Branched-Chain Amino Acid Supplementation Does Not Preserve Lean Mass or Affect Metabolic Profile in Adults with Overweight or Obesity in a Randomized Controlled Weight Loss Intervention.

BACKGROUND: Branched-chain amino acid (BCAA) supplementation has been shown to increase muscle mass or prevent muscle loss during weight loss. OBJECTIVE: We aimed to investigate the effects of a BCAA-supplemented hypocaloric diet on lean mass preservation and insulin sensitivity. METHODS: A total of 132 Chinese adults (63 men and 69 women aged 21-45 y, BMI 25-36 kg/m2) were block randomly assigned by gender and BMI into 3 hypocaloric diet (deficit of 500 kcal/d) groups: standard-protein (14%) with placebo (control, CT) or BCAA supplements at 0.1 g · kg-1 body weight · d-1 (BCAA) or high-protein (27%) with placebo (HP). The subjects underwent 16 wk of dietary intervention with provision of meals and supplements, followed by 8 wk of weight maintenance with provision of supplements only. One-way ANOVA analysis was conducted to analyze the primary (lean mass and insulin sensitivity) and secondary outcomes (anthropometric and metabolic parameters) among the 3 groups. Paired t-test was used to analyze the change in each group. RESULTS: The 3 groups demonstrated similar significant reductions in body weight (7.97%), fat mass (13.8%), and waist circumference (7.27%) after 16 wk of energy deficit. Lean mass loss in BCAA (4.39%) tended to be lower than in CT (5.39%) and higher compared with HP (3.67%) (P = 0.06). Calf muscle volume increased 3.4% in BCAA and intramyocellular lipids (IMCLs) decreased in BCAA (17%) and HP (18%) (P < 0.05) over 16 wk. During the 8 wk weight maintenance period, lean mass gain in BCAA (1.03%) tended to be lower compared with CT (1.58%) and higher than in HP (-0.002%) (P = 0.04). Lean mass gain differed significantly between CT and HP (P = 0.03). Insulin sensitivity and metabolic profiles did not differ among the groups throughout the study period. CONCLUSIONS: BCAA supplementation does not preserve lean mass or affect insulin sensitivity in overweight and obese adults during weight loss. A higher protein diet may be more advantageous for lean mass preservation.

Fall Risk and Balance Confidence in Patients With Diabetic Peripheral Neuropathy: An Observational Study.

Objective: Individuals with diabetic peripheral neuropathy (DPN) have functional deficits that increase their risk of falling. However, psychological aspects such as loss of confidence in undertaking activities could also contribute to this risk. We examined correlations between balance confidence and fall risk among individuals with DPN. Methods: This was a cross-sectional study of 146 individuals with DPN. Elevated fall risk was determined by timed up-and-go test with standard cut-off time of 13.5 seconds, and balance confidence was measured by 16-item Activities Specific Balance Confidence scale. Functional parameters assessed included functional reach, body sway velocity during quiet standing and muscle strength at ankle and toe. Results: Twenty percent of the DPN patients were at increased risk of falls. Every unit increase in balance confidence was associated with 9% (95% confidence interval: 0.88, 0.95; p<0.001) reduced odds of falling, after adjusting for socio-demographic, health and functional characteristics. No other functional parameters had significant associations with fall risk in adjusted analyses. Conclusions: Psychological factors like balance confidence appear to be more important for fall risk among DPN patients, compared to objective functional performance. Interventions targeting balance confidence may be beneficial in reducing the risk of falls in this population.

Associations between health literacy and health care utilization and mortality in patients with coexisting diabetes and end-stage renal disease: A prospective cohort study.

