Alison Venn

BACKGROUND: Obesity in childhood is associated with increased cardiovascular risk. It is uncertain whether this risk is attenuated in persons who are overweight or obese as children but not obese as adults. METHODS: We analyzed data from four prospective cohort studies that measured childhood and adult body-mass index (BMI, the weight in kilograms divided by the square of the height in meters). The mean length of follow-up was 23 years. To define high adiposity status, international age-specific and sex-specific BMI cutoff points for overweight and obesity were used for children, and a BMI cutoff point of 30 was used for adults. RESULTS: Data were available for 6328 subjects. Subjects with consistently high adiposity status from childhood to adulthood, as compared with persons who had a normal BMI as children and were nonobese as adults, had an increased risk of type 2 diabetes (relative risk, 5.4; 95% confidence interval [CI], 3.4 to 8.5), hypertension (relative risk, 2.7; 95% CI, 2.2 to 3.3), elevated low-density lipoprotein cholesterol levels (relative risk, 1.8; 95% CI, 1.4 to 2.3), reduced high-density lipoprotein cholesterol levels (relative risk, 2.1; 95% CI, 1.8 to 2.5), elevated triglyceride levels (relative risk, 3.0; 95% CI, 2.4 to 3.8), and carotid-artery atherosclerosis (increased intima-media thickness of the carotid artery) (relative risk, 1.7; 95% CI, 1.4 to 2.2) (P ≤ 0.002 for all comparisons). Persons who were overweight or obese during childhood but were nonobese as adults had risks of the outcomes that were similar to those of persons who had a normal BMI consistently from childhood to adulthood (P>0.20 for all comparisons). CONCLUSIONS: Overweight or obese children who were obese as adults had increased risks of type 2 diabetes, hypertension, dyslipidemia, and carotid-artery atherosclerosis. The risks of these outcomes among overweight or obese children who became nonobese by adulthood were similar to those among persons who were never obese. (Funded by the Academy of Finland and others.).

BACKGROUND: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear. METHODS: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression. RESULTS: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events. CONCLUSIONS: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).

OBJECTIVE: Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or cerebrovascular lesions are feasible links between T2DM and cognitive function. RESEARCH DESIGN AND METHODS: This cross-sectional study used magnetic resonance imaging (MRI) scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. With voxel-based morphometry, we studied the regional distribution of atrophy in T2DM. We measured cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) while blinded to T2DM status. With use of multivariable regression, we examined for mediation or effect modification of the association between T2DM and cognitive measures by MRI measures. RESULTS: T2DM was associated with more cerebral infarcts and lower total gray, white, and hippocampal volumes (all P < 0.05) but not with microbleeds or WMH. T2DM-related gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobes, and white matter loss was distributed in frontal and temporal regions. T2DM was associated with poorer visuospatial construction, planning, visual memory, and speed (P ≤ 0.05) independent of age, sex, education, and vascular risk factors. The strength of these associations was attenuated by almost one-half when adjusted for hippocampal and total gray volumes but was unchanged by adjustment for cerebrovascular lesions or white matter volume. CONCLUSIONS: Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer disease. Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment.