Adipose Tissue Expandability and Type 2 Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Limited Adipose Tissue Expandability as a Risk Factor for Development of Type 2 Diabetes: the Role of Preadipocytes

Conditions
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Type2 Diabetes Mellitus

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Offspring of type 2 diabetic patients<br>Group 1: 25 healthy lean men (age 30-45, BMI <28) with genetic predisposition for type 2 diabetes mellitus (T2DM) - i.e. their two first-degree relatives (parents, siblings) or one first-degree relative and two second-degree relatives with type 2 diabetes (grandparents, uncle, aunt) were diagnosed with T2DM. Exclusion criteria: any prior history of obesity, elevated triglyceride concentration, hypertension, thyroid or other endocrine disease, smoking, drug abuse. | |
| Control subjects<br>Group 2: 25 healthy lean men (age 30-45, BMI <28) without any family history of T2DM. Exclusion criteria: any prior history of obesity, elevated triglyceride concentration, hypertension, thyroid or other endocrine disease, smoking, drug abuse. Subjects matched for BMI, fat mass and age to subjects in Group 1 will be recruited. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adipogenic capacity of preadipocytes | proliferation assays, messenger ribonucleic acid (mRNA) gene expression | 3 months from the establishment of the cell culture | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Glucose disposal measured by hyperinsulinemic-euglycemic clamp | 3 hours investigation of the subject at the start of the study | 
| Glucose tolerance | Oral glucose tolerance test (OGTT) | 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 | 3 months from the establishment of the cell culture | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes, adipose tissue, preadipocytes, expandability, hypertrophy, hyperplasia, lipogenesis, adipogenesis, insulin sensitivity