Objectives Health literacy encompasses a broad skill set linked to patients' self-management ability and the complexity of their health care environments. Self-management in the context of multimorbidity is particularly challenging, placing patients at risk of poor clinical outcomes. This study aimed to explore the prognostic associations between health literacy domains, depression, and 12-month health care utilization and mortality in patients with diabetes and end-stage renal disease (DM-ESRD). Design Observational study. Methods Patients with DM-ESRD undergoing haemodialysis were recruited. Information on all-cause hospitalization/admission and mortality of participants was recorded. Negative binomial and Cox regressions were used to model risk factors for hospitalization and mortality. Results A total 221 participants [median age: 59 years, 61.6% men, 54.8% Chinese] were recruited. Differences in health literacy were found as a function of age, ethnicity, relationship status, and education. After adjusting for demographic and clinical factors, the HLQ domain Actively Managing My Health remained independently associated with lower rates of hospitalization (incidence rate ratio (IRR) = 0.674, 95% CI [0.490, 0.925], p = .02) and mortality (hazard ratio = 0.382, 95% CI [0.160, 0.848], p = .02). Cumulative hospitalization days were associated with employment status (IRR = 2.242, 95% CI [1.223, 4.113], p = .009), albumin (IRR = 0.918, 95% CI [0.854, 0.988], p = .02), HbA1c (IRR = 1.183, 95% CI [1.028, 1.360], p = .02), comorbidity burden (IRR = 1.137, 95% CI [1.003, 1.289], p = .04), and depression (IRR = 1.059, 95% CI [1.003, 1.118], p = .04) but no health literacy domains. Conclusions Health literacy skills related to Actively Managing My Health predict hospitalization and mortality independently of other risk factors. The HLQ provides an assessement of novel health literacy parameters which offer new insights into patients' status and behaviours and may strengthen interventions to improve clinical services, and patient outcomes in DM-ESRD. Statement of contribution What is already known on this subject? Patients with diabetes (DM) comprise the fastest growing segment of patients with end-stage renal disease (ESRD). Health literacy (HL) is pivotal for managing the complex treatment guidelines for DM-ESRD. Most prior work on HL focused on functional HL and shown significant associations with mortality and hospitalization. Limited research has investigated wider HL skills in relation to clinical outcomes. What does this study add? Supporting patients in Actively Managing my health liteacy skills is critical in decreasing probability of hospitalization and morbidity. The presence of symptoms of depression is associated with longer hospitalization period.

Altered Motor and Motor Perceptual Cognitive Imagery Task-Related Activation in Diabetic Peripheral Neuropathy: Insights From Functional MRI.

OBJECTIVE: To compare central nervous system (CNS) activation in patients with and without diabetic peripheral neuropathy (DPN) during motor and motor imagery tasks and to correlate activation with functional performance. RESEARCH DESIGN AND METHODS: Twenty-six participants (13 with DPN, 13 without DPN) underwent functional MRI during three tasks: ankle dorsi plantar flexion (motor task [MT]) and motor imagery tasks of walking on a smooth surface (SMIT) and rough surface (RMIT). Functional assessment included gait analysis, ankle muscle strength, and ankle range of motion. RESULTS: The tasks activated the sensorimotor, motor preparation, visual processing, and decision-making regions. Activation was significantly lower in patients with DPN than in those without DPN during MT and SMIT but not RMIT. Poor functional performance in patients with DPN was associated with greater activation in motor preparation regions. CONCLUSIONS: In patients with DPN, CNS responses appear muted compared with patients without DPN, but they remain capable of enhancing CNS activation when tasks are more challenging or when functional deficits are substantial.

