Prevalence of Diabetes Mellitus and Impaired Glucose Tolerance in the Middle-Aged Population of Three Areas in Finland

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1 International Journal of Epidemiology International Epidemiological Association 1991 Vol. 20, 4 Printed in Great Britain Prevalence of Diabetes Mellitus and Impaired Glucose Tolerance in the Middle-Aged Population of Three Areas in Finland JAAKKO TUOMILEHTO*, HEIKKI J KORHONEN*. LEENA KARTOVAARA\ VEIKKO SALOMAA*, JARI H STENGARD*. MATTI PITKANEN*, AIMTTI ARO # «, KAIJA JAVELA*\ MATTI UUSITUPAt AND JANNE PITKANIEMI* Tuomilehto J (Department of Epidemiology, National Public Health Institute, Elimaenkatu 25, 6th Floor, Helsinki, Finland). Korhonen H J, Kartovaara L, Salomaa V, Stenglrd J H, Pitkanen M, Aro A, Javela K, Uusitupa M and Pitkaniemi J. Prevalence of diabetes mellitus and impaired glucose tolerance in the middle-aged population of three areas in Finland. International Journal of Epidemiology 1991; 20: The prevalence of diabetes mellitus and impaired glucose tolerance () was determined in a random sample of the population aged years in three areas of Finland. The two-hour oral glucose tolerance test was repeated in subjects whose first test suggested abnormal glucose tolerance. In the final classification, based on the results of the two tests, the age-standardized prevalence of diabetes, according to the WHO criteria was 5.7 (95 confidence interval (CD: -7.1) in men and (95 Cl: 3.6-) in women. The prevalence of was 3.1 (95 Cl: 2.1-) in men and (95 Cl: ) in women. Among those aged years the prevalence was 6.9 in men and 7.5 in women. The prevalence of diabetes and were not different between the three areas. The age-specific mean values of fasting and two-hour blood concentrations and the 90th percentiles of the blood glucose distributions were also not different between the areas. The prevalence of and diabetes increased with age more steeply among women than men. The median of fasting blood glucose did not change, but the 90th percentile increased with increasing age. The entire distribution of two-hour blood glucose shifted towards higher values with ageing, but the major increase was seen for the 95th percentile. The majority of the diabetic subjects were aware of their condition. The awareness was better among men than women. According to drug sales statistics the consumption of antidiabetic agents is higher in Finland than in other Nordic countries. 1 This is not only due to the high levels of insulin use as a consequence of the highest incidence, in the world, of insulin-dependent diabetes mellitus in Finland, 2 but particularly due to the common use of oral antidiabetic drugs. An earlier survey in elderly Finnish men has suggested that the occurrence of non-insulin dependent diabetes mellitus (NIDDM) and impaired glucose tolerance () are also high in Finland. 3 The same conclusion can be drawn from questionnaire survey data. 45 However, the prevalence Department of Epidemiology, National Public Health Institute, Elimaenkatu 25, 6th Floor, Helsinki, Finland. "Department of Biochemistry, National Public Health Institute, Mannerheimintie 166, Helsinki. fdepartment of Clinical Nutrition, University of,, Finland of NIDDM in middle-aged Finns has not previously been estimated using standard diabetes survey methods. Standardized diabetes surveys in representative samples of the middle-aged population have been carried out in relatively few countries. 6 Therefore, knowledge about the occurrence of NIDDM and is insufficient in most western countris, including Finland. In Finland the risk of coronary heart disease (CHD) is exceptionally high, especially in the eastern part of the country. 7 This is partly, but not fully explained by high serum cholesterol and high prevalence of hypertension. 89 Thus, it is important to compare the prevalence of DM and in Finland with that in other western countries, and to find out whether the prevalence of abnormal glucose tolerance varies between east and west Finland. As a part of the Finnish contribution to the WHO MONICA Project we carried out a large cardio-

