Eric Yin Hao Khoo

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

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.

Body Fat Partitioning Does Not Explain the Interethnic Variation in Insulin Sensitivity Among Asian Ethnicity: The Singapore Adults Metabolism Study

We previously showed that ethnicity modifies the association between adiposity and insulin resistance. We sought to determine whether differential body fat partitioning or abnormalities in muscle insulin signaling associated with higher levels of adiposity might underlie this observation. We measured the insulin sensitivity index (ISI), percentage of body fat (%body fat), visceral (VAT) and subcutaneous (SAT) adipose tissue, liver fat, and intramyocellular lipids (IMCL) in 101 Chinese, 82 Malays, and 81 South Asians, as well as phosphorylated (p)-Akt levels in cultured myoblasts from Chinese and South Asians. Lean Chinese and Malays had higher ISI than South Asians. Although the ISI was lower in all ethnic groups when %body fat was higher, this association was stronger in Chinese and Malays, such that no ethnic differences were observed in overweight individuals. These ethnic differences were observed even when %body fat was replaced with fat in other depots. Myoblasts obtained from lean South Asians had lower p-Akt levels than those from lean Chinese. Higher adiposity was associated with lower p-Akt levels in Chinese but not in South Asians, and no ethnic differences were observed in overweight individuals. With higher %body fat, Chinese exhibited smaller increases in deep SAT and IMCL compared with Malays and South Asians, which did not explain the ethnic differences observed. Our study suggests that body fat partitioning does not explain interethnic differences in insulin sensitivity among Asian ethnic groups. Although higher adiposity had greater effect on skeletal muscle insulin sensitivity among Chinese, obesity-independent pathways may be more relevant in South Asians.

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.

Variability in fasting lipid and glycogen contents in hepatic and skeletal muscle tissue in subjects with and without type 2 diabetes: a 1H and 13C MRS study.

The measurement of tissue lipid and glycogen contents and the establishment of normal levels of variability are important when assessing changes caused by pathology or treatment. We measured hepatic and skeletal muscle lipid and glycogen levels using 1H and 13C MRS at 3 T in groups of subjects with and without type 2 diabetes. Within‐visit reproducibility, due to repositioning and instrument errors was determined from repeat measurements made over 1 h. Natural variability was assessed from separate measurements made on three occasions over 1 month. Hepatic lipid content was greater in subjects with diabetes relative to healthy subjects (p = 0.03), whereas levels of hepatic and skeletal muscle glycogen, and of intra‐ and extra‐myocellular lipid, were similar. The single‐session reproducibility values (coefficient of variation, CV) for hepatic lipid content were 12% and 7% in groups of subjects with and without diabetes, respectively. The variability of hepatic lipid content over 1 month was greater than the reproducibility, with CV = 22% (p = 0.08) and CV = 44% (p = 0.004) in subjects with and without diabetes, respectively. Similarly, levels of variation in basal hepatic glycogen concentrations (subjects with diabetes, CV = 38%; healthy volunteers, CV = 35%) were significantly larger than single‐session reproducibility values (CV = 17%, p = 0.02 and CV = 13%, p = 0.05, respectively), indicating substantial biological changes in basal concentrations over 1 month. There was a decreasing correlation in measurements of both hepatic lipid and glycogen content with increasing time between scans. Levels of variability in intra‐ and extra‐myocellular lipid in the soleus muscle, and glycogen concentrations in the gastrocnemius muscle, tended to be larger than expected from single‐session reproducibility, although these did not reach significance. Copyright

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/m2. 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 (Kendalls 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 R2 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.

Improving outcomes in patients with coexisting multimorbid conditions—the development and evaluation of the combined diabetes and renal control trial (C-DIRECT): study protocol

Introduction Diabetes mellitus (DM) is the most common cause of end-stage renal disease (ESRD). Patients with diabetes on dialysis have worse clinical outcomes and increased psychological burden. The need to manage the combined treatment demands for both conditions is particularly challenging yet there is paucity of data of the barriers preventing optimal management to combined therapy for diabetes and kidney failure. The study aims to explore needs of patients and develop an intervention to enable people with diabetes and ESRD to better manage both their conditions. Methods and analysis A two-phase study comprising a mixed method observational study (phase I) and a feasibility trial (phase II). Phase I will seek to document outcomes and needs of the population (patients with DM-ESRD) and seek input on preferred delivery/implementation for the programme. Data will be collected with in-depth interviews with patients, caregivers and healthcare providers (N=50), and from a questionnaire-based survey (N=170). Phase 2 will build on these data to design and test the feasibility of a practical, low-intensity, clinic-integrated intervention using a self-management paradigm. The intervention will primarily seek to support behavioural change so as to improve adherence and clinical outcomes for DM as well as for ESRD. For the feasibility trial, we will be evaluating acceptability, retention and completion rates of the programme. Ethics and dissemination The study protocol has been approved by the local ethics committee and written informed consent is required from every participant. Findings will be disseminated through journals, conferences and will be used to create a fully manualised intervention (materials) and training course for facilitators.

