153

Atherosclerosis, 88 (1991) 153-161 0 1991 Elsevier Scientific Publishers Ireland, Ltd. 0021-9150/91/$03.50 ADONIS 0021915091001198

ATHERO 04636

Asymptomatic hyperglycemia and cardiovascular risk factors in the elderly Leena Mykkinen Depmrtments of

‘, Markku

Laakso

‘, Ilkka Penttib

* and Kalevi Py6rSi



’Medicine and ’ Clinical Chemistry, Kuopio Unkersity Central Hospital, Kuopio (Finland) (Received 14 September, 1990) (Revised, received 25 January, 1991) (Accepted 28 January, 1991)

Summary We studied the levels of cardiovascular risk factors in a population sample of 511 men and 920 women aged 65-74 years and living in East Finland. Altogether 312 men and 515 women had normal glucose tolerance, 84 men and 158 women impaired glucose tolerance (IGT), 33 men and 59 women newly diagnosed non-insulin-dependent diabetes (NIDDM) detected at the survey, and 82 men and 188 women previously diagnosed NIDDM. Subjects with IGT or newly diagnosed NIDDM had higher levels of total triglycerides and apolipoprotein B and lower levels of HDL cholesterol and apolipoprotein A, than subjects with normal glucose tolerance, similarly as in previously diagnosed NIDDM. Furthermore, subjects with IGT or newly diagnosed NIDDM were more obese, had higher waist-hip ratio, and more frequently hypertension than subjects with normal glucose tolerance. Thlls, asymptomatic hyperglycemia in the elderly is not a benign phenomenon, but is associated with similar adverse changes in cardiovascular risk factors as in middle-aged subjects.

Key words: Aged; Coronary heart disease; Diabetes mellitus, non-insulin-dependent; Lipids; Lipoproteins; Obesity; Hypertension

Introduction Coronary heart disease is found in excess in middle-aged subjects with asymptomatic hyperglycemia, impaired glucose tolerance (IGT) or

Correspondence to: Leena Mykklnen, MD, Department of Medicine, Kuopio University Central Hospital, SF-70210 Kuopio, Finland. Fax: 358-71-173993.

Hyperglycemia;

newly diagnosed non-insulin-dependent diabetes (NIDDM) U-31, similarly as ~II sllbjects with previously diagnosed NIDDM 141. Several studies have reported that middle-aged subjects with IGT or NIDDM are more obese and have more frequently hypertension than subjects with normal glucose tolerance [5-101. Furthermore, elevated total triglyceride levels have been a rather consistent finding in subjects with IGT or NIDDM, but results on the association of reduced HDL

154 cholesterol level with IGT are still controversial [9,11-141. Thus, middle-aged subjecs with asymptomatic hyperglycemia show a similar clustering of cardiovascular risk factors as subjects with previously diagnosed NIDDM [8,9,15]. Although abnormalities of glucose tolerance are frequent in the elderly [16,17], little is known about the association between IGT or newly diagnosed NIDDM and cardiovascular risk factors in older age groups. However, we have recently found in a population survey from East Finland that asymptomatic hyperglycemia is associated with an increased prevalence of coronary heart disease in subjects aged 65-74 years, similarly as in middle-aged subjects [18]. On the basis of that study one would expect to find changes in cardiovascular risk factors favoring atherosclerosis in elderly subjects with asymptomatic hyperglycemia. In this paper, we report our findings on the levels of cardiovascular risk factors by glucose tolerance status based on the same study population of elderly subjects in which we found an increased prevalence of coronary heart disease associated with asymptomatic hyperglycemia [181.

Subjects and methods Subjects

The study was conducted in Kuopio, East Finland, between February 1986 and April 1988. Altogether 1910 subjects born between 1912 and 1921 were randomly selected from the population register including all inhabitants of Kuopio. This random sample covered 35% of all residents in the age group of 65-74 years. In addition, 183 subjects with diabetes born between 1912 and 1921 were selected from the patient registers of general practitioners working at the Kuopio Health Center. This sample was identified from all diabetic subjects aged 65-74 years who visited the Kuopio Health Center during the consecutive 6 months (from 1st January to 30th June, 1985). A postal questionnaire containing questions about diagnosis of diabetes, ability to move, and willingness to participate in the study was sent to these subjects. 262 subjects from the random sample and 20 from the diabetes sample did not respond to the repeated postal questionnaire and 85 sub-

