Abstract. Frailty is a state of vulnerability and a consequence of cumulative decline in multiple physiological systems over a lifespan. The occurrence of frailty depends on deterioration in muscle and nerve function, declining cardiopulmonary reserve and loss of executive function. Diabetes mellitus (DM) often causes functional impairment in each of the above systems, thus leading to a loss of whole body homeostasis and deterioration in physical function. Inability of self-management in DM patients may also have considerable impact on the development of sarcopenia/frailty. Thus, there may be positive feedback between the progression of diabetic complications and frailty/sarcopenia. While various factors are involved in this process, insulin resistance or insulin depletion may be an important factor in the progression of frailty in diabetes patients since insulin is well known to be an anabolic hormone in muscle. Interestingly, in our study targeting elderly DM patients, low HbA1c was a significant and independent risk factor for frailty, as assessed using a broad sense frailty scale, the Clinical Frailty Scale (CSF), suggesting that reverse metabolism due to malnutrition in elderly type 2 DM patients might be involved. Therefore, an intervention that includes proper nutrition and exercise training may be essential for the prevention of frailty. The pathogenesis of frailty in DM patients is extensively discussed in this review.

Aims/IntroductionPreviously, a study using a narrowly defined (physical base) frailty scale reported that both good and bad (U‐shaped curve) glycated hemoglobin (HbA1c) levels were frailty risk factors in patients with type 2 diabetes mellitus. However, no such studies in Japan have shown this. We aimed to evaluate the frailty risk factors including HbA1c in elderly Japanese patients with type 2 diabetes mellitus using a broadly defined (both physical and psychosocial base) frailty scale, the Clinical Frailty Scale (CFS).Materials and MethodsWe randomly enrolled 132 elderly patients with type 2 diabetes mellitus (aged ≥65 years) and categorized the patients into nine stages of frailty using CFS. Because no patient had CFS 9, patients with a CFS score of 1–4 and 5–8 were defined as non‐frail and frail, respectively. We attempted to identify the risk factors of frailty by investigating the association between CFS stage and various patient factors.ResultsMultiple regression analysis showed that an increase in age, low levels of albumin, high‐density lipoprotein cholesterol, systolic blood pressure, HbA1c, total cholesterol, and bodyweight were statistically significant and strong independent risk factors for frailty, suggesting that reverse metabolism owing to malnutrition in elderly type 2 diabetes mellitus patients might be involved.ConclusionsHbA1c level was not a U‐shaped risk for frailty, suggesting that relatively good glycemic control might be more important for frailty than poor control in elderly type 2 diabetes mellitus patients.

Context Elderly patients with type 2 diabetes mellitus (T2DM) have a high prevalence of frailty and/or sarcopenia. Sarcopenia is thought to be related to discordant secretions of the adrenal hormones cortisol and dehydroepiandrosterone (DHEA), as well as the sulfate ester of DHEA (DHEA-S). The current study sought to evaluate the risk factors for sarcopenia in elderly patients with T2DM. Design and Patients We enrolled 108 consecutive elderly patients aged ≥65 years with T2DM (mean age, 76.2 ± 7.3 years; 43.5% males). Sarcopenia was assessed and diagnosed based on the Asian version of the diagnostic criteria regarding muscular strength, physical function, and muscle mass. We assessed various physical parameters, blood tests, and atherosclerosis markers and statistically determined the risk factors for sarcopenia. Results Multiple regression analysis showed that the independent risk factors for sarcopenia were a serum cortisol/DHEA-S ratio ≥0.2, diastolic blood pressure <70 mm Hg, Hb concentration <13 g/dL, and an ankle brachial index <1.0. The strongest risk factor for sarcopenia was a serum cortisol/DHEA-S ratio ≥0.2. An increase in the serum cortisol/DHEA-S ratio reflected higher cortisol values and lower DHEA-S values in patients with sarcopenia compared with those in nonsarcopenic patients. The concentrations of cortisol and DHEA-S, as well as the cortisol/DHEA-S ratio, changed in accordance with the severity of sarcopenia. Conclusions A relative increase in cortisol may reflect the presence of stress and stimulate muscle catabolism, whereas a relative decrease in DHEA-S may cause a decrease in the anabolic action of DHEA on muscle; the combination of these factors may lead to sarcopenia.