2 DIABETES MELLITUS AND IMPAIRED GLUCOSE TOLERANCE IN FINLAND 1011 vascular risk factor survey in 1987 which also included the assessment of glucose tolerance. This report describes the prevalence of diabetes and, and the distribution of blood glucose values in the yearold population in three geographical areas of Finland. MATERIAL AND METHODS The survey was carried out in January to April 1987 in two provinces in eastern Finland ( and ) and in a third area in southwestern part of the country (Turku-Loimaa area). A stratified random sample was drawn from the national population register. The sampling scheme and survey procedures are described in detail elsewhere. 810 The subjects received by mail an invitation to a clinical examination and a self-administered questionnaire on various aspects of health behaviour, medical history and socioeconomic background. The clinical examinations were carried out by specially trained nurses between 11 am and 6 pm. The examination included measurements of waist and hip circumference, weight, height and blood pressure. A venous blood sample was drawn from antecubital vein. The subjects were asked to fast for at least four hours before the scheduled examination time and to avoid eating any fatty meals for the whole examination day. The mean fasting time was 6.1 hours, ranging from 0 to 25 hours. There was only little variation in the fasting time among the three areas and between men and women. However, the fasting time was significantly longer among older than younger subjects: the mean values were 5.3,, 6.3 and 7.0 hours for,,, year-old subjects (p<0.001). From subjects aged 45 to 64 years a blood sample was taken in a tube containing fluoride for the determination of fasting blood glucose. An oral glucose tolerance test was administered with a standard 75 g of glucose in 330 ml solution. The post-challenge blood sample was drawn two hours after the glucose load. All responders who were not treated with insulin were invited to the oral glucose tolerance test. Of 3982 eligible subjects in the sample fasting blood glucose was determined in 78.3 (Figure 1). All participants who in the first examination had an abnormal glucose tolerance according to the WHO Study Group criteria," i.e. either diabetic values of fasting blood glucose (^6.7 mmol/1) and/or two-hour post-challenge blood glucose (^10.0 mmol/1), or values (two-hour post-challenge blood glucose between 6.7 and 10.0 mmol/1) were invited to a second test. In addition to these subjects who had an abnormal glucose tolerance, a similar number of people (matched for sex and five-year age group), with normal blood glucose were also invited to the retesting. Insulin-treated diabetics had neither a glucose tolerance test at the first examination nor were they invited to the retesting. At the re-examination in May-June 1987 the glucose tolerance test was carried out according to the WHO standard recommendation." All the glucose tolerance tests were started between 8 am and 10 am after an overnight fast (at least 12 hours). About 85 of the invited subjects participated in the second examination (Figure 1). The final diagnostic classification of the subjects into categories: diabetes, and normal glucose tolerance was primarily done on the basis of the second, standardized test. In cases where valid information was available only from the first test, it was used. Subjects with blood glucose values indicating at the first test but normal at the second test were classified as having normal glucose tolerance. If the fasting time was less than four hours in the first test or if the blood sample for two-hour post-challenge blood glucose in the first or the second test was drawn more thanfiveminutes too early or too late, the blood glucose values were not accepted and these subjects were not classified for glucose tolerance status in our present analyses. Such technical problems applied to of men and 3.7 in women (Table 1), and they were slightly more common in younger than older subjects. Of those 501 subjects who could not be classified for their glucose status 474 subjects had, however, their fasting blood glucose determined; in only one of them it exceeded 6.7 mmol/1. Blood glucose was determined in the central laboratory from venous full blood drawn into tubes containing oxalate-fluoride. The tubes were mailed daily to the central laboratory from different clinics and the determination of blood glucose was done as early as possible after samples were received. The concentration of blood glucose was determined with hexokinaseglucose-6-phosphate dehydrogenase method after deproteinization (Boehringer Mannheim Pat No ). The within-assay imprecision of the method was 1.3 (level 5 mmol/1) and 1.8 (level 10 mmol/1), the between-assay imprecision was 1.9 (level 5 mmol/1) and 2.3 (level 10 mmol/1). Subjects with antidiabetic medication (insulin or oral hypoglycaemic drugs) were classified as diabetic. Of these 40 were not tested. Age-standardized prevalence was calculated using ten-year age groups and the 'World Standard Population' as the standard. The 95 confidence intervals (CI) were calculated assuming a normal distribution. Newly diagnosed diabetic subjects were those without a self-reported history of

