Protocol for the combined cardiometabolic deep phenotyping and registry-based 20-year follow-up study of the Inter99 cohort.

INTRODUCTION: The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50-80 years old Inter99 participants. METHODS AND ANALYSIS: The Inter99 cohort comprises individuals aged 30-60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999. Age-stratified and sex-stratified random subgroups were invited to participate in either a lifestyle intervention (N=13 016) or questionnaires (N=5264), while the rest served as a reference population (N=43 021). Of the 13 016 individuals assigned to the lifestyle intervention group, 6784 (52%) accepted participation in a baseline health examination in 1999, including screening for cardiovascular risk factors and prediabetic conditions. In total, 6004 eligible participants, who participated in the baseline examination, will be invited to participate in the deep phenotyping 20-year follow-up clinical examination including measurements of anthropometry, blood pressure, arterial stiffness, cardiometabolic biomarkers, coronary artery calcification, heart rate variability, heart rhythm, liver stiffness, fundus characteristics, muscle strength and mass, as well as health and lifestyle questionnaires. In a subsample, 10-day monitoring of diet, physical activity and continuous glucose measurements will be performed. Fasting blood, urine and faecal samples to be stored in a biobank. The established database will form the basis of multiple analyses. A main purpose is to investigate whether low birth weight independent of genetics, lifestyle and glucose tolerance predicts later common T2D cardiometabolic comorbidities. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee, Capital Region, Denmark (H-20076231) and by the Danish Data Protection Agency through the Capital Region of Denmark's registration system (P-2020-1074). Informed consent will be obtained before examinations. Findings will be disseminated in peer-reviewed journals, at conferences and via presentations to stakeholders, including patients and public health policymakers. TRIAL REGISTRATION NUMBER: NCT05166447.

Age-related decrease in energy expenditure at rest parallels reductions in mass of internal organs.

This study explores to what extent the mass of internal organs may impact the age-related decrease in energy expenditure at rest (EErest). The relationship between direct measurements of EErest in elderly women and predicted EErest based on equations deriving from the metabolic activity in tissue from younger women were also elucidated. Body composition of elderly women was measured by an impedance method. EErest was measured by the Douglas bag method after an overnight fast. These data were compared with predicted values of EErest based on equations derived from studies in younger women. The mass of internal organs was obtained from autopsy material. Young women (mean age 31.7 years, range 14-60, n = 104) and elderly women of 65 years (n = 22), 75 years (n = 26), and 85 years (n = 31) participated in this study. Autopsy data were obtained from women (n = 238) from the same birth cohorts as the elderly women who died at ages 42-87 years. EErest showed a progressive age-related decline, which appeared to parallel a similar reduction in the mass of internal organs derived from autopsy material of women who died at the same ages. In contrast, FFM was identical in the group of 65 and 75-year-old women, but was lower in the 85-year-old women. Predicted and measured EErest revealed a strong correlation in elderly women. Modest reductions in the mass of internal organs with a high metabolic rate appear to contribute markedly to the decline in EErest observed in aging. Further, it is also possible to predict EErest from the body composition of elderly women using equations developed from younger women.