Short-term strength and balance training does not improve quality of life but improves functional status in individuals with diabetic peripheral neuropathy: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this study was to test the effectiveness of a structured strength and balance training intervention in improving health-related quality of life (HRQoL) and functional status in individuals with diabetic peripheral neuropathy (DPN). METHODS: The study was a single-blind parallel-group randomised controlled trial comparing 2 months of once-weekly home-based strength and balance training against standard medical therapy. Participants were patients with physician-diagnosed type 2 diabetes and neuropathy recruited from five public sector institutions in Singapore between July 2014 and October 2017. Participants were block-randomised to intervention or control arms. Outcomes were assessed at baseline, 2 months and 6 months by a trained assessor blinded to group assignment. Primary outcomes were change in physical component summary (PCS) score of SF-36v2 (a 36-item generic HRQoL instrument that has been validated for use in Singapore) and EQ-5D-5L index score (derived from a five-item generic HRQoL instrument [EQ-5D-5L]) over 6 months. Secondary outcomes were change in functional status (timed up-and-go [TUG], five times sit-to-stand [FTSTS], functional reach, static balance, ankle muscle strength and knee range of motion) and balance confidence over 6 months. Mean differences in scores between groups were compared using mixed models. RESULTS: Of the 143 participants randomised (intervention, n = 70; control, n = 73), 67 participants were included in each arm for the final intention-to-treat analysis. The two groups were similar, except in terms of sex. There were no significant differences between groups on the primary outcomes of PCS score (mean difference [MD] 1.56 [95% CI -1.75, 4.87]; p = 0.355) and EQ-5D-5L index score (MD 0.02 [95% CI -0.01, 0.06]; p = 0.175). There were significant improvements in TUG test performance (MD -1.14 [95% CI -2.18, -0.1] s; p = 0.032), FTSTS test performance (MD -1.31 [95% CI -2.12, -0.51] s; p = 0.001), ankle muscle strength (MD 4.18 [95% CI 0.4, 7.92] N; p = 0.031), knee range of motion (MD 6.82 [95% CI 2.87, 10.78]°; p = 0.001) and balance confidence score (MD 6.17 [95% CI 1.89, 10.44]; p = 0.005). No adverse events due to study participation or study intervention were reported. CONCLUSIONS/INTERPRETATION: Short-term structured strength and balance training did not influence HRQoL but produced sustained improvements in functional status and balance confidence at 6 months. More intensive interventions may be needed to influence HRQoL in these individuals. However, this intervention may be a useful treatment option for individuals with DPN to reduce the risk of falls and injuries. TRIAL REGISTRATION: ClinicalTrials.gov NCT02115932 FUNDING: This work was supported by the National Medical Research Council, Singapore.

Risk factors and direct medical cost of early versus late unplanned readmissions among diabetes patients at a tertiary hospital in Singapore.

OBJECTIVE: To examine the risk factors and direct medical costs associated with early (≤30 days) versus late (31-180 days) unplanned readmissions among patients with type 2 diabetes in Singapore. METHODS: Risk factors and associated costs among diabetes patients were investigated using electronic medical records from a local tertiary care hospital from 2010 to 2012. Multivariable logistic regression was used to identify risk factors associated with early and late unplanned readmissions while a generalized linear model was used to estimate the direct medical cost. Sensitivity analysis was also performed. RESULTS: A total of 1729 diabetes patients had unplanned readmissions within 180 days of an index discharge. Length of index stay (a marker of acute illness burden) was one of the risk factors associated with early unplanned readmission while patient behavior-related factors, like diabetes-related medication adherence, were associated with late unplanned readmission. Adjusted mean cost of index admission was higher among patients with unplanned readmission. Sensitivity analysis yielded similar results. CONCLUSIONS: Existing routinely captured data can be used to develop prediction models that flag high risk patients during their index admission, potentially helping to support clinical decisions and prevent such readmissions.

Functional status mediates the association between peripheral neuropathy and health-related quality of life in individuals with diabetes.

