Wen-Ya Ma

Serum IL-6, albumin and comorbidities are closely correlated with symptoms of depression in patients on maintenance haemodialysis

BACKGROUND Depression may be associated with activation of pro-inflammatory cytokines and increased long-term mortality in patients on maintenance haemodialysis (MHD). There are numerous reports regarding the association of depression with inflammatory status, co-morbidities and nutritional condition, but few of these studies have explored the possible correlations between depression, age and economic status. The study explores the possible correlations between depression and demographic, socio-economic, clinical and laboratory variables. METHODS One hundred and forty-six MHD patients (65 males and 81 females, mean age: 63.8±15.2 years) were enrolled in this cross-sectional study. Demographic and socio-economic status as well as clinical and laboratory variables including co-morbidities were obtained. The self-administered Beck Depression Inventory (BDI) was used to determine the presence or absence of depression symptoms. Biochemical parameters (serum albumin, triglyceride, cholesterol, etc.) and dialysis dosage delivery (Kt/V and urea reduction rate or URR) were examined. All the patients were on high-flux biocompatible dialysers for MHD. The presence of an inflammatory state was assessed by determinations of plasma interleukin-6 (IL-6) levels. RESULTS The prevalence of depression (BDI≥14) was 45.9%. In patients found to have symptoms of depression, no statistically significant difference was shown with respect to age, gender, smoking habits or clinical characteristics. However, these patients were more likely to have a number of co-morbidities. They also had higher levels of serum IL-6 and total cholesterol as well as lower serum albumin and Kt/V values. The BDI correlated significantly with Kt/V values (r=-0.19; P<0.05), levels of serum albumin (r=-0.28; P<0.005) and serum IL-6 (r=0.47; P<0.001). Multivariate stepwise forward logistic regression analysis showed a direct correlation between BDI and IL-6 levels (P=0.001; OR=1.537) and between BDI and co-morbidities (P=0.037; OR=3.584). There was an inverse correlation between BDI and serum albumin levels (P=0.006; OR=0.145) and between BDI and age (P=0.007; OR=0.96). The rate of depression was significantly lower for the elderly patients (age≥75 years) compared with those below 64 years of age. The percentage of personal monthly disposable income at or above Taiwan dollar (TWD)>10,000 was similar in patients aged≥75 and those below 64 years old. CONCLUSIONS Maintenance haemodialysis patients with symptoms of depression may have higher serum IL-6 and lower serum albumin levels. The prevalence of depression was lower in elderly patients at or above 75 years old, and no correlation was found with socio-economic status. Factors including co-morbid conditions, serum IL-6, albumin and age may help predict which patients may be predisposed to develop symptoms of depression.

Variability in hemoglobin A1c predicts all-cause mortality in patients with type 2 diabetes

BACKGROUND To evaluate the relationship between hemoglobin A1c variability and all-cause mortality in type 2 diabetic patients. METHODS This was a retrospective cohort study in type 2 diabetic patients followed for at least 2 years between 2003 and 2009. A1C variability was determined from the standard deviation or coefficient of variation of serial A1C values (A1C(SD) or A1C(CV)). Subjects were categorized into either the high or low A1C variability group according to their A1C(CV) median. Hazard ratios (HRs) of various factors for all-cause mortality were determined from Coxs proportional hazard models. RESULTS A total of 881 subjects (422 men, 459 women) were included and 73 (8.3%) died during follow-up. The follow-up period was 4.7 ± 2.3 years. All-cause mortality was higher in subjects with high A1C(CV) (11.0% vs. 5.4%, p=0.002). In the Kaplan-Meier failure curve, subjects with higher A1C(CV) demonstrated a trend of higher mortality (p=0.1). In multivariate Coxs proportional hazards models, A1C(SD) and A1C(CV) significantly predicted all-cause mortality with an HR of 1.987 (p=0.02) and 1.062 (p=0.013), respectively, after adjusting for age, gender, body mass index, duration of diabetes, mean systolic blood pressure, use of antihypertensives and statins, mean LDL-cholesterol, smoking status, chronic kidney disease, and mean A1C values (A1C(MEAN)). The ability of A1C(SD) and A1C(CV) to predict all-cause mortality was more evident in subjects with relatively low A1C(MEAN.) CONCLUSIONS A1C variability is an important risk factor for all-cause mortality in type 2 diabetic patients.

