J. Tuomilehto

Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle among Subjects with Impaired Glucose Tolerance

BACKGROUND Type 2 diabetes mellitus is increasingly common, primarily because of increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known. METHODS We randomly assigned 522 middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean body-mass index [weight in kilograms divided by the square of the height in meters], 31) with impaired glucose tolerance to either the intervention group or the control group. Each subject in the intervention group received individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity. An oral glucose-tolerance test was performed annually; the diagnosis of diabetes was confirmed by a second test. The mean duration of follow-up was 3.2 years. RESULTS The mean (+/-SD) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group (P<0.001 for both comparisons between the groups). The cumulative incidence of diabetes after four years was 11 percent (95 percent confidence interval, 6 to 15 percent) in the intervention group and 23 percent (95 percent confidence interval, 17 to 29 percent) in the control group. During the trial, the risk of diabetes was reduced by 58 percent (P<0.001) in the intervention group. The reduction in the incidence of diabetes was directly associated with changes in lifestyle. CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects.

Catch-up growth in childhood and death from coronary heart disease: longitudinal study

Abstract Objective: To examine whether catch-up growth during childhood modifies the increased risk of death from coronary heart disease that is associated with reduced intrauterine growth. Design: Follow up study of men whose body size at birth was recorded and who had an average of 10 measurements taken of their height and weight through childhood. Setting: Helsinki, Finland. Subjects: 3641 men who were born in Helsinki University Central Hospital during 1924-33 and who went to school in Helsinki. Main outcome measures: Hazard ratios for death from coronary heart disease. Results: Death from coronary heart disease was associated with low birth weight and, more strongly, with a low ponderal index at birth. Men who died from coronary heart disease had an above average body mass index at all ages from 7 to 15 years. In a simultaneous regression the hazard ratio for death from the disease increased by 14% (95% confidence interval 8% to 19%; P<0.0001) for each unit (kg/m3) decrease in ponderal index at birth and by 22% (10% to 36%; P=0.0001) for each unit (kg/m2) increase in body mass index at 11 years of age. Body mass index in childhood was strongly related to maternal body mass index, which in turn was related to coronary heart disease. The extent of crowding in the home during childhood, although related to body mass index in childhood, was not related to later coronary heart disease. Conclusion: The highest death rates from coronary heart disease occurred in boys who were thin at birth but whose weight caught up so that they had an average or above average body mass from the age of 7 years. Death from coronary heart disease may be a consequence of poor prenatal nutrition followed by improved postnatal nutrition.

Early growth and coronary heart disease in later life: longitudinal study

Abstract Objective: To determine how growth during infancy and childhood modifies the increased risk of coronary heart disease associated with small body size at birth. Design: Longitudinal study. Setting: Helsinki, Finland. Subjects: 4630 men who were born in the Helsinki University Hospital during 1934–44 and who attended child welfare clinics in the city. Each man had on average 18.0 (SD 9.5) measurements of height and weight between birth and age 12 years. Main outcome measures: Hospital admission or death from coronary heart disease. Results: Low birth weight and low ponderal index (birth weight/length3) were associated with increased risk of coronary heart disease. Low height, weight, and body mass index (weight/height2) at age 1 year also increased the risk. Hazard ratios fell progressively from 1.83 (95% confidence interval 1.28 to 2.60) in men whose body mass index at age 1 year was below 16 kg/m2 to 1.00 in those whose body mass index was >19 (P for trend=0.0004). After age 1 year, rapid gain in weight and body mass index increased the risk of coronary heart disease. This effect was confined, however, to men with a ponderal index <26 at birth. In these men the hazard ratio associated with a one unit increase in standard deviation score for body mass index between ages 1 and 12 years was 1.27 (1.10 to 1.47; P=0.001). Conclusion: Irrespective of size at birth, low weight gain during infancy is associated with increased risk of coronary heart disease. After age 1 year, rapid weight gain is associated with further increase in risk, but only among boys who were thin at birth. In these boys the adverse effects of rapid weight gain on later coronary heart disease are already apparent at age 3 years. Improvements in fetal, infant, and child growth could lead to substantial reductions in the incidence of coronary heart disease. What is already known on this topic Coronary heart disease is associated with low birth weight One study has shown that irrespective of size at birth, low weight gain in infancy is also associated with increased risk of the disease among men Rapid weight gain after age 6 years is associated with further increase in risk What this study adds The association with low weight gain in infancy is confirmed The adverse effects of rapid childhood weight gain on risk of coronary heart disease are already apparent at age 3 years and occur only in boys who were thin at birth

Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study

Objective: To evaluate the impact of midlife elevated serum cholesterol levels and blood pressure on the subsequent development of mild cognitive impairment (MCI) and to investigate the prevalence of MCI in elderly Finnish population, applying the MCI criteria devised by the Mayo Clinic Alzheimer’s Disease Research Center. Background: MCI has been considered as a predictor of AD. Vascular risk factors may be important in the development of cognitive impairment and AD. However, the role of vascular risk factors in MCI and the prevalence of MCI still remain virtually unknown. Methods: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1,449 subjects aged 65 to 79 years were reexamined in 1998. Results: Eighty-two subjects, 6.1% of the population (average age, 72 years) met the criteria for MCI. Midlife elevated serum cholesterol level (≥6.5 mmol/L) was a significant risk factor for MCI (OR, 1.9; 95% CI, 1.2 to 3.0, adjusted for age and body mass index); the effect of systolic blood pressure approached significance. Conclusion: Data point to a role for midlife vascular risk factors in the development of MCI in late life.

Concordance for Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland

SummaryWe studied the cumulative incidence, concordance rate and heritability for diabetes mellitus in a nationwide cohort of 13,888 Finnish twin pairs of the same sex. The twins were born before 1958 and both co-twins were alive in 1967. Data on diabetes were derived through computerized record linkage from death certificates, the National Hospital Discharge Register and the National Drug Register. Records were reviewed in order to assign a diagnostic category to the 738 diabetic patients identified. Of these patients 109 had Type 1 (insulin-dependent) diabetes, 505 Type 2 (non-insulin-dependent) diabetes, 46 gestational diabetes, 24 secondary diabetes, 38 impaired glucose tolerance and 16 remained unclassified. The cumulative incidence of diabetes was 1.4 % in men and 1.3 % in women aged 28–59 years and 9.3 % and 7.0 % in men and women aged 60 years and over, respectively. The cumulative incidence did not differ between monozygotic and dizygotic twins. The concordance rate for Type 1 diabetes was higher among monozygotic (23 % probandwise and 13 % pairwise) than dizygotic twins (5 % probandwise and 3 % pairwise). The probandwise and pairwise concordance rates for Type 2 diabetes were 34% and 20% among monozygotic tiwns and 16% and 9 % in dizygotic twins, respectively. Heritability for Type 1 diabetes was greater than that for Type 2 where both genetic and environmental effects seemed to play a significant role.

Growth in utero and during childhood among women who develop coronary heart disease: longitudinal study

Abstract Objective: To examine whether women who develop coronary heart disease have different patterns of fetal and childhood growth from men in the same cohort who develop the disease. Design: Follow up study of women whose body size at birth was recorded and who had an average of 10 measurements of height and weight during childhood. Setting: Helsinki, Finland. Subjects: 3447 women who were born in Helsinki University Central Hospital during 1924-33 and who went to school in Helsinki. Main outcome measures: Hazard ratios for hospital admission for or death from coronary heart disease. Results Coronary heart disease among women was associated with low birth weight (P=0.08 after adjustment for gestation, P=0.007 after adjustment for placental weight) and was more strongly associated with short body length at birth (P=0.001 and P>0.0001, respectively). The hazard ratio for women developing coronary heart disease increased by 10.2% (95% confidence interval 4.3 to 15.7) for each cm decrease in length at birth. The effect of short length at birth was greatest in women whose height “caught up” after birth so that as girls they were tall. Such girls tended to have tall mothers. In contrast, men in the same cohort who developed the disease were thin at birth rather than short, showed “catch up” growth in weight rather than height, and their mothers tended to be overweight rather than tall. Conclusions: Coronary heart disease among both women and men reflects poor prenatal nutrition and consequent small body size at birth combined with improved postnatal nutrition and “catch up” growth in childhood. The disease is associated with reductions in those aspects of body proportions at birth that distinguish the two sexes—short body length in women and thinness in men. Key messages Coronary heart disease in women is associated with low birth weight but more strongly with short body length at birth Among men in the same cohort coronary heart disease is also associated with low birth weight but more strongly with thinness at birth In the whole cohort body proportions at birth differed in the two sexes: the girls were short and the boys were thin These differences may reflect intrinsic sex differences in rates of fetal growth at similar levels of maternal nutrition The slower fetal growth of females may underlie their lower rates of coronary heart disease

Mother's weight in pregnancy and coronary heart disease in a cohort of finnish men: follow up study

