Role of KATP Channel Loss in Type 2 Diabetes

NCT06830096 | Recruiting DMC

• 2 other identifiers: 2024060755P30DK056341
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity and Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Insulin secretion

  Insulin secreted by pancreas into plasma measured over 90 minutes after glipizide ingestion. Insulin secretion will be calculated using a stepwise insulin secretion rate function to fit plasma C-peptide concentrations to a two-compartment model of C-peptide kinetics using population-based C-peptide model parameters.

  90 minutes after glipizide ingestion

Study Arms (4)

Lean with normal glucose tolerance

EXPERIMENTAL

Body mass index ≥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%.

Drug: 10 mg glipizide ingestion

Obesity with normal glucose tolerance

EXPERIMENTAL

Body mass index ≥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%.

Drug: 10 mg glipizide ingestion

Obesity with impaired fasting glucose

EXPERIMENTAL

Body mass index ≥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.

Drug: 10 mg glipizide ingestion

Obesity with type 2 diabetes

EXPERIMENTAL

Body mass index ≥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 type 2 diabetes and currently using anti-diabetic medications.

Drug: 10 mg glipizide ingestion

Interventions

10 mg glipizide ingestion DRUG

A single dose of 10 mg glipizide will be ingested

Lean with normal glucose tolerance; Obesity with impaired fasting glucose; Obesity with normal glucose tolerance; Obesity with type 2 diabetes

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Regular use of tobacco products.
• Excessive consumption of alcohol (≥3 drinks/day for men and ≥2 drinks/day for women).
• Use of medications that are known to affect the study outcome measures (e.g., steroids, non-statin lipid-lowering medications) or increase the risk of study procedures (e.g., anticoagulants) and that cannot be temporarily discontinued for this study.
• Anemia (Hemoglobin \<10.0 g/dL).
• Pregnant or breastfeeding.
• Unable or unwilling to follow the study protocol or for any reason the research team believes the volunteer is not an appropriate candidate for this study, including non-compliance with screening appointments or previous medical visits.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Washington University in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Central Study Contacts

Kyle Timmons

CONTACT

314-273-1879; nutritionresearch@wustl.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2025
• First Posted: February 17, 2025
• Study Start: March 7, 2025
• Primary Completion: March 31, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 4, 2025

Record last verified: 2025-07

Locations

US (1)