Diurnal Variation of Blood Ketone Bodies in Insulin-Dependent Diabetes mellitus and Noninsulin-Dependent Diabetes mellitus Patients: The Relationship to Serum C-Peptide Immunoreactivity and Free Insulin

Abstract

We examined whether the rise in ketone body concentration around midnight and in the early morning was due to the lack of free insulin (IRI) or excess of insulin counterregulatory hormones such as human growth hormone (hGH), cortisol and glucagon in noninsulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) patients and whether the monitoring of blood ketone body concentration was clinically useful as an index of metabolic control for deciding to increase or decrease the insulin dose in the treatment of diabetes mellitus. Serum levels of 3-hydroxybutyrate (3-OHBA), acetoacetate (AcAc) and 3-OHBA/AcAc ratio before breakfast were significantly increased in insulin-treated NIDDM patients with well-controlled fasting plasma glucose levels and IDDM patients compared to those in normal subjects. Mirror image diurnal changes were found between serum concentrations of 3-OHBA and serum C-peptide or free IRI in normal subjects and NIDDM patients treated with diet alone or sulfonylurea during the 24-hour daily profiles. However, there were no correlations between 3-OHBA and free IRI in the NIDDM patients treated with insulin and IDDM patients who had a much larger increase in the mean concentration of serum 3-OHBA at 6 a.m. caused by a low concentration of free IRI. Counterregulatory hormones were not increased in IDDM patients compared to normal subjects in the early morning. Cortisol/free IRI and hGH/free IRI molar ratios were significantly increased in NIDDM and IDDM patients compared to normal subjects in the early morning, but glucagon/free IRI molar ratio was not changed between IDDM and normal subjects. In conclusion, the early morning rising of ketone body concentration in insulin-treated diabetic patients, particularly IDDM patients, is due to the absolute lack of free IRI and/or the relative lack of free IRI to the levels of hGH or cortisol, and the monitoring of 3-OHBA is clinically useful as a more sensitive index of metabolic control.