Adipose Tissue Expandability and Type 2 Diabetes

NCT03155412 | Completed

• 1 other identifier: 16-14048S
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Type2 Diabetes Mellitus

Keywords

Type 2 Diabetes; adipose tissue; preadipocytes; expandability; hypertrophy; hyperplasia; lipogenesis; adipogenesis; insulin sensitivity

Outcome Measures

Primary Outcomes (1)

• Adipogenic capacity of preadipocytes

  proliferation assays, messenger ribonucleic acid (mRNA) gene expression

  3 months from the establishment of the cell culture

Secondary Outcomes (3)

• Insulin sensitivity

  3 hours investigation of the subject at the start of the study

• Glucose tolerance

  2 hours investigation of the subject at the start of the study

• Lipid metabolism

  3 months from the establishment of the cell culture

Study Arms (2)

Offspring of type 2 diabetic patients

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

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.

Eligibility Criteria

• Age: 30 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

50 healthy lean men (age 30-45, BMI \<26). Two groups of subjects (n=25) matched for BMI, fat mass and age.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Charles University, Czech Republic: lead

Study Sites (1)

Third Faculty of Medicine, Charles University

Prague, 100 00, Czechia

Location

Related Publications (6)

• Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008 May;9(5):367-77. doi: 10.1038/nrm2391.

  PMID: 18401346 BACKGROUND

• Lu Q, Li M, Zou Y, Cao T. Induction of adipocyte hyperplasia in subcutaneous fat depot alleviated type 2 diabetes symptoms in obese mice. Obesity (Silver Spring). 2014 Jul;22(7):1623-31. doi: 10.1002/oby.20705. Epub 2014 Feb 11.

  PMID: 24435986 BACKGROUND

• Alligier M, Gabert L, Meugnier E, Lambert-Porcheron S, Chanseaume E, Pilleul F, Debard C, Sauvinet V, Morio B, Vidal-Puig A, Vidal H, Laville M. Visceral fat accumulation during lipid overfeeding is related to subcutaneous adipose tissue characteristics in healthy men. J Clin Endocrinol Metab. 2013 Feb;98(2):802-10. doi: 10.1210/jc.2012-3289. Epub 2013 Jan 2.

  PMID: 23284008 BACKGROUND

• Medina-Gomez G, Gray SL, Yetukuri L, Shimomura K, Virtue S, Campbell M, Curtis RK, Jimenez-Linan M, Blount M, Yeo GS, Lopez M, Seppanen-Laakso T, Ashcroft FM, Oresic M, Vidal-Puig A. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 2007 Apr 27;3(4):e64. doi: 10.1371/journal.pgen.0030064.

  PMID: 17465682 BACKGROUND

• Rossmeislova L, Malisova L, Kracmerova J, Tencerova M, Kovacova Z, Koc M, Siklova-Vitkova M, Viquerie N, Langin D, Stich V. Weight loss improves the adipogenic capacity of human preadipocytes and modulates their secretory profile. Diabetes. 2013 Jun;62(6):1990-5. doi: 10.2337/db12-0986. Epub 2013 Feb 1.

  PMID: 23378611 BACKGROUND

• Koc M, Siklova M, Sramkova V, Stepan M, Krauzova E, Stich V, Rossmeislova L. Signs of Deregulated Gene Expression Are Present in Both CD14+ and CD14- PBMC From Non-Obese Men With Family History of T2DM. Front Endocrinol (Lausanne). 2021 Feb 15;11:582732. doi: 10.3389/fendo.2020.582732. eCollection 2020.

  PMID: 33658980 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

adipose tissue plasma / serum preadipocytes (cells)

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertrophy; Hyperplasia; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Hyperinsulinism

Study Officials

• Vladimir Stich, prof

  Third faculty of medicine, Charles University in Prague

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MUDr

Study Record Dates

• First Submitted: May 15, 2017
• First Posted: May 16, 2017
• Study Start: January 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: January 1, 2019
• Last Updated: February 13, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)