SAT-032 - Superior Insulin Sensitivity Despite Long Disease Duration and Aging Exacerbates Dysglycemia in Elderly Acromegaly: A Role for Lower IGF-1?

Objective:  Acromegaly with excess of growth hormone (GH) is strongly associated with dysglycemia. This study aimed to compare key metabolic parameters, insulin sensitivity indices and pancreatic beta-cell function, between elderly and non-elderly patients with acromegaly.

Methods:  In this retrospective, case-control study, 86 patients with confirmed acromegaly were enrolled and divided into two age-matched groups: the Elderly group (age ≥65 years, n=43) and the Non-Elderly group (age < 65 years, n=43). Data on demographics, disease duration, anthropometrics (BMI), blood pressure, tumor size, and biochemical parameters (GH, IGF-1, HbA1c) were collected. Comprehensive assessment of glucose metabolism was performed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Beta-cell function (HOMA-B), the triglyceride-glucose (TyG) index derived from oral glucose tolerance tests. The study protocol was approved by the Institutional Biomedical Research Ethics Committee of West China Hospital and written informed consent was obtained from all participants.Continuous variables were presented as median (interquartile range) and compared using the Mann-Whitney U test. Categorical variables were compared using the Chi-square test.

Results:  The two groups were matched for sex distribution and BMI. As expected, the Elderly group had a longer disease duration [10.00 (5.00, 19.50) vs. 5.00 (2.25, 8.00) years, p=0.018]. Despite comparable GH levels (p=0.187), circulating IGF-1 was significantly lower in the Elderly group [283.88 (145.23, 510.50) vs. 433.28 (257.60, 600.00) ng/mL, p=0.044]. Notably, profound differences were observed in metabolic indices. The Elderly group exhibited markedly better preserved beta-cell function (HOMA-B: 69.00 vs. 135.15, p< 0.001) and superior whole-body insulin sensitivity, as indicated by a lower HOMA-IR (2.11 vs. 3.42, p=0.023) and a significantly higher Matsuda index (87.93 vs. 51.78, p=0.003). No significant differences were found in HbA1c, TyG index, or tumor diameter between the groups.

Conclusion:  Elderly acromegaly present with a distinct metabolic phenotype. Contrary to the typical age-related decline in metabolic health, our data reveal that elderly acromegalic patients have significantly better insulin sensitivity and relatively lower HOMA-B, suggesting less compensatory hyperinsulinemia. This may occur in the context of lower IGF-1 bioactivity despite similar GH levels. These findings highlight a complex interaction between somatotropinoma activity and aging on glucose homeostasis. Understanding this phenotype is crucial for tailoring management strategies, as elderly patients might have a different risk profile for metabolic sequelae. Further research is needed to explore the underlying mechanisms, including GH/IGF-1 axis dynamics and tissue-specific insulin signaling in aging acromegaly.

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