Adipose Tissue Expandability and Type 2 Diabetes

Charles University, Czech Republic44 enrolled

Overview

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.

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 Type

OBSERVATIONAL

Enrollment

Conditions

Type2 Diabetes Mellitus

Eligibility

Sex: MALEMin age: 30 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Third Faculty of Medicine, Charles University

Prague, Czechia

Outcomes

Primary Outcomes

Adipogenic capacity of preadipocytes

proliferation assays, messenger ribonucleic acid (mRNA) gene expression

Time frame: 3 months from the establishment of the cell culture

Secondary Outcomes

Insulin sensitivity

Glucose disposal measured by hyperinsulinemic-euglycemic clamp

Time frame: 3 hours investigation of the subject at the start of the study

Glucose tolerance

Oral glucose tolerance test (OGTT)

Time frame: 2 hours investigation of the subject at the start of the study

Lipid metabolism

Lipolysis, lipogenesis in cell cultures of adipocytes derived from the subjects

Time frame: 3 months from the establishment of the cell culture

Data from ClinicalTrials.gov

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