Frailty status and altered dynamics of circulating energy metabolism hormones after oral glucose in older women.
OBJECTIVE
Frailty status is associated with altered glucose-insulin dynamics. Here, we sought to investigate whether alteration in the dynamics of other circulating energy metabolism hormones after oral glucose is associated with frailty status.


METHODS
Substudy of older women in a prospective cohort.


METHODS
Baltimore, Maryland.


METHODS
Seventy-three community-dwelling women aged 84-95 years without a diagnosis of diabetes who were enrolled in the Women's Health and Aging Study II.


METHODS
We examined stimulus-response dynamics of free fatty acids (FFA), gut- (ghrelin,GLP-1) and adipocyte-derived hormones (leptin, adiponectin, resistin), growth hormone (GH), insulin-like growth factor 1 (IGF-1), and interleukin-6 (IL-6) at 0, 30, 60, 120, and 180-minutes after a 75-g glucose challenge according to frailty status (non-frail, pre-frail, or frail).


RESULTS
On average, frail women had higher fasting levels of glucose-raising hormones (FFA, resistin, GH, and IL-6) and lower fasting levels of glucose-lowering hormones (ghrelin, adiponectin, GLP-1 and IGF-1) versus non-frail women but these results were not statistically significant. Frail women also had higher fasting levels of leptin with relative adiposity compared to their counterparts, suggestive of leptin-resistance. Integrated area under the curve (AUC) values for each hormone followed similar trends by frailty status. After age and BMI adjustment, frail versus non-frail women were more likely to be in the lowest tertile of fasting ghrelin levels and 120-min ghrelin levels (both p<0.05) in logistic regression analyses. No large differences were found for other hormones in adjusted models.


CONCLUSIONS
Our findings suggest dysregulation of the orexigenic hormone ghrelin in the frailty syndrome. Further studies are needed to explore the role of ghrelin dysregulation in the clinical manifestation of frailty.
Division of Endocrinology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. rrastogi@jhmi.edu
R R
RR
Kalyani
R
R
Varadhan
C O
CO
Weiss
L P
LP
Fried
A R
AR
Cappola
D054392:Adipokines / Q000097:blood; D050154:Adiposity; D000369:Aged, 80 and over; D015142:Baltimore; D015992:Body Mass Index; D015331:Cohort Studies; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D016330:Frail Elderly; D015577:Geriatric Assessment; D054439:Ghrelin / Q000097:blood*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D015850:Interleukin-6 / Q000097:blood; D008137:Longitudinal Studies; D011446:Prospective Studies
D054392:Adipokines; D005230:Fatty Acids, Nonesterified; C515349:GHRL protein, human; D054439:Ghrelin; C508600:IL6 protein, human; D015850:Interleukin-6; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005947:Glucose