3 1012 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Random sample of men and women aged years Eligible subjects in the sample: subjects Questionnaire data: 3404 subjects Attended the survey examination: subjects Died or migrated before the survey: 18 subjects Non-participants in the survey: 578 subjectb (1) No survey examination: 105 subjects (2.6) Fasting blood glucose adequately determined, either at the 1st or 2nd visit: subjects No adequate fasting blood glucose values: 180 subjects No adequate 2-hour blood glucose values: -No glucose load: 328 subjects -Test inadequate: 146 subjects -Known diabetic,.lot tested: 29 subjects 2-hour post-challenge blood glucose values adequately determined No adequate 2-hour blood glucose values: -Known diabetic, not tested: 7 subjects -No glucose load: 100 subjects -Test inadequate: 7 subjects Classified subjects: FIGURE 1 Flow diagram of the F1NMON1CA diabetes survey in diabetes and whose two-hour blood glucose was 10.0 mmol/1 or above. RESULTS The overall age-standardized prevalence of diabetes mellitus was according to the first screening oral glucose tolerance test 5.9 in men and in women, and according to the final diagnostic classification 5.7 in men and in women (Table 2). Among the year-olds the prevalence in the final classifi- TABLE 1 Number of subjects classified as having diabetes, impaired glucose tolerance () or normal glucose tolerance by sex, age and geographical area All areas Sex and age (years) Classified Not classifiable () Classified Not classifiable () Classified Not classifiable () Classified Not classifiable ()* (7.4) 12(7.3) 6(3.4) 6(3.8) 35(5.4) 11() 8() 8() 6(3.3) 33() (7.7) 2(2.4) 7(6.9) 2(2.7) 19(5.3) 6(6.6) 8(7.7) 2(2.0) 1(1.0) 17() () 2(2.7) 1(1.3) 7(2.1) 4() 3(3.7) 2(2.2) 9(2.6) (6.6) 16() 14(3.9) 8(2.6) 61 () 20(5.3) 17() 12(3.1) 6(1.6) 55 (3.7) "Non-classification was due to inadequate fasting or any technical failure during the test. Subjects with antidiabetic medication were classified as diabetic whether tested or not.

4 DIABETES MELLITUS AND IMPAIRED GLUCOSE TOLERANCE IN FINLAND 1013 TABLE 2 Age-specific and age-standardized prevalence of impaired glucose tolerance () and diabetes mellitus (DM) in the year-old population of Finland by sex and residence. Results based on thefirstscreening test only and on thefinalclassification where data from two tests were used, are shown separately All Areas Together Sex and age (years) DM DM DM DM First screening classification* Age standardized* total () Age standardized* total () ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) (5.3-1) ( ) ( ) ( ) ( ) ( ) (-7.8) ( ) Final classification! Age standardized* total () Age standardized* total () (1.4-) ( ) (-8.1) ( ) (1.0-) ( ) ( ) ( ) ( ) 5.8 ( ) ( ) ( ) ( ) ( ) (-7.1) (3.6-) The oral glucose tolerance test results were not accepted if the fasting time was less than four hours or if the post-load blood sample was drawn <115 minutes or >125 minutes after administration of glucose load. Results are based on the first screening oral glucose tolerance test only. tresults are based primarily on the second, standardized oral glucose tolerance test. cation was 6.9 and 7.5 in men and women, respectively. The prevalence of was about two to three TABLE 3 Proportion of newly-diagnosed and known diabetes cases. All areas together Sex and age group (years) Prevalence () New diabetic Known diabetic Ratio New:known times higher in the first oral glucose tolerance test than after retesting. No statistically significant differences were found in the prevalence of diabetes or between the three geographical areas. Overall, 9 of the population aged years had an abnormal glucose tolerance according to the final diagnostic classification. The majority of the diabetic subjects were aware of their condition before the survey (Table 3). The awareness of diabetes was better in men than in women: for every ten known cases of diabetic men there were two previously undiagnosed men, and for every ten known female cases, five previously undiagnosed diabetic women were first detected by the survey. The mean fasting and two-hour post-load blood glucose values, given in Table 4 by the diagnostic category

