Individuals with diabetes are more likely to experience cardiovascular morbidity and mortality than those without diabetes (14). We sought to investigate prevalence relationships of electrocardiogram (ECG) abnormalities and risk indicators that might be intervened upon in people with long-duration type 1 diabetes.

The study was population based. It consisted of survivors of a cohort (identified in 1979–1980) who were diagnosed with diabetes before 30 years of age, taking insulin, and receiving care in 11 counties in Wisconsin (5). The institutional review board approved the study, which conformed to the principles of the Declaration of Helsinki. Informed consent was obtained. Participants have been seen every 4–6 years for examinations (6) and are contacted annually. At the 2000–2001 examination, the following measures were added: waist and hip circumference; sitting (7), standing, and supine blood pressures; peak expiratory flow rate (PEFR) (8); and ECG. Standard fundus photographs were omitted from the 2000–2001 examination. Blood was obtained for measurement of LDL (9) and HDL (10) cholesterol and serum triglycerides (11), fasting blood glucose (12), and GHb (13). A standard medical history was obtained at all examinations. ECGs were analyzed at EPICARE Center, Wake Forest University (14). Data analyses included multiple linear and logistic regressions in which age and sex were incorporated in every model.

The mean ± SD age of the 565 participants was 45.5 ± 10.1 years, duration of diabetes 31.2 ± 8.0 years, GHb 7.9 ± 1.5%, sitting systolic blood pressure 128 ± 18 mmHg, and sitting diastolic blood pressure 76 ± 11 mmHg. A total of 51% were men. Those who had died before this examination were older, had higher blood pressure, were more likely to be smokers, had proteinuria, and had higher GHb.

Twenty-one (3.2%) subjects had evidence of an old myocardial infarction, 17 (3.0%) had isolated ST segment abnormalities, and 7 (1.2%) had major T-wave abnormalities in ECGs. In total, 66 major (not mutually exclusive) ECG abnormalities occurred in 56 subjects, and 1 or more minor abnormalities occurred in 121 subjects. Means ± SDs of the quantitative traits of cardiac autonomic neuropathy (CAN) were: QT Index (QTI) 99 ± 5%, square root of the mean of squared differences (RMSSD) of successive RR intervals 16 ± 22 ms, and SD of successive RR intervals (SDNN) 16 ± 19 ms. RMSSD and SDNN, both measures of heart rate variability, were highly correlated with each other (r = 0.93) and were inversely correlated with heart rate (−0.39 and −0.35, respectively). They were both negatively correlated with QTI, an index of prolonged QT interval adjusted for heart rate (r = −0.16 and −0.19, respectively).

Multivariable analyses found that age, sex (women), GHb, fibrinogen, triglycerides, and end-stage renal disease (ESRD) were associated with (longer) QTI and that age, sex (women), triglycerides (higher), GHb (higher), hypertension, and ESRD were associated with decreased RMSSD and SDNN. Age, sex, fibrinogen level, sedentary lifestyle, PEFR, and ESRD were significantly associated with a major ECG abnormality; however, GHb, serum lipids, and blood pressures were not. The quantitative CAN traits were associated with many other complications of diabetes (Table 1).

The quantitative CAN traits were distributed in ways that were typical of persons with diabetes and differed from published data from participants in the Atherosclerosis Risk in Communities Study (15), a general population study. As such, the QTI was prolonged, and measures of heart rate variability (RMSSD and SDNN) were decreased. These findings may be related to the poor cardiovascular experience of those with diabetes, as they may be predisposed to fatal arrhythmias (1622) and to end diastolic dysfunction (23). Major and minor ECG abnormalities were associated with PEFR. It is possible that diminished pulmonary function precedes the ECG abnormalities. It is also possible that they are comorbid results of long-term diabetes.

The relationships of several complications of diabetes in our study, some related to autonomic dysfunction including quantitative traits of CAN, are displayed in Table 1. Zeigler (24) adds exercise intolerance, intraoperative blood pressure, lability, gastric distress, intermittent diarrhea, constipation, bladder dysfunction, and sudomotor abnormalities to the list. It is possible that better control of glycemia, hypertension, and triglycerides, factors we found related to CAN, might ameliorate some of these problems.

The study is limited in that the population was first identified in 1979–1982, but ECGs were not obtained until 2000–2001. Thus, we are not certain when any of these abnormalities were first manifested, and we cannot be certain of the temporal relationships of risk indicators to them. Many of the original study participants died before the 2000–2001 examinations. This may have caused a decrease in the estimated frequency of ECG abnormalities because many may have been associated with death. Further, many correlates of ECG abnormalities may not be obvious now due to both lower sample size and to altered levels of risk factors that may have accompanied long-duration type 1 diabetes. Nevertheless, the data we present are likely to be representative of such individuals and they may suggest possible areas of interventions that might ultimately impact ECG abnormalities in them.

Supported by a grant from the National Heart, Lung and Blood Institute HL59259 (to B.E.K.K. and R.K.).

We thank Lisa Grady and Janet Klosterman for manuscript preparation.

