The role of triglyceride-glucose index in the prediction of the development of hypertension – findings from a community cohort in Singapore / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#Triglyceride-glucose index (TyGI) is an emerging surrogate marker of insulin resistance. We aim to explore the role of triglyceride-glucose index in the prediction of the development of hypertension.@*Methodology@#nducted a retrospective cohort study that included 3,183 study participants identified from a community health screening programme who had no baseline hypertension and were then followed up after an average of 1.7 years. Cox proportional-hazard model was used to assess the association between risk of incident hypertension and TyGI in quartiles, while adjusting for demographics and clinical characteristics.@*Results@#Hypertension occurred in 363 study participants (11.4%). Those who developed hypertension had higher TyGI [8.6 (IQR 8.2-9.0)] than those who did not [8.2 (IQR 8.0-8.7)] (p<0.001). Significant association between TyGI and hypertension was observed in both the unadjusted and proportional hazard model [Quartile (Q)2, p=0.010; Q3, p<0.001 and Q4, p<0.001] and the model that adjusted for demographics (Q2, p=0.016; Q3, p=0.003; Q4, p<0.001). In the model adjusted for clinical covariates, the hazard of developing hypertension remained higher in TyGI Q4 compared to TyGI Q1(Hazard Ratio=2.57; 95% Confidence Interval: 1.71, 3.87). Increasing triglyceride-glucose index accounted for 16.4% of the association between increasing BMI and incident hypertension, after adjusting for age, gender, ethnicity and baseline HDL cholesterol (p<0.001).@*Conclusion@#Triglyceride-glucose index was an independent predictor of the development of hypertension. It may potentially be used as an inexpensive indicator to predict the development of hypertension and risk-stratify individuals to aid management in clinical practice.

Insulin Therapy in Type 2 Diabetes Mellitus

@#Initiation of insulin therapy is challenging in the primary care setting without nursing support. Doctors have to prepare their practices to deal with these challenges in order not to delay insulin therapy when needed.

Clinical Determinants of Diabetes Progression in Multiethnic Asians with Type 2 Diabetes - A 3-Year Prospective Cohort Study

INTRODUCTION@#The risk for diabetes progression varies greatly in individuals with type 2 diabetes mellitus (T2DM). We aimed to study the clinical determinants of diabetes progression in multiethnic Asians with T2DM.@*MATERIALS AND METHODS@#A total of 2057 outpatients with T2DM from a secondary-level Singapore hospital were recruited for the study. Diabetes progression was defined as transition from non-insulin use to requiring sustained insulin treatment or glycated haemoglobin (HbA1c) ≥8.5% when treated with 2 or more oral hypoglycaemic medications. Multivariable logistic regression (LR) was used to study the clinical and biochemical variables that were independently associated with diabetes progression. Forward LR was then used to select variables for a parsimonious model.@*RESULTS@#A total of 940 participants with no insulin use or indication for insulin treatment were analysed. In 3.2 ± 0.4 (mean ± SD) years' follow-up, 163 (17%) participants experienced diabetes progression. Multivariable LR revealed that age at T2DM diagnosis (odds ratio [95% confidence interval], 0.96 [0.94-0.98]), Malay ethnicity (1.94 [1.19-3.19]), baseline HbA1c (2.22 [1.80-2.72]), body mass index (0.96 [0.92-1.00]) and number of oral glucose-lowering medications (1.87 [1.39-2.51]) were independently associated with diabetes progression. Area under receiver operating characteristic curve of the parsimonious model selected by forward LR (age at T2DM diagnosis, Malay ethnicity, HbA1c and number of glucose-lowering medication) was 0.76 (95% CI, 0.72-0.80).@*CONCLUSION@#Young age at T2DM diagnosis, high baseline HbA1c and Malay ethnicity are independent determinants of diabetes progression in Asians with T2DM. Further mechanistic studies are needed to elucidate the pathophysiology underpinning progressive loss of glycaemic control in patients with T2DM.

