Regulation of Tissue Lipolysis by Insulin in Type 2 Diabetes

NCT01680133 | Completed

• 2 other identifiers: 07-3-03791611074
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Inadequate suppression of intramuscular and adipose tissue lipolysis, and consequent excessive delivery of fatty acids to ectopic tissues (e.g. muscle, pancreas and liver) could play an important role in the development and exacerbating of insulin resistance. Therefore, the investigators propose to study the regulation of adipose tissue and skeletal muscle lipolysis, as well as further characterize the intracellular lipolytic pathways within these tissues, in obese normoglycaemic versus long-term diagnosed type 2 diabetic subjects.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Change from baseline in insulin sensitivity of adipose tissue and skeletal muscle lipolysis

  Changes from baseline in glycerol (lactate, pyruvate and glucose) in tissue microdialysate during a 3 step euglycemic hyperinsulinemic clamp (8, 20 and 40mU of insulin), every step for 2h

  8, 20 and 40 mU insulin (2 hours)

Secondary Outcomes (2)

• Baseline adipose tissue and skeletal muscle gene expression

  baseline

• Baseline skeletal muscle lipid accumulation

  Baseline

Study Arms (2)

NGT

Normal glycaemic healthy control men, age between 45-65, BMI 25-35 kg/m2

Other: Hyperinsulinemic euglycemic clamp

T2D

Type 2 diabetic men, age 45-65 yrs, BMI 25-35, diagnosed \>5yrs and Hba1c 7-9%

Other: Hyperinsulinemic euglycemic clamp

Interventions

Hyperinsulinemic euglycemic clamp OTHER

NGT; T2D

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Healthy normoglycemic men and type 2 diabetic men

You may qualify if:

• Caucasian
• Normal blood pressure (SBP 100-140 mmHg, DBP 60-90 mmHg)
• weight stable in last 3 months

You may not qualify if:

• Smokers
• people with intensive fitness training (e.g. athletes \> 3 times/week)
• History of cardiovascular diseases
• Bleeding disorders
• Use of medication interfering with the study endpoints/hypotheses (e.g. beta-blockers)
• Not to be able to understand the study information
• Subjects on a special diet or vegetarian
• Blood donation 2 months prior to the study and during the study
• Participating in an other study

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Netherlands Organisation for Scientific Research: collaborator
• European Foundation for the Study of Diabetes: collaborator

Study Sites (1)

Department of Human Biology, Maastricht University Medical Centre

Maastricht, 6200MD, Netherlands

Location

Related Publications (5)

• Jocken JW, Moro C, Goossens GH, Hansen D, Mairal A, Hesselink MK, Langin D, van Loon LJ, Blaak EE. Skeletal muscle lipase content and activity in obesity and type 2 diabetes. J Clin Endocrinol Metab. 2010 Dec;95(12):5449-53. doi: 10.1210/jc.2010-0776. Epub 2010 Sep 15.

  PMID: 20843949 BACKGROUND

• Jocken JW, Roepstorff C, Goossens GH, van der Baan P, van Baak M, Saris WH, Kiens B, Blaak EE. Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation. Diabetes. 2008 Jul;57(7):1834-41. doi: 10.2337/db07-0857. Epub 2008 Apr 8.

  PMID: 18398140 BACKGROUND

• Jocken JW, Goossens GH, van Hees AM, Frayn KN, van Baak M, Stegen J, Pakbiers MT, Saris WH, Blaak EE. Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous adipose tissue lipolysis in lean and obese men. Diabetologia. 2008 Feb;51(2):320-7. doi: 10.1007/s00125-007-0866-y. Epub 2007 Dec 5.

  PMID: 18060661 BACKGROUND

• Boon H, Blaak EE, Saris WH, Keizer HA, Wagenmakers AJ, van Loon LJ. Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery. Diabetologia. 2007 Jan;50(1):103-12. doi: 10.1007/s00125-006-0482-2. Epub 2006 Nov 28.

  PMID: 17131144 BACKGROUND

• Jocken JW, Goossens GH, Boon H, Mason RR, Essers Y, Havekes B, Watt MJ, van Loon LJ, Blaak EE. Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance. Diabetologia. 2013 Oct;56(10):2255-65. doi: 10.1007/s00125-013-2995-9. Epub 2013 Aug 2.

  PMID: 23907381 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

adipose tissue and skeletal muscle biopsies

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Ellen Blaak, PhD

  Maastricht University Medical centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2012
• First Posted: September 7, 2012
• Study Start: June 1, 2007
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: October 12, 2012

Record last verified: 2012-10

Locations

NL (1)