jects from the random sample and 5 from the diabetes sample were originally unwilling to participate. 83 subjects from the random sample and 14 from the diabetes sample were excluded because they were too ill to participate. Of those who were invited, 80 subjects from the random sample and 4 from the diabetes sample died, moved outside of the study area, or became seriously ill before clinical examination. 100 subjects from the random sample and 6 from the diabetes sample refused later on to participate in the examination, giving an overall participation rate of 71%. All patients in Finland needing drug therapy for chronic diseases such as diabetes, hypertension and cardiac failure are provided medication free of charge and registered. Representativeness of the study population was evaluated on the basis of this register. The mean age of subjects who participated (71%) in the study was similar to that of those (29%) who failed to participate (69 vs. 69 years in men, 69 vs. 70 yrs in women). There were no differences in the proportion of subjects receiving drug therapy for diabetes (9.6 vs. 10.6% in men, 11.7 vs. 13.8% in women, NS) or in the duration of diabetes (8 vs. 8 yrs in men, 8 vs. 9 yrs in women) between participants and non-participants. Also the proportion of subjects receiving drug therapy for hypertension was similar among participants and non-participants (27.3 vs. 30. 7% in men, 39.6 vs. 42.2% in women, NS). Male participants did not, however, have drug therapy for heart failure as frequently as non-participants (15.0 vs. 22.5%, P < 0.05), but this difference was not seen among women (24.4 vs. 26.5%, NS). Thus, the study population was a representative sample of subjects aged 65-74 yrs and living in Kuopio. Methods

Standing height and body weight were measured without shoes in light clothes. Body mass index (BMI) was calculated from the formula weight (kg)/height cm>‘. Obesity was defined as BMI 2 27 kg/m2 in men and 2 25 kg/m2 in women [19]. Body fat distribution pattern was measured as waist-hip ratio. Waist circumference was measured to the nearest 1 cm at the level of the umbilicus with the subject standing

155 and breathing normally. Hip circumference was measured to the nearest 1 cm at the level of the greatest hip girth. All anthropometric measurements were performed by the same specially trained nurse. Blood pressure was measured in the supine position after a 5 min rest. Measurements were taken in the right arm with a mercury sphygmomanometer (cuff size 12.5 x 40 cm). Two readings were taken (interval 1.5 min), and the latter one was used in statistical analyses. Systolic and diastolic blood pressure were read to the nearest 2 mm Hg. The disappearance of sounds (Korotkoff’s 5th phase) was recorded as diastolic blood pressure. A subject was defined as having hypertension if systolic blood pressure was 2 160 mm Hg, or diastolic blood pressure 2 95 mm Hg, or if he/she was receiving drug treatment for hypertension. Alcohol consumption was determined according to the subject’s estimate of the average number of glasses of beer, wine, or other alcoholic drinks ingested per week and transformed to absolute alcohol ingested in g/week. In all statistical analyses, subjects were classified as alcohol users or nonusers. The World Health Organization criteria for diabetes mellitus were used in the classification of subjects without previously known diabetes [20]. The criteria are as follows: (1) diabetes mellitus, fasting venous plasma glucose 2 7.8 mM or 2-h venous plasma glucose 2 11.1 mM in an oral glucose tolerance test (75 g glucose); (2) IGT, fasting venous plasma glucose < 7.8 mM and 2-h venous plasma glucose 7.8-l 1.1 mM; and (3) normal glucose tolerance, fasting and 2-h venous plasma glucose < 7.8 mM. Previously known diabetes was considered to be present, if the diagnosis of diabetes had previously been made by a physician. Medical records were checked for those diabetic subjects who had been treated with diet only and who showed normal glucose tolerance test. A subject was considered to have diabetes if his/her fasting venous blood glucose had been 2 6.7 mM on two visits to the health center. Three insulin-treated diabetic subjects whose C-peptide levels 6 min after intravenous glucagon (1 mg) stimulation [21] were < 0.20 nM were regarded as having insulin-de-

pendent diabetes [22] and they were excluded from the study. In this paper IGT and newly diagnosed NIDDM detected at the survey were considered together as a category of “asymptomatic hyperglycemia”. Laboratory methods Blood samples were taken between 7.30 and 9.30 a.m. after a 12-h fast. All subjects, except for those receiving insulin, underwent an oral glucose tolerance test (75 g glucose in 10% solution). Venous blood samples for glucose determinations were taken before and 1 and 2 h after the glucose load. Plasma glucose was determined by the glucose oxidase method (Glucose Auto & Stat HGA-1120 analyzer, Daiici, Kyoto, Japan). Diabetic subjects who used insulin had C-peptide levels measured at fasting and 6 min after intravenous glucagon administration [21]. Plasma Cpeptide was determined from samples stored at -70°C by a commercial radioimmunoassay (Cpeptide of insulin 1255 RIA kit, Incstar Co., Stillwater, MN, U.S.A.) with a detection limit of 0.07 nM and an intra-assay variation < 5.0% [23]. Serum HDL cholesterol was determined after precipitation of low density and very low density lipoproteins with dextran sulphate-MgCl, [24]. Commercial enzymatic methods were used in the determination of cholesterol [24,25] (Monotest, Boehringer Mannheim, F.R.G.) and triglycerides [26] (Peridocrome, Boehringer Mannheim, F.R.G.). Commercial control serums were used to standardize the measurements of cholesterol and triglycerides (Seronorm, Seronorm Lipid, Nycorned, Oslo, Norway). Serum apolipoproteins A, and B were determined from samples stored at - 70°C. The determinations were performed by a commercial immunochemical method (Kone Diagnostics, Espoo, Finland) which was based on the measurement of immunoprecipitation at 340 nm [27]. The standardization of apolipoprotein measurements were carried out utilizing a calibrator. The day-to-day and intra-assay variations in apolipoprotein assays were < 5%. Statistical methods Data analyses were conducted with the SPSSX programs [28]. The results for continuous vari-