5 1014 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY TABLE4 fasting* and two-hour post-load blood glucose levels (mmolll) by glucose tolerance status afterfinaldiagnostic classification. All areas together Glucose tolerance status mean mean Normal New diabetes Known diabetes Fasting blood glucose 2-hour post-load blood glucose Fasting blood glucose 2-hour post-load blood glucose Fasting blood glucose 2-hour post-load blood glucose Fasting blood glucose 2-hour post-load blood glucoset (-) (^1.4) (-) ( ) (-9.5) (11.0-1) ( ) ( ) (^1.2) (-) (-4) ( ) ( ) (11.2-1) ( ) ( ) *Subjects who had been fasting ^4 hours before the blood drawing included only. tsubjects on insulin treatment were not tested and some other patients with known diabetes were refused oral glucose tolerance test. according to the final classification, did not differ between men and women. In subjects with newly diagnosed diabetes the blood glucose values tended to be slightly, but not significantly lower than in subjects with known diabetes. The mean values of fasting and twohour blood glucose were not different between men and women nor between the three areas (Table 5 and 6). The means of two-hour blood glucose rose with age whereas fasting blood glucose did not vary by age, although such a tendency was seen. The increment in two-hour blood glucose with age was similar in men and women. The median (50th percentile) of the fasting blood glucose distribution did not change, but the 90th and 95th percentiles increased with increasing age (Table 7). The entire distribution of two-hour postchallenge blood glucose shifted towards higher values with age, but the major increase was seen from the 95th percentile (Table 8). DISCUSSION This is the first study reporting data on the prevalence of diabetes mellitus and in a representative sample of middle-aged Finnish subjects based on standardized diabetes survey methods. Approximately people currently use antidiabetic drugs in Finland, most of them oral antidiabetic drugs.' Previous epidemiological studies based on the information about the use of antidiabetic medication have sug- TABLE 5 values (mmolll) and 95 confidence intervals (CI) offasting blood glucose by age group in year old men and women by age group and area First screening Final classification Age group and area years years years years - ^1.5 ^ > ^ ^1.2 ^ ^1.3-4.^ - ^t.6 ^» ^t (M.2 ^ years

6 DIABETES MELLITUS AND IMPAIRED GLUCOSE TOLERANCE IN FINLAND 1015 TABLE 6 values (mmolll) and 95 confidence intervals (CI) of two-hour post-load blood glucose concentration* by age group in year old men and women by age group and area First screening Final classification Age group and area years years years years 5.8 M.5 ^ ^t years Subjects on insulin treatment were excluded and some other known diabetics were refused oral glucose tolerance test. gested that type 2 diabetes is common in middle-aged Finnish population. 4 > 5 ' 12 The present data confirm this and also demonstrates that abnormal glucose tolerance is common in this population. Both the prevalence of diabetes mellitus and were, however, lower in middle-aged men in the present study than those reported previously in men aged 65 to 84 years. 3 This is partly due to the fact that the prevalence of diabetes increases with age. On the other hand, in our present study oral glucose tolerance tests were carried out twice, in contrast to most other sur- TABLE 7 The distribution of fasting blood glucose concentration (mmol/l) in the first screening oral glucose tolerance test in year, old men and women by age group and sex. The three areas together. Percentiles Age group Subjects (years) All All veys which have used one test only. 613 Another factor which may have reduced the prevalence estimates in our study is the application of strict quality assurance procedures leading to the exclusion of many abnormal values which did not fulfil the data quality criteria. Thirdly, we measured glucose concentration from venous whole blood which had been taken one to two days earlier. Although fluoride in the tubes should pro- TABLE 8 The distribution of two-hour post-load blood glucose concentration* (mmol/l) in thefirstscreening oral glucose tolerance test in year old men and women by age group and sex. The three areas are together. Age group (years) All All Subjects Percentiles 'Subjects on insulin treatment were excluded and some other known diabetics were refused oral glucose tolerance test.

