Pathophysiology of ketoacidosis in Type 2 diabetes mellitus

Pathophysiology of ketoacidosis in Type 2 diabetes mellitus
P. Linfoot , C. Bergstrom and E. Ipp

Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA

Correspondence to: Eli Ipp MD, Harbor-UCLA Medical Center, 1000 W. Carson Street, Box 16, Torrance, CA 90509-2910, USA. E-mail: ipp@labiomed.org
Copyright © 2005 Diabetes UK
KEYWORDS

C-peptide Ô insulin Ô ketoacidosis Ô Type 2 diabetes

Diabet. Med. 22, 1414 Ò1419 (2005)
Abstract
Abstract Introduction Materials and methods Results Discussion References

Aims Despite an increasing number of reports of ketoacidosis in populations with Type 2 diabetes mellitus, the pathophysiology of the ketoacidosis in these patients is unclear. We therefore tested the roles of three possible mechanisms: elevated stress hormones, increased free fatty acids (FFA), and suppressed insulin secretion.

Methods Forty-six patients who presented to the Emergency Department with decompensated diabetes (serum glucose > 22.2 mmol/l and/or ketoacid concentrations ≥ 5 mmol/l), had blood sampled prior to insulin therapy. Three groups of subjects were studied: ketosis-prone Type 2 diabetes (KPDM2, n = 13) with ketoacidosis, non-ketosis-prone subjects with Type 2 diabetes (DM2, n = 15), and ketotic Type 1 diabetes (n = 18).

Results All three groups had similar mean plasma glucose concentrations. The degree of ketoacidosis (plasma ketoacids, bicarbonate and anion gap) in Type 1 and 2 subjects was similar. Mean levels of counterregulatory hormones (glucagon, growth hormone, cortisol, epinephrine, norepinephrine), and FFA were not significantly different in DM2 and KPDM2 patients. In contrast, plasma C-peptide concentrations were approximately three-fold lower in KPDM2 vs. non-ketotic DM2 subjects (P = 0.0001). Type 1 ketotic subjects had significantly higher growth hormone (P = 0.024) and FFA (P < 0.002) and lower glucagon levels (P < 0.02) than DM2.

Conclusions At the time of hospital presentation, the predominant mechanism for ketosis in KPDM2 is likely to be greater insulinopenia.

Accepted 19 December 2005
DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1464-5491.2005.01660.x About DOI