The Role of Diminished ~ Cell Reserve and Insulin Resistance in Secondary Sulfonylurea Failure of Type 2 Diabetes Mellitus
CHATCHALIT RATTARASARN, M.D.*, RA TTANA LEELA WATT ANA, M.D.*, WORA WONG SETASUBAN, M.D.*, ATCHARA THAMPRASIT, B.N.*, SUPAMAI SOONTHORNPUN, M.D.*,
Affiliation : * Division of Endocrinology & Metabolism, Department of Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
Introduction : The correction of hyperglycemia by insulin treatment has been shown to
ameliorate ~cell function and insulin sensitivity in SU failure patients, and there also appears to have
disparity between tests of ~ cell function among these patients. The objectives of this study were
to determine ~ cell secretory reserve and insulin resistance of secondary SU failure type 2 diabetic
patients who had fairly good glycemic control compared with those who were SU responsive and the
disparity of ~ cell responses to glucose and non-glucose stimuli were examined in these two groups.
Subjects and
Method : 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 (OGTI) as well as
short intravenous insulin tolerance test using arterialized venous blood were randomly performed on
separate occasions to assess ~ cell secretory reserve and insulin sensitivity, respectively.
Results : Basal (0.37±0.05 (SEM) vs 0.80±0.14 nmol/1; p=0.02) and stimulated c-peptide
levels (0.66±0.08 vs 1.16±0.14 nmol/1; p=0.007) after glucagon as well as basal (0.46±0.06 vs
0.73±0.10 nmol/1; p=0.046) and maximal c-peptide responses (1.41±0.14 vs 1.97±0.14 nmol/1; 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
nmoVl) and glucose (AUC : 36.9±7.6 vs 47.9±4.5 nmoVVh) 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, res-
pectively). Insulin sensitivity did not differ between the two groups.
Conclusion : This study demonstrated that decreased basal, but not stimulated, insulin
secretion was possibly a major factor associated with secondary SU failure in type 2 diabetic patients.
With comparable glycemic control, there was no disparate ~ cell responses to glucose and glucagon
in patients with or without secondary SU failure.
Keywords : Glucagon Test, Oral Glucose Tolerance Test, Insulin Resistance, Insulin Tolerance Test, Sulfonylurea Failure, Type 2 Diabetes Mellitus