Insulin Therapy in Type 2 Diabetes Mellitus

@#Initiation of insulin therapy is challenging in the primary care setting without nursing support. Doctors have to prepare their practices to deal with these challenges in order not to delay insulin therapy when needed.

Effect of bariatric surgery on diabetic nephropathy in obese type 2 diabetes patients in a retrospective 2-year study: A local pilot.

PURPOSE: To determine the effects of bariatric surgery on albuminuria in obese patients with type 2 diabetes mellitus. METHODS: Retrospective analyses of clinical records of obese patients with type 2 diabetes mellitus who had either micro- or macroalbuminuria and had undergone various bariatric surgery were retrieved from a local hospital database. Their clinical data from follow-up appointments including albuminuria were analysed. RESULTS: Of the 46 subjects with type 2 diabetes mellitus, 15 subjects had diabetic nephropathy and had pre- and post-bariatric surgery urine albumin-to-creatinine ratio or urine protein-to-creatinine ratio data available for analysis; 13 out of the 15 subjects (86.7%) showed improvement of urine albumin-to-creatinine ratio or urine protein-to-creatinine ratio after surgery; 2 showed equivocal results; 9 of 13 subjects (69.2%) showed remission of diabetic nephropathy; 7 of these 9 patients had microalbuminuria before surgery, 2 had macroalbuminuria before surgery. There were significant improvements to glycosylated haemoglobin, fasting plasma glucose, blood pressure and body weight post surgery. The usage of insulin and oral medications dropped significantly post surgery for all subjects. CONCLUSION: This study shows that bariatric surgery significantly improves diabetic nephropathy in obese type 2 diabetes mellitus subjects. The results suggest that in our local type 2 diabetes mellitus patients, it is possible not only to improve metabolic parameters, but also to reverse what may be considered established microvascular complications by means of bariatric surgery.

Short-term outcomes of patients with Type 2 diabetes mellitus treated with canagliflozin compared with sitagliptin in a real-world setting

<p><b>INTRODUCTION</b>We aimed to evaluate the effectiveness and safety of canagliflozin as compared to sitagliptin in a real-world setting among multiethnic patients with Type 2 diabetes mellitus (T2DM) in Singapore.</p><p><b>METHODS</b>This was a new-user, active-comparator, single-centre retrospective cohort study. Patients aged 18-69 years with T2DM and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m were eligible for inclusion if they were initiated and maintained on a steady daily dose of canagliflozin 300 mg or sitagliptin 100 mg between 1 May and 31 December 2014, and followed up for 24 weeks.</p><p><b>RESULTS</b>In total, 57 patients (canagliflozin 300 mg, n = 22; sitagliptin 100 mg, n = 35) were included. The baseline patient characteristics in the two groups were similar, with overall mean glycated haemoglobin (HbA1c) of 9.4% ± 1.4%. The use of canagliflozin 300 mg was associated with greater reductions in HbA1c (least squares [LS] mean change -1.6% vs. -0.4%; p < 0.001), body weight (LS mean change -3.0 kg vs. 0.2 kg; p < 0.001) and systolic blood pressure (LS mean change: -9.7 mmHg vs. 0.4 mmHg; p < 0.001), as compared with sitagliptin 100 mg. About half of the patients on canagliflozin 300 mg reported mild osmotic diuresis-related side effects that did not lead to drug discontinuation.</p><p><b>CONCLUSION</b>Our findings suggest that canagliflozin was more effective than sitagliptin in reducing HbA1c, body weight and systolic blood pressure in patients with T2DM, although its use was associated with an increased incidence of mild osmotic diuresis-related side effects.</p>

Ethnic disparity in inter-arm systolic blood pressure difference and its determinants among Asians with type 2 diabetes: A cross-sectional study / Journal of the ASEAN Federation of Endocrine Societies

