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

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

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Early adiposity rebound in childhood and risk of Type 2 diabetes in adult life

Aims/hypothesis: Type 2 diabetes is associated with a small body size at birth and a high BMI in adult life. The aim of our study was to assess the associations between Type 2 diabetes and birth size, infant growth and age at adiposity rebound.Methods: We carried out a longitudinal study of 8760 subjects born in Helsinki during 1934 to 1944. On average, they had 18 measurements of height and weight between birth and 12 years of age. In western countries BMI usually decreases after the age of 2 years and rises again at around 6 years--the so-called adiposity rebound. We defined age at adiposity rebound by the age of lowest BMI between one and 12 years. We identified people with Type 2 diabetes using a national register.Results: A total of 290 individuals developed Type 2 diabetes in adult life. The cumulative incidence of Type 2 diabetes decreased progressively from 8.6% in persons whose adiposity rebound occurred before the age of 5 years to 1.8% in those in whom it occurred after 7 years (p&lt;0.001). Early adiposity rebound was preceded by low weight gain between birth and 1 year (p&lt;0.001).Conclusion/interpretation: Large differences in the incidence of Type 2 diabetes are associated with growth rates in utero, weight gain in infancy and age at adiposity rebound

Size at birth, childhood growth and obesity in adult life

BACKGROUND: Several studies have shown tracking of obesity from childhood to adult life. People who develop obesity in adult life may therefore have had a particular path of growth from birth through childhood.OBJECTIVE: To examine the relationship of obesity to size at birth and childhood growth.DESIGN: Birth cohort study.PARTICIPANTS: A total of 5210 individuals alive and living in Finland in 1997, who were born at the Helsinki University Central Hospital between 1924 and 1933 and who went to school in Helsinki were sent a questionnaire in order to get information about adult weight and height. Detailed birth and school health records were available for all subjects. In all, 3847 responded and 3659 (1552 men and 2107 women) with adequate data are included in the present study.MEASUREMENTS: Incidence of obesity based upon lifetime maximum body mass index (BMI) ascertained from a postal questionnaire and defined as a BMI&gt;30 kg/m2. The main explanatory measurements were size at birth and childhood growth in height, weight and BMI.RESULTS: The cumulative incidence of obesity was 34.2% in men and 33.9% in women. The incidence rose with increasing birth weight and ponderal index (birthweight/length3; P=0.01 and P=0.04, respectively). These associations were statistically significant only among males. By the age of 7 y the mean weights, heights and BMI of people who later became obese exceeded the average and remained above average at all ages from 7 to 15 y. In both men and women there was a 3-fold increase in obesity associated with a BMI&gt;16 kg/m2 at age 7 compared with a BMI&lt;14.5 kg/m2 (P&lt;0.0001). Boys and girls whose mothers had a high BMI in pregnancy had more rapid childhood growth and an increased risk of becoming obese. This effect was stronger among boys (P=0.008).CONCLUSIONS: Obesity is initiated early in life. These results emphasise the importance of early preventive measures for its treatment