Vitamin D, IGF-I levels predict frailty status in older men

ORLANDO, Fla. — In older men, higher levels of certain anabolic hormones may predict a lower risk for worsening frailty, according to study findings presented here.

“In recent years, frailty has been recognized as one of the most important health care issues in the aging population,” Agnieszka Swiecicka, MD, a clinical research fellow at the University of Manchester in Manchester, U.K., said during a press conference discussing the findings at ENDO 2017. “Much research has focused on investigating its etiology and natural history to help identify individuals at risk and facilitate the development of new prevention and treatment strategies.”

Agnieszka Swiecicka

The pathophysiology of frailty is not well understood, Swiecicka said. Decline in muscle mass and function is thought to be central to the development of frailty, she said, and anabolic hormones are considered one of the key factors responsible for muscle growth and repair. “Therefore, age-related decline in levels of anabolic hormones and [their] regulation within the endocrine system have been suggested as potential etiological factors for frailty,” Swiecicka said. “The evidence, however, is limited, and prospective data is largely lacking.”

In a prospective, observational study, Swiecicka and colleagues analyzed data from 3,369 men aged 40 to 79 years without adrenal or pituitary diseases from eight European centers, followed for a mean of 4.3 years beginning between 2003 and 2005. Participants provided blood samples to measure insulin-like growth factor I, IGF-I binding protein 3 (IGFBP3), DHEAs, 25-hydroxyvitamin D and parathyroid hormone (standardized as z scores) at baseline and again at 4 years. Researchers used both frailty phenotype (n = 2,114) and frailty index (n = 2,458) to determine frailty status in the cohort at baseline and at the 4-year follow-up, and they used logistic regression analysis to assess relationships between baseline hormone levels and any change in frailty. Researchers also used negative binomial regression to assess relationships between hormonal predictors and follow-up frailty index.

Within the cohort, 459 men experienced a deterioration in frailty status; frailty status did not change for 1,443 men. Compared with men whose frailty status did not change, those whose frailty status worsened were older (mean age, 61 years vs. 57 years; P < .001), had a lower BMI (mean BMI, 27 kg/m² vs. 28 kg/m²; P = .035) and were more likely to have diabetes (8% vs. 5%; P = .001).

Researchers found that risk for worsening frailty phenotype decreased with each SD increase in IGF-I (OR = 0.82; 95% CI, 0.73-0.93), as well as IGFBP3 (OR = 0.84; 95% CI, 0.74-0.94), and 25-(OH)D (OR = 0.86; 95% CI, 0.76-0.97) after adjustment for age and baseline frailty status. Similar risk reduction was found for frailty index with each SD increase in IGF-I (beta = –0.04; 95% CI, –0.06 to –0.02), IGFBP3 (beta = –0.04; 95% CI, –0.06 to –0.01) and 25-(OH)D (beta = –0.05; 95% CI, –0.07 to –0.02).

In a secondary analysis, researchers also observed that DHEA was associated with a lower risk for worsening frailty phenotype in men aged at least 70 years, Swiecicka said (OR = 0.57; 95% CI, 0.35-0.92). No baseline hormones predicted improvement or recovery from frailty.

“These findings enhance our understanding of the etiology of frailty and the relative role of the endocrine system,” Swiecicka said. “Clinical trials are required to find out if supplementing these hormones to middle age and older men could prevent frailty progression or development.” – by Regina Schaffer

Reference:

Swiecicka A, et al. SUN-425. Presented at: The Endocrine Society Annual Meeting; April 1-4, 2017; Orlando, Fla.

Disclosures: Swiecicka reports no relevant financial disclosures.