Predictive utility of childhood anthropometric measures on adult glucose homeostasis measures: a 20-year cohort study

Background/Objectives: Childhood body mass index (BMI) predicts adult glucose homeostasis measures and type 2 diabetes mellitus, but little is known about the predictive utility of other anthropometric measures in childhood. We aimed to identify the anthropometric measure in childhood that best predicts adult glucose homeostasis measures and examine if the combination of additional anthropometric measures further improves predictive utility.Methods: A 20-year follow-up of children participating in the Childhood Determinants of Adult Health Study (n = 2345, aged 7-15 years at baseline). Baseline anthropometric measures were waist circumference (WC), WC adjusted for height, weight adjusted for height, hip circumference, waist-hip-ratio, waist-height-ratio, BMI, conicity index, abdominal volume index (AVI), body adiposity index, and a body shape index. Fasting glucose and insulin levels measured at follow-up were used to define insulin resistance (HOMA2-IR), low beta-cell function (HOMA2-β), high fasting insulin, and impaired fasting glucose (IFG).Results: All child anthropometric measures were significantly associated with HOMA2-IR, HOMA2-β, and high fasting insulin (relative risk = 1.12-1.55), but not IFG. AVI had the largest area under receiver-operating curve (AUC) in predicting adult HOMA2-IR (AUC, 95% confidence interval: 0.610, 0.584-0.637), HOMA2-β (0.615, 0.588-0.642) and high fasting insulin (0.613, 0.587-0.639). Combining each additional anthropometric measure with AVI did not appreciably increase predictive utility (an increase of 0.001-0.002 in AUC, p > 0.05 for all).Conclusions: Anthropometric measures from a single time-point in childhood are associated with insulin-related outcomes 20-year later in adulthood. However, overall predictive utility was low and was not substantially enhanced by combining multiple different child anthropometric measures

Evidence For The Control Of Aggrecanases By Insulin And Glucose In Alzheimer'S Disease

Objective: Alzheimer's disease (AD) is a progressive and irreversible central nervous system disease, which slowly destroys cognitive skills and memory, and eventually even the ability to handle the simplest tasks. The initiation and progression of AD is a poorly understood complex process. Here, we have investigated possible biological mechanisms that could be responsible for the increased risk for diminished brain function associated with diabetes in AD. Method: The U87 cell line (human primary glioblastoma cell line) was cultured in Dulbecco's modified Eagle's medium. Cells were incubated with insulin (10 mu g/ml), low glucose (11 mM, 2 mg/ml) and high glucose (55 mM, 10 mg/ml) for 48 hours. Cells were harvested and protein isolations were performed. Primary anti-ADAMTS5, anti-IL-33, anti-NF kappa B, and anti-GAPDH antibodies were used to detect corresponding proteins and to measure band densities in Western membranes using a specific program. Results: Western blot analysis showed ADAMTS5 protein decreases in insulin-applied U87 cells. High glucose application led to a notable increase in ADAMTS5 levels in cells, while low glucose application caused a moderate increase in ADAMTS5 levels. An apparent induction of IL-33 protein was observed in high glucose-applied cells, while a moderate decrease was noted in the low-glucose applied group. Insulin administration led to a decrease in IL-33 levels. Immunoreaction of NF kappa B with corresponding antibody was found to be sharply decreased in insulin-applied cells while low and high glucose application led to a moderate decrease in NF kappa B. Conclusion: This is the first reported study that has investigated both aggrecanases and inflammation mediators in the same experimental setup with U87 cells and interpreted the results in the various aspects of AD pathophysiology related to diabetes and hyperglycemia. Our findings suggest that insulin and glucose may have important functions in the synthesis of ADAMTS, IL-33, and NF kappa B through undefined mechanism(s). Further investigations dealing with all aggrecanases and other class of ADAMTS enzymes should be carried out together with the above-mentioned parameters with the collaboration of molecular biology, genetics, immunology, and other related disciplines in order to elaborate the pathophysiological importance of ADAMTS enzymes and inflammation mediators in AD.WoSScopu