ALCOHOL-RELATED DIOLS CAUSE ACUTE INSULIN-RESISTANCE IN-VIVO

Epidemiological studies suggest that alcohol consumption is an indepen dent risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM). Alcoholism is known to be associated with increased plasma levels of two novel diols. 2,3-butanediol and 1,2-propanediol, metabolites known to impair insulin action in isolated adipocytes. Th is study examines whether 2,3-butanediol and 1,2-propanediol have the capacity to impair insulin action acutely in vivo in the rat. Using th e euglycemic-hyperinsulinemic clamp, it is shown that the two diols re duce whole-body glucose utilization (by similar to 30%), with the onse t of insulin resistance in vivo occurring at plasma concentrations of 2,3-butanediol (33 mu mol/L) at least one order of magnitude (P < .001 ) lower than 1,2-propanediol (432 mu mol/L). Tracer methodologies usin g [U-C-14]glucose and 2-deoxy[1-H-3]glucose indicate that the reductio n in whole-body glucose utilization is accompanied by a reduction in g lucose uptake and glycogen synthesis in the skeletal muscle and heart. The association between elevated plasma diol levels and insulin resis tance demonstrated in this report raises the question of whether there is a link between the high plasma diol levels in alcohol abusers and their increased susceptibility to NIDDM. Copyright (C) 1998 by W.B. Sa unders Company.