The glucagon response to oral glucose challenge in Type 1 Diabetes Mellitus: Lack of Impact of euglycemia

  1. Bernard Zinman CM, MD1,2,4
  1. 1Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada
  2. 2Division of Endocrinology, University of Toronto, Toronto, Canada
  3. 3Division of General Internal Medicine, University of Toronto, Toronto, Ontario
  4. 4Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
  1. Correspondence: Dr. Bernard Zinman Email: zinman{at}


Objectives Previous studies have demonstrated aberrant glucagon physiology in the setting of type 1 diabetes (T1DM) but have not addressed the potential impact of ambient glycemia on this glucagon response. Thus, our objective was to evaluate the impact of euglycemia vs hyperglycemia on the glucagon response to an oral glucose challenge in T1DM.

Research Design and Methods Ten adults with T1DM [mean age 56.6±9.0 years, duration of diabetes 26.4±7.5 years, HbA1c 7.5%±0.77 and BMI 24.1 Kg/m2 (22.6-25.4)] underwent 3-hour 50g oral glucose tolerance tests (OGTT) on two separate days at least 24 hours apart in random order under conditions of pre-test euglycemia [plasma glucose (PG) between 4-6 mmol/l] and hyperglycemia [PG between 9-11 mmol/l], respectively.

Results Glycemic excursion on the OGTT was similar between the euglycemic and hyperglycemic tests (P=0.72 for interaction between time post-challenge and glycemic setting). Interestingly glucagon levels increased in response to the OGTT under both glycemic conditions (P<0.001) and there were no differences in glucagon response between the euglycemic and hyperglycemic days (P=0.40 for interaction between time post-challenge and glycemic setting). In addition, the incretin responses to the OGTT (glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, glucagon-like peptide-2) were also not different between the euglycemic and hyperglycemic settings.

Conclusions In patients with T1DM, there is a paradoxical increase in glucagon in response to oral glucose which is not reversed when euglycemia is achieved prior to the test. This abnormal glucagon response likely contributes to the postprandial hyperglycemia in T1DM irrespective of ambient glycemia.


  • * CKK and CAB share co-first authorship on this study

  • Received October 8, 2013.
  • Accepted November 11, 2013.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

This Article

  1. Diabetes Care
  1. All Versions of this Article:
    1. dc13-2339v1
    2. 37/4/1076 most recent