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.

Ethnic Differences in the Role of Adipocytokines Linking Abdominal Adiposity and Insulin Sensitivity Among Asians.

CONTEXT Among Asian ethnic groups, Chinese or Malays are more insulin sensitive than South Asians, in particular in lean individuals. We have further reported that body fat partitioning did not explain this ethnic difference in insulin sensitivity. OBJECTIVE We examined whether adipocytokines might explain the ethnic differences in the relationship between obesity and insulin resistance among the three major ethnic groups in Singapore. DESIGN AND PARTICIPANTS This was a cross-sectional study of 101 Chinese, 82 Malays, and 81 South Asian men. Insulin sensitivity index (ISI) was measured using hyperinsulinemic euglycemic clamp. Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were quantified using magnetic resonance imaging. MAIN OUTCOME MEASURES Plasma total and high-molecular-weight adiponectin, leptin, visfatin, apelin, IL-6, fibroblast growth factor 21 (FGF21), retinol binding protein-4 (RBP 4), and resistin were measured using enzyme-linked immunoassays. RESULTS Principle component (PC) analysis on the adipocytokines identified three PCs, which explained 49.5% of the total variance. Adiponectin loaded negatively, and leptin and FGF21 loaded positively onto PC1. Visfatin, resistin, and apelin all loaded positively onto PC2. IL-6 loaded positively and RBP-4 negatively onto PC3. Only PC1 was negatively associated with ISI in all ethnic groups. In the path analysis, SAT and VAT were negatively associated with ISI in Chinese and Malays without significant mediatory role of PC1. In South Asians, the relationship between VAT and ISI was mediated partly through PC1, whereas the relationship between SAT and ISI was mediated mainly through PC1. CONCLUSIONS The relationships between abdominal obesity, adipocytokines and insulin sensitivity differ between ethnic groups. Adiponectin, leptin, and FGF21 play a mediating role in the relationship between abdominal adiposity and insulin resistance in South Asians, but not in Malays or Chinese.

Psychometric Properties of the Problem Areas in Diabetes (PAID) Instrument in Singapore

Background Emotional distress is an important dimension in diabetes, and several instruments have been developed to measure this aspect. The Problem Areas in Diabetes (PAID) scale is one such instrument which has demonstrated validity and reliability in Western populations, but its psychometric properties in Asian populations have not been examined. Methods This was a secondary analysis of data from patients with Type 2 diabetes mellitus recruited through convenience sampling from a diabetes specialist outpatient clinic in Singapore. The following psychometric properties were assessed: Construct validity through confirmatory factor analysis (CFA) and Rasch analysis, concurrent validity through correlation with related scales (Kessler Psychological Distress Scale, Diabetes Health Profile—psychological distress, Audit of Diabetes Dependent Quality of Life), reliability through assessment of internal consistency and floor and ceiling effects, and sensitivity by estimating effect sizes for known clinical and social functioning groups. Results 203 patients with mean age of 45±12 years were analysed. None of the previously published model structures achieved a good fit on CFA. On Rasch analysis, four items showed poor fit and were removed. The abridged 16-item PAID mapped to a single latent trait, with a high degree of internal consistency (Cronbach ɑ 0.95), but significant floor effect (24.6% scoring at floor). Both 20-item and 16-item PAID scores were moderately correlated with scores of related scales, and sensitive to differences in clinical and social functioning groups, with large effect sizes for glycemic control and diabetes related complications, nephropathy and neuropathy. Conclusion The abridged 16-item PAID measures a single latent trait of emotional distress due to diabetes whereas the 20-item PAID appears to measures more than one latent trait. However, both the 16-item and 20-item PAID versions are valid, reliable and sensitive for use among Singaporean patients with diabetes.

Validation of prediction equations for resting energy expenditure in Singaporean Chinese men

Accurate prediction of resting energy expenditure (REE) is important in establishing adequate dietary intake goals for effective weight management. Previous studies have shown that the validity of an energy prediction equation may depend on the ethnicity of the population. Validation studies are lacking in the Singaporean Chinese population. A total of 96 healthy Singaporean Chinese males of age 21–40 years and body mass index (BMI) 18.5–30.0 kg/m2 participated in this study. REE was measured by indirect calorimetry and compared with REE predicted using existing equations. Validity was evaluated on the basis of mean bias and percentage of subjects predicted within ±10% of REE measured. In addition, Bland and Altman analyses were performed. No significant difference was observed between the mean levels of measured and predicted REE derived from the Owen equation. The Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU), Harris–Benedict and Mifflin equations significantly overestimated the mean measured REE by 7.5%, 6.0% and 2.4% respectively. Percentage of valid predictions for FAO/WHO/UNU, Harris–Benedict, Mifflin and Owen equations were 60%, 67%, 75% and 73% respectively. Bland and Altman analyses demonstrated poor agreement for all equations. The Owen equation provided a valid estimation of REE in Singaporean Chinese men at a group level. However, the individual errors of the equations were unacceptable high and may have limited utility in making clinical decisions on nutritional requirements.