Measurement of Waist Circumference Midabdominal or iliac crest

OBJECTIVE Waist circumference (WC) is used to define central obesity. This study aimed to compare the performance of two recommended locations of WC measurement. RESEARCH DESIGN AND METHODS A cohort of 1,898 subjects who were without diabetes from 2006 to 2012 were followed for a median of 31 months (Taiwan Lifestyle Study). The WC-IC, recommended by the National Cholesterol Education Program Third Adult Treatment Panel, was measured at the superior border of the iliac crest, and the WC-mid, recommended by World Health Organization and International Diabetes Federation, was measured midway between the lowest ribs and the iliac crest. The abdominal subcutaneous fat area (SFA) and visceral fat area (VFA) were assessed by computed tomography. RESULTS There was greater difference between WC-IC and WC-mid measurements in women than in men (P < 0.001). Both WC-IC and WC-mid correlated significantly with BMI, VFA, and SFA (all P < 0.001). WC-mid was better correlated to VFA than WC-IC, particularly in women, and it correlated more strongly to blood pressure, plasma glucose, hemoglobin A1c, triglyceride levels, HDL cholesterol, and C-reactive protein (all P < 0.05). The association of WC-mid with hypertension, diabetes, and metabolic syndrome was slightly better than that of WC-IC (area under the receiver operator curve 0.7 vs. 0.69, 0.71 vs. 0.68, and 0.75 vs. 0.7, respectively; all age-adjusted P < 0.05). With 90 cm (male)/80 cm (female) as criteria for central obesity, WC-mid, but not WC-IC, predicted the incidence of diabetes development (age-adjusted P = 0.003). CONCLUSIONS WC-mid is a better measurement to define central obesity than WC-IC, particularly in women.

Low serum sex hormone-binding globulin: Marker of inflammation?

BACKGROUND Low sex hormone-binding globulin (SHBG) is associated with metabolic syndrome (MetS), but its relationship with inflammation is unclear. METHODS This cross-sectional study included 696 subjects (255 men, 235 pre-menopausal women, and 206 postmenopausal women). Body mass index, waist circumference, blood pressure, lipid profiles, plasma glucose, insulin, FSH, LH, total testosterone (TT), estradiol, SHBG, dehydroepiandrosterone sulfate (DHEA-S), and hs-CRP concentrations were measured. MetS was defined according to the updated National Cholesterol Education Program criteria with modification of waist circumference for Asians. RESULTS Serum hs-CRP and SHBG were negatively correlated in men (r=-0.29, p<0.001), pre-menopausal women (r=-0.38, p<0.001), and postmenopausal women (r=-0.27, p<0.001). In men, TT and hs-CRP showed a negative association (r=-0.25, p<0.001), but the association was attenuated after adjusting for SHBG (r=-0.14, p=0.039). Multivariate regression models showed that SHBG was independently associated with hs-CRP in men (r=-0.18, p=0.009), pre-menopausal women (r=-0.15, p=0.025), and postmenopausal women (r=-0.21, p=0.005), adjusted for age, MetS components, insulin resistance, low-density lipoprotein-cholesterol, and serum sex hormone levels. CONCLUSIONS Serum SHBG and hs-CRP concentrations were inversely correlated in men, pre-menoposal, and post-menopausal women independently.