7 1016 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY vide a good protection against the breakdown of glucose, it is generally believed that in whole blood there is an initial rapid fall in glucose of up to 10 at room temperature, but any subsequent decline in fluoride tubes will be slow. Whole blood values are generally about 15 lower than corresponding plasma values in subjects with normal haematocrit."' 14 " 16 According to the Central Drug Registry of the Social Insurance Institution the prevalence of antidiabetic treatment among people aged 30 years and over was 3.4 in eastern and 2.4 in southwestern Finland at the end of We could not find any significant East-West difference within Finland in the prevalence of diabetes and in our study. This may indirectly suggest that it is unlikely that glucose intolerance would substantially contribute to the almost twofold differential in the risk of CHD between eastern and western Finland. An earlier population-based study among elderly men also reported similar prevalence of diabetes for eastern and western Finland. 3 Interestingly, Laakso et al. reported an even higher East-West difference in symptomatic CHD and claudication for diabetic compared to non-diabetic Finnish men. 17 This may have been due to the exaggerated East-West difference in serum lipids in diabetic subjects in their study. However, blood pressure levels have also been shown to be higher in eastern than in western Finland. 8>9-18 It has been proposed that glucose intolerance and hypertension may share a common genetic or environmental aetiology leading to premature CHD. 19 " 22 However, our data do not give strong support for the hypothesis that the considerable East-West difference in CHD incidence in Finland could be explained by genetic factors related to diabetes or. The second National Health and Nutrition Examination Survey (NHANESII) in the USA found a prevalence of diabetes mellitus of 7.8 in Caucasoid people aged 45 to 54 years and 12.5 in those aged 55 to 64 years. 23 The prevalence of in the two age groups was 13.6 and 15.3 respectively. In the present study the prevalence values were lower than those obtained in the NHANES II study. The differences in the diabetes prevalence between these two studies may in part be a result of different classification procedures. It the NHANES II survey, as in many other studies, responders with self-reported 'known diabetes' have been excluded from the glucose tolerance test. Also in the NHANES II survey subjects who followed a written diet for diabetes were classified as diabetic without a further verification of blood glucose. This method overestimates the proportion of diabetic subjects. In NHANES II more than half of all diabetic subjects were not tested for glucose tolerance and the authors estimated that approximately 14 of self-reported diabetic subjects in their study were not truly diabetic. A similar overreporting of diabetes may also explain why the prevalence of diabetes in the PROCAMstudy, West Germany, was slightly higher than ours. 19 Such a reporting bias was avoided in our study because only insulin-treated patients were primarily excluded from the two-hour glucose tolerance test. The prevalence of in our study was based on abnormal findings in two consecutive oral glucose tolerance tests. Subjects with at the first test but normal glucose tolerance in the second test were classified as normal. This procedure reduces the number of subjects with more than by half. 23 It may explain, at least in part, the relatively low prevalence of in our study as compared with several other studies. 613 ' 23 ' 25 The participation rate in our survey was high and, therefore, it is not likely that we would have missed very many cases of diabetes as non-responders. It is also unlikely that among non-responders the frequency of diabetic subjects would have been particularly low. Even though we used relatively strict criteria in the classification of glucose intolerance status, only 3-4 of all subjects could not be accurately classified. According to the fasting blood glucose values available for most of these subjects, the likelihood of diabetes among those who were excluded was very small. Awareness of diabetes was generally good. Surprisingly the awareness was considerably better in men than in women. In the Mini-Finland survey in the prevalence of previously known NIDDM, based on self-reported oral drug and diet therapy, was among people aged years, 512 which agrees with our present results concerning 'known diabetes'. In our study, the proportion of newly diagnosed cases detected during the oral glucose tolerance test was higher in older than younger people. Data from the US show that the ratio 'new/known' diabetes was about 1:1, i.e. much higher compared with our findings, and it showed hardly any variation by age. 23 The US data also suggested that the awareness was slightly better in men than in women. Recent data from a large survey in Mauritius revealed an even larger proportion of undiagnosed cases of diabetes (ratio 1:1.3), and undiagnosed cases were more common in men than in women. 26 In conclusion, diabetes is one of the major noncommunicable diseases in Finland. Awareness among diabetic subjects is relatively good, although not excellent. Little is known about the determinants of NIDDM, the major type of diabetes among the middle-aged, in the Finnish population. Further analysis of our data and the follow-up of the FINMONICA

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