
29 +
Krotkiewski M, Björntorp P, Sjöström L, Smith U.  Impact of obesity on metabolism in men and women: importance of regional adipose tissue distribution . J Clin Invest. 1983;;72:1150-1162.
30 +
Evans DJ, Hoffmann RG, Kalkhoff RK, et al.  Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopause women . J Clin Endrocrinol Metab. 1983;;57:304-310.
31 +
Seidell JC, Cigolini M, Deurenberg P, Oosterlee A, Doornbos G.  Fat distribution, androgens, and metabolism in nonobese women . Am J Clin Nutr. 1989;;50:269-273.
32 +
Krotkiewski R, Björntorp P.  Muscle tissue in obesity with different distribution of adipose tissue effects of physical training . Int J Obes. 1986;;10: 331-341.
33 +
Peiris AN, Sothmann MS, Hennes MI, et al.  Relative contribution of obesity and body fat distribution to alterations in glucose insulin homeostasis: predictive values of selected indices in premenopausal women . Am J Clin Nutr. 1989;;49:758-764.
34 +
Lapidus L.  Ischaemic heart disease, stroke, and total mortality in women: results from a prospective population study in Gothenburg, Sweden . Acta Med Scand . 1985;;705( (suppl) ):2-42.
35 +
Ostlund RE Jr, Staten M, Kohrt WM, Schultz J, Malley M.  The ratio of waist-to-hip circumference, plasma insulin level, and glucose intolerance as independent predictors of the HDL2 cholesterol level in older adults . N Engl J Med. 1990;;322:229-234.
36 +
Chang RJ, Nakamura RM, Judd HL, Kaplan SA.  Insulin resistance in nonobese patients with polycystic ovarian disease . J Clin Endocrinol Metab. 1983;;57:356-359.
37 +
Jialal I, Naiker P, Reddi K, Moodley J, Joubert SM.  Evidence for insulin resistance in nonobese patients with polycystic ovarian disease . J Clin Endocrinol Metab. 1987;;64:1066-1069.
38 +
Wild RA, Painter PC, Coulson PB, Carruth KB, Ranney GB.  Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome . J Clin Endocrinol Metab. 1985;;61:946-951.
39 +
Wild RA, Bartholomew MJ.  The influence of body weight on lipoprotein lipids in patients with polycystic ovary syndrome . Am J Obstet Gynecol. 1988;;159:423-427.
40 +
Kissebah AH, Evans DJ, Peiris A, Wilson CR.  Endocrine characteristics in regional obesities: role of sex steroids . In: Vague J, Björntorp P, Guy-Grand B, Rebuffé-Scrive M, Vague P, eds. Metabolic Complications of Human Obesities . New York, NY: Elsevier Science Publishing Co Inc; 1985;:115-131.
41 +
Poretsky L, Kalin MF.  The gonadotropic function of insulin . Endocr Rev. 1987;;8:132-141.

