Significant Association of Diabetes With Mortality of Chronic Hemodialysis Patients, Independent of the Presence of Obesity, Sarcopenia, and Sarcopenic Obesity.

OBJECTIVES: This retrospective cohort study investigated the association of diabetes with mortality in hemodialysis patients with regard to obesity, sarcopenia, and sarcopenic obesity, along with examining the prevalence of each group and diabetes. METHODS: Muscle strength, muscle mass, and fat mass were evaluated using a hand dynamometer and dual-energy X-ray absorptiometry, respectively, in 308 chronic hemodialysis patients (age 58.0 ± 11.9 years, hemodialysis duration 6.5 ± 6.0 years, males 60.1%, diabetes 32.8%). Sarcopenia was defined according to the new criteria established by the Asian Working Group on Sarcopenia 2019. Obesity was defined by percent body fat mass (males ≥25%, females ≥35%). RESULTS: The enrolled patients were divided into the normal (38.7%), obesity (18.8%), sarcopenia (26.9%), and sarcopenic obesity (15.6%) groups. The prevalence of diabetes was significantly skewed among the 4 groups (χ2 test, P = .0057), being higher in the sarcopenic obesity group (54.2%) compared to the others (25.9-33.7%). Multivariate regression analysis revealed that diabetes was significantly and independently associated with sarcopenic obesity (odds ratio 3.495, 95% confidence interval 1.683-7.255, P = .0008) after adjustments for several cofounders, but not significantly associated with sarcopenia. During the follow-up period of 76 ± 35 months, 100 patients died. Those in the sarcopenia and sarcopenic obesity groups had significantly higher rates of all-cause mortality compared to patients in the normal and obesity groups (P = .0004, log-rank test). Furthermore, multivariate Cox proportional hazards analysis revealed that presence of diabetes was significantly associated with higher all-cause mortality in all 308 patients, after adjustments for several factors, including the presence of each group in 4 models. CONCLUSION: Sarcopenic obesity is highly prevalent in chronic hemodialysis patients. Diabetes was found to be a significant and independent contributor to the presence of sarcopenic obesity. Diabetes was shown to be a significant predictor of all-cause mortality, independent of the present normal, obesity, sarcopenia, and sarcopenic obesity groups.

REM sleep latency as an independent risk for cardiovascular events in hemodialysis patients.

BACKGROUND: Clinical significance of objectively measured poor sleep quality (SQ) as a risk for cardiovascular disease (CVD) events is not well known in hemodialysis (HD) patients, independently of sleep-related breathing disorders (SRBDs) and sleep-related metabolic abnormality. METHODS: The present study investigated baseline levels of objective sleep architecture together with obstructive sleep apnea (OSA) and central sleep apnea (CSA) using polysomnography in 88 HD study participants (M/F, 56/32; age 68.4 ± 9.3). Then, HD study participants were monitored for the occurrence of new-onset CVD events with a median (range) follow-up period of 33 (1-64) months. RESULTS: Among various measures of SQ, log (REM sleep latency [REM-SL]) (interval between sleep-onset and the first REM period) alone correlated in negative manners with triglycerides and non-HDL-C in all study participants and with fasting plasma glucose and HbA1c in study participants with type-2 diabetes mellitus. In the Kaplan-Meier analysis, HD study participants with shorter REM-SL had a significantly higher rate of new-onset CVD events than those with longer REM-SL. Stepwise logistic regression analysis and multivariate Cox proportional hazard regression analysis identified shorter REM-SL as an independent risk factor for the development of a new-onset CVD events, independent of mean oxygen saturation, log (AHI+1), log (central AHI+1), diabetes mellitus, CVD history, systolic blood pressure, statins use, and non-HDL-C. CONCLUSIONS: The present study demonstrated that reduction of REM-SL is independently associated with a higher rate of new-onset of CVD events, independent of SRBDs (OSA and CSA) and diabetes mellitus, non-HDL-C in HD study participants, suggesting impaired SQ as a potential CVD risk factor, and thus a definite treatment target to protect against CVD specifically in HD study participants. REM-SL might be a new risk factor of CVD events in HD patients with SRBDs.

Inverse association of fat mass, but not lean mass, with glycated albumin in hemodialysis patients with or without diabetes mellitus.

Background: Glycated albumin (GA), which is independent of anemia and/or use of erythropoiesis-stimulating agents, might provide a more precise measure than glycated hemoglobin (HbA1c) in hemodialysis patients. The present study examines whether body composition is associated with GA besides glycemic control in hemodialysis patients. Methods: This study included 90 hemodialysis patients with diabetes mellitus (DM) and 86 hemodialysis patients without DM. We examined blood parameters after an overnight fast and body fat and lean mass using dual X-ray absorptiometry 21-24 h after completing the dialysis session. Results: The mean body mass index (BMI) was 22.0 kg/m2. BMI and truncal fat mass were significantly higher, and total fat mass tended to be higher in hemodialysis patients with DM than in those without DM. GA exhibited inverse correlations with BMI, total lean mass, total fat mass, and truncal fat mass in hemodialysis patients with and without DM; however, there was a lack of correlation with total lean mass in patients without DM. In multiple regression analysis including total fat mass and total lean mass simultaneously as independent variables, total fat mass (with DM: ß = -0.322, p = .006) (without DM: ß = -0.391, p < .001), but not total lean mass, in addition to log fasting plasma glucose, emerged as an independent factor associated with GA in hemodialysis patients with and without DM. When total fat mass was replaced with truncal fat mass (with DM: ß = -0.311, p = .007) (without DM: ß = -0.396, p < .001), the association remained significant and independent with GA in both patient groups. Conclusions: Higher total fat mass, particularly truncal fat mass, might be associated with lower GA levels, beside glycemic control, in hemodialysis patients with or without DM.

Paradoxical positive association of serum adiponectin with all-cause mortality based on body composition in Japanese haemodialysis patients.

We have previously reported a paradoxical association of serum adiponectin with aortic calcification in haemodialysis patients. Because serum adiponectin is a nutritional marker, we examined the association between serum adiponectin and all-cause mortality based on body composition in haemodialysis patients. The trunk and total body fat were determined. The patients were divided into two groups based on serum adiponectin levels. In Kaplan-Meier analysis, the higher adiponectin group showed higher mortality than the lower adiponectin group. Serum adiponectin showed an inverse correlation with the percentage of truncal fat, suggesting serum adiponectin as an inverse marker for adiposity in haemodialysis patients. However, even after adjustment for other factors, multivariate Cox proportional hazards analysis identified higher serum adiponectin as an independent factor positively associated with higher mortality in haemodialysis patients. This association held true even when the total fat mass was replaced with the percentage of truncal fat, and when total fat mass and percentage of truncal fat were simultaneously included. Thus, we found a paradoxical association of higher serum adiponectin with higher all-cause mortality in Japanese haemodialysis patients, independent of adiposity.

The association of serum adiponectin with abdominal aortic calcification in Japanese male hemodialysis patients: a cross-sectional observational study.

The negative relation of serum adiponectin to atherosclerosis becomes a positive association in patients with chronic kidney disease (CKD). We conducted a small-scale cross-sectional observational study, in 101 Japanese male hemodialysis patients, to examine the relationship of serum adiponectin and leptin to abdominal aortic calcification (AAC). The presence of AAC was evaluated from simple X-ray radiographs of the left lateral abdomen. Serum adiponectin was significantly higher in AAC-positive patients [18.8 (13.0-28.1) µg/mL] than in AAC-negative patients [15.4 (8.9-22.8) µg/mL] (p = 0.03), whereas serum leptin did not differ significantly between the two groups. Multiple logistic regression analysis showed that log adiponectin, but not log leptin, was independently and significantly associated in a positive manner with AAC (odds ratio: 16.31, 95% confidence interval: 1.70-156.41, p = 0.02), after adjustment for age, body weight, percentage body fat, hemodialysis duration, prevalence of diabetes mellitus, and other risk factors. In conclusion, we found a positive and independent association of serum adiponectin with AAC in male hemodialysis patients, indicating that the reversed association between serum adiponectin and atherosclerosis in patients with CKD dose not result from increased serum adiponectin due to the impaired urinary secretion.

Significant association between bone-specific alkaline phosphatase and vascular calcification of the hand arteries in male hemodialysis patients.

BACKGROUND/AIMS: Bone-specific alkaline phosphatase (BAP) hydrolyzes pyrophosphate, which inhibits vascular calcification. We examined association between serum BAP and vascular calcification of male hemodialysis patients. METHODS: Hand roentgenography of 167 male maintenance hemodialysis patients was conducted, and visible vascular calcification of the hand arteries was evaluated. Serum levels of 3 bone formation markers (BAP, osteocalcin, and N-terminal propeptide of type I collagen) and 2 bone resorption markers (C-terminal telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured, along with serum intact parathyroid hormone (PTH). RESULTS: Of 167 patients, visible vascular calcification was seen in 37 patients. Among the bone formation and resorption markers, serum BAP was significantly higher in patients with vascular calcification than in those without (p<0.05); although the other 5 serum bone markers were not significantly different between them. Multivariate logistic regression analyses revealed that log [BAP] was significantly associated with vascular calcification after adjustment for age, hemodialysis duration, presence of diabetes, log [intact PTH] and each of the other 5 bone markers (p<0.0001). CONCLUSIONS: Higher serum BAP, but not other bone markers, is significantly associated with the presence of vascular calcification in male hemodialysis patients.

Relationship between serum sclerostin, bone metabolism markers, and bone mineral density in maintenance hemodialysis patients.

BACKGROUND: Sclerostin, which is secreted exclusively by osteocytes, is a negative regulator of bone formation. The role of sclerostin in chronic kidney disease-mineral and bone disorder is not well known. In the present study, we examined the relationship between serum sclerostin levels, bone turnover markers, and bone mineral density (BMD) of the radius in maintenance hemodialysis patients. METHODS: This was a cross-sectional study that analyzed sclerostin, bone alkaline phosphatase (a bone formation marker), and tartrate-resistant acid phosphatase 5b (a bone resorption marker) in stored serum samples from 181 hemodialysis patients (age, 68 ± 11 y; 105 males and 76 females; hemodialysis duration, 6.9 ± 5.9 y). The BMD in the distal one-third of the radius and in the ultradistal radius, which are enriched with cortical and cancellous bone, respectively, was examined by dual-energy x-ray absorptiometry. RESULTS: Serum sclerostin was 125 ± 53 pmol/L (mean ± SD). Serum sclerostin correlated significantly and negatively with serum bone alkaline phosphatase and tartrate-resistant acid phosphatase 5b (r = -0.265, P < .001; r = -0.218, P < .01, respectively). The BMD in the distal one-third of the radius and in the ultradistal radius both correlated significantly and positively with serum sclerostin levels (r = 0.454, P < .0001; r = 0.329, P < .0001, respectively). In multiple regression analysis, serum sclerostin was associated significantly and independently with BMD of both parts of the radius (ß = 0.200, P < .001; ß = 0.218, P < .05), after adjustment for age, hemodialysis duration, and bone metabolism markers. CONCLUSION: Serum sclerostin was associated significantly, independently, and positively with BMD of both cortical and cancellous bone. Sclerostin is considered to be one of the factors associated with chronic kidney disease-mineral and bone disorder in hemodialysis patients.

Significant positive association between parathyroid hormone and fat mass and lean mass in chronic hemodialysis patients.

BACKGROUND: It has been reported that there is a significant positive relationship between PTH and body weight or body mass index in the general population. However, little is known about this relationship in dialysis patients in whom PTH levels are higher. It is also not known whether fat mass or lean mass is associated with serum PTH among these patients. In the present study, we examined the association of intact PTH with fat mass and lean mass in hemodialysis patients. METHODS: Serum intact PTH, calcium, and phosphate were measured in 590 hemodialysis patients (age, 60.2 ± 12.2 y; median hemodialysis duration, 59.6 mo; 343 males and 247 females; diabetics, 27.7%). Fat mass and lean mass were measured by dual-energy x-ray absorptiometry. RESULTS: Intact PTH correlated significantly and positively with body weight and body mass index in all patients. Intact PTH correlated significantly and positively with fat mass and lean mass in males (P < .01), and tended to correlate positively with fat mass and lean mass in females (P < .1). In multiple regression analyses after adjustment for age, gender, hemodialysis duration, calcium, phosphate, vitamin D use, and phosphate binder use, intact PTH was associated significantly with body weight (ß = .190; P < .0001), body mass index (ß = .177; P < .0001), fat mass (ß = .142; P < .0005), and lean mass (ß = .192; P < .01). Furthermore, intact PTH was associated significantly and independently with both fat mass and lean mass after adjustment (R(2) = .206; P < .0001). CONCLUSION: Serum intact PTH in chronic hemodialysis patients is associated significantly and positively with body composition of fat mass and lean mass.

Significant positive relationship between serum magnesium and muscle quality in maintenance hemodialysis patients.

BACKGROUND/AIMS: Serum magnesium (Mg) levels have been associated with muscle performance in the general population. We hypothesized that serum Mg would be associated with muscle quality in hemodialysis patients. METHODS: A total of 310 patients were examined (age: 58 ± 12 years, hemodialysis duration: 6.4 ± 6.0 years, 60.6% men, and 36.1% diabetics). Arm lean mass was measured by dual energy X-ray absorptiometry (DXA) on the dominant side. Arm muscle quality was defined as the ratio of the handgrip strength to the arm lean mass of the same side (kg/kg). RESULTS: Serum Mg was 1.15 ± 0.16 mmol/L (2.8 ± 0.4 mg/dL), being higher than the reference range of normal subjects. There was a significant negative correlation between muscle quality and age (r = -0.326, p<0.0001) and duration of hemodialysis (r = -0.253, p<0.0001). The muscle quality of the diabetics was significantly lower than that of the non-diabetics (p<0.001). There was a significant, positive correlation between muscle quality and serum Mg (r = 0.118, p<0.05), but not serum calcium or phosphate. In multiple regression analysis, age, gender, hemodialysis duration, diabetes, and serum Mg (ß = 0.129, p<0.05) were significantly and independently associated with muscle quality (R(2) = 0.298, p<0.0001). CONCLUSION: These results demonstrated that a lower serum Mg concentration was significantly associated with poor muscle quality in hemodialysis patients. Further studies are needed to explore the mechanism by which lower serum Mg affects muscle quality.