Return of First-phase Insulin Secretion in Type 2 Diabetes is Associated With Depletion of Pancreas Lipid

Clinical Trial ID: NCT03430310

Description

The hypothesis for this study is that pancreas lipid will be more closely associated with first-phase beta-cell response in African-Americans than in European-Americans, both at baseline and in response to treatment. The investigators will determine whether race influences the association of pancreas lipid with beta-cell function.The proposed research builds upon the investigators preliminary observations in non-diabetic adults that reduction in dietary glycemic load, in the absence of weight loss, selectively reduces visceral adipose tissue and ectopic lipid, and is associated with improvements in insulin sensitivity and beta-cell function. No study has attempted to test the hypothesis that selective reduction in pancreatic lipid with a simple change in diet composition, in the absence of energy restriction, will lead to the recovery of beta-cell function in patients with early Type 2 Diabetes (T2D). The investigators hypothesize that participants following a Low Glycemic Diet will show a greater decrease in pancreas lipid. Specifically, the investigators will be the first to demonstrate that a weight-maintaining low-glycemic diet improves glucose tolerance by increasing first-phase insulin secretion. Results may be particularly relevant to African-Americans who are at greater risk for T2D.

The decline in first-phase insulin secretion is a key event in the etiology of type 2 diabetes (T2D). Although the cause of beta-cell failure is not clear, "lipotoxicity" has been proposed. Bariatric surgery and very-low calorie diets in patients with T2D induce disease remission, characterized by a return of first-phase insulin secretion and a depletion of pancreas lipid. However, these are extreme approaches to treating T2D, and non-invasive, sustainable, yet equally effective, treatments are needed. The investigators have shown in individuals at risk for T2D that an intervention with a weight-maintaining low-glycemic (LG) diet selectively depletes visceral adipose tissue and ectopic lipid in muscle while preserving thigh subcutaneous adipose and lean body mass. This observation suggests that such diets are able to "remodel" body composition by re-partitioning energy away from metabolically harmful lipid stores. Participants on the LG diet also demonstrated improved insulin sensitivity and a dramatic (9-fold) increase in first-phase insulin secretion. Thus, the investigators hypothesize that a weight-maintaining LG diet will selectively deplete ectopic adipose tissue, including pancreatic lipid, and will permit recovery of beta-cell function in individuals with T2D. Rescue of beta-cell function may be particularly important in African-Americans (AA), who as a group demonstrate a high prevalence of T2D, for reasons that cannot be explained by lifestyle. AA are likely to be vulnerable to beta-cell failure due to inherently high beta-cell responsiveness (demonstrable in healthy young children). Further, it has been shown that pancreas lipid is a determinant of prediabetes specifically in AA. Thus, the investigators hypothesize that an LG diet will be particularly beneficial to beta-cell function and glycemic control among AA.


Criteria

Inclusion Criteria: - Diagnosed with Type 2 Diabetes within the past 5 years - Treated with diet, Metformin, or dipeptidyl peptidase 4 (DPP-IV) inhibitors - Adult men and women age 35-65 yr - Have a Hemoglobin A1c <7.0 - African American or European American race - Will be overweight (BMI 25-45 kg/m2) but have a stable BMI (<5 kg change in the past 6 months) Exclusion Criteria: - Use of glucocorticoids - Estimated glomerular filtration rate <60 - Alanine aminotransferase >2.5-fold above the normal upper limit - Tobacco or recreational drug use - Unable to undergo MRI

  • Start Date

    2018-10-09

  • Last Updated

    2019-11-11

  • Sponsor

    University of Alabama at Birmingham

  • Condition Name

    Type 2 Diabetes Mellitus

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