Elevated Plasma β-Hydroxybutyrate Concentrations without Ketonuria in Healthy Insulin-Dependent Diabetic Patients*

Abstract

Plasma beta-hydroxybutyrate (beta-OHB) concentrations and simultaneous urine tests for ketonuria (nitroprusside reaction) were evaluated every 4 h throughout a 24-h study in 10 healthy insulin-dependent diabetics who had poor control based on home urine tests and elevated hemoglobin A1C. Concurrent measurements of the major carbohydrate regulatory hormones were made in the diabetic group and in a control population of 20 age-matched subjects. In the diabetics, 73% of the beta-OHB measurements were elevated. Only 43% of the abnormal beta-OHB values were associated with ketonuria. The diabetic subjects also showed exaggerated diurnal patterns for plasma beta-OHB and cortisol. There were no significant differences for the other regulatory hormones in the diabetic and normal groups. We conclude that 1) abnormal plasma beta-OHB levels without ketonuria are prevalent in poorly controlled diabetics; 2) negative nitroprusside tests for ketonuria underestimate the presence of ketonemia due to increased beta-OHB concentrations; 3) both insulin deficiency and glucocorticoid excess may influence ketone body metabolism in insulin-dependent diabetic patients.

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

“…We found it at 6 a.m. in both of them. We agree with the results of Harano et al [2] and MacGillivray et al [6,7], Ketogenesis is accelerated by an aug mented supply of FFA, the precursor of ke tone synthesis to the liver and the rate of the hepatic metabolism away from FFA to FFA oxidation in the liver [21][22][23][24][25]. In our results, there were no different changes in the con centration of FFA between NIDDM treated with insulin and IDDM patients, but 3-OHBA levels before breakfast in IDDM pa tients were higher than those in NIDDM treated with insulin.…”

“…Harano et al [2] reported that 3-OHBA levels were highest before breakfast in NIDDM patients. MacGillivray et al [6,7] also had similar results. We could not find the peak concentration of 3-OHBA at 11 p.m. in both our normal sub jects and diabetic patients.…”

“…MacGillivray et al [6,7] re ported the elevation of plasma cortisol levels in the early morning in poorly controlled IDDM patients. In another report, Waldhausl et al [26] reported that 3-OHBA and AcAc were increased during infusion of cor tisol.…”

“…It is not clear whether the midnight and early morning rising in ketone body con centration is due to the lack of free insulin (IRI) and/or the excess of insulin counterregulatory hormones in diabetic patients with conventional insulin therapy [6,7). In this study, diurnal variations of blood ketone bodies, serum C-peptide (S-CPR), free IRI and insulin counterregulatory hormones were examined in noninsulin-dependent dia betes mellitus (NIDDM) patients with wellcontrolled fasting plasma glucose levels (<120 mg/dl) by conventional therapy (diet, sulfonylurea, insulin) and IDDM patients with almost well-controlled fasting plasma glucose levels (< 150 mg/dl) by conventional insulin therapy in order to find out whether the midnight and early morning rising in ketone body concentration was due to the lack of free IRI or the excess of insulin coun terregulatory hormones such as human growth hormone (hGH), cortisol and gluca gon in NIDDM and IDDM patients.…”

Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome

“…Clinical studies have shown that elevations of ␤-hydroxybutyrate levels are extremely common in patients with poorly controlled diabetes, even in the absence of positive urinary ketones. 48 The use of home glucoseketone meters may allow early recognition of impending ketoacidosis, which may help to guide insulin therapy at home and may possibly prevent hospitalization for DKA.…”