AIMS: To examine differences in health-related quality of life (HRQoL) between patients with and without diabetic peripheral neuropathy (DPN), and whether these differences can be explained by functional deficits. METHODS: This was a cross-sectional study of 160 patients with type 2 diabetes mellitus, 80 with DPN and 80 without. Assessments included HRQoL (health utility score derived from EQ-5D-5L), functional status measurements [muscle strength, timed up and go (TUG), five times sit-to-stand (FTSTS), functional reach, body sway velocity] and self-reported balance confidence [Activities-specific Balance Confidence (ABC) scale]. RESULTS: Mean utility scores were 0.67 ± 0.14 and 0.77 ± 0.16 in patients with and without DPN, respectively (p < 0.001). Patients with DPN had lower great toe extensor strength (6.4 ± 1.8 vs 7.6 ± 2.8 lbs, p = 0.001), greater body sway velocity (2.40 ± 1.31 vs 1.90 ± 0.52 mm/s, p = 0.002), slower TUG (12.1 ± 4.6 vs 10.1 ± 2.3 s, p < 0.001) and FTSTS (15.8 ± 5.8 vs 13.9 ± 5.4 s, p = 0.03) scores, and lower ABC score (73.4 ± 21.3 vs 82.6 ± 16.9, p = 0.003), compared to those without DPN. On stepwise multiple regression, DPN status, FTSTS, body sway velocity, BMI, diabetes duration, pain, and gender explained 38% of HRQoL variance. Addition of ABC score into the model explained 45% of variance. Results from structural equation modelling showed that DPN had direct effects on HRQoL and indirect effects through FTSTS, body sway velocity, and ABC score, with χ 2 = 8.075 (p = 0.044), root mean square error of approximation = 0.103 (lower bound 0.015, upper bound 0.191), Comparative Fit Index = 0.966, Tucker-Lewis Index = 0.887, and Standardized Root Mean Square Residual = 0.053. CONCLUSIONS: Patients with DPN have worse HRQoL compared to patients without DPN, partly mediated by functional status parameters. Effective interventions targeting functional status may be beneficial in improving HRQoL in these patients.

Factors associated with diabetes-related distress over time among patients with T2DM in a tertiary hospital in Singapore.

BACKGROUND: Persistent diabetes-related distress (DRD) is experienced by patients with Type 2 Diabetes Mellitus. Knowing factors associated with persistent DRD will aid clinicians in prioritising interventions efforts. METHODS: A total of 216 patients were recruited from a tertiary hospital in Singapore, an Asian city state, and followed for 1.5 years (2011-2014). Data was collected by self-completed questionnaires assessing DRD (measured by the Problem Areas in Diabetes score) and other psychosocial aspects such as social support, presenteeism, depression, health-related quality of life (HRQoL) and excessive daytime sleepiness (EDS) at three time points. Clinical data (body-mass-index and glycated haemoglobin) was obtained from medical records. Change score was calculated for each clinical and psychosocial variable to capture changes in these variables from baseline. Generalized Linear Model with Generalized Estimating Equation method was used to assess whether baseline and change scores in clinical and psychosocial are associated with DRD over time. RESULTS: Complete data was available for 73 patients, with mean age 44 (SD 12.5) years and 67% males. Persistent DRD was experienced by 21% of the patients. In the final model, baseline HRQoL (OR = 0.56, p < 0.05) and change score of EDS (OR = 1.22, p < 0.05) was significantly associated with DRD over time. CONCLUSIONS: EDS might be a surrogate marker for persistent DRD and should be explored in larger samples of population to confirm the findings from this study.

Managing multiple chronic conditions in Singapore - Exploring the perspectives and experiences of family caregivers of patients with diabetes and end stage renal disease on haemodialysis.

OBJECTIVE: Diabetes mellitus (DM) is the commonest cause of end stage renal disease (ESRD). Despite increasing DM-ESRD prevalence and high dependency on care, there is a lack of literature on DM-ESRD caregivers. We sought to explore the perspectives and experiences of caregivers of patients with DM undergoing haemodialysis in Singapore. DESIGN: This study employed an exploratory, qualitative design comprising in-depth interviews with caregivers of DM-ESRD patients. METHODS: Semi-structured interviews were conducted with a sample of 20 family caregivers (54.2 ± 12.6 years; 75% female) of DM-ESRD patients. Data were analysed using Thematic Analysis. RESULTS: Key caregiving challenges identified were managing diet, care recipients' emotions and mobility dependence. Patients' emotional reactions caused interpersonal conflicts and hindered treatment management. Difficulties in dietary management were linked to patients' erratic appetite, caregivers' lack/poor understanding of the dietary guidelines and caregivers' low perceived competence. Limited resources in terms of social support and finances were also noted. Physical and psychological well-being and employment were adversely affected by caregiving role. CONCLUSION: This study highlights distinctive aspects of the DM-ESRD caregiving experience, which impact on caregivers' health and challenge care. Disease management programmes should be expanded to support caregivers in dealing with multimorbidity.

