Prediabetes Increases the Risk of Frailty in Prefrail Older Adults With Hypertension: Beneficial Effects of Metformin

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 81; no. 7; pp. 1637 - 1643
• Main Authors: Santulli, Gaetano, Visco, Valeria, Varzideh, Fahimeh, Guerra, Germano, Kansakar, Urna, Gasperi, Maurizio, Marro, Anna, Wilson, Scott, Ferrante, Mario Nicola Vittorio, Pansini, Antonella, Pirone, Armando, Di Lorenzo, Francesco, Tartaglia, Domenico, Iaccarino, Guido, Macina, Gaetano, Agyapong, Esther Densu, Forzano, Imma, Jankauskas, Stanislovas S., Komici, Klara, Ciccarelli, Michele, Mone, Pasquale
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.07.2024
• Subjects: Aged; Aged, 80 and over; Blood Glucose - drug effects; Blood Glucose - metabolism; Cognitive Dysfunction - epidemiology; Cognitive Dysfunction - etiology; Cognitive Dysfunction - prevention & control; Female; Frail Elderly; Frailty - epidemiology; Humans; Hypertension - drug therapy; Hypertension - epidemiology; Hypoglycemic Agents - therapeutic use; Insulin Resistance; Male; Metformin - therapeutic use; Prediabetic State - drug therapy; frailty; hyperglycemia; metformin; prediabetic state; aging; cognitive dysfunction; diabetes
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.124.23087

BACKGROUND: Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and frailty among older individuals. METHODS: We screened elders with prefrail hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months. RESULTS: We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r, 0.880; P<0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r, 0.809; P<0.0001). Prediabetes was found to significantly (P<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (P<0.0001). CONCLUSIONS: Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.