A Population'based Study of

Transcription

1 A Population'based Study of Diabetes Mortality JAMES W. OCHI, M.D., L. JOSEPH MELTO III, M.D., PASQUALE J. PALUMBO, M.D., AD CHU-PI CHU, M.S. In a population-based investigation among the residents of Rochester, Minnesota, the diabetes mortality rate was 8. per, person-years with diabetes as the underlying cause of death, 3. per, person-years with diabetes as an underlying or contributory cause, and 8.7 per, person-years if all deaths among diabetic individuals were counted. Diabetes was not mentioned on the certificate in 6% of the 8 diabetic deaths during 6-7. When the clinical characteristics of the subgroup of mortality cases in 6 were compared with those of the prevalence cases on January 7, it was found that mortality cases tended to be older, were more often on insulin therapy, and were more likely to have macro- and microvascular complications. Because mortality data are sometimes used to infer trends and characteristics for the diabetic population at large, it is important to recognize these biases. DIABETES CARE 8; 8:-. Cause-specific mortality data are routinely collected on the entire population of this country, and it is tempting to use this information in the management of disease control programs. Unfortunately, mortality data have well-recognized deficiencies where diabetes mellitus is concerned. Attention has been focused on the incomplete reporting of diabetes as an underlying or contributing cause of death, " but selection bias, in terms of those diabetes-related deaths that are and are not reported, may also pose a problem. Moreover, little is known of the quantitative and qualitative relationships between the mortality cases and the living diabetic individuals in the community. The objectives of the present study were () to make a population-based comparison of diabetic mortality rates determined from death certificates versus the actual death rate among diabetic residents of the community and () to contrast the clinical characteristics of the mortality cases with those of the resident population of living diabetic patients. MATERIALS AD METHODS Rochester, Minnesota, is well suited for studies of the natural history of diabetes mellitus because comprehensive unit medical records for the residents are available and because these records are accessible through a central index of diagnoses made by essentially all medical care providers utilized by the local population. This index includes the diagnoses made among outpatients seen in clinic consultations (including all office visits), emergency room visits, house calls, and nursing home care, as well as diagnoses recorded among hospital inpatients, at autopsy, and on death certificates. The potential of this data system for population-based studies has been described previously. The original medical records of the patients identified through the index were retrieved and reviewed for an initial diagnosis of diabetes in the 3-yr period, -7- The diagnostic criteria used for diabetes mellitus have been reported in detail in an earlier paper. 6 While our criteria were somewhat more generous than those proposed by the ational Diabetes Data Group, 7 we have shown that the differences have little practical effect on the resulting clinical spectrum of diabetes or on survival rates. 8 The diagnostic criteria used resulted in an incidence cohort of 3 Rochester residents with diabetes mellitus newly diagnosed between and 6, while 33 additional incidence cases were identified between 7 and 7- The prevalence of diabetes among Rochester residents was assessed on January 7 and again on January 7. Because of the incidence and prevalence data and the rather complete follow-up available on these patients, we were confident of identifying all diabetic individuals who were local residents at the time of death in the -yr period, 6-7. Diabetes mortality rates were determined from this group of deaths using as a denominator the entire population of Rochester; age- and sex-specific person-years at risk were estimated from DIABETES CARE, VOL. 8 O. 3, MAY-JUE 8

2 POPULATIO-BASED STUDY OF DIABETES MORTALITY/J. W. OCHI AD ASSOCIATES decennial census data. The underlying cause of death was obtained from each death certificate, and these were grouped into cause-specific categories for this report. Diabetes was accepted as a contributing cause of death if mentioned on either part or part of the death certificate. Clinical characteristics near the time of death for the mortality cases who died during calendar year 6 were compared with those of the prevalence cases on January 7. The fasting blood glucose value used in this comparison was the value closest to January 7. The fasting blood glucose levels were divided as recommended by West into "mildly elevated" (^ mg/dl whole venous blood), "moderately elevated" (- mg/dl), and "severely elevated" (> 3 mg/dl). Obesity was approximated by relative weight, expressed as percentage of standard weight for height and calculated using recommended height-weight tables; patients were considered