Weight loss therapy improves pancreatic endocrine function in obese older adults.
OBJECTIVE
Obesity and aging increase the risk of type 2 diabetes (T2D). We evaluated whether weight loss therapy improves pancreatic endocrine function and insulin sensitivity in obese older adults.


METHODS
Twenty-four obese (BMI: 38 +/- 2 kg/m(2)) older (age: 70 +/- 2 years) adults completed a 6-month randomized, controlled trial. Participants were randomized to diet and exercise (treatment group) or no therapy (control group). beta-Cell function (assessed using the C-peptide minimal model), alpha-cell function (assessed by the glucagon response to an oral glucose load), insulin sensitivity (assessed using the glucose minimal model), and insulin clearance rate were evaluated using a 5-h modified oral glucose tolerance test.


RESULTS
Body weight decreased in the treatment group, but did not change in the control group (-9 +/- 1% vs. 0 +/- 1%; P < 0.001). Insulin sensitivity doubled in the treatment group and did not change in the control group (116 +/- 49% vs. -11 +/- 13%; P < 0.05). Even though indices of beta-cell responsivity to glucose did not change (P > 0.05), the disposition index (DI), which adjusts beta-cell insulin response to changes in insulin sensitivity, improved in the treatment group compared with the control group (100 +/- 47% vs. -22 +/- 9%; P < 0.05). The glucagon response decreased in the treatment but not in the control group (-5 +/- 2% vs. 4 +/- 4%; P < 0.05). Insulin secretion rate did not change (P > 0.05), but insulin clearance rate increased (51 +/- 25%; P < 0.05), resulting in lower plasma insulin concentrations.


CONCLUSIONS
Weight loss therapy concomitantly improves beta-cell function, lowers plasma glucagon concentrations, and improves insulin action in obese older adults. These metabolic effects are likely to reduce the risk of developing T2D in this population.
Villareal
Dennis T
DT
Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. dvillare@wustl.edu
Banks
Marian R
MR
Patterson
Bruce W
BW
Polonsky
Kenneth S
KS
Klein
Samuel
S
D000368:Aged; D000375:Aging / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D004038:Diet, Reducing; D015444:Exercise / Q000502:physiology*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology; D007515:Islets of Langerhans / Q000503:physiopathology*; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D012307:Risk Factors; D015431:Weight Loss / Q000502:physiology*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005934:Glucagon