@#<p><strong>OBJECTIVES:</strong> An inter-arm difference in systolic blood pressure (IADSBP) of 10 mmHg or more has been associated with cardiovascular disease (CVD) and increased mortality in T2DM patients. We aim to study ethnic disparity in IADSBP and its determinants in a multi-ethnic T2DM Asian cohort.<br /><strong>METHODOLOGY:</strong> Bilateral blood pressures were collected sequentially in Chinese (n=654), Malays (n=266) and Indians (n=313). IADSBP was analyzed as categories (<br /><strong>RESULTS:</strong> Malays (27.4%) and Indians (22.4%) had higher prevalence of IADSBP ?10 mmHg than Chinese (17.4%) (p=0.002). After adjustment for age, gender, duration of diabetes, hemoglobin A1c, body mass index (BMI), heart rate, pulse wave velocity (PWV), estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), smoking, hypertension, soluble receptor for advanced glycation end products (sRAGE), and usage of hypertension medications, ethnicity remained associated with IADSBP. While Malays were more likely to have IADSBP ?10 mmHg than Chinese (OR=1.648, 95%CI: 1.138-2.400, p=0.009), Indians had comparable odds with the Chinese. BMI (OR=1.054, 95%CI: 1.022-1.087, p=0.001) and hypertension (OR=2.529, 95%CI: 1.811-3.533, p<0.001) were also associated with IADSBP ?10 mmHg.<br /><strong>CONCLUSION:</strong> IADSBP in Malays were more likely to be ?10 mmHg than the Chinese which may explain their higher risk for CVD and mortality. Measuring bilateral blood pressures may identify high-risk T2DM individuals for intensive risk factor-management.</p>

Prevalence of Chronic Kidney Disease in Adults with Type 2 Diabetes Mellitus

<p><b>INTRODUCTION</b>Diabetes mellitus (DM) is a major cause of chronic kidney disease (CKD). The epidemiology of CKD secondary to type 2 DM (T2DM) (i.e. diabetic nephropathy (DN)) has not been well studied in Singapore, a multi-ethnic Asian population. We aimed to determine the prevalence of CKD in adult patients with T2DM.</p><p><b>MATERIALS AND METHODS</b>We conducted a cross-sectional study on patients (n = 1861) aged 21 to 89 years with T2DM who had attended the DM centre of a single acute care public hospital or a primary care polyclinic between August 2011 and November 2013. Demographic and clinical data were obtained from patients using a standard questionnaire. Spot urine and fasting blood samples were sent to an accredited hospital laboratory for urinary albumin, serum creatinine, HbA1c and lipid measurement. CKD was defined and classified using the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and classification.</p><p><b>RESULTS</b>The distribution by risk of adverse CKD outcomes was: low risk, 47%; moderate risk, 27.2%; high risk, 12.8%; and very high risk, 13%. The prevalence of CKD in patients with T2DM was 53%. Variables significantly associated with CKD include neuropathy, blood pressure ≥140/80 mmHg, triglycerides ≥1.7 mmol, body mass index, duration of diabetes, HbA1c ≥8%, age, cardiovascular disease, and proliferative retinopathy.</p><p><b>CONCLUSION</b>CKD was highly prevalent among patients with T2DM in Singapore. Several risk factors for CKD are well recognised and amenable to intervention. Routine rigorous screening for DN and enhanced programme for global risk factors reduction will be critical to stem the tide of DN.</p>

Fasting during Ramadan and Associated Changes in Glycaemia, Caloric Intake and Body Composition with Gender Differences in Singapore

