Clinical trial

Role of KATP Channel Loss in Type 2 Diabetes

Recruiting now · Not applicable · 1 countries · Registry ID NCT06830096

Recruiting nowNot applicableInterventional

What this study is about

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.

A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.

Basic eligibility

Age18 Years to 65 Years
SexAll
Healthy volunteersAccepted
ConditionObesity and Type 2 Diabetes

Full registry criteria

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Treatments and study arms

10 mg glipizide ingestion

Drug

A single dose of 10 mg glipizide will be ingested

Primary outcomes

Insulin secretion90 minutes after glipizide ingestion

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.

Study locations

1 locations were listed when this page was built. The first 40 are shown.

Washington University in St. Louis🇺🇸 St Louis, Missouri, United States
Kyle TimmonsContact
Nathaniel York, PhDPrincipal Investigator