Pathophysiology of ketoacidosis in Type 2 diabetes mellitus.
OBJECTIVE
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 > or = 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.
Linfoot
P
P
Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
Bergstrom
C
C
Ipp
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D016883:Diabetic Ketoacidosis / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology; D007659:Ketones / Q000097:blood; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood
D000906:Antibodies; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D007659:Ketones; D019382:Human Growth Hormone; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine