Phase angle and extracellular water-to-total body water ratio estimated by bioelectrical impedance analysis are associated with levels of hemoglobin and hematocrit in patients with diabetes.

Anemia is one of the common complications of diabetes and is associated with mortality. Phase angle (PhA), ratio of extracellular water to total body water (ECW/TBW) and skeletal muscle mass index (SMI) estimated by bioelectrical impedance analysis (BIA) have been used as prognostic indicators for various chronic diseases and frailty. We aimed to clarify the clinical significance of PhA, ECW/TBW and SMI for anemia in patients with diabetes. The values of PhA, ECW/TBW and SMI were estimated by a portable BIA device and blood samples were collected in 371 Japanese patients with diabetes. The relationships of PhA, ECW/TBW and SMI with hemoglobin (Hgb) and hematocrit (Hct) were statistically evaluated. In simple linear regression analysis, PhA and SMI were positively correlated with Hgb and Hct levels in total subjects, male subjects and female subjects. In contrast, ECW/TBW was negatively correlated with Hgb and Hct levels regardless of sex. Multivariate regression analysis showed that both PhA and ECW/TBW but not SMI independently contributed to Hgb and Hct levels after adjustment of clinical confounding factors in both males and females. PhA and ECW/TBW but not SMI were associated with levels of Hgb and Hct in patients with diabetes. Therefore, aberrant values of PhA and ECW/TBW suggest a risk of anemia in diabetic patients.

Hori T ，Nakamura S ，Yamagami H ，Yasui S ，Hosoki M ，Hara T ，Mitsui Y ，Masuda S ，Kurahashi K ，Yoshida S ，Harada T ，Kuroda A ，Otoda T ，Yuasa T ，Endo I ，Matsuhisa M ，Abe M ，Aihara KI ... -  《Heliyon》

Extracellular water to total body water ratio may mediate the association between phase angle and mortality in patients with cancer cachexia: A single-center, retrospective study.

Recently, prognostic factors for cancer cachexia patients have been reported. We hypothesized that phase angle (PhA), which is measured by bioelectrical impedance analysis (BIA), might be a promising marker for assessing the nutritional status and prognosis of cancer patients. This study aimed to evaluate the predictive utility of PhA, which is mediated by several BIA factors and other anthropometric parameters, such as calf circumference, for the prognosis of cancer cachexia patients. Consecutive patients (114, both outpatients and inpatients) with an unselected stage of cancer cachexia were recruited between July 2018 and December 2019 in Fujita Health University Hospital for this retrospective cohort study. Their mean age was 74.0 years (standard deviation, 8.5); among the total, 70 were men and 44 women. A time-dependent Cox proportional-hazards regression analysis (adjusted for age and sex) was performed to assess the following: 1) the association between potential mediators and mortality; 2) the association between five PhAs and statistically significant mediators from 1); and 3) the association between the five PhAs and mortality. Finally, Kaplan-Meier survival curves were constructed and compared between the two groups based on the patients' median baseline ratio of extracellular water (ECW) to total body water (TBW) using a log-rank test. The ECW/TBW ratio (hazard ratio [HR] per 1-interquartile range [IQR] increase: 2.87; 95% confidence interval [CI]: 1.46, 5.46; p < 0.001) and skeletal muscle mass index (HR per 1-IQR increase: 0.67; 95% CI: 0.51, 0.89; p = 0.001) were associated with mortality. All five PhAs were associated with the ECW/TBW ratio (p < 0.001). Before adjustment for the ECW/TBW ratio, all five PhAs were associated with mortality (p < 0.001); only the association of the PhAs of the left arm and the trunk retained the statistical significance after adjusting for confounders (p < 0.05). The median survival times in the low (370 days; 95% CI: 168, not calculated) and high ECW/TBW groups (101 days; 95% CI: 61, 219) differed significantly (p < 0.001). The association between PhA and mortality in cancer cachexia patients was largely mediated by the ECW/TBW ratio. We believe that adjusting PhA for the ECW/TBW ratio may improve the prognostication of cancer patients with cachexia, ultimately improving their palliative care.

Katsura N ，Yamashita M ，Ishihara T 《Clinical Nutrition ESPEN》

Extracellular water-to-total body water ratio is an essential confounding factor in bioelectrical impedance analysis for sarcopenia diagnosis in women.

Hioka A ，Akazawa N ，Okawa N ，Nagahiro S ... -  《European Geriatric Medicine》

Influence of aging on extracellular water-to-total body water ratio in community-dwelling females.

The European Working Group of Sarcopenia in Older People 2 has emphasized the significance of evaluating not only muscle mass but also muscle quality as a diagnostic criterion for sarcopenia. The extracellular water-to-total body water ratio (ECW/TBW), measured using bioelectrical impedance analysis (BIA), has recently received attention as an indicator of muscle quality. However, the influence of aging on the ECW/TBW remains unclear. If ECW/TBW increases with age, it is important to know whether the timing of the decrease in SMI and the increase in ECW/TBW are the same or different. This study aimed to investigate the influence of aging on ECW/TBW in community-dwelling females. This cross-sectional study included 237 community-dwelling females aged 20-89 years who could perform activities of daily living independently. ECW/TBW and SMI were measured using BIA. Multiple linear regression analyses of ECW/TBW and SMI were conducted. Age, body mass index (BMI), number of medications, pain, and medical history were considered independent variables in the multiple linear regression. The participants were divided into three (20-39, 40-64, and 65-89 years) or four (20-39, 40-64, 65-74, and 75-89 years) groups based on age. Analysis of covariance adjusted for the BMI, number of medications, pain, and medical history was conducted to determine the differences in ECW/TBW and SMI among the three or four groups. In the multiple linear regression analysis, age was significantly and independently associated with ECW/TBW and SMI. When the participants were divided into three groups based on age, an increase in ECW/TBW and a decrease in SMI in the 65-89-year group were confirmed compared with the 20-39 and 40-64-year groups. When the participants were divided into four groups based on age, an increase in ECW/TBW in the 75-89-year group was confirmed compared with the 65-74-year group. However, there were no significant differences in SMI among the four groups. This study revealed that ECW/TBW increases with aging in community-dwelling females. Moreover, the negative influences of aging were confirmed earlier in ECW/TBW than in SMI. Assessing muscle mass alone may not be adequate to capture the influences of aging on muscle composition, and evaluating ECW/TBW may be crucial for diagnosing sarcopenia.

Hioka A ，Akazawa N ，Okawa N ，Nagahiro S ... -  《Clinical Nutrition ESPEN》

The extracellular-to-total body water ratio reflects improvement in the activities of daily living in patients who experienced acute stroke.

To determine the relationship between bioelectrical impedance analysis (BIA) parameters, including the extracellular water-to-total body water ratio (ECW/TBW), and the activities of daily living (ADL) improvement, in patients who experienced acute stroke. This retrospective cohort study included 307 patients (mean age, 72 years; 39 % female) who experienced acute stroke and were admitted to the stroke unit of the Nippon Medical School Hospital (Bunkyo-ku, Tokyo, Japan) between April 2021 and March 2022. The Functional Independence Measure (FIM) was assessed at initial rehabilitation and discharge, and FIM effectiveness was calculated as ADL improvement in the participating acute care hospitals. BIA markers included the skeletal muscle mass index (SMI), phase angle (PhA), and ECW/TBW. Multiple linear regression models were used to estimate the relationship between the FIM effectiveness and each BIA marker. The mean (±SD) FIM effectiveness was 0.45 ± 0.36. The proportions of low SMI (male, <7.0 kg/m2; female, <5.7 kg/m2) and low PhA (male <5.36 degrees, female <3.85 degrees), were 48.9 % and 43.3 %, respectively. In addition, the proportions of of low (<0.36), normal (0.36-0.40), and high (>0.4) ECW/TBW ratios were 1.3 %, 78.5 %, and 20.2 %, respectively. After adjustments for demographic and clinical variables, low PhA, low ECW/TBW, and high ECW/TBW were all significantly associated with FIM effectiveness (P < 0.05), with β coefficients of -0.126, -0.089, and -0.117, respectively. Low and High ECW/TBW and low PhA levels were negatively correlated with improvements in ADL. The ECW/TBW ratio may be an additional indicator of rehabilitation trainability in patients who experience acute stroke.

Ishiyama D ，Toi K ，Aoyagi Y ，Suzuki K ，Takayama T ，Yazu H ，Yoshida M ，Kimura K ... -  《-》