Abstract Objective: To determine whether restricted growth in utero is associated with an increased risk of coronary heart disease among men in Finland, where rates of the disease are among the highest in the world. Design: Follow up study. Setting: Helsinki, Finland. Subjects: 3302 men born in Helsinki University Central Hospital during 1924–33 who went to school in the city of Helsinki and were resident in Finland in 1971. Main outcome measures: Standardised mortality ratios for coronary heart disease. Results: Men who were thin at birth, with low placental weight, had high death rates from coronary heart disease. Men whose mothers had a high body mass index in pregnancy also had high death rates. In a multivariate analysis the hazard ratio for coronary heart disease was 1.37 (95% confidence interval 1.20 to 1.57) (P<0.0001) for every standard deviation decrease in ponderal index at birth and 1.24 (1.10 to 1.39) (P=0.0004) for every standard deviation increase in mothers body mass index. The effect of mothers body mass index was restricted to mothers of below average stature. Conclusion: These findings suggest a new explanation for the epidemics of coronary heart disease that accompany Westernisation. Chronically malnourished women are short and light and their babies tend to be thin. The immediate effect of improved nutrition is that women become fat, which seems to increase the risk of coronary heart disease in the next generation. With continued improvements in nutrition, women become taller and heavier; their babies are adequately nourished; and maternal fatness no longer increases the risk of coronary heart disease, which therefore declines. Key messages Men who were thin at birth have high death rates from coronary heart disease If, in addition, their mothers were short and heavy they have evenhigher rates Women tend to be short and heavy in populations at an intermediatestage between chronic malnutrition and adequate nutrition This may explain why rates of coronary heart disease rise as nutrition improves in a population; rates then decline with continuing nutritional improvement

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland. Study design and 1-year interim report on the feasibility of the lifestyle intervention programme.

Aims/hypothesis. The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance. Methods. A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were randomised to either a control or intervention group. The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits. The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aimed at reducing weight, the intake of saturated fat and increasing the intake of dietary fibre. Intervention subjects were also guided individually to increase their physical activity. Results. During the first year, weight loss in the first 212 study subjects was 4.7 ± 5.5 vs 0.9 ± 4.1 kg in the intervention and control group, respectively (p < 0.001). The plasma glucose concentrations (fasting: 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l, p < 0.001; and 2-h 7.8 ± 1.8 vs 8.5 ± 2.3 mmol/l, p < 0.05) were significantly lower in the intervention group after the first year of intervention. Favourable changes were also found in blood pressure, serum lipids and anthropometric indices in the intervention group. Conclusion/interpretation. The interim results show the efficacy and feasibility of the lifestyle intervention programme. [Diabetologia (1999) 42: 793–801]

Genetic and environmental components of interindividual variation in circulating levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3.

We assessed the magnitude of the genetic component in the variation of circulating levels of insulin-like growth factors I and II (IGF-I and IGF-II), and their binding proteins IGFBP-1 and IGFBP-3 by measuring their serum concentrations in 32 monozygotic and 47 dizygotic adult twin pairs of the same sex. The intrapair correlation for the IGF-I levels was r = 0.41 (P < 0.009) for monozygotic twins and r = 0.12 (P < 0.22) for dizygotic twins. For the IGF-II concentration the intrapair correlations were r = 0.66 (P < 0.0001) for the monozygotic and r = 0.34 (P < 0.01) for the dizygotic twins. No significant intrapair correlation was found for IGFBP-1 levels in either group. The correlations for IGFBP-3 concentration were r = 0.65 (P < 0.0001) and r = 0.23 (P < 0.06) for monozygotic and dizygotic twins, respectively. Women had higher IGF-II levels than men (635+/-175 vs. 522+/-144 microg/liter; P < 0.0001) and IGFBP-3 levels were also higher in women compared with men (5441+/-1018 vs. 4496+/-1084 microg/liter; P < 0.001). The proportion of variance attributable to genetic effects was 38% for the IGF-I concentration, 66% for the IGF-II concentration, and 60% for the IGFBP-3 concentration. No significant heritability was found for the IGFBP-1 concentrations. Our results show that, in adults, there is a substantial genetic contribution responsible for interindividual variation of the circulating levels of IGF-I, IGF-II, and IGFBP-3, but not for the IGFBP-1 levels.

Effects of size at birth and childhood growth on the insulin resistance syndrome in elderly individuals

Abstract.Aims/hypothesis: A study of 7086 men and women born in Helsinki, Finland, has shown that the development of Type II (non-insulin-dependent) diabetes mellitus is associated with low birth weight followed by accelerated gain in height and weight during childhood and with high maternal BMI but the processes which underlie these associations are largely not known. Methods: We carried out standard oral glucose tolerance tests, and measured plasma insulin and proinsulin, serum lipid concentrations and blood pressure in 474 patients from the Helsinki cohort. Results: We used four indices of insulin resistance: fasting and 2-h plasma insulin, and fasting proinsulin and 32–33 split proinsulin concentrations. These were associated with small body size at birth and during childhood, rapid growth in height and low maternal BMI. Conclusion/interpretation: Insulin resistance and Type II diabetes share common associations with retarded fetal growth and accelerated growth during childhood. They are dissimilar, however, in that insulin resistance is associated with thinness in childhood and low maternal BMI, while Type II diabetes is associated with high BMI in childhood and high maternal BMI. [Diabetologia (2002) 45: 342–348]