Background: Frailty is broadly characterized by vulnerability and decline in physical, mental and social activities and is more common in elderly patients with type 2 diabetes mellitus (T2DM). Frailty is closely associated with nutrition, muscle strength, inflammation, and hormones etc. In hormones, dehydroepiandrosterone sulfate (DHEA-S) and cortisol are suggested to be such candidates affecting frailty. Little investigation has been performed using a wider range of measures of frailty to clarify risk factors for frailty including the above two hormones. Methods: We performed a cross-sectional study to investigate the risk factors for frailty in elderly T2DM patients (n = 148; ≥65 years), using a broad assessment, the clinical frailty scale. We compared parameters between the nonfrail and frail groups using the unpaired t and Mann-Whitney U tests. The Jonckheere-Therpstra test was used to identify relationships with the severity of frailty, and risk factors were identified using binary regression analysis. Results: Simple regression analysis identified a number of significant risk factors for frailty, including DHEAS < 70 μg/dL and cortisol/DHEA-S ratio ≥ 0.2. Multiple regression analysis showed that low albumin (< 4.0 g/dl) (odds ratio [OR] = 5.79, p < 0.001), low aspartate aminotransferase (AST) activity (< 25 IU/L) (OR = 4.34, p = 0.009), and low body mass (BM) (< 53 kg) (OR = 3.85, p = 0.012) were independent risk factors for frailty. A significant decrease in DHEA-S and a significant increase in the cortisol/DHEA-S ratio occurred alongside increases in the severity of frailty. DHEA-S concentration positively correlated with both serum albumin and BM. Conclusions: Hypoalbuminemia, low AST, and low BM are independent risk factors for frailty in elderly T2DM patients, strongly implying relative malnutrition in these frail patients. DHEA-S may be important for the maintenance of liver function and BM. A decrease in DHEA-S and an increase in the cortisol/DHEAS ratio may be involved in the mechanism of the effect of malnutrition in elderly T2DM patients.

Background: Frailty is broadly characterized by vulnerability and decline in physical, mental and social activities and is more common in elderly patients with type 2 diabetes mellitus (T2DM). Frailty is closely associated with nutrition, muscle strength, inflammation, and hormones etc. In hormones, dehydroepiandrosterone sulfate (DHEA-S) and cortisol are suggested to be such candidates affecting frailty. Little investigation has been performed using a wider range of measures of frailty to clarify risk factors for frailty including the above two hormones. Methods: We performed a cross-sectional study to investigate the risk factors for frailty in elderly T2DM patients (n=148; ≥65 years), using a broad assessment, the clinical frailty scale. We compared parameters between the non-frail and frail groups using the unpaired t and Mann-Whitney U tests. The Jonckheere-Therpstra test was used to identify relationships with the severity of frailty, and risk factors were identified using binary regression analysis.Results: Simple regression analysis identified a number of significant risk factors for frailty, including DHEAS <70 µg/dL and cortisol/DHEA-S ratio ≥0.2. Multiple regression analysis showed that low albumin (<4.0 g/dl) (odds ratio [OR]=5.79, p<0.001), low aspartate aminotransferase (AST) activity (<25 IU/L) (OR=4.34, p=0.009), and low body mass (BM) (<53 kg) (OR=3.85, p=0.012) were independent risk factors for frailty. A significant decrease in DHEA-S and a significant increase in the cortisol/DHEA-S ratio occurred alongside increases in the severity of frailty. DHEA-S concentration positively correlated with both serum albumin and BM.Conclusions: Hypoalbuminemia, low AST, and low BM are independent risk factors for frailty in elderly T2DM patients, strongly implying relative malnutrition in these frail patients. DHEA-S may be important for the maintenance of liver function and BM. A decrease in DHEA-S and an increase in the cortisol/DHEAS ratio may be involved in the mechanism of the effect of malnutrition in elderly T2DM patients.

Background:Relatively low dehydroepiandrosterone sulfate (DHEA-S) and high cortisol/DHEA ratio have been suggested to be associated with frailty as evaluated using a physical scale. However, the significance of these two hormones for frailty in elderly patients with type 2 diabetes mellitus (T2DM) has not been assessed using a wider range of measures of frailty, including physical, mental, and social indices. Methods:We performed a cross-sectional study to investigate the significance of these two hormones for frailty in elderly T2DM patients (n=148; ≥65 years), using a broad assessment, the clinical frailty scale, and to reevaluate the risk factors for frailty in elderly T2DM patients. We compared parameters between the non-frail and frail groups using the unpaired t and Mann-Whitney U tests. The Jonckheere-Therpstra test was used to identify relationships with the severity of frailty and risk factors were identified using binary regression analysis. Results: Simple regression analysis identified a number of significant risk factors for frailty, including DHEAS <70 µg/dL and cortisol/DHEA-S ratio ≥0.2. Multiple regression analysis showed that low albumin (<4.0 g/dl) (odds ratio [OR]=5.79, p<0.001), low aspartate aminotransferase (AST) activity (<25 IU/L) (OR=4.34, p=0.009), and low body mass (BM) (<53 kg) (OR=3.85, p=0.012) were independent risk factors for frailty. A significant decrease in DHEA-S and a significant increase in the cortisol/DHEA-S ratio occurred alongside increases in the severity of frailty. DHEA-S concentration positively correlated with both serum albumin and BM. Conclusions: Hypoalbuminemia, low AST, and low BM are independent risk factors for frailty in elderly T2DM patients, strongly implying relative malnutrition in these frail patients. DHEA-S may be important for the maintenance of liver function and BM. A decrease in DHEA-S and an increase in the cortisol/DHEAS ratio may be involved in the mechanism of the effect of malnutrition in elderly T2DM patients. trial registration number: UMIN (number 000031357) Ann Clin Lab Sci. 1986;16(2):79-93. 26.KjeldbyIK, Fosnes GS, Ligaarden SC, Farup PG. Vitamin B6 deficiency and diseases in elderly people--a study in nursing homes.

