Long-term effects of bariatric surgery on cardiovascular risk factors in Singapore.

INTRODUCTION: Bariatric surgery is considered an effective treatment for weight loss and for improving the metabolic profile of patients with obesity. Obesity-related comorbidities such as hyperlipidaemia and type 2 diabetes mellitus (DM) are significant cardiovascular risk factors. Additionally, prospective clinical trials have shown that statins increase the risk of development of DM, and many patients with obesity are on statins. We retrospectively examined the effect of bariatric surgery on lipid profile, DM control and weight loss at the five-year follow-up. METHODS: In total, 104 patients undergoing bariatric surgery from 2008 to 2012 were retrospectively studied. 36 patients were on preoperative statins. Their lipid profile, DM control and weight loss were examined at the one-year and five-year follow-ups. RESULTS: Both high-density lipoprotein and triglyceride levels showed significant improvement at the one-year and five-year follow-ups (p = 0.01). Total cholesterol showed significant improvement at the one-year follow-up (-0.30 mmol/dL, p = 0.0338); however, better control was not sustained at the five-year follow-up (-0.15 mmol/dL, p = 0.133). Low-density lipoprotein did not show any considerable improvement at the one- and five-year follow-ups (-0.27 mmol/dL, p = 0.150 and -0.24 mmol/dL, p = 0.138, respectively). A statistically significant improvement in DM control was observed in these patients and in those on preoperative statins. Weight loss was sustained at one and five years. CONCLUSION: Bariatric surgery does not confer a uniform improvement in lipid profile in the long term. It does, however, induce efficient weight loss and improvement in diabetic profile, even in patients on preoperative statins.

Effects of external counter-pulsation on endothelial function assessed by peripheral artery tonometry, levels of glycaemia and metabolic markers in individuals with type 2 diabetes mellitus.

BACKGROUND AND AIMS: External counter-pulsation (ECP) generates sheer stress thereby improving endothelial function and anginal symptoms in coronary artery disease. Endothelial dysfunction is also involved in the pathogenesis of T2DM. The aim of this pilot study was to investigate the use of ECP at different doses in improving endothelial function and glycaemic markers in T2DM. METHODS: This prospective study involved 46 subjects with T2DM randomly assigned to receive 35 sessions of ECP at different regimens (0.5 h versus 1 h) and duration (7 versus 12 weeks). Endothelial function was evaluated by reactive hyperaemia index (RHI) via peripheral arterial tonometry at the start, midpoint and end of study. Other secondary outcomes included fasting glucose, HOMA-IR, HbA1c, blood pressure, lipid profile, weight and vibration sense. RESULTS: There was no change in RHI across all 3 regimens of ECP individually or collectively at the end of the study (ΔRHI +0.01%, p = 0.458). Glycaemic markers also remained unchanged at endpoint. Subgroup analysis showed an improvement in RHI (ΔRHI +20.6%, p = 0.0178) in subjects with more severe endothelial dysfunction at baseline. CONCLUSION: ECP did not show a beneficial effect on endothelial function or glycemic control in this South-East Asian population with T2DM at any of the three regimens. This may partly be explained by less severe endothelial dysfunction and less insulin resistance in our population at baseline.

Robust estimation of the effect of an exposure on the change in a continuous outcome.

BACKGROUND: The change in two measurements of a continuous outcome can be modelled directly with a linear regression model, or indirectly with a random effects model (REM) of the individual measurements. These methods are susceptible to model misspecifications, which are commonly addressed by applying monotonic transformations (e.g., Box-Cox transformation) to the outcomes. However, transforming the outcomes complicates the data analysis, especially when variable selection is involved. We propose a robust alternative through a novel application of the conditional probit (cprobit) model. METHODS: The cprobit model analyzes the ordered outcomes within each subject, making the estimate invariant to monotonic transformation on the outcome. By scaling the estimate from the cprobit model, we obtain the exposure effect on the change in the observed or Box-Cox transformed outcome, pending the adequacy of the normality assumption on the raw or transformed scale. RESULTS: Using simulated data, we demonstrated a similar good performance of the cprobit model and REM with and without transformation, except for some bias from both methods when the Box-Cox transformation was applied to scenarios with small sample size and strong effects. Only the cprobit model was robust to skewed subject-specific intercept terms when a Box-Cox transformation was used. Using two real datasets from the breast cancer and inpatient glycemic variability studies which utilize electronic medical records, we illustrated the application of our proposed robust approach as a seamless three-step workflow that facilitates the use of Box-Cox transformation to address non-normality with a common underlying model. CONCLUSIONS: The cprobit model provides a seamless and robust inference on the change in continuous outcomes, and its three-step workflow is implemented in an R package for easy accessibility.

Measurement equivalence of the English, Chinese and Malay versions of the World Health Organization quality of life (WHOQOL-BREF) questionnaires.

BACKGROUND: The WHOQOL-BREF is a widely used questionnaire for measuring quality of life. It is important to establish the measurement equivalence of various language versions of WHOQOL-BREF so that scores from different language versions may be pooled together. The primary aim of this article was to evaluate the measurement equivalence of the English, Chinese and Malay versions of the WHOQOL-BREF. METHODS: We analysed data from the previously published, cross-sectional, WONDERS study and used linear regression models to adjust for potential confounding variables. Based on equivalence clinical trial methods, measurement equivalence was assessed by comparing 90% confidence interval (CI) of differences in scores across language versions with a predefined equivalence margin of 0.3 SD. Equivalence was achieved if the 90% CI fell within 0.3 SD. Data from 1203 participants, aged above 21 years, were analysed. RESULTS: Participants who completed the different language versions of WHOQOL-BREF expectedly differed in age, ethnicity, highest education level, marital status, smoking status and Body Mass Index (BMI). The English and Malay language versions were definitely equivalent for all domains. The English and Chinese language versions were definitely equivalent for physical and environmental domains but inconclusive for psychological and social domains. Likewise, for Chinese and Malay versions. CONCLUSION: The English, Chinese and Malay language versions of the WHOQOL-BREF questionnaire may be considered equivalent, with evidence being more robust for some domains than the others. Given the large number of people who speak/ read Chinese and Malay, this study has widespread relevance.

A stratification approach using logit-based models for confounder adjustment in the study of continuous outcomes.

The control of confounding is an area of extensive epidemiological research, especially in the field of causal inference for observational studies. Matched cohort and case-control study designs are commonly implemented to control for confounding effects without specifying the functional form of the relationship between the outcome and confounders. This paper extends the commonly used regression models in matched designs for binary and survival outcomes (i.e. conditional logistic and stratified Cox proportional hazards) to studies of continuous outcomes through a novel interpretation and application of logit-based regression models from the econometrics and marketing research literature. We compare the performance of the maximum likelihood estimators using simulated data and propose a heuristic argument for obtaining the residuals for model diagnostics. We illustrate our proposed approach with two real data applications. Our simulation studies demonstrate that our stratification approach is robust to model misspecification and that the distribution of the estimated residuals provides a useful diagnostic when the strata are of moderate size. In our applications to real data, we demonstrate that parity and menopausal status are associated with percent mammographic density, and that the mean level and variability of inpatient blood glucose readings vary between medical and surgical wards within a national tertiary hospital. Our work highlights how the same class of regression models, available in most statistical software, can be used to adjust for confounding in the study of binary, time-to-event and continuous outcomes.

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.