Figures

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Wingard DL.  The sex differential in morbidity, mortality, and lifestyle . Annu Rev Public Health. 1984;;5:433-458.
2 +
Barrett-Connor E, Orchard T.  Diabetes and heart disease . In: Harris MI, Hamman RF, eds. Diabetes in America . Bethesda, Md: National Institutes of Health;1985;:1-41. NIH Publication 85-1468.
3 +
Pyöräla K, Laakso M.  Macrovascular disease in diabetes mellitus . In: Mann JI, Pyöräla K, Teuscher A, eds. Diabetes in Epidemiological Perspective . New York, NY: Churchill Livingstone Inc; 1983;:183-264.
4 +
Barrett-Connor E, Wingard DL.  Sex differential in ischemic heart disease mortality in diabetics . Am J Epidemiol. 1983;;118:489-496.
5 +
Criqui M, Barrett-Connor E, Austin M.  Differences between respondents and nonrespondents in a population-based cardiovascular disease study . Am J Epidemiol. 1978;;108:367-372.
6 +
Austin MA, Criqui MH, Barrett-Connor E, Holdbrook MJ.  The effect of response bias on the odds ratio . Am J Epidemiol. 1981;;114:137-143.
7 +
The International Classification of Diseases, Ninth Revision, Clinical Modification: ICD-9-CM . 2nd ed. Washington, DC: US Dept of Health and Human Services, Public Health Service; 1980;.
8 +
Cox DR.  Regression models and life tables (with discussion) . J R Stat Soc. 1972;;8:187-220.
9 +
Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data . New York, NY: John Wiley & Sons Inc; 1980;.
10 +
Barrett-Connor E.  The prevalence of diabetes mellitus in an adult community as determined by history or fasting hyperglycemia . Am J Epidemiol. 1980;;111:705-712.
11 +
Barrett-Connor E, Criqui MH, Klauber MR, Holdbrook MJ.  Diabetes and hypertension in a community of older adults . Am J Epidemiol. 1981;;113:276-284.
12 +
Barrett-Connor E, Grundy SM, Holdbrook MJ.  Plasma lipids and diabetes mellitus in an adult community . Am J Epidemiol. 1982;;115:657-663.
13 +
Wingard DL, Sinsheimer P, Barrett-Connor EL, McPhillips JB.  Community-based study of prevalence of NIDDM in older adults . Diabetes Care . 1990;;13( (suppl 2) ):3-8.
14 +
Harris MI, Hadden WC, Knowler WC, et al.  Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in US population aged 20-74 years . Diabetes. 1987;;36:523-534.
15 +
Blunt BA, Barrett-Connor E, Wingard DL.  Evaluation of fasting plasma glucose as a screening test for diabetes mellitus in older Americans: Rancho Bernardo study . Presented at the 50th Scientific Sessions Meeting, American Diabetes Association; June 17,1990 ; Atlanta, Ga.
16 +
Barrett-Connor E.  Factors associated with the distribution of fasting plasma glucose in an adult community . Am J Epidemiol. 1980;;112:518-523.
17 +
Eaker ED, Castelli WP.  Coronary heart disease and its risk factors among women in the Framingham Study . In: Baker ED, Packard B, Wenger NK, Clarkson TB, Tyroler HA, eds. Coronary Heart Disease in Women . New York, NY: Haymarket Doyma Inc; 1987;:122-130.
18 +
Kleinman JC, Donahue RP, Harris MI, et al.  Mortality among diabetics in a national sample . Am J Epidemiol. 1988;;128:389-401.
19 +
Pan W-H, Cedres LB, Liu K, et al.  Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease mortality in men and women . Am J Epidemiol. 1986;;123: 504-516.
20 +
Diabetes Drafting Group.  Prevalence of small vessel and large vessel disease in diabetic patients from 14 centres: the WHO multinational study of vascular disease in diabetics . Diabetologia. 1985;;28:615-640.
21 +
Robertson WB, Strong JP.  Atherosclerosis in persons with hypertension and diabetes mellitus . Lab Invest. 1968;;18:538-551.
22 +
Walden CE, Knopp RH, Wahl PW, et al.  Sex differences in the effect of diabetes mellitus on lipoprotein triglyceride and cholesterol concentrations . N Engl J Med. 1984;;311:953-959.
23 +
Barrett-Connor E, Witztum JL, HoldbrookM.  A community study of high-density lipoproteins in adult non—insulin-dependent diabetics . Am J Epidemiol. 1983;;117:186-192.
24 +
Nelson RG, Sievers ML, Knowler WC, et al.  Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non—insulin-dependent diabetes . Circulation . 1990;;81: 987-995.
25 +
Gordon DJ, Probstfield JL, Garrison RJ, et al.  High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies . Circulation . 1989;;79:8-15.
26 +
Crouse JR III.  Gender, lipoproteins, diet, and cardiovascular risk: sauce for the goose may not be sauce for the gander . Lancet . 1989;;2:318-320.
27 +
Barrett-Connor E, Wingard DL, Criqui MH, Suarez L.  Is borderline fasting hyperglycemia a risk factor for cardiovascular death? J Chron Dis. 1984;;37:773-779.
28 +
Kissebah AH, Vydelingum N, Murray R, et al.  Relation of body fat distribution to metabolic complications of obesity . J Clin Endocrinol Metab. 1982;;54:254-260.
29 +
Krotkiewski M, Björntorp P, Sjöström L, Smith U.  Impact of obesity on metabolism in men and women: importance of regional adipose tissue distribution . J Clin Invest. 1983;;72:1150-1162.
30 +
Evans DJ, Hoffmann RG, Kalkhoff RK, et al.  Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopause women . J Clin Endrocrinol Metab. 1983;;57:304-310.
31 +
Seidell JC, Cigolini M, Deurenberg P, Oosterlee A, Doornbos G.  Fat distribution, androgens, and metabolism in nonobese women . Am J Clin Nutr. 1989;;50:269-273.
32 +
Krotkiewski R, Björntorp P.  Muscle tissue in obesity with different distribution of adipose tissue effects of physical training . Int J Obes. 1986;;10: 331-341.
33 +
Peiris AN, Sothmann MS, Hennes MI, et al.  Relative contribution of obesity and body fat distribution to alterations in glucose insulin homeostasis: predictive values of selected indices in premenopausal women . Am J Clin Nutr. 1989;;49:758-764.
34 +
Lapidus L.  Ischaemic heart disease, stroke, and total mortality in women: results from a prospective population study in Gothenburg, Sweden . Acta Med Scand . 1985;;705( (suppl) ):2-42.
35 +
Ostlund RE Jr, Staten M, Kohrt WM, Schultz J, Malley M.  The ratio of waist-to-hip circumference, plasma insulin level, and glucose intolerance as independent predictors of the HDL2 cholesterol level in older adults . N Engl J Med. 1990;;322:229-234.
36 +
Chang RJ, Nakamura RM, Judd HL, Kaplan SA.  Insulin resistance in nonobese patients with polycystic ovarian disease . J Clin Endocrinol Metab. 1983;;57:356-359.
37 +
Jialal I, Naiker P, Reddi K, Moodley J, Joubert SM.  Evidence for insulin resistance in nonobese patients with polycystic ovarian disease . J Clin Endocrinol Metab. 1987;;64:1066-1069.
38 +
Wild RA, Painter PC, Coulson PB, Carruth KB, Ranney GB.  Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome . J Clin Endocrinol Metab. 1985;;61:946-951.
39 +
Wild RA, Bartholomew MJ.  The influence of body weight on lipoprotein lipids in patients with polycystic ovary syndrome . Am J Obstet Gynecol. 1988;;159:423-427.
40 +
Kissebah AH, Evans DJ, Peiris A, Wilson CR.  Endocrine characteristics in regional obesities: role of sex steroids . In: Vague J, Björntorp P, Guy-Grand B, Rebuffé-Scrive M, Vague P, eds. Metabolic Complications of Human Obesities . New York, NY: Elsevier Science Publishing Co Inc; 1985;:115-131.
41 +
Poretsky L, Kalin MF.  The gonadotropic function of insulin . Endocr Rev. 1987;;8:132-141.

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