obese whose relative weight was % or more of the standard value for a given height. Therapeutic regimens were classified as insulin (with or without other therapy), oral agent (with or without diet but without insulin), or diet alone (no insulin or oral agents) as of the time nearest to January 7. The characterization of specific clinical types of diabetes generally followed ational Diabetes Data Group recommendations, 7 although as explained in detail in a separate report some modifications were required in the context of a retrospective study using existing medical records. Diabetic "complications" were classified as macrovascular (angina pectoris, myocardial infarction, sudden unexpected death, stroke, transient ischemic attack, or peripheral vascular disease) or microvascular (retinopathy or diabetic renal disease). Complications on the prevalence day and before death included a history of any one or more of these. RESULTS Four hundred twenty-eight Rochester residents (3 men and women) who had diabetes according to the study criteria died in the -yr period, 6 7. Of these, diabetes was listed as the underlying cause of death in (.3%), including two instances where diabetes was also the direct cause of death. For additional fatalities (7.8%), diabetes was listed as a contributing cause of death. Diabetes was mentioned nowhere on the death certificate in 6 cases (6.%). Mortality rates would vary, of course, based on the definition of a diabetes-related death. Consequently, we calculated the rates in three different ways: from death certificates where diabetes () was listed as the underlying cause of death, or () was listed as an underlying or contributing cause, and (3) counting all deaths that occurred among diabetic indi- TABLE Diabetes mellitus mortality rates using different sources of data among Rochester, Minnesota, residents (6-7) Diabetes listed as underlying cause Diabetes listed as underlying or contributory cause Total diabetic deaths age group Rate* Rate" Rate* Men < Subtotal Women < Subtotal Total (crude) (adjusted)! 'Mortality per, person-years. tdirectly adjusted to the age and sex distribution of 7 United States whites. DIABETES CARE, VOL. 8 O. 3, MAY-JUE 8

3 POPULATIO-BASED STUDY OF DIABETES MORTALTIY/J. W. OCH AD ASSOCIATES viduals, regardless of the death certificate information. Diabetes mortality rates using these different definitions are displayed in Table. The diabetes mortality rate calculated in the usual manner, employing the underlying cause of death, was 8. per, person-years (adjusted.3 per, person-years; % confidence interval 6. to.), based on 7,6 person-years at risk. If a diabetic death were taken to mean any death where diabetes was mentioned on the death certificate, the mortality rate would be 3. per, person-years (adjusted 3. per, person-years; % confidence interval 3.3--), almost four times as great as the traditionally calculated figure. Diabetes was listed as a contributing cause of death about three times as often as it was claimed to be the underlying cause of death. Finally, if a diabetic death were taken to mean any death in an individual with previously diagnosed diabetes by our criteria, the overall diabetes mortality rate would be 8.7 per, person-years (adjusted -6 per, person-years; % confidence interval ), a figure over g times as great as the all-death-certificate rate and almost times higher than the rate based on the underlying cause of death. For purposes of comparison, the total crude mortality rate among Rochester residents in 7 was 78 per, population. Although the actual age- and sex-specific mortality rates would be quite different depending on the definition used (Table ), the proportionate distribution of deaths by age and sex would be roughly comparable in each instance except for the excess of elderly women noted when the underlying cause of death was diabetes. Mortality rates with the latter definition were greater among women than men (.3 versus 6. per, person-years); this difference persisted even after age adjustment (.3 versus 8. per, person-years) but was not statistically significant (P >.). Under the second definition, the diabetes death rate among men was greater than that for women (3.8 versus 3. per, personyears), although this difference was greatly augmented by age adjustment of the rates (. versus 7.8 per, personyears; P <.). This difference resulted from the greater male death rate with diabetes as a contributory cause of death (36.6 versus 8. per, person-years after age adjustment). Although not shown in Table, male rates were also greater for those deaths where diabetes was not mentioned on the death certificate (8. versus. per, personyears after age adjustment). Thus, the male:female ratio of age-adjusted mortality rates for all diabetic deaths was.: (8. versus 6. per, person-years; P <.). The distributions of underlying cause of death were fairly comparable for those deaths where diabetes was listed anywhere on the death certificate and for the total diabetic deaths in Rochester during 6-7 (Table ), although there were some