Type2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes, adipose tissue, preadipocytes, expandability, hypertrophy, hyperplasia, lipogenesis, adipogenesis, insulin sensitivity
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.
Interventions
None listed
Sponsors
Charles University, Czech Republic
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
MALE
Age
30 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adipogenic capacity of preadipocytes | 3 months from the establishment of the cell culture | proliferation assays, messenger ribonucleic acid (mRNA) gene expression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Czechia
Outcome results
None listed