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. 2024 Jul;81(7):1637-1643.
doi: 10.1161/HYPERTENSIONAHA.124.23087. Epub 2024 May 16.

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

Gaetano Santulli  1   2   3   4 , Valeria Visco  5 , Fahimeh Varzideh  1 , Germano Guerra  3   6 , Urna Kansakar  2 , Maurizio Gasperi  6 , Anna Marro  7 , Scott Wilson  1 , Mario Nicola Vittorio Ferrante  7 , Antonella Pansini  7 , Armando Pirone  7 , Francesco Di Lorenzo  1 , Domenico Tartaglia  7 , Guido Iaccarino  8 , Gaetano Macina  7 , Esther Densu Agyapong  1 , Imma Forzano  4 , Stanislovas S Jankauskas  1 , Klara Komici  6 , Michele Ciccarelli  5 , Pasquale Mone  1   6   7   9
Affiliations

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

Gaetano Santulli et al. Hypertension. 2024 Jul.

Erratum in

Abstract

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.

Keywords: aging; cognitive dysfunction; diabetes; frailty; hyperglycemia; metformin; prediabetic state.

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Conflict of interest statement

Disclosures None.

Figures

Figure 1:
Figure 1:
Study flow-chart.
Figure 2:
Figure 2:
Correlation between MoCA Score and TyG index (Panel A; r: 0.880). Correlation between 5-meter gait speed (5mGS) and TyG index (Panel B; r: 0.809).
Figure 3:
Figure 3:
Kaplan-Meier curves showing that prediabetes significantly increases the risk of frailty at one-year follow-up (p<0.0001).
Figure 4:
Figure 4:
Metformin treatment reduces frailty levels after 6 months (p<0.0001).
See this image and copyright information in PMC

References

    1. Santulli G, Visco V, Ciccarelli M, Ferrante MNV, De Masi P, Pansini A, Virtuoso N, Pirone A, Guerra G, Verri V, Macina G, Taurino A, Komici K and Mone P. Frail hypertensive older adults with prediabetes and chronic kidney disease: insights on organ damage and cognitive performance - preliminary results from the CARYATID study. Cardiovasc Diabetol. 2024;23:125. - PMC - PubMed
    1. Rizzo M, Pansini A, Colucci M, Boccalone E and Mone P. Frailty in nursing home residents. Eur J Intern Med. 2023;115:152–153. - PubMed
    1. Ijaz N, Buta B, Xue QL, Mohess DT, Bushan A, Tran H, Batchelor W, deFilippi CR, Walston JD, Bandeen-Roche K, Forman DE, Resar JR, O’Connor CM, Gerstenblith G and Damluji AA. Interventions for Frailty Among Older Adults With Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022;79:482–503. - PMC - PubMed
    1. Rooney MR, Rawlings AM, Pankow JS, Echouffo Tcheugui JB, Coresh J, Sharrett AR and Selvin E. Risk of Progression to Diabetes Among Older Adults With Prediabetes. JAMA Intern Med. 2021;181:511–519. - PMC - PubMed
    1. Mone P, Pansini A, Calabro F, De Gennaro S, Esposito M, Rinaldi P, Colin A, Minicucci F, Coppola A, Frullone S and Santulli G. Global cognitive function correlates with P-wave dispersion in frail hypertensive older adults. J Clin Hypertens (Greenwich). 2022;24:638–643. - PMC - PubMed