Return of First-phase Insulin Secretion in Type 2 Diabetes is Associated With Depletion of Pancreas Lipid
| Status: | Recruiting |
|---|---|
| Conditions: | Diabetes, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 35 - 65 |
| Updated: | 11/1/2018 |
| Start Date: | October 9, 2018 |
| End Date: | June 2023 |
| Contact: | Laura Lee Goree, MS, RD, LD |
| Email: | LLG@uab.edu |
| Phone: | 205-934-4386 |
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.
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.
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.
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
We found this trial at
1
site
1720 2nd Ave S
Birmingham, Alabama 35233
Birmingham, Alabama 35233
(205) 934-4011
Principal Investigator: Barbara Gower, PhD
Phone: 205-934-4386
University of Alabama at Birmingham The University of Alabama at Birmingham (UAB) traces its roots...
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