Diminished basal, but not stimulated, insulin secretion is a major factor associated with secondary sulfonylurea failure in type 2 diabetic patients

Chatchalit Rattarasarn, Assoc. Prof., D. of Internal Medicine, F. of Medicine, PSU.
Atchara Thamprasit, Nurse, D. of Internal Medicine, F. of Medicine, PSU.
Rattana Leelawattana, Asst. Prof., D. of Internal Medicine, F. of Medicine, PSU.
Supamai Soonthornpun, Asst. Prof., D. of Internal Medicine, F. of Medicine, PSU.
Worawong Setasuban, D. of Internal Medicine, F. of Medicine, PSU.
Corresponding e-mail : rchatcha@medicine.psu.ac.th

Grant : Prince of Songkla University
Published : Research Report
Key words : glucagon test, oral glucose tolerance test, insulin sensitivity, insulin tolerance test,sulfonylurea failure, type 2 diabetes mellitus

Introduction : Since correction of hyperglycemia by insulin treatment has been shown to ameliorate b cell function and insulin sensitivity in SU failure patients, therefore it is possible that the apparent decrease in b cell function is in part the result of hyperglycemia. There also appears to have disparity between tests of b cell function among these patients. The objectives of this study were to determine b cell secretory reserve and insulin sensitivity of secondary SU failure type 2 diabetic pa-tients compared with those of SU responsive and examine the disparity of b cell responses to glucose and non-glucose stimuli between these two groups.
Subjects and Methods : Eight secondary SU failure, insulin-treated and 11 SU responsive type 2 diabetic patients who were matched for age, degree of obesity, duration of diabetes as well as HbA1c were studied. Intravenous glucagon and oral glucose tolerance tests (OGTT) as well as short intra-venous insulin tolerance test using arterialized venous blood were randomly performed on separate occasion to assess b cell secretory reserve and insulin sensitivity, respectively.
Results : Basal (0.37±0.05 (SEM) VS 0.80±0.14 nmol/l; p=0.02) and stimulated c-peptide levels (0.66±0.08 VS 1.16±0.14 nmol/l; p=0.007) after glucagon as well as basal (0.46±0.06 VS 0.73±0.10 nmol/l; p=0.046) and maximal c-peptide responses (1.41±0.14 VS 1.97±0.14 nmol/l; p=0.021) to glucose stimulation were significantly lower in SU failure than SU responsive patients. However, the incremental changes of c-peptide over basal after glucagon (0.29±0.06 VS 0.37±0.09 nmol/l) and glucose (AUC : 36.9±7.6 VS 47.9±4.5 nmol/l/hr) were not different between both groups. There were strong positive relationships between basal and stimulated c-peptide responses to glucagon (r=0.818; p=0.002) and glucose (r=0.85; p=0.001) in SU responsive patients but these relationships were not as strong in SU failure patients (r=0.682; p=0.062 and r=0.41; p=NS, respectively). Insulin sensitivity did not differ between both groups.
Conclusions : This study demonstrated that decreased basal, but not stimulated, insulin secre-tion was a major factor associated with secondary SU failure in type 2 diabetic patients. With com-parable glycemic control, there was no disparate b cell responses to glucose and glucagon in patients with or without secondary SU failure.
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