Serum Glycated Albumin to Guide the Diagnosis of Diabetes Mellitus

In the diagnosis of diabetes mellitus, hemoglobin A1c (HbA1c) is sometimes measured to determine the need of an oral glucose tolerance test (OGTT). However, HbA1c does not accurately reflect glycemic status in certain conditions. This study was performed to test the possibility that measurement of serum glycated albumin (GA) better assesses the need for OGTT. From 2006 to 2012, 1559 subjects not known to have diabetes or to use anti-diabetic medications were enrolled. Serum GA was measured, and a 75-g OGTT was then performed to diagnose diabetes. Serum GA correlated significantly to age (r = 0.27, p<0.001), serum albumin (r = -0.1179, age-adjusted p = 0.001), body mass index (r = -0.24, age-adjusted p<0.001), waist circumference (r = -0.16, age-adjusted p<0.001), and plasma GA (r = 0.999, p<0.001), but was unaffected by diet (p = 0.8). Using serum GA at 15% for diagnosis of diabetes, the sensitivity, specificity, and area under the receiver-operating characteristic curve were 74%, 85%, and 0.86, respectively. Applying a fasting plasma glucose (FPG) value of < 100 mg/dL to exclude diabetes and of ≥ 126 mg/dL to diagnose diabetes, 14.4% of the study population require an OGTT (OGTT%) with a sensitivity of 78.8% and a specificity of 100%. When serum GA value of 14% and 17% were used to exclude and diagnose diabetes, respectively, the sensitivity improved to 83.3%, with a slightly decrease in specificity (98.2%), but a significant increase in OGTT% (35%). Using combined FPG and serum GA cutoff values (FPG < 100 mg/dL plus serum GA < 15% to exclude diabetes and FPG ≥ 126 mg/dL or serum GA ≥ 17% to diagnose diabetes), the OGTT% was reduced to 22.5% and the sensitivity increased to 85.6% with no change in specificity (98.2%). In the diagnosis of diabetes, serum GA measurements can be used to determine the need of an OGTT.

Bone turnover markers predict changes in bone mineral density after parathyroidectomy in patients with renal hyperparathyroidism

Objective  Patients on long‐term dialysis may develop secondary hyperparathyroidism (SHPT), which causes varying degrees of bone mass loss. This condition is treated with parathyroidectomy (PTX). We investigated whether serial serum bone turnover markers could predict changes in bone mineral density (BMD) after PTX.

Haemoglobin A1c is associated with carotid intima–media thickness in a Chinese population

Background  The association between haemoglobin A1c (HbA1c) levels and subclinical atherosclerosis in carotid arteries in Chinese populations is unknown.

BMI Correlates Better to Visceral Fat and Insulin Sensitivity Than BAI

TO THE EDITOR: BMI has been used for a long time but is often regarded as an inadequate measurement of obesity. Bergman et al. in their article “A Better Index Of Body Adiposity” (1) developed the body adiposity index (BAI) from hip circumference and height only to reflect the percent body fat, as measured by the dualenergy X-ray absorptiometry. Although BAI is highly correlated with percent body fat, the relationship of BAI and visceral adipose tissue is currently unknown. We investigate the relationship of BAI and visceral adipose tissue and compare with the performance of BMI. The participants were mainly healthy volunteers in Taiwan Life Study cohort (2). Abdominal adiposity was measure by noncontrast computed tomography. Subcutaneous abdominal fat area and visceral fat areas were measured on one cross-sectional scan obtained at the level of umbilicus (3). Total abdominal fat area was defined as the sum of subcutaneous and visceral fat area. BAI was calculated as (hip (in cm)/(height (in m))) − 18 (1). Pearson’s correlation coefficients were calculated among BAI or BMI and total abdominal fat area, subcutaneous abdominal fat area, and visceral fat area. Body fat area was logarithmically transformed for statistical analysis. A bootstrap resampling method with 1,000 replications was used to compare the correlation coefficients. Insulin resistance was calculated by fasting insulin and sugar according to HOMA2 method as proposed by Levy et al. (4). The statistical analyses were performed with Stata/SE 11.0 for Windows (StataCorp LP, College Station, TX). There were 424 participants, including 151 men and 273 women. The mean (s.d.) age, BMI, BAI, total abdominal fat area, subcutaneous abdominal fat area, and visceral fat area were 52 (12), 24.1 (3.3), 29.2 (4.2), 279 (11) cm, 179 (72) cm2, and 100 (55) cm2, respectively. As shown in the table, BMI and BAI correlated significantly to body fat. However, BMI correlates better to total abdominal fat area, visceral fat area, visceralto-subcutaneous abdominal fat area ratio, and HOMA2-IR than BAI in both genders. The relationships of subcutaneous fat area to BMI or BAI were similar in all subjects but showed better correlation with BMI when compared separately in men and women. In present study, we found that BMI correlates better to visceral fat than BAI. Visceral fat area, as measured in a singleslice computed tomography scan, has a closer relationship than subcutaneous abdominal fat area or total fat area to the development of adverse metabolic and cardiovascular events (5,6). Indeed, BMI also correlates better to insulin sensitivity index HOMA2-IR than BAI in our population. Therefore, based on the findings from Bergman et al. and ours, further study is needed to clarify the relationship between BAI and adverse metabolic and cardiovascular events.