<p><b>INTRODUCTION</b>Millions of Muslim patients with diabetes mellitus (DM) fast during Ramadan. However, little is known about the metabolic impact of Ramadan fasting. We aimed to study the changes in body composition and metabolic profile in this group of patients.</p><p><b>MATERIALS AND METHODS</b>We studied 29 Southeast Asian Muslim patients with type 2 diabetes; all underwent pre-Ramadan education. Study variables were weight change, body composition (using multifrequency bioimpedance method, InBody S20®, Biospace, South Korea), blood pressure (BP), glycated haemoglobin (HbA1c), fasting lipid profile, and caloric intake assessment using FoodWorks® nutrient analysis software.</p><p><b>RESULTS</b>Twenty-three subjects fasted ≥15 days; mean ± SD: 57 ± 11 years; 52% were males. HbA1c improved significantly (8.6 ± 2.4% pre-Ramadan vs 8.0 ± 2.3% end-Ramadan, P = 0.017). Despite similar body weight, there was reduction in body fat mass (BFM) (30.9 ± 11 kg vs 29.2 ± 12.2 kg, P = 0.013). Multivariate analysis suggested that the reduction in HbA1c was attributed by reduction in BFM (β = -0.196, P = 0.034). There was no change in visceral adiposity (visceral fat area (VFA)) but stratification by gender showed a reduction amongst females (137.6 ± 24.5 cm2 to 132.5 ± 25.7 cm2, P = 0.017). These changes occurred despite similar total caloric intake (1473.9 ± 565.4 kcal vs 1473.1 ± 460.4 kcal, P = 0.995), and proportion of carbohydrate (55.4 ± 6.3% vs 53.3 ± 7.5%, P = 0.25) and protein intake (17.6 ± 4.1% vs 17.3 ± 5.4%, P = 0.792), before and during Ramadan respectively, but with increased proportion of fat intake (11.9 ± 2.4% vs 13 ± 11.7%, P = 0.04). Seven out of 23 patients had medications adjusted to avert symptomatic hypoglycaemia but none of the patients developed severe hypoglycaemia.</p><p><b>CONCLUSION</b>Ramadan fasting can be practiced safely with prior patient education and medication adjustment. It also confers modest benefits on metabolic profile and body composition, especially among females.</p>

Development and validation of a carbohydrate and insulin dosing knowledge quiz in adults with diabetes mellitus / Journal of the ASEAN Federation of Endocrine Societies

@#<b>OBJECTIVES</b>: We aimed to develop and validate a carbohydrate and insulin dosing knowledge quiz for adult Asian patients with diabetes mellitus. <br /><br /><b>METHODOLOGY</b>: A self-administered quiz was developed to test carbohydrate recognition; single food carbohydrate estimation; meal carbohydrate estimation and food label reading; and insulin dosing calculation for carbohydrate, blood glucose and for a meal in a multi-ethnic Asian population. The subjects’ carbohydrate knowledge and insulin dosing ability were rated by the study dietitian and the subjects’ primary physicians, respectively. We compared the quiz scores with the dietitians’ and physician ratings and the subjects’ HbA1c. Reliability of the quiz was tested by measuring internal consistency and split half reliability. <br /><br /><b>RESULTS</b>: Seventy-five subjects completed the study. Median (inter-quartile range) quiz score was 71.9 (60.2 to 83.6)%. The quiz score was found to be correlated with the healthcare provider assessments (r=0.652, p<0.001) and the subjects’ HbA1c (r=-0.375, p=0.001). Cronbach alpha was 0.897 and Guttman split half coefficient was 0.930. <br /><br /><b>CONCLUSIONS</b>: Our analysis suggested that this newly developed quiz had good reliability and validity for testing carbohydrate and insulin dosing knowledge in a group of Asian subjects with diabetes mellitus. This can be a useful screening tool in clinical practice.

Low-density lipoprotein cholesterol levels in adults with type 2 diabetes: an alternative equation for accurate estimation and improved cardiovascular risk classification.

Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic disease. Despite its limitations, Friedewald-calculated LDL-C (F-LDL-C) remains widely used for LDL-C determination. In this observational study of 1999 adults with type 2 diabetes mellitus (T2DM), we compare the accuracy of F-LDL-C to directly measured LDL-C (M-LDL-C) and derived and validated a new [SMART2D (Singapore Study of MAcro-angiopathy and Micro-Vascular Reactivity in Type 2 Diabetes)] formula to estimate LDL-C. From 1000 randomly selected patients, M-LDL-C was compared to F-LDL-C. Using multiple linear regression to identify independent predictors for M-LDL-C, the SMART2D equation was derived and subsequently validated in the next 981 patients. F-LDL-C was 0.367 (0.216) mmol/L lower than M-LDL-C. This difference was -0.009 (0.189) for SMART2D-LDL-C. Using F-LDL-C, 27% with M-LDL-C ≥2.6 mmol/L were classified as LDL-C <2.6 mmol/L, reduced to 2.1% when using SMART2D-LDL-C. With F-LDL-C, misclassification was greater when triglycerides were ≥2.2 mmol/L, especially for the lower LDL-C cut-offs (1.8 and 2.6 mmol/L), and this was markedly improved with SMART2D-LDL-C. In conclusion, in T2DM, F-LDL-C underestimates M-LDL-C, with misclassifications that may potentially have an impact on therapeutic decisions in T2DM. The SMART2D equation improves accuracy of estimate, reducing misclassifications. Trials will be needed to ascertain the clinical significance of these findings.

Osteoprotegerin is independently associated with metabolic syndrome and microvascular complications in type 2 diabetes mellitus.

AIMS: Osteoprotegerin (OPG) is a glycoprotein from tumour necrosis factor receptor superfamily, responsible for osteoclastogenesis inhibition and associated with arterial calcification and stiffness. We describe the association between metabolic syndrome (MS) and OPG in type 2 diabetes mellitus patients. METHODOLOGY: We consecutively enrolled 1220 patients from our institution's Diabetes Centre from August 2011. Anthropometric data such as fasting blood/urine were obtained, and OPG was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean (standard deviation (SD)) of age and diabetes duration was 57.4 (10.9) years and 11.2 (8.9) years, respectively. Prevalence of MS was 64.3% (95% confidence interval (CI): 61.3%-67.2%) and associated with significantly higher OPG (5.44 vs 4.47 pmol/L) and microvascular complications. The presence of microvascular complications was associated with higher OPG: nephropathy (5.54 (2.20) vs 4.65 (1.70) pmol/L, p < 0.0001), neuropathy (6.33 (2.64) vs 5.06 (1.91) pmol/L, p < 0.0001) and retinopathy (6.08 (2.47) vs 5.00 (1.95) pmol/L, p < 0.0001). After adjusting for age, gender, ethnicity, glucose and microvascular complications, OPG remained an independent predictor of MS: (odds ratio (OR) = 1.102 (95% CI: 1.015-1.196), p = 0.021). CONCLUSION: Higher OPG levels were associated with risk of MS and microvascular complications. Studies are needed to test whether OPG could be a useful biomarker identifying patients at risk of vascular complications and whether further exploration of this pathway may lead novel therapeutic options.

Diabetes Management and Hyperglycemia in Safety Sensitive Jobs

The chronic and acute effects of hyperglycemia affecting cognition and work are as important as those of hypoglycemia. Its impact, considering that majority of diabetic patients fail to reach therapeutic targets, would be potentially significant. Self monitoring of blood glucose, recognition of body cues and management interventions should be geared not only towards avoidance of disabling hypoglycemia, but also towards unwanted hyperglycemia. Over the long term, chronic hyperglycemia is a risk for cognitive decline. Acute episodes of hyperglycemia, above 15 mmol/L have also been shown to affect cognitive motor tasks. Maintaining blood sugar to avoid hyperglycemia in diabetic workers will help promote safety at work.