differences in the distribution of underlying causes for those diabetic deaths where diabetes was not mentioned. Cardiovascular disease, especially coronary heart disease but also arteriosclerosis and stroke, represented the most common cause of death, accounting for 7%, %, and %, respectively, of the three groups shown in Table. Diabetes per se was overrepresented, of course, among those with diabetes noted on the death certificate. Malignancy and "other" causes were more frequent among diabetic residents whose death certificates did not mention diabetes. The distributions of the other, less common, causes of death were not strikingly different from one patient group to the next. The mortality cases were quite unrepresentative, however, TABLE Distribution of underlying causes of death using different sources of data among Rochester, Minnesota, residents with diabetes who died 6-7 Underlying cause of death Diabetes listed on death certificate % Diabetes not mentioned on death certificate % Total diabetic deaths % Coronary heart disease Arteriosclerosis Stroke Diabetes Malignancy Pneumonia Liver disease Renal disease Obstructive pulmonary disease Rheumatic heart disease Pulmonary embolism Other DIABETES CARE, VOL. 8 O. 3, MAY-JUE 8

4 POPULATIO-BASED STUDY OF DIABETES MORTALITY/J. W. CH AD ASSOCIATES - QMen - E Women Incidence cases (-6) Age at initial diagnosis Distribution by age Mortality cases (6-7) and sex (Percent of total) S* Age at death o m Prevalence cases ( Jan 7) Age on prevalence day F/G. I. Distribution by age and sex of Rochester, Minnesota, residents with diabetes, comparing incidence, prevalence, and mortality cases. of incidence and prevalence cases of diabetes in the community. As might be expected, the mortality cases were relatively much older than either incidence or prevalence patients (Figure ). However, substantial differences were also noted when the clinical characteristics near the time of death for the mortality cases of 6 were compared with those of the 8 prevalence cases on January 7 (Table 3). The distribution of clinical types of diabetes was fairly comparable between mortality and prevalence cases, but the proportion of mortality cases on insulin therapy was greater and the proportion on diet alone much less than for prevalence cases (P =.). The 6 mortality cases had fasting blood glucose levels much like those of the prevalence cases and a similarly low proportion with the classic triad of diabetes symptoms. A greater proportion of mortality cases were thin, as indicated by being less than % of the standard weight for height, but the distributions of relative weight for mortality and prevalence cases were not statistically significantly different (P >.). However, the patients who had died were much more likely to have had one or more of the microvascular (P <.) and especially the macrovascular complications (P <.) of diabetes as compared with the prevalence cases. DISCUSSIO The fact that diabetes mellitus is a major public health problem is apparent despite any inaccuracies and biases in the mortality data. However, the nature and magnitude of potential biases is of great importance to those who would use routinely collected mortality data to study diabetes epidemiology or to manage diabetes control programs. Underestimation of diabetes-related deaths is the bias that has received the most attention. The existing mortality reporting system only allows for one condition as the underlying cause of death, even though other significant and sometimes related diseases exist in the same patient. We found that diabetes was listed as the underlying cause of death on 7% of the death certificates in which diabetes was mentioned as either an underlying or contributing cause. This is similar to the proportion found in other studies, " 3 " although reported values vary from % 3 to %. The Rochester figure is identical to the average reported for states in the ational Diabetes Control Program. This form of underestimation of diabetes' contribution to mortality seems to result mostly from the recording of vascular complications (directly or indirectly related to diabetes mellitus), which are listed instead as the underlying cause of death. Mi3 A second and more difficult source of underestimation lies with the deaths among diabetic individuals that are not acknowledged on the death certificate at all. Diabetes was not mentioned on 33% of the death certificates of members of the British Diabetic Association. 3 However, these individuals may have been unrepresentative of the larger population of diabetic patients since about one-third were under yr of age when enrolled. Among diabetic patients known to the Joslin Clinic,.8% had no mention of diabetes on their death certificates. Reporting may be better among those more severely affected patients and those who are attended at tertiary care centers, however, since population-based studies TABLE 3 Clinical characteristics of Rochester, Minnesota, diahetic residents near the time of death during calendar year 6, or on prevalence day January 7 Clinical type (%) Insulin-dependent Obese non-insulin-dependent onohese non-insulin-dependent Secondary diabetes Treatment (%) Insulin Oral agents Diet alone Fasting blood glucose Median value Mild (%) Moderate (%) Severe (%) Classic symptoms One or more (%) Relative weight (%) <% -% >% Complications present Macrovascular (%) Microvascular (%) Mortality cases 6 ( = ) mg/dl Prevalence cases 7 ( = 8) mg/dl DIABETES CARE, VOL. 8 O. 3, MAY-JUE 8 7

