Role of osteocalcin in mood and cognitive complications of type 2 diabetes
This study will determine if lower blood osteocalcin concentrations are associated with 1) depressive symptoms and 2) poorer cognitive performance in people with type 2 diabetes. The study will also determine if increased osteocalcin due to a structured exercise invervention correlates with antidepressant and cognitive benefits, and if baseline osteocalcin levels predict antidepressant and cognitive responses. Recent studies have established bone as an endocrine organ important in the regulation of metabolism. Circulating concentrations of the bone-derived hormone osteocalcin are often low in type 2 diabetes, and recent studies suggest that a specific form of this hormone, the undercarboxylated form (unOC), can cross the blood-brain-barrier where it may be needed to maintain healthy mood states and cognitive function. We will recruit 60 patients with type 2 diabetes entering a standardized 6-month exercise (combined aerobic and resistance training) program. At baseline, and after 6 months, we will compare unOC concentrations (from fasting serum samples) to mood symptoms (Beck Depression Inventory, 2nd Ed.) and cognitive performance (Hachinski's standardized battery of tests). These outcome assessments coincide with clinical assessments of fitness, glycemic control, exercise performance and body composition, which will be explored as covariates in addition to age and gender. We will also explore bone-turnover markers as possible covariates, and conduct a subgroup analysis in men to obviate possible effects of menopause. Bio-specimens will be banked and made available for future hypothesis-generating studies. If successful, results will suggest new ways to monitor, predict and treat mood and cognitive symptoms in people with type 2 diabetes. The study will inform future research and drug development specifically to address the common and debilitating central nervous system complications of type 2 diabetes. This study will also help to understand the phenomenon of exercise futility in type 2 diabetes, and suggest mechanisms to enhance the brain benefits of exercise.