Measurement of Visceral Fat: Should We Include Retroperitoneal Fat?

Objective Whether retroperitoneal fat should be included in the measurement of visceral fat remains controversial. We compared the relationships of fat areas in peritoneal, retroperitoneal, and subcutaneous compartments to metabolic syndrome, adipokines, and incident hypertension and diabetes. Methods We enrolled 432 adult participants (153 men and 279 women) in a community-based cohort study. Computed tomography at the umbilicus level was used to measure the fat areas. Results Retroperitoneal fat correlated significantly with metabolic syndrome (adjusted odds ratio (OR), 5.651, p<0.05) and the number of metabolic abnormalities (p<0.05). Retroperitoneal fat area was significantly associated with blood pressure, plasma glycemic indices, lipid profile, C-reactive protein, adiponectin (r = −0.244, P<0.05), and leptin (r = 0.323, p<0.05), but not plasma renin or aldosterone concentrations. During the 2.94±0.84 years of follow-up, 32 participants developed incident hypertension. Retroperitoneal fat area (hazard ration (HR) 1.62, p = 0.003) and peritoneal fat area (HR 1.62, p = 0.009), but not subcutaneous fat area (p = 0.14) were associated with incident hypertension. Neither retroperitoneal fat area, peritoneal fat area, nor subcutaneous fat areas was associated with incident diabetes after adjustment. Conclusions Retroperitoneal fat is similar to peritoneal fat, but differs from subcutaneous fat, in terms of its relationship with metabolic syndrome and incident hypertension. Retroperitoneal fat area should be included in the measurement of visceral fat for cardio-metabolic studies in human.

Glycated albumin is independently associated with estimated glomerular filtration rate in nondiabetic patients with chronic kidney disease.

BACKGROUND Glycated albumin (GA) may contribute to diabetic nephropathy, but the clinical significance of GA in patients with chronic kidney disease (CKD) is unknown. METHODS Patients were classified with the NKF/DOQI classification system as mild (stage I, II), moderate (stage III), or advanced CKD (stage IV). Those undergoing dialysis or with CKD stage V were excluded. GA was measured using the Lucica TM GA-L assay kit. The relationship between GA and renal dysfunction was analyzed in patients with or without diabetes. RESULTS A total of 187 subjects were enrolled. GA values in those with normal, mild, moderate and advanced CKD were 18.4 ± 1.4%, 18.4 ± 3.1%, 19.0 ± 3.8%, 20.4 ± 6.4%, respectively, in diabetic patients (N=67, p=0.5), and were 14.1 ± 1.9%, 14.2 ± 2.2%, 15.9 ± 1.9%, 15.0 ± 1.7%, respectively, in nondiabetic patients (N=120, p=0.004). GA value was negatively correlated to eGFR in nondiabetic patients (r=-0.35, p<0.001) but not in diabetic patients (r=-0.11, p=0.39). In the adjusted model, GA is independently correlated to eGFR only in nondiabetic subjects. CONCLUSIONS Increased GA concentrations are independently associated with renal dysfunction in nondiabetic patients with CKD.