Adipose Tissue Expandability and Type 2 Diabetes

Completed

• Conditions: Type2 Diabetes Mellitus

• Registration Number: NCT03155412
• Lead Sponsor: Charles University, Czech Republic

Brief Summary

The goal of the study is to analyze deviations in adipogenic potential and metabolic properties of preadipocytes in subjects with genetic predisposition to type 2 diabetes, and thus identify factors that underlie hypertrophic growth of adipose tissue associated with the development of this disease.

Detailed Description

Adipose tissue (AT) expands in response to excessive energy intake by hyperplasia or hypertrophy. While hyperplasia is associated with preservation of insulin sensitivity, hypertrophic AT exerts a number of metabolic defects. The mechanisms by which hyperplasia is suppressed at the expense of AT hypertrophy remain unknown, but it is expected that the hypertrophy of adipocytes is primarily driven by insufficient recruitment and differentiation of available preadipocytes. The limitation of hyperplasia occurs already in non-obese healthy subjects who are genetically predisposed to Type 2 Diabetes. Using these and control subjects, the LIMEX project aims to analyze the mechanisms of AT expandability. The project will combine in vivo characterization of AT and in vitro studies on human preadipocytes derived from AT biopsies obtained during clinical study. In vitro, proliferation, adipogenesis and lipogenesis of adipose cells will be monitored and these properties will be related to the degree of AT hypertrophy in vivo, insulin sensitivity and genetic predisposition to metabolic complications.

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2017-05-15
• Study First Submitted QC: 2017-05-15
• Study First Posted: 2017-05-16
• Primary Completion: 2018-03
• Study Completion: 2019-01
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-12
• Last Update Posted: 2020-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 44

Inclusion Criteria

• healthy non-obese men
• subject has genetic predisposition for T2DM- i.e. two first-degree relatives (parents, siblings) or one first-degree relative and two second-degree relatives with type 2 diabetes (grandparents, uncle, aunt) diagnosed with T2DM OR
• subject without any family history of T2DM.

Exclusion Criteria

• any prior history of obesity
• elevated triglyceride concentration (above 1.7 mmol/l)
• hypertension
• thyroid or other endocrine disease
• smoking
• drug abuse

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Adipogenic capacity of preadipocytes	3 months from the establishment of the cell culture	proliferation assays, messenger ribonucleic acid (mRNA) gene expression

Secondary Outcome Measures

Name	Time	Method
Insulin sensitivity	3 hours investigation of the subject at the start of the study	Glucose disposal measured by hyperinsulinemic-euglycemic clamp
Glucose tolerance	2 hours investigation of the subject at the start of the study	Oral glucose tolerance test (OGTT)
Lipid metabolism	3 months from the establishment of the cell culture	Lipolysis, lipogenesis in cell cultures of adipocytes derived from the subjects

Trial Locations

Locations (1)

Third Faculty of Medicine, Charles University; 🇨🇿 Prague, Czechia