Impaired incretin secretion and pancreatic dysfunction with older age and diabetes.
OBJECTIVE
To estimate the impact of aging and diabetes on insulin sensitivity, beta-cell function, adipocytokines, and incretin production.


METHODS
Hyperglycemic clamps, arginine tests and meal tolerance tests were performed in 50 non-obese subjects to measure insulin sensitivity (IS) and insulin secretion as well as plasma levels of glucagon, GLP-1 and GIP. Patients with diabetes and healthy control subjects were divided into the following groups: middle-aged type 2 diabetes (MA-DM), aged Type 2 diabetes (A-DM) and middle-aged or aged subjects with normal glucose tolerance (MA-NGT or A-NGT).


RESULTS
IS, as determined by the homeostasis model assessment, glucose infusion rate, and oral glucose insulin sensitivity, was reduced in the aged and DM groups compared with MA-NGT, but it was similar in the MA-DM and A-DM groups. Insulinogenic index, first and second phase insulin secretion and the disposition indices, but not insulin response to arginine, were reduced in the aged and DM groups. Postprandial glucagon production was higher in MA-DM compared to MA-NGT. Whereas the GLP-1 production was reduced in A-DM, no differences between groups were observed in GIP production.


CONCLUSIONS
In non-obese subjects, diabetes and aging impair insulin sensitivity. Insulin production is reduced by aging, and diabetes exacerbates this condition. Aging associated defects superimposed diabetic physiopathology, particularly regarding GLP-1 production. On the other hand, the glucose-independent secretion of insulin was preserved. Knowledge of the complex relationship between aging and diabetes could support the development of physiopathological and pharmacological based therapies.
University of Campinas (UNICAMP), Laboratory of Investigation on Metabolism and Diabetes (LIMED), GASTROCENTRO, Campinas, Sao Paulo, Brazil; National Institute of Science and Technology on Obesity and Diabetes, Brazil. Electronic address: bgeloneze@terra.com.br.
Bruno
B
Geloneze
University of Campinas (UNICAMP), Laboratory of Investigation on Metabolism and Diabetes (LIMED), GASTROCENTRO, Campinas, Sao Paulo, Brazil.
Maria da Saude
Mda S
de Oliveira
University of Campinas (UNICAMP), Laboratory of Investigation on Metabolism and Diabetes (LIMED), GASTROCENTRO, Campinas, Sao Paulo, Brazil; School of Applied Sciences, University of Campinas (UNICAMP).
Ana Carolina Junqueira
AC
Vasques
University of Campinas (UNICAMP), Laboratory of Investigation on Metabolism and Diabetes (LIMED), GASTROCENTRO, Campinas, Sao Paulo, Brazil.
Fernanda Satake
FS
Novaes
University of Campinas (UNICAMP), Laboratory of Investigation on Metabolism and Diabetes (LIMED), GASTROCENTRO, Campinas, Sao Paulo, Brazil; National Institute of Science and Technology on Obesity and Diabetes, Brazil.
José Carlos
JC
Pareja
National Institute of Science and Technology on Obesity and Diabetes, Brazil; University of Campinas (UNICAMP), Department of Endocrinology, Campinas, SP, Brazil.
Marcos Antonio
MA
Tambascia
D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D015536:Down-Regulation; D005749:Gastric Inhibitory Polypeptide / Q000097:blood / Q000378:metabolism; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D006801:Humans; D054795:Incretins / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000503:physiopathology*; D019518:Postprandial Period; D015854:Up-Regulation
C499918:ADIPOQ protein, human; D052242:Adiponectin; D054795:Incretins; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
Beta-cell function; GLP-1; Glucagon; Incretin; Insulin sensitivity