A prospective trial of risk factors for sulfonylurea-induced hypoglycemia in type 2 diabetes mellitus.
BACKGROUND
Retrospective studies have identified oral sulfonylureas, age, and fasting as major risk factors for hypoglycemia in patients with type 2 diabetes. Sulfonylureas may be withheld from elderly patients out of concern for hypoglycemia.


OBJECTIVE
To evaluate the hypoglycemic effects of maximum doses of once-daily second-generation sulfonylureas administered to fasting elderly patients.


METHODS
A prospective, randomized, double-blind clinical trial.


METHODS
The University of New Mexico General Clinical Research Center.


METHODS
Fifty-two sulfonylurea-treated subjects with type 2 diabetes with a mean (SD) age of 65.1 (5.7) years.


METHODS
Subjects were randomly assigned to glyburide or glipizide gastrointestinal therapeutic system (GITS). Each subject participated in three 23-hour fasting studies after the sequential administration of 1 week of placebo and 1 week of 10 mg and 1 week of 20 mg of the assigned sulfonylurea.


METHODS
Occurrence of hypoglycemia (defined as plasma glucose level <3.33 mmol/L [60 mg/dL]) and hormonal parameters during the final 9 hours of the 23-hour fast in patients who had taken sulfonylureas vs placebo.


RESULTS
No hypoglycemia was observed during 156 fasting studies. Plasma glucose level was decreased (nadir, 4.9 mmol/L [88 mg/dL] for a 20-mg dose of glyburide vs 8.3 mmol/L [150 mg/dL] for placebo; nadir, 5.8 mmol/L [105 mg/dL] for a 20-mg dose of glipizide GITS vs 8.7 mmol/L [157 mg/dL] for placebo), and serum insulin was increased in the sulfonylurea studies compared with placebo (P<.001). Plasma glucose parameters did not differ between the 2 sulfonylureas, but C peptide concentrations were increased in the glyburide group compared with glipizide GITS in the 20-mg study (P=.05). Concentrations of epinephrine were increased in the sulfonylurea studies compared with placebo (P<.001). Epinephrine secretion increased when glucose concentration fell below the mean (SD) level of 9.10 (2.66) mmol/L (164 [48] mg/dL) in the 10-mg study and 8.77 (2.83) mmol/L (158 [51] mg/ dL) in the 20-mg study.


CONCLUSIONS
Fasting was well tolerated among these elderly patients with type 2 diabetes treated with sulfonylureas. Older age should not be considered a contraindication to sulfonylurea treatment for diabetes. Stimulation of epinephrine secretion at normal or elevated plasma glucose levels appears to be the primary mechanism of protection against hypoglycemia in this study.
Burge
M R
MR
Department of Medicine/Endocrinology, University of New Mexico School of Medicine, Albuquerque 87131, USA. mburge@salud.UNM.edu
Schmitz-Fiorentino
K
K
Fischette
C
C
Qualls
C R
CR
Schade
D S
DS
D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D001774:Blood Chemical Analysis; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D005215:Fasting; D005260:Female; D005913:Glipizide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005905:Glyburide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008297:Male; D010455:Peptides / Q000097:blood; D011446:Prospective Studies; D012307:Risk Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; C050632:polypeptide C; D005905:Glyburide; D005913:Glipizide; D004837:Epinephrine