Kavita Venkataraman

Associations between complications and health‐related quality of life in individuals with diabetes

Type 2 diabetes and associated complications adversely affect health‐related quality of life (HRQoL). However, it is unclear whether different complications have the same or different associations with HRQoL. We examined associations between retinopathy, nephropathy, peripheral neuropathy (microvascular), coronary heart disease, stroke and peripheral arterial disease (macrovascular) in diabetes and HRQoL.

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.

Associations Between Ethnicity, Body Composition, and Bone Mineral Density in a Southeast Asian Population

CONTEXT AND OBJECTIVE Chinese men in Singapore have a higher incidence of hip fractures than Malay and Indian men. We investigated whether there were corresponding ethnic differences in peak bone mineral density (BMD) in young men and whether differences in body composition influenced peak BMD. DESIGN AND SETTING This was a cross-sectional study of healthy volunteers in a tertiary medical center. PARTICIPANTS A total of 100 Chinese, 82 Malay, and 80 Indian men aged 21 to 40 years, with body mass index between 18 and 30 kg/m(2) underwent dual-energy x-ray absorptiometry to assess BMD, lean mass (LM) and fat mass (FM), and magnetic resonance imaging to quantify abdominal subcutaneous and visceral adipose tissue. Multiple linear regression models, with adjustment for age and height (as a proxy for skeletal size), were used. RESULTS Malay and Indian men had significantly higher BMD than Chinese men at the lumbar spine (Malay: B, 0.06 ± 0.02, P = .001; Indian: B, 0.03 ± 0.02, P = .049), femoral neck (Malay: B 0.04 ± 0.02, P = .034; Indian: B, 0.04 ± 0.02, P = .041), hip (Malay: B, 0.05 ± 0.02, P = .016; Indian: B, 0.06 ± 0.02, P = .001), and ultradistal radius (Malay: B, 0.03 ± 0.01, P < .001; Indian: B, 0.02 ± 0.01, P = .029), and this difference was retained after adjustment for LM and FM, except in Malay men at the femoral neck and in Indian men at the ultradistal radius. LM was an important independent determinant of BMD at all sites, whereas FM, subcutaneous adipose tissue, and visceral adipose tissue were not significantly associated with BMD at any site. CONCLUSIONS Lower peak BMD in Chinese men may partly explain the higher fracture incidence in this ethnic group. Further studies are needed to elucidate the reasons for these ethnic differences in bone accumulation.

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.

Platform Comparison for Evaluation of ALK Protein Immunohistochemical Expression, Genomic Copy Number and Hotspot Mutation Status in Neuroblastomas

ALK is an established causative oncogenic driver in neuroblastoma, and is likely to emerge as a routine biomarker in neuroblastoma diagnostics. At present, the optimal strategy for clinical diagnostic evaluation of ALK protein, genomic and hotspot mutation status is not well-studied. We evaluated ALK immunohistochemical (IHC) protein expression using three different antibodies (ALK1, 5A4 and D5F3 clones), ALK genomic status using single-color chromogenic in situ hybridization (CISH), and ALK hotspot mutation status using conventional Sanger sequencing and a next-generation sequencing platform (Ion Torrent Personal Genome Machine (IT-PGM)), in archival formalin-fixed, paraffin-embedded neuroblastoma samples. We found a significant difference in IHC results using the three different antibodies, with the highest percentage of positive cases seen on D5F3 immunohistochemistry. Correlation with ALK genomic and hotspot mutational status revealed that the majority of D5F3 ALK-positive cases did not possess either ALK genomic amplification or hotspot mutations. Comparison of sequencing platforms showed a perfect correlation between conventional Sanger and IT-PGM sequencing. Our findings suggest that D5F3 immunohistochemistry, single-color CISH and IT-PGM sequencing are suitable assays for evaluation of ALK status in future neuroblastoma clinical trials.

Determinants of individuals' participation in integrated chronic disease screening in Singapore.

Background A large pool of patients with chronic diseases remains undiagnosed globally and in Singapore. We explored factors associated with participation in a health screening exercise, using revealed preference, that is, actual attendance, to understand why people remain undiagnosed with chronic diseases. Methods A cross-sectional, community-based sample of Singapore residents was invited to participate in home interviews, and subsequently to attend centre-based health screening, between 2004 and 2007. Determinants of health screening participation were identified using logistic regression models based on Andersens Behavioral Model. Results Of the 6366 participants who completed health interview, 4092 attended the health screening, while 2274 did not. Older age, Chinese or Indian ethnicity, higher education levels, greater intake of monounsaturated fat, greater transport and leisure-time physical activity were the key predisposing factors associated with greater health screening participation. Greater family cohesion was the key associated enabling factor, while previous diagnosis of dyslipidaemia or musculoskeletal conditions, absence of previously diagnosed diabetes or hypertension and lower perceived physical health were the associated need factors. Conclusions Our study suggests that ethnicity, education, family cohesion, healthy behaviour patterns and perceived physical health status were key determinants of health screening participation. Enhancing the cultural competence of preventive health services may help increase participation of these groups in screening efforts and reduce the proportions of undiagnosed chronic disease in the community.

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.

Psychometric analysis of an eating behaviour questionnaire for an overweight and obese Chinese population in Singapore

OBJECTIVES Previous studies reveal that the Three-Factor Eating Questionnaire (TFEQ), which assesses eating behaviour, performs differently across population groups and cultures. We aimed to identify the factor structure that is most appropriate to capture eating behaviour in an overweight and obese Chinese population in Singapore. METHODS TFEQ-51 was administered to 444 Chinese subjects pooled from four separate studies and scored according to various alternative versions of the TFEQ. Confirmatory factor analyses and goodness of fit indices were used to determine the most appropriate factor structure. Known-group validity analyses were conducted. RESULTS Niemeiers Disinhibition Factors and the TFEQ-R18 factor structures were found to be the most applicable in our population based on goodness of fit indices, with a x(2)/df ratio of <3, RMSEA of ≤ 0.6 and a CFI value of >0.9 for both. Only two of three factors (Emotional Eating and Uncontrolled Eating) of the TFEQ-R18 showed good internal consistency, while none of Niemeiers Disinhibition Factors showed good internal consistency. Known-group validity showed that Emotional Eating and Internal Disinhibition were significantly associated with higher BMI. CONCLUSION We found that the TFEQ-R18 factor structure is the most appropriate and practical for use in measuring eating behaviour in an overweight and obese Chinese population in Singapore.