Background: Relatively low dehydroepiandrosterone sulfate (DHEA-S) and high cortisol/DHEA ratio have been suggested to be associated with frailty, evaluated using a physical scale. However, the significance of these two hormones for frailty in elderly patients with type 2 diabetes mellitus (T2DM) has not been assessed using a wider range of measures of frailty, including physical, mental, and social indices. Methods: We performed a cross-sectional study to investigate the significance of these two hormones for frailty in elderly T2DM patients (n=148; ≥65 years), using a broad assessment, the clinical frailty scale, and to reevaluate the risk factors for frailty in elderly T2DM patients. We compared parameters between the non-frail and frail groups using the unpaired t and Mann-Whitney U tests. The Jonckheere-Therpstra test was used to identify relationships with the severity of frailty and risk factors were identified using binary regression analysis. Results: Simple regression analysis identified a number of significant risk factors for frailty, including DHEAS <70 µg/dL and cortisol/DHEA-S ratio ≥0.2. Multiple regression analysis showed that low albumin (<4.0 g/dl) (odds ratio [OR]=5.79, p <0.001), low aspartate aminotransferase (AST) activity (<25 IU/L) (OR=4.34, p =0.009), and low body mass (BM) (<53 kg) (OR=3.85, p =0.012) were independent risk factors for frailty. A significant decrease in DHEA-S and a significant increase in the cortisol/DHEA-S ratio occurred alongside increases in the severity of frailty. DHEA-S concentration positively correlated with both serum albumin and BM. Conclusions: Hypoalbuminemia, low AST, and low BM are independent risk factors for frailty in elderly T2DM patients, strongly implying relative malnutrition in these frail patients. DHEA-S may be important for the maintenance of liver function and BM. A decrease in DHEA-S and an increase in the cortisol/DHEAS ratio may be involved in the mechanism of the effect of malnutrition in elderly T2DM patients.

Background: Frailty is broadly characterized by vulnerability and decline in physical, mental and social activities and is more common in elderly patients with type 2 diabetes mellitus (T2DM). Frailty is closely associated with nutrition, muscle strength, inflammation, and hormones etc. In hormones, dehydroepiandrosterone sulfate (DHEA-S) and cortisol are suggested to be such candidates affecting frailty. Little investigation has been performed using a wider range of measures of frailty to clarify risk factors for frailty including the above two hormones. Methods: We performed a cross-sectional study to investigate the risk factors for frailty in elderly T2DM patients (n=148; ≥65 years), using a broad assessment, the clinical frailty scale. We compared parameters between the non-frail and frail groups using the unpaired t and Mann-Whitney U tests. The Jonckheere-Therpstra test was used to identify relationships with the severity of frailty and risk factors were identified using binary regression analysis.Results: Simple regression analysis identified a number of significant risk factors for frailty, including DHEAS <70 µg/dL and cortisol/DHEA-S ratio ≥0.2. Multiple regression analysis showed that low albumin (<4.0 g/dl) (odds ratio [OR]=5.79, p<0.001), low aspartate aminotransferase (AST) activity (<25 IU/L) (OR=4.34, p=0.009), and low body mass (BM) (<53 kg) (OR=3.85, p=0.012) were independent risk factors for frailty. A significant decrease in DHEA-S and a significant increase in the cortisol/DHEA-S ratio occurred alongside increases in the severity of frailty. DHEA-S concentration positively correlated with both serum albumin and BM.Conclusions: Hypoalbuminemia, low AST, and low BM are independent risk factors for frailty in elderly T2DM patients, strongly implying relative malnutrition in these frail patients. DHEA-S may be important for the maintenance of liver function and BM. A decrease in DHEA-S and an increase in the cortisol/DHEAS ratio may be involved in the mechanism of the effect of malnutrition in elderly T2DM patients. trial registration number: UMIN (number 000031357)