Comparison of existing methods of low-density lipoprotein cholesterol estimation in patients with type 2 diabetes mellitus.

Introduction: Elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). Direct LDL-C measurement is not widely performed. LDL-C is routinely calculated using the Friedewald equation (FLDL), which is inaccurate at high triglyceride (TG) or low LDL-C levels. We aimed to compare this routine method with other estimation methods in patients with type 2 diabetes mellitus (T2DM), who typically have elevated TG levels and ASCVD risk. Method: We performed a retrospective cohort study on T2DM patients from a multi-institutional diabetes registry in Singapore from 2013 to 2020. LDL-C values estimated by the equations: FLDL, Martin/Hopkins (MLDL) and Sampson (SLDL) were compared using measures of agreement and correlation. Subgroup analysis comparing estimated LDL-C with directly measured LDL-C (DLDL) was conducted in patients from a single institution. Estimated LDL-C was considered discordant if LDL-C was <1.8mmol/L for the index equation and ≥1.8mmol/L for the comparator. Results: A total of 154,877 patients were included in the final analysis, and 11,475 patients in the subgroup analysis. All 3 equations demonstrated strong overall correlation and goodness-of-fit. Discordance was 4.21% for FLDL-SLDL and 6.55% for FLDL-MLDL. In the subgroup analysis, discordance was 21.57% for DLDL-FLDL, 17.31% for DLDL-SLDL and 14.44% for DLDL-MLDL. All discordance rates increased at TG levels >4.5mmol/L. Conclusion: We demonstrated strong correlations between newer methods of LDL-C estimation, FLDL, and DLDL. At higher TG concentrations, no equation performed well. The Martin/Hopkins equation had the least discordance with DLDL, and may minimise misclassification compared with the FLDL and SLDL.

Baseline characteristics of participants in the Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) Program.

OBJECTIVE: The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) Program is a diabetes prevention trial comparing the diabetes conversion rate at 3 years between the intervention group, which receives the incentivized lifestyle intervention program with stepwise addition of metformin, and the control group, which receives the standard of care. We describe the baseline characteristics and compare Pre-DICTED participants with other diabetes prevention trials cohort. RESEARCH DESIGN AND METHODS: Participants were aged between 21 and 64 years, overweight (body mass index (BMI) ≥23.0 kg/m2), and had pre-diabetes (impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)). RESULTS: A total of 751 participants (53.1% women) were randomized. At baseline, mean (SD) age was 52.5 (8.5) years and mean BMI (SD) was 29.0 (4.6) kg/m2. Twenty-three per cent had both IFG and IGT, 63.9% had isolated IGT, and 13.3% had isolated IFG. Ethnic Asian Indian participants were more likely to report a family history of diabetes and had a higher waist circumference, compared with Chinese and Malay participants. Women were less likely than men to meet the physical activity recommendations (≥150 min of moderate-intensity physical activity per week), and dietary intake varied with both sex and ethnicity. Compared with other Asian diabetes prevention studies, the Pre-DICTED cohort had a higher mean age and BMI. CONCLUSION: The Pre-DICTED cohort represents subjects at high risk of diabetes conversion. The study will evaluate the effectiveness of a community-based incentivized lifestyle intervention program in an urban Asian context.

Trends in cardiovascular risk factors and treatment goals in patients with diabetes in Singapore-analysis of the SingHealth Diabetes Registry.

BACKGROUND: Asian populations are at high risk of diabetes and related vascular complications. We examined risk factor control, preventive care, and disparities in these trends among adults with diabetes in Singapore. METHODS: The sample included 209,930 adults with diabetes aged≥18 years from a multi-institutional SingHealth Diabetes Registry between 2013 and 2019 in Singapore. We performed logistic generalized estimating equations (GEEs) regression analysis and used linear mixed effect modeling to evaluate the temporal trends. RESULTS: Between 2013 and 2019, the unadjusted control rates of glycated hemoglobin (4.8%, 95%CI (4.4 to 5.1) and low-density lipoprotein cholesterol (LDL-C) (11.5%, 95%CI (11.1 to 11.8)) improved, but blood pressure (BP) control worsened (systolic BP (SBP)/diastolic BP (DBP) <140/90 mmHg: -6.6%, 95%CI (-7.0 to -6.2)). These trends persisted after accounting for the demographics including age, gender, ethnicity, and housing type. The 10-year adjusted risk for coronary heart disease (CHD) (3.4%, 95% (3.3 to 3.5)) and stroke (10.4%, 95% CI (10.3 to 10.5)) increased. In 2019, the control rates of glycated hemoglobin, BP (SBP/DBP<140/90 mmHg), LDL-C, each, and all three risk factors together, accounted for 51.5%, 67.7%, 72.2%, and 24.4%, respectively. CONCLUSIONS: Trends in risk factor control improved for glycated hemoglobin and LDL-C, but worsened for BP among diabetic adults in Singapore from 2013 to 2019. Control rates for all risk factors remain inadequate.

Psychiatry in primary care and training: a Singapore perspective.

Proactive steps have been taken by the public healthcare sector in Singapore to bring about awareness of mental health in terms of mental health promotion, early recognition and seeking help, with an increasing focus on making mental healthcare accessible and delivering it within the community setting where possible. Examples are the Mental Health General Practitioner Partnership Programme, National Mental Health Blueprint and Community Mental Health Masterplan. The current challenge is to train and involve more primary care doctors in the care of persons with mental health conditions. This paper describes the goals of psychiatric training in primary care and the avenues for training that are available to family medicine residents and family physicians.