Diagnosis of diabetes mellitus using HbA1c in Asians: relationship between HbA1c and retinopathy in a multiethnic Asian population.

CONTEXT: Hemoglobin A1c (HbA1c) ≥ 6.5% (47.5 mmol/mol) has recently been included as a criterion for the diagnosis of diabetes mellitus. It is unclear whether this criterion is appropriate in Asians. OBJECTIVE: To examine the relationship between HbA1c and diabetes-specific moderate retinopathy in Asian ethnic groups. DESIGN, SETTING, AND PARTICIPANTS: Four independent population-based cross-sectional studies (2004-2011) in Singapore representing the three major Asian ethnic groups (n = 13 170 adults aged ≥ 25 y: Chinese, 5834; Malays, 3596; and Indians, 3740). MAIN OUTCOME: Moderate retinopathy was assessed from digital retinal photographs and defined as a level >43 using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Sensitivity, specificity, positive and negative predictive values, and the area under the receiver operating characteristic curve for detecting moderate retinopathy were compared across ethnic groups at different HbA1c cut-points. RESULTS: HbA1c levels were higher in Indians and Malays compared to Chinese (P < .001). The prevalence of moderate retinopathy below HbA1c <6.5% was <1% in all ethnic groups. At HbA1c ≥ 6.5%, the sensitivity for detecting moderate retinopathy was lower in Chinese subjects compared to Indians and Malays (75.8 vs 86.0 and 85.3%), but specificity (89.7 vs 71.9 and 76.3%) was higher; however, positive predictive value and negative predictive value were similar among Chinese, Indians, and Malays (10.5, 12.3, 12.4%; and 99.6, 99.1, 99.2%, respectively). The AUCs were similar across all three ethnic groups (0.861, 0.851, and 0.853). CONCLUSIONS: Our study supports the use of HbA1c for diagnosing diabetes in Asians. Despite some interethnic variation in the relationship of HbA1c and retinopathy, a cut-point of 6.5% performs reasonably well in the three major Asian ethnic groups.

Automated segmentation of visceral and subcutaneous (deep and superficial) adipose tissues in normal and overweight men.

PURPOSE: To develop an automatic segmentation algorithm to classify abdominal adipose tissues into visceral fat (VAT), deep (DSAT), and superficial (SSAT) subcutaneous fat compartments and evaluate its performance against manual segmentation. MATERIALS AND METHODS: Data were acquired from 44 normal (BMI 18.0-22.9 kg/m(2) ) and 38 overweight (BMI 23.0-29.9 kg/m(2) ) subjects at 3T using a two-point Dixon sequence. A fully automatic segmentation algorithm was developed to segment the fat depots. The first part of the segmentation used graph cuts to separate the subcutaneous and visceral adipose tissues and the second step employed a modified level sets approach to classify deep and superficial subcutaneous tissues. The algorithmic results of segmentation were validated against the ground truth generated by manual segmentation. RESULTS: The proposed algorithm showed good performance with Dice similarity indices of VAT/DSAT/SSAT: 0.92/0.82/0.88 against the ground truth. The study of the fat distribution showed that there is a steady increase in the proportion of DSAT and a decrease in the proportion of SSAT with increasing obesity. CONCLUSION: The presented technique provides an accurate approach for the segmentation and quantification of abdominal fat depots.

New measure of insulin sensitivity predicts cardiovascular disease better than HOMA estimated insulin resistance.

