This study was designed to reproduce candidate single nucleotide variants found by whole exome sequencing in some type 2 diabetic patients dependent on sulfonylurea in a separate patient group. The validation of the dependence-related variations performed in this study is expected to help decision-making in the clinical use of sulfonylurea in the future.

Sulfonylurea, one of the oral hypoglycemic agents, is the oldest and most widely used drug. The use of sulfonylurea was overwhelming compared to metformin especially in East Asia, where insulin secretion was notable during the pathophysiology of type 2 diabetes. However, sulfonylurea causes hypoglycemia and weight gain, increases cardiovascular disease and mortality compared to other oral preparations. With the recent development of other oral hypoglycemic agents for lowering blood glucose without the risk of hypoglycemia and with cardiovascular protection, sulfonylurea is in a decreasing state of use worldwide.

But some patients tend to be highly dependent on sulfonylurea for blood glucose control. It suggests that there will be a group of patients whose the action of sulfonylurea is strongly influenced by genetic factor, since insulin secretion of pancreatic beta cells is very hereditary, genetic variations that increase the risk of type 2 diabetes are found mainly in genes related to beta cell dysfunction rather than insulin resistance, and the more risk variants of type 2 diabetes, the less likely the effect of sulfonylurea is.

The investigators had performed whole exome sequencing in patients showing dependence on sulfonylurea and identified tens of candidate variants.

In this study, the investigators will select patients with dependence on sulfonylurea by prospective intervention (by discontinuing and resuming sulfonylurea) and perform genetic tests.

Inclusion Criteria:

Among patients with type 2 diabetes who visited Seoul National University Hospital endocrinology outpatient clinic, all of criteria (1)-(4) are satisfied

1. Adults over 19 years
2. More than 10 years of diabetes
3. Low dose sulfonylurea use: Equivalent capacity 2 mg or less of glimepiride
4. Less than 7.5% of glycated hemoglobin for more than 6 months
5. estimated glomerular filtration rate > 50 mL/min/1.73㎡

Exclusion Criteria:

• Type 1 diabetics
• Insulin user
• Patients diagnosed with cardiovascular disease, cancer, and other critical illness within 6 months before the study
• Patients with severe hypertension
• Patients with treatment or diseases that may have a significant effect on blood glucose levels, such as glucocorticoids and thyrotoxicosis