Changes in carnitine metabolism with ketone body production in obese glucose-intolerant patients

To elucidate the relationship between carnitine metabolism and plasma ketone body concentrations in moderately obese patients with mild glucose intolerance, the ketone body and carnitine levels in the basal state were determined in 72 obese patients: 20 with normal glucose tolerance (NGT), 29 with impaired glucose tolerance (IGT), and 23 with non-insulin-dependent diabetes mellitus (NIDDM) having a fasting plasma glucose (FPG) level of less than 200 mg/dl. Total ketone body (TKB) levels significantly (P < 0.05) increased in the order of NGT, IGT, NIDDM, while the FPG and free fatty acid (FFA) concentrations were significantly (P < 0.05) higher in the NIDDM group than in the other two groups. In contrast, the insulin, glucagon and glycerol levels were comparable in the three groups. The plasma short-chain acylcarnitine (SCAC) concentration and the acylcarnitine/free carnitine (AC/FC) ratio were similar in the IGT and NIDDM groups, and significantly (P < 0.05) greater than those in the NGT group. The AC/FC ratio correlated significantly with the FPG and FFA, but not with the TKB. These results suggest that the combination of IGT with simple obesity may trigger the acceleration of hepatic ketogenesis in conjunction with an elevated SCAC and an increased AC/FC ratio. In addition, the data also imply that, in patients with mild NIDDM, factors other than the carnitines may play a greater role in enhancing ketonemia.