CONTEXT: Accurate assessment of insulin sensitivity may better identify individuals at increased risk of cardio-metabolic diseases. OBJECTIVES: To examine whether a combination of anthropometric, biochemical and imaging measures can better estimate insulin sensitivity index (ISI) and provide improved prediction of cardio-metabolic risk, in comparison to HOMA-IR. DESIGN AND PARTICIPANTS: Healthy male volunteers (96 Chinese, 80 Malay, 77 Indian), 21 to 40 years, body mass index 18-30 kg/m(2). Predicted ISI (ISI-cal) was generated using 45 randomly selected Chinese through stepwise multiple linear regression, and validated in the rest using non-parametric correlation (Kendall's tau τ). In an independent longitudinal cohort, ISI-cal and HOMA-IR were compared for prediction of diabetes and cardiovascular disease (CVD), using ROC curves. SETTING: The study was conducted in a university academic medical centre. OUTCOME MEASURES: ISI measured by hyperinsulinemic euglycemic glucose clamp, along with anthropometric measurements, biochemical assessment and imaging; incident diabetes and CVD. RESULTS: A combination of fasting insulin, serum triglycerides and waist-to-hip ratio (WHR) provided the best estimate of clamp-derived ISI (adjusted R(2) 0.58 versus 0.32 HOMA-IR). In an independent cohort, ROC areas under the curve were 0.77±0.02 ISI-cal versus 0.76±0.02 HOMA-IR (p>0.05) for incident diabetes, and 0.74±0.03 ISI-cal versus 0.61±0.03 HOMA-IR (p<0.001) for incident CVD. ISI-cal also had greater sensitivity than defined metabolic syndrome in predicting CVD, with a four-fold increase in the risk of CVD independent of metabolic syndrome. CONCLUSIONS: Triglycerides and WHR, combined with fasting insulin levels, provide a better estimate of current insulin resistance state and improved identification of individuals with future risk of CVD, compared to HOMA-IR. This may be useful for estimating insulin sensitivity and cardio-metabolic risk in clinical and epidemiological settings.

Patterns of physical activity in different domains and implications for intervention in a multi-ethnic Asian population: a cross-sectional study.

BACKGROUND: The benefits of regular physical activity for quality of life and disease prevention have been well documented. Identification of low activity groups would facilitate interventional programs. Many studies have focussed on leisure time activity, which may not capture the spectrum of physical activity relevant to disease prevention. Furthermore, few studies have been conducted in urban Asian settings. METHODS: We evaluated physical activity in different domains (leisure time, occupational, household and transportation) and its sociodemographic determinants in 4750 adult Chinese, Malay, and Asian Indian Singaporeans. Physical activity was assessed using locally validated questionnaires. RESULTS: Occupational and household activity contributed substantially more to total physical activity than leisure time or transportation activity. However, when only activity of at least moderate intensity was considered leisure time activity contributed most to total physical activity. Higher socio-economic status was associated with more leisure time activity, but less total physical activity due to reduced activity in the other domains. Chinese ethnicity was also associated with less total physical activity as a result of less activity in non-leisure time domains. CONCLUSIONS: In assessing levels of physical activity and recommending changes, it is important to consider physical activity in different domains. Focus on leisure-time physical activity alone could identify the wrong groups for intervention and miss opportunities for increasing physical activity in populations.

Alström syndrome and cecal volvulus in 2 siblings.

Alström syndrome (ALMS1, MIM 203800) is a rare, autosomal recessively inherited monogenic condition caused by mutations in the ALMS1 gene located on the short arm of chromosome 2. ALMS1 is a multisystem condition characterized by childhood onset of blindness, dilated cardiomyopathy, sensorineural hearing loss, renal failure, fibrotic lung disease, and metabolic abnormalities, including hypertriglyceridemia, liver steatosis, insulin resistance, type 2 diabetes mellitus, and obesity. We describe 2 siblings with ALMS who presented with the potentially life-threatening condition of acute cecal volvulus, an association not previously reported. Cecal volvulus may, therefore, represent a significant new feature of the Alström syndrome.