To assess the significance of ketogenesis in the management of
diabetes mellitus, we analyzed the factors associated with the diurnal variation of the plasma
ketone body levels. The subjects consisted of 220 patients with
type 2 diabetes, aged 60 ± 15 years, without advanced complications. They ate a standardized, low-fat meal at 8:00, 12:00, and 18:00. The plasma levels of
3-hydroxybutyrate (3HB) and
free fatty acid (FFA) were increased before breakfast and before dinner. The plasma
glucose concentration was almost the same at any blood sampling time point among age quartiles. However, the 3HB levels were significantly decreased with age, which was most obvious before dinner. The FFA levels also decreased with age, but the decline was mild. A multiple regression analysis with stepwise selection revealed that age was an independent, negative contributor and that the pre-breakfast FFA concentration was an independent, positive contributor to the pre-breakfast 3HB levels. Regarding the pre-dinner 3HB levels, in addition to age and the pre-dinner FFA concentration, the uses of sulfonylurea and dipeptidyl peptidase-4 inhibitors were independent negative contributors. The metabolism of
ketone bodies is an alternative energy source for the brain under conditions of
starvation. While excessive ketogenesis leads to critical
ketoacidosis, inadequate
ketone body production could be associated with a propensity to develop neurohypoglycemia in elderly patients treated with
insulin secretagogues. Because age-related changes in ketogenesis were the most significant before dinner, attention should be paid not only to fasting but also to the pre-dinner levels of 3HB.