[The effect of genetic risk of diabetes on the correlations in bone and energy homeostasis]

Type 2 diabetes is associated with increased risk of bone fractures, and the connection between bone remodeling and carbohydrate homeostasis is decoupled. It is not known whether these phenomena are the consequence of the deteriorating glucose metabolism, and the increasing insulin resistance or they belong to the genetic risk of type 2 diabetes.The aim of the authors was to clarify the impact of genetic risk on bone and carbohydrate homeostasis connections.Hyperinsulinemic-normoglycemic clamps, and oral and iv. glucose loads were done to select 18 metabolically healthy females with first degree type 2 diabetic relatives -and 26 without diabetic relatives.The connections between total body glucose utilization and the activity of the bone metabolic unit were missing in healthy females with the genetic risk of type 2 diabetes, like in those with manifest diabetes. In this risk group the level of low-density-large molecular sized LDL lipids were decreased, while the high-density LDL group with low molecular size was increased. The latter change was in significant connection with increased interleukin-6 levels and increased bone resorption within the bone metabolic unit.These data suggest that the missing connection between glucose and bone metabolism is not the consequence of the developing insulin resistance and deteriorating glucose metabolism, but rather it belongs to the inherited diabetes risk. The etiology of this early alteration, which develops prior to glucose intolerance and insulin resistance is unknown and needs further investigations.