1
Savage PJ: Cardiovascular complications of diabetes mellitus: what we know and what we need to know about their prevention.
Ann Intern Med
124
:
123
–126,
1996
2
Donahue RP, Orchard TJ: Diabetes mellitus and macrovascular complications: an epidemiological perspective.
Diabetes Care
15
:
1141
–1155,
1992
3
Geiss LS, Herman WH, Smith PJ: Mortality in non-insulin-dependent diabetes. In
Diabetes in America
. 2nd ed. Harris MI, Cowie CC, Stern MP, Boyko EJ, Reiber GE, Bennett PH, Eds. Bethesda, MD, National Institutes of Health,
1995
, p.
233
–257 (NIH publ. no. 95-1468)
4
Portuese EI, Kuller L, Becker D, Ellis D, Lloyd CE, Orchard TJ: High mortality from unidentified CVD in IDDM: time to start screening?
Diabetes Res Clin Pract
30
:
223
–231,
1995
5
Klein R, Klein BE, Moss SE, DeMets DL, Kaufman I, Voss PS: Prevalence of diabetes mellitus in southern Wisconsin.
Am J Epidemiol
119
:
54
–61,
1984
6
Klein R, Klein BE, Moss SE, Davis MD, DeMets, DL: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years.
Arch Ophthalmol
102
:
520
–526,
1984
7
Hypertension Detection and Follow-up Program Cooperative Group: The Hypertension Detection and Follow-up Program.
Prev Med
5
:
207
–215,
1976
8
Taylor JO, Wallace RB, Ostfeld AM, Blazer DG:
Established Populations for Epidemiologic Studies of the Elderly: Resource Book
. Cornoni-Huntley J, Brock DD, Ostfeld AM, Taylor JO, Wallace RB, Eds. Bethesda, MD, National Institutes of Health,
1986
(National Institute on Aging, NIH publ. no. 86-2443)
9
Lipid and lipoprotein analysis. In
Lipid Research Clinics Program Manual of Operations
. 
Vol. 1.
Bethesda, MD, National Institutes of Health,
1974
(National Heart, Lung, and Blood Institute, NIH publ. no. 75-268)
10
Davies C, Fahie-Wilson MN: Use of magnesium acetate in high-density lipoprotein cholesterol assay (Letter).
Clin Chem
25
:
1510
,
1979
11
Kohlmeier M: Direct enzymic measurement of glycerides in serum in lipoprotein fractions.
Clin Chem
32
:
63
–66,
1986
12
Stein MW: D-glucose determination with hexokinase and glucose-6-phosphate dehydrogenase. In
Methods of Enzymatic Analysis
. Bergmeyer HU, Ed. New York, Academic Press,
1963
, p.
117
13
Goldstein DE, Little RR, Wiedmeyer HM, England JD, Rohlfing CL, Wilke AL: Is glycohemoglobin testing useful in diabetes mellitus? Lessons from the Diabetes Control and Complications Trial.
Clin Chem
40
:
1637
–1640,
1994
14
Rautaharju PM, Park LP, Chaitman BR, Rautaharju F, Zhang ZM: The Novacode criteria for classification of ECG abnormalities and their clinically significant progression and regression.
J Electrocardiol
31
:
157
–187,
1998
15
Carnethon MR, Golden SH, Folsom AR, Haskell W, Liao D: Prospective investigation of autonomic nervous system function and the development of type 2 diabetes: the Atherosclerosis Risk in Communities Study, 1987–
1998
.
Circulation
107
:
2190
–2195,
2003
16
Ong JJ, Sarma JS, Venkataraman K, Levin SR, Singh BN: Circadian rhythmicity of heart rate and QTc interval in diabetic autonomic neuropathy: implications for the mechanism of sudden death.
Am Heart
125
:
744
–752,
1993
17
Wheeler SG, Ahroni JH, Boyko EJ: Prospective study of autonomic neuropathy as a predictor of mortality in patients with diabetes.
Diabetes Res Clin Prac
58
:
131
–138,
2002
18
Task force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology: Heart rate variability: standards of measurement, physiological interpretations and clinical use.
Eur Heart J
17
:
354
–381,
1996
19
Gonin JM, Kadrofske MM, Schmaltz S, Bastyr EJ 3rd, Vinik AI: Corrected Q-T interval prolongation as diagnostic tool for assessment of cardiac autonomic neuropathy in diabetes mellitus.
Diabetes Care
13
:
68
–71,
1990
20
Kahn JK, Sisson JC, Vinik AI: QT interval prolongation and sudden cardiac death in diabetic autonomic neuropathy.
J Clin Endocrinol Metab
64
:
751
–754,
1987
21
Didangelos TP, Arsos GA, Karamitsos DT, Athyros VG, Karatzas ND: Left ventricular systolic and diastolic function in normotensive type 1 diabetic patients with or without autonomic neuropathy: a radionuclide ventriculography study.
Diabetes Care
26
:
1955
–1960,
2003
22
Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vicentini A, Spazzolini C, Nastoli J, Bottelli G, Folli R, Cappelletti D: Risk stratification in the long-QT syndrome.
N Engl J Med
348
:
1866
–1874,
2003
23
Schouten EG, Dekker JM, Meppelink P, Kok FJ, Vandenbroucke JP, Pool J: QT interval prolongation predicts cardiovascular mortality in an apparently healthy population.
Circulation
84
:
1516
–1523,
1991
24
Ziegler D: Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment.
Diabetes Metab Rev
10
:
339
–383,
1994

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.