156 ables are given as mean t_ SEM. Student’s twotailed t-test for independent samples was used in the assessment of the significance of the differences between two group means. Chi-square test (x2> was used in the assessment of the significance of the differences in prevalence rates of risk factors. Analysis of variance (ANOVA) was used in testing the differences between more than two group means. Adjustment of the risk factors for age, BMI and waist-hip ratio was done by analysis of covariance (ANCOVA). Results Altogether 1431 subjects participated in the study; 312 men and 515 women had normal glucose tolerance, 84 men and 158 women impaired glucose tolerance (IGT), 33 men and 59 women newly diagnosed non-insulin-dependent diabetes

(NIDDM) detected at the survey, and 82 men and 188 women previously diagnosed NIDDM (38% were treated with diet, 56% with oral hypoglycemic drugs and 6% with insulin) (Table 1). Men with normal glucose tolerance, IGT, and newly or previously diagnosed NIDDM were similar with respect to age, but women with previously diagnosed NIDDM were somewhat older than women with normal glucose tolerance. Among both men and women, subjects with IGT or NIDDM had higher mean values of body mass index (BMI, kg/m21 and waist-hip ratio than subjects with normal glucose tolerance. Also the proportion of obese subjects (BMI 2 27 kg/m2 in men and r 25 kg/m2 in women) was higher in men and women with IGT or NIDDM than in subjects with normal glucose tolerance. Tables 2 and 3 show the levels of cardiovascular risk factors in men and women. Subjects with

TABLE 1 CHARACTERISTICS

OF THE STUDY POPULATION

Values are mean f SEM. NIDDM = non-insulin-dependent Sex, variable

BY GLUCOSE TOLERANCE

STATUS AND SEX

diabetes, BMI = body mass index, WHR = waist-hip ratio.

Glucose tolerance status Normal glucose tolerance

Impaired glucose tolerance

Newly diagnosed NIDDM

Previously diagnosed NIDDM

Men Age (yrs) BMI (kg/m*) BMI 2 27 (%I WHR Fasting plasma glucose (mmol/l) 2 h plasma glucose (mmol/lI

(n = 312) 68.9 kO.2 26.0 kO.2 37.8 0.97 + 0.01

(n = 84) 68.9 kO.3 27.9 +0.4 *** 57.1 ** 1.01+ 0.01 * * *

(n = 33) 68.8 *0.4 28.9 +0.8 ** 63.6 ** 1.02-,0.01 ***

(n = 82) 69.3 +0.3 27.1 kO.4 ** 48.8 1.00+0.01 **

5.7 +0.03

6.1 kO.07 ***

8.0 kO.44 ***

5.8 kO.07

8.9 +0.09 ***

Women Age (yr) BMI (kg/m*) BMI 2 25 (%I WHR Fasting plasma glucose (mol/l) 2 h plasma glucose (mmol/lI

(n = 515) 69.1 +O.l 27.1 +0.2 70.4 0.88+0.01

Asymptomatic hyperglycemia a

P-value b

(n = 117) 68.9 +0.3 28.2 +0.4 *** 59.0 *** 1.01* 0.01 * * *

NS < 0.001 < 0.001 < 0.001

11.4 +0.44 ***

6.7 +O.l ***

< 0.001

13.6 +0.72 ***

19.5 kO.84 ***

10.2 +0.3 ***

< 0.001

(n = 158) 68.6 kO.2 29.1 +0.4 *** 842 *** 0:90 + 0.01 * * *

(n = 59) 69.9 i-O.4 30.3 +0.7 *** 89.8 ** 0.93 + 0.01 * * *

(n = 188) 69.7 kO.2 * 29.2 +0.3 *** 77.3 0.92 + 0.01 * * *

(n = 217) 69.0 kO.2 29.4 +0.3 *** 857 *** 0:91+0.01 ***

< < <

Asymptomatic hyperglycemia and cardiovascular risk factors in the elderly.

We studied the levels of cardiovascular risk factors in a population sample of 511 men and 920 women aged 65-74 years and living in East Finland. Alto...
934KB Sizes 0 Downloads 0 Views