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Effect of age and frailty on ghrelin and cholecystokinin responses to a meal test^1,2,3

¹ From Unidad de Investigación, Consorci Sanitari del Maresme and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain (MS-P); Unidad de Investigación, Consorci Sanitari del Maresme, Barcelona, Spain (EP); Unidad Pruebas Funcionales Digestivas, Hospital de Mataró and CIBEREHD, Barcelona, Spain (PC); and Servicio Endocrinología, Hospital Clínic, Universidad de Barcelona, Barcelona, Spain (MP-D).

² Supported by a grant (FIS exp. PI 051120) from the Spanish Ministry of Health. CIBEREHD is funded by the Instituto de Salud Carlos III.

³ Reprints not available. Address correspondence to M Serra-Prat, Unitat de Recerca, Hospital de Mataró, Caretera de Cirera s/n 08304 Mataró, Barcelona, Spain. E-mail: mserra{at}csdm.cat.

Background: Ghrelin and cholecystokinin (CCK) are among the peripheral signals that regulate hunger and satiety.

Objective: The objective was to assess whether ghrelin and CCK responses to a standard nutritional load are related to age and frailty.

Design: Ghrelin, CCK, insulin, glucose, and 4-h visual analog hunger scale curves after a standard nutritional load test (380 kcal) were described and compared between 3 groups: old (>75 y) and frail persons (group A), old (>75 y) but nonfrail persons (group B), and young (25–65 y) adults (group C).

Results: Frail persons showed no postprandial ghrelin suppression, and old subjects, frail and nonfrail, showed no significant postprandial ghrelin recovery compared with young adults. Frailty was also associated with lower fasting ghrelin concentrations. No differences in fasting CCK were observed between young and old persons; however, postprandial CCK concentrations were enhanced in young persons, whereas no frailty effect on the CCK curve was observed in the old subjects. No correlations between mean ghrelin and hunger values over time were found, but strong negative correlations were shown between CCK and hunger (group A: r_s = –0.88, P = 0.009; group B: r_s = –0.86, P = 0.014; group C: r_s = –0.71, P = 0.071) and insulin and hunger (group A: r_s = –0.901, P = 0.006; group B: r_s = –0.964, P < 0.001; group C: r_s = –0.929, P = 0.003).

Conclusions: Advanced age determines a poorer ghrelin postprandial recuperation phase, a reduced CCK postprandial response, and an exaggerated postprandial insulin release. A loss of ghrelin prandial rhythm is present in old frail persons. The impaired response of these hunger regulatory hormones with age might contribute to the mechanisms of anorexia associated with aging.