Age-related changes in the diurnal variation of ketogenesis in patients with type 2 diabetes and relevance to hypoglycemic medications.
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.
Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.
Hitomi
H
Nakayama
Ichiro
I
Tokubuchi
Nobuhiko
N
Wada
Munehisa
M
Tsuruta
Tsuyoshi
T
Ohki
Tamami
T
Oshige
Yuko
Y
Sasaki
Shinpei
S
Iwata
Naoka
N
Kato
Yoshie
Y
Ohtsuka
Yuko
Y
Matsuo
Yuji
Y
Tajiri
Kentaro
K
Yamada
D000367:Age Factors; D000368:Aged; D001786:Blood Glucose; D002940:Circadian Rhythm / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000097:blood*; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D007657:Ketone Bodies