Disentangling the relationship between falls, fear of falling, physical function and walking by applying a socioecological framework to the International Mobility in Aging Study

Introduction:The relationships between falls, fear of falling, poor mobility, and PA avoidance occur in a cyclic, multi-directional fashion. Aim: This study investigates the concomitant associations of fall history, fear of falling, and physical performance (SPPB) on physical activity using a cross-national sample of community-dwelling older adults from middle and high-income countries.Methods:Linear mixed-effects models looking at the influence of individual and environmental factors were used and participants were nested within each study site.Results:Estimated walking minutes was 52% lower for those with low SPPB compared to high SPPB, 20% lower for those with medium level fear of falling compared to low levels, and 50% lower for those with high level fear of falling compared to low levels.Conclusion:An individual’s fear of falling and physical performance may be important to consider when making PA recommendations to older adults regardless of sex, age, and environment

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 b-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 3 10-4), improved b-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