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

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

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.

MeSH terms

  • 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

Substances

  • Metformin
  • Hypoglycemic Agents
  • Blood Glucose