The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) program: study protocol for a randomized controlled trial.

BACKGROUND: Community-based diabetes prevention programs varied widely in effectiveness, and the intervention strategy consisting of lifestyle interventions, stepwise addition of metformin, and financial incentives has not been studied in real-world clinical practice settings. The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) trial is a pragmatic trial that aims to compare the effectiveness of a community-based stepwise diabetes prevention program with added financial incentives (intervention) versus the standard of care (control) in reducing the risk of type 2 diabetes over 3 years among overweight or obese individuals with pre-diabetes. METHODS: This is an open-label, 1:1 randomized controlled trial which aims to recruit 846 adult individuals with isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), or both IFG and IGT from Singapore. Intervention arm participants attend 12 group-based sessions (2 nutrition workshops, 9 exercise sessions, and a goal-setting workshop) delivered at community sites (weeks 1 to 6), receive weekly physical activity and nutrition recommendations delivered by printed worksheets (weeks 7 to 12), and receive monthly health tips delivered by text messages (months 4 to 36). From month 6 onwards, intervention arm participants who remain at the highest risk of conversion to diabetes are prescribed metformin. Intervention arm participants are also eligible for a payment/rewards program with incentives tied to attendance at the group sessions and achievement of the weight loss target (5% of baseline weight). All participants are assessed at baseline, month 3, month 6, and every 6 months subsequently till month 36. The primary endpoint is the proportion of participants with diabetes at 3 years. Secondary endpoints include the mean change from baseline at 3 years in fasting plasma glucose, 2-hour plasma glucose, HbA1c, body weight, body mass index, physical activity, and dietary intake. DISCUSSION: The Pre-DICTED trial will provide evidence of the effectiveness and feasibility of a community-based stepwise diabetes prevention program with added financial incentives for individuals with pre-diabetes in Singapore. The study will provide data for a future cost-effectiveness analysis, which will be used to inform policymakers of the value of a nationwide implementation of the diabetes prevention program. TRIAL REGISTRATION: ClinicalTrials.gov NCT03503942 . Retrospectively registered on April 20, 2018. Protocol version: 5.0 Date: 1 March 2019.

Precise quantification of cellular uptake of cell-penetrating peptides using fluorescence-activated cell sorting and fluorescence correlation spectroscopy.

Cell-penetrating peptides (CPPs) have emerged as a potentially powerful tool for drug delivery due to their ability to efficiently transport a whole host of biologically active cargoes into cells. Although concerted efforts have shed some light on the cellular internalization pathways of CPPs, quantification of CPP uptake has proved problematic. Here we describe an experimental approach that combines two powerful biophysical techniques, fluorescence-activated cell sorting (FACS) and fluorescence correlation spectroscopy (FCS), to directly, accurately and precisely measure the cellular uptake of fluorescently-labeled molecules. This rapid and technically simple approach is highly versatile and can readily be applied to characterize all major CPP properties that normally require multiple assays, including amount taken up by cells (in moles/cell), uptake efficiency, internalization pathways, intracellular distribution, intracellular degradation and toxicity threshold. The FACS-FCS approach provides a means for quantifying any intracellular biochemical entity, whether expressed in the cell or introduced exogenously and transported across the plasma membrane.

Diabetes mellitus: the first visit.

Diabetes mellitus is an 'insulin problem' as the maintenance of normoglycaemia is affected by either reduced pancreatic insulin production or cellular insulin resistance. During a patient's first visit for type 2 diabetes mellitus, there are several consultation tasks that the doctor should consider. First, the doctor has to disclose the diagnosis. Second, there is a need to correct any myths and misconceptions that the patient may have on the disease. Next, to allow the doctor to provide patient-specific disease education and advice on lifestyle modifications and goal setting, the biopsychosocial impact of the disease on the patient should be assessed, and relevant lifestyle information gathered. Lastly, screening for the complications of diabetes mellitus and its associated medical conditions should be planned.

Limited knowledge of chronic kidney disease among primary care patients--a cross-sectional survey.

BACKGROUND: Kidney disease is the 9th leading cause of death in Singapore. While preventive effects have focused on early detection and education, little is known about the knowledge level of chronic kidney disease (CKD) locally. We seek to evaluate the knowledge of CKD among primary care patients. METHODS: We conducted a cross-sectional survey of a convenience sample of 1520 patients from 3 primary care centers. Those with existing CKD or on dialysis were excluded. Knowledge was assessed based on 7 questions on CKD in the self-administered questionnaire. One point was given for each correct answer with a maximum of 7 points. RESULTS: 1435 completed all 7 questions on CKD. Mean age was 48.9 ± 5.0 (SD) years. 50.9% were male. 62.3% had a secondary and below education and 52.4% had a monthly household income of ≤ $2000. 43.7% had chronic diseases. Mean score was 3.44 ± 1.53 (out of a maximum of 7). Median score was 4. In multivariate logistic regression, being older {>60 years [Odds Ratio (OR) 0.50, 95% Confidence Interval (CI) 0.32-0.79]; 40-60 years (OR 0.62, 95% CI 0.43,0.89)}, less educated [up to primary education (OR 0.33, 95% CI 0.22-0.49)], having a lower monthly household income [