Improving Beta Cell Function in Mexican American Women With Prediabetes

Pre-Diabetes Clinical Trial

Official title:

Improving Beta Cell Function in Mexican American Women With Prediabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02488057
• Other study ID #: 2014H0478
• Status: Completed
• Phase: Phase 4
• Start date: May 2016
• Est. completion date: March 2019

Study information

• Verified date: August 2019
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will examine the benefits of weight loss alone or in combination with a GLP1 receptor agonist, liraglutide, on beta cell function in young adult Mexican American (MA) women with prediabetes. The Investigators have chosen to focus on MA women because MA women are at very high risk for progression to diabetes and have not traditionally been involved in weight management studies since they are thought to be difficult to recruit and retain in such programs. However, investigators have had particular success in working with young MA women using specifically developed ethnic and gender conscious programs. Because weight loss does not prevent all progression to diabetes, some participants will receive the diabetes medication, liraglutide, which has been shown to stabilize beta cell function. The study will also interrogate for polymorphisms of known T2DM genes to correlate with beta cell response to weight loss and liraglutide treatment. Additionally, this investigation targets serious health disparities in metabolic disease in a highly vulnerable, rapidly growing population, testing novel gender and culturally focused intervention strategies and identifying genetic biomarkers of response to a pharmacologic intervention that targets the pancreatic ßcell.

These results will help to a) understand mechanisms of disease, b) personalize treatment through identification of a high risk group that may be amenable to specific therapy, and c) ultimately, sets the stage for an intervention trial to prevent diabetes, a major chronic and costly disease, in Mexican Americans.

Description:

Investigators will test the hypothesis that liraglutide, because of its actions on the β-cell, will amplify the effects of lifestyle management to improve β-cell function. Investigators will recruit MA ages 18-40, since above this age the incidence of T2DM in obese MA women in our experience approaches 50%. The primary endpoint will be β-cell function (AIRg) in response to lifestyle change with and without GLP-1 agonist at 3 months. Secondary endpoints will be reversal of metabolic syndrome and changes in plasma biomarkers. By the end of 3 months, the prediabetic subject will be in the best possible metabolic control, and investigators would predict that the liraglutide group would reveal better β-cell function. Thus, data from this time point will be used for pharmacogenetic studies. The program will be continued for 3 more months for transition to regular healthy meals with the goal of weight maintenance. During this second 3 months, subjects will be off liraglutide to determine the sustainability of the improved β-cell function. In the absence of weight re-gain, investigators predict that the intensive weight loss alone group would maintain improved β-cell function, but the intensive weight loss+liraglutide group would display even better function. These results will provide useful information about improving β-cell function in the management of young women with pre-diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Mexican-american

• Female

• BMI 30-42

• willingness to complete protocol

• pre-diabetic

• English or Spanish literate

Exclusion Criteria:

• pregnant

• 30 min or more of moderate to vigorous activity more than 3 times per week

• cardiovascular disease

• physical limitations that might be aggravated by moderate physical activity

• planning to move in next 12-24 months

• diabetic

Related Conditions & MeSH terms

• Pre-Diabetes
• Prediabetic State

Intervention

Drug:
• Liraglutide
Active comparator. See arm descriptions.

Behavioral:
• Weight loss
Active comparator. See arm descriptions.

Locations

Country	Name	City	State
United States	Denver Harbor Multi-service Center	Houston	Texas
United States	Magnolia Multiservice Center	Houston	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	L.A. Biomedical Research Institute	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University

Country where clinical trial is conducted

United States, 

References & Publications (10)

Bergman RN, Ader M, Huecking K, Van Citters G. Accurate assessment of beta-cell function: the hyperbolic correction. Diabetes. 2002 Feb;51 Suppl 1:S212-20. Review. — View Citation

Degn KB, Juhl CB, Sturis J, Jakobsen G, Brock B, Chandramouli V, Rungby J, Landau BR, Schmitz O. One week's treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes. 2004 May;53(5):1187-94. — View Citation

Goodarzi MO, Taylor KD, Scheuner MT, Antoine HJ, Guo X, Shah PK, Rotter JI. Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts. Pharmacogenomics J. 2007 Feb;7(1):66-73. Epub 2006 Jun 6. — View Citation

Hsueh WA, Orloski L, Wyne K. Prediabetes: the importance of early identification and intervention. Postgrad Med. 2010 Jul;122(4):129-43. doi: 10.3810/pgm.2010.07.2180. Review. — View Citation

Krauss RM, Mangravite LM, Smith JD, Medina MW, Wang D, Guo X, Rieder MJ, Simon JA, Hulley SB, Waters D, Saad M, Williams PT, Taylor KD, Yang H, Nickerson DA, Rotter JI. Variation in the 3-hydroxyl-3-methylglutaryl coenzyme a reductase gene is associated with racial differences in low-density lipoprotein cholesterol response to simvastatin treatment. Circulation. 2008 Mar 25;117(12):1537-44. doi: 10.1161/CIRCULATIONAHA.107.708388. Epub 2008 Mar 10. — View Citation

Look AHEAD Research Group, Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010 Sep 27;170(17):1566-75. doi: 10.1001/archinternmed.2010.334. — View Citation

Mangravite LM, Medina MW, Cui J, Pressman S, Smith JD, Rieder MJ, Guo X, Nickerson DA, Rotter JI, Krauss RM. Combined influence of LDLR and HMGCR sequence variation on lipid-lowering response to simvastatin. Arterioscler Thromb Vasc Biol. 2010 Jul;30(7):1485-92. doi: 10.1161/ATVBAHA.110.203273. Epub 2010 Apr 22. — View Citation

Mari A, Degn K, Brock B, Rungby J, Ferrannini E, Schmitz O. Effects of the long-acting human glucagon-like peptide-1 analog liraglutide on beta-cell function in normal living conditions. Diabetes Care. 2007 Aug;30(8):2032-3. Epub 2007 Apr 27. — View Citation

Matveyenko AV, Butler PC. Relationship between beta-cell mass and diabetes onset. Diabetes Obes Metab. 2008 Nov;10 Suppl 4:23-31. doi: 10.1111/j.1463-1326.2008.00939.x. — View Citation

Villareal DT, Banks MR, Patterson BW, Polonsky KS, Klein S. Weight loss therapy improves pancreatic endocrine function in obese older adults. Obesity (Silver Spring). 2008 Jun;16(6):1349-54. doi: 10.1038/oby.2008.226. Epub 2008 Apr 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Beta Cell Function	disposition index: x10^-5min-1	3 months
Secondary	Waist Circumference	inches	3 months
Secondary	Fasting Glucose	mg/dL	3 months
Secondary	Triglycerides	mg/dL	3 months
Secondary	HDL cholesterol	mg/dL	3 months
Secondary	Blood Pressure	mmHg	3 months
Secondary	Heart Sensitive C-reactive protein	hsCRP, mg/L	3 months
Secondary	Presence of genetic polymorphisms	yes or no	3 months