Background
Type 2 diabetes is a heterogeneous disease characterized insulin secretion and insulin resistance. Insulin secretion is one of important factors determining glycemic control of patients with diabetes.　Glucagon stimulation test is one of older methods evaluating insulin secretion and is common in Japan. Glucagon stimulation test is well known experimentally but does not be reported so much to keep glycemic control good for the long term. In recent years, dipeptidyl peptidase 4 (DPP4) inhibitor, glucagon like peptide 1 (GLP1) agonist and inhibitor of sodium glucose cotransporter 2 (SGLT2) have been launched. These medicines make glycemic control in patients with type 2 diabetes easier.
Aim
We aim to know whether we can still predict glycemic control for the long term by insulin secretion evaluated by glucagon stimulation test.
Method
Japanese type 2 diabetes patients without medication with HbA1c >8.0 were evaluated for β-cell function by increments of C-peptide immunoreactivity in glucagon stimulation test (GST-ΔCPR) within 3 months from first visit. We retrospectively examined 101 patients in the first visit from April 2012 to Dec 2016. They were divided into quartiles by GST-ΔCPR (4.3±0.7, 2.8±0.3, 1.8±0.2, 1.1±0.1).
Results
At baseline, HbA1c and BMI had no significant change among each quartile (HbA1c 11.0±1.5, 10.8±1.7, 11.6±2.1, 11.3±2.4%, n.s., BMI 27.6±5.6, 27.1±6.6, 26.1±6.2, 24.7±5.0kg/m2, n.s.). HbA1c of highest quartile of GST-ΔCPR tended to be better than lowest quartile of GST-ΔCPR group after 6-18 month from first visit (6M 6.4±1.1%, 7.1±1.0%, p<0.07, 12M 6.4±1.0%, 7.1±1.1%, p<0.07, 18M 6.6±1.0%, 7.3±1.1%, p<0.09), although HbA1c had no significant change among each group after 3 and 24 month(3M 7.1±1.1, 7.4±1.0, n.s., 24M 6.6±0.8, 7.0±0.8, n.s.). Numbers of categories of drugs taken in highest quartile of GST-ΔCPR were more than lowest quartile after 12 month (1.7±0.8, 2.4±1.2, p<0.05), although numbers of categories of drugs taken had no significant difference among each group after 3 month and 24 month(3M 1.4±1.0, 1.8±0.7, n.s., 24M 1.9±0.6, 2.4±1.3, n.s.). After 12 month, patients whose GST-ΔCPR was low had worse HbA1c and fewer number of categories of drugs taken than that whose GST-ΔCPR was low. After 24 month, it might have poor statistical power that HbA1c and number of categories of drugs taken did not significantly change between highest and lowest quartiles.
Discussion
Evaluation of insulin secretion by glucagon stimulation test contributes not only to choosing appropriate therapeutic medicine but also predicting glycemic control for the long term. Glucagon stimulation test is one of valuable tools by which we know insulin secretion of patients with type 2 diabetes.

Evaluation of insulin secretion by glucagon stimulation test predicts long-term glycemic control in type 2 diabetes