Role of KATP Channel Loss in Type 2 Diabetes

ConditionObesity and Type 2 Diabetes

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18-65

SponsorWashington University School of Medicine

About this trial

Insulin is a hormone that is made by β-cells in the pancreas and when released into the bloodstream helps control blood sugar levels. Insulin release is regulated by electrical activity in the β-cell which is generated by the ATP-sensitive potassium (KATP) channel. While reduced KATP activity is associated with increased insulin secretion, animals lacking KATP exhibit reduced secretion. This crossover from hypersecretion to undersecretion with KATP loss mirrors insulin secretion during type 2 diabetes. Intriguingly, evidence from cell and animal models suggest that chronically stimulated β-cells can lose KATP revealing a possible role for KATP loss in the failure of insulin secretion and poor control of blood sugar observed in type 2 diabetes. This study will therefore examine insulin responses following ingestion of a single dose of a sulfonylurea called glipizide that inhibits KATP channels in people with and without type 2 diabetes. The goal is to determine whether KATP channel activity is reduced during type 2 diabetes progression.

Eligibility criteria

Qualifiers

Lean-normoglycemic group (n=10): BMI ≥18.5 and <25.0 kg/m², fasting plasma glucose concentration <95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140-mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.

Obesity-normoglycemic group (n=10): BMI ≥30 and <50 kg/m², fasting plasma glucose concentration <95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140 mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.

Obesity-impaired fasting glucose group (n=10): BMI ≥30 and <50 kg/m², fasting plasma glucose concentration 100-125 mg/dl, and 2-hr oral glucose tolerance test plasma glucose concentration <200 mg/dl.

Obesity-type 2 diabetes group (n=10): BMI ≥30 and <50 kg/m²; HbA1C 6.5-9.5%, fasting plasma glucose ≥126 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≥200 mg/dl and/or medical history of T2DM and currently using anti-diabetic medications.

Disqualifiers

Diabetes therapy with insulin at >0.5 units/kg/day.

Any change in diabetes medication in previous 3 months.

Unstable weight (>2% change during the last 2 months before entering the study).

Evidence of significant organ system dysfunction or disease other than obesity and T2D.

Trial design

Treatments tested in this trial

10 mg glipizide ingestion

Treatment groups

40 Participants

are divided into 4 treatment groups

Sponsors and collaborators

Washington University School of Medicine

Lead sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Source ClinicalTrials.gov