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

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.

Frail hypertensive older adults with prediabetes and chronic kidney disease: insights on organ damage and cognitive performance - preliminary results from the CARYATID study.

BACKGROUND: Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR). METHODS: We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min. RESULTS: 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable. CONCLUSIONS: Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.

Insulin resistance drives cognitive impairment in hypertensive pre-diabetic frail elders: the CENTENNIAL study.

AIMS: Pre-diabetes is a condition that confers an increased cardiovascular risk. Frailty is very common in hypertensive patients, and insulin resistance has been linked to frailty in older adults with diabetes. On these grounds, our aim was to evaluate the association between insulin resistance and cognitive impairment in hypertensive and pre-diabetic and frail older adults. METHODS AND RESULTS: We studied consecutive pre-diabetic and hypertensive elders with frailty presenting at the Avellino local health authority of the Italian Ministry of Health (ASL AV) from March 2021 to March 2022. All of them fulfilled the following inclusion criteria: a previous diagnosis of hypertension with no clinical or laboratory evidence of secondary causes, a confirmed diagnosis of pre-diabetes, age >65 years, Montreal Cognitive Assessment (MoCA) Score <26, and frailty. We enrolled 178 frail patients, of which 141 successfully completed the study. We observed a strong inverse correlation (r = -0.807; P < 0.001) between MoCA Score and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The results were confirmed by a linear regression analysis using MoCA Score as dependent variable, after adjusting for several potential confounders. CONCLUSION: Taken together, our data highlight for the first time the association between insulin resistance and global cognitive function in frail elders with hypertension and pre-diabetes.

In this study, we demonstrate that insulin resistance correlates with cognitive impairment in a population of frail hypertensive older adults with pre-diabetes. • We successfully studied 141 patients with hypertension, pre-diabetes, and frailty. • We observed a correlation between two parameters used to assess cognitive decline and insulin resistance.