Diabetes Management and Hypoglycemia in Safety Sensitive Jobs

The majority of people diagnosed with diabetes mellitus are in the working age group in developing countries. The interrelationship of diabetes and work, that is, diabetes affecting work and work affecting diabetes, becomes an important issue for these people. Therapeutic options for the diabetic worker have been developed, and currently include various insulins, insulin sensitizers and secretagogues, incretin mimetics and enhancers, and alpha glucosidase inhibitors. Hypoglycemia and hypoglycaemic unawareness are important and unwanted treatment side effects. The risk they pose with respect to cognitive impairment can have safety implications. The understanding of the therapeutic options in the management of diabetic workers, blood glucose awareness training, and self-monitoring blood glucose will help to mitigate this risk. Employment decisions must also take into account the extent to which the jobs performed by the worker are safety sensitive. A risk assessment matrix, based on the extent to which a job is considered safety sensitive and based on the severity of the hypoglycaemia, may assist in determining one's fitness to work. Support at the workplace, such as a provision of healthy food options and arrangements for affected workers will be helpful for such workers. Arrangements include permission to carry and consume emergency sugar, flexible meal times, self-monitoring blood glucose when required, storage/disposal facilities for medicine such as insulin and needles, time off for medical appointments, and structured self-help programs.

Impact of depression on health related quality of life in patients with diabetes

<p><b>INTRODUCTION</b>Diabetes mellitus (DM) is a serious chronic illness that has a major impact on the quality of life of the individuals. Our aim was to examine the determinants of health-related quality of life (HRQOL) in patients with DM.</p><p><b>MATERIALS AND METHODS</b>Adult outpatients attending a Diabetes Centre were recruited on consecutive basis between August 2006 and February 2007. Clinical data were collected from interviews with the subjects and from medical records. Assessment of depressive symptoms was done using the Center for Epidemiologic Studies Depression Scale (CES-D) and HRQOL using the Short Form 36 Health Survey (SF-36). A two-step regression analysis was conducted for identifying factors affecting patients' quality of life.</p><p><b>RESULTS</b>Five hundred and thirty-seven patients participated in the study. The mean (SD) age of the participants was 54.7 (13.3) years and 315 (58.7%) were males. The prevalence of depressive symptoms was 31.1% (n = 167). After adjusting for other variables, the effects of depressive symptoms persisted for all the 8 domains of SF-36 (P <0.001 for all). The medical factors that were negatively associated with HRQOL were a diagnosis of Type 1 DM, duration of the illness of more than 10 years, HbA1c levels of ≥7%, and comorbidity of stroke and retinopathy. Being male and a regular exerciser had a positive effect on HRQOL.</p><p><b>CONCLUSION</b>These findings highlight the importance of detecting and treating comorbid depression in DM.</p>

Measuring the quality of care of diabetic patients at the specialist outpatient clinics in public hospitals in Singapore

<p><b>INTRODUCTION</b>This study aims to measure the quality of care for patients with diabetes mellitus at selected Specialist Outpatient Clinics (SOCs) in the National Healthcare Group.</p><p><b>MATERIALS AND METHODS</b>The cross-sectional study reviewed case-records of patients from 6 medical specialties who were on continuous care for a minimum of 15 months from October 2003 to April 2005. Disproportionate sampling of 60 patients from each specialty, excluding those co-managed by Diabetes Centres or primary care clinics for diabetes, was carried out. Information on demographic characteristics, process indicators and intermediate outcomes were collected and the adherence rate for each process indicator compared across specialties. Data analysis was carried out using SPSS version 13.0.</p><p><b>RESULTS</b>A total of 575 cases were studied. The average rate for 9 process indicators by specialty ranged from 47.8% to 70.0%, with blood pressure measurement consistently high across all specialties (98.4%). There was significant variation (P <0.001) in rates across the specialties for 8 process indicators; HbA1c, serum creatinine and lipid profile tests were over 75%, while the rest were below 50%. The mean HbA1c was 7.3% +/- 1.5%. "Optimal" control of HbA1c was achieved in 51.2% of patients, while 50.6% of the patients achieved "optimal" low-density lipoprotein (LDL)-cholesterol control. However, 47.3% of patients had "poor" blood pressure control. Adherence to process indicators was not associated with good intermediate outcomes.</p><p><b>CONCLUSIONS</b>There was large variance in the adherence rate of process and clinical outcome indicators across specialties, which could be improved further.</p>