Adipose Tissue Expandability and Type 2 Diabetes

Type2 Diabetes Mellitus Clinical Trial

— LIMEX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03155412
• Other study ID #: 16-14048S
• Status: Completed
• Start date: January 2016
• Est. completion date: January 2019

Study information

• Verified date: February 2020
• Source: Charles University, Czech Republic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 2019
• Est. primary completion date: March 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 30 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type2 Diabetes Mellitus

Locations

Country	Name	City	State
Czechia	Third Faculty of Medicine, Charles University	Prague

Sponsors (1)

Lead Sponsor	Collaborator
Charles University, Czech Republic

Country where clinical trial is conducted

Czechia, 

References & Publications (5)

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. — View Citation

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. Review. — View Citation

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. — View Citation

Medina-Gomez G, Gray SL, Yetukuri L, Shimomura K, Virtue S, Campbell M, Curtis RK, Jimenez-Linan M, Blount M, Yeo GS, Lopez M, Seppänen-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. — View Citation

Rossmeislová L, Malisová L, Kracmerová J, Tencerová M, Kovácová Z, Koc M, Siklová-Vítková 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adipogenic capacity of preadipocytes	proliferation assays, messenger ribonucleic acid (mRNA) gene expression	3 months from the establishment of the cell culture
Secondary	Insulin sensitivity	Glucose disposal measured by hyperinsulinemic-euglycemic clamp	3 hours investigation of the subject at the start of the study
Secondary	Glucose tolerance	Oral glucose tolerance test (OGTT)	2 hours investigation of the subject at the start of the study
Secondary	Lipid metabolism	Lipolysis, lipogenesis in cell cultures of adipocytes derived from the subjects	3 months from the establishment of the cell culture