5 POPULATIO-BASED STUDY OF DIABETES MORTALITY/J. W. CH AD ASSOCIATES indicate that diabetes is not mentioned in from one-half 6 to three-quarters 7 of the deaths that actually occur in this group of patients. We discovered that diabetes was not listed on the death certificates of 6% of the deaths among patients with known diabetes. This figure is very similar to the estimated 6% underreporting of diabetic deaths nationally, as judged using death certificate data and a total number of diabetic deaths derived from differences between estimated national incidence and prevalence rates (Dr. Maureen Harris, personal communication). The distribution of causes of death also varied somewhat depending on how diabetic deaths were defined. Other investigators " agree with our finding that circulatory disorders dominate the recorded underlying causes of death in diabetic patients, with coronary heart disease comprising the major portion. However, the mortality cases in the present study who did not have diabetes listed on the death certificate were relatively much more likely to die from malignancy or "other" causes, i.e., trauma; 3 and it may be true that diabetes played no role in many of these deaths. Other work has shown, for example, that the risk of subsequent malignancy is not increased among individuals with diabetes. 8 When the incidence cohort of diabetic Rochester residents was studied, 8 the actuarially estimated cumulative death rate was 6% by yr after the initial diagnosis of diabetes, while the expected rate for members of the general population of like age and sex was 6%. With an attributable risk of death on the order of 3%, it is reasonable to assume that a substantial portion of diabetic deaths may be related to the underlying disease but that the majority of deaths are unrelated. This issue has been discussed at length by others.' It is most important to note, however, that the mortality cases cannot be taken to represent a sample of incidence nor even of prevalence cases of diabetes in the community. The total mortality rate for diabetic residents 6-7 was only % of the prevalence rate for diabetes in Rochester on January 7. Thus, the mortality data vastly underestimate diabetes prevalence. Moreover, the mortality cases were much older, on average, and had quite different clinical characteristics. Mortality cases appear to provide a very unreliable indicator of the clinical spectrum of diabetes among those still alive, by virtue of greatly overestimating the impact of the macro- and microvascular complications of diabetes mellitus. Because mortality data are sometimes used to infer trends and characteristics for the diabetic population at large, it is important to recognize the biases that occur with this approach. ACKOWLEDGMETS: The authors thank Lois Bartz for help in data collection and Janet R. King for assistance in preparing the manuscript. This investigation was supported in part by research grants from the American Diabetes Association and the ational Institutes of Health (AM-38). From Mayo Medical School, Department of Medical Statistics and Epidemiology, and Division of Endocrinology, Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Address reprint requests to Dr. L. J. Melton III, Department of Medical Statistics and Epidemiology, Mayo Clinic, Rochester, Minnesota. REFERECES Tokuhata, G. K., Miller, W., Digon, E., and Hartman, T.: Diabetes mellitus: an underestimated public health problem. J. Chronic Dis. 7; 8:3-3. Marks, H. H.: Diabetes mortality in the general population. In Joslin's Diabetes Mellitus. Marble, A., White, P., Bradley, R. R, and Krall, L. P., Eds. Philadelphia, Lea & Febiger, 7:3-. 3 Bale, G. S., and Entmacher, P. S.: Estimated life expectancy of diabetics. Diabetes 77; 6:3-38. 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6 POPULATIO-BASED STUDY OF DIABETES MORTALITY/J. W. OCHI AD ASSOCIATES 6 O'Sullivan, J. B., and Mahan, C. M: Mortality related to l8 Ragozzino, M., Melton, L. J., Chu, C. P., and Palumbo, P. J.: diabetes and blood glucose levels in a community study. Am. J. Subsequent cancer risk in the incidence cohort of Rochester, Min- Epidemiol. 8; 6: nesota, residents with diabetes mellitus. J. Chronic Dis. 8; 3:3-7 Bender, A. P., Sprafka, J. M., Jagger, H., Wannamaker, J.,. and Muckala, K. H.: Incidence, prevalence, mortality and popu- Melton, L. J., Ochi, J. W., Palumbo, P. J., and Chu, C. P.: lation-based profile of diabetes mellitus in Wadena, Minnesota, 8. Sources of disparity in the spectrum of diabetes mellitus at incidence Minn. Med. 83; 66:-6. and prevalence. Diabetes 83; 6:7-3. DIABETES CARE, VOL. 8 O. 3, MAY-JUE 8