Associations of young onset age and genetic risk of beta cell dysfunction with glycaemic progression in individuals with type 2 diabetes.

AIM: To study the relationship between genetic risk of beta cell dysfunction, young onset age and glycaemic progression in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: 1385 T2D outpatients were included in cross-sectional sub-study and 730 insulin-naïve outpatients were followed for 3 years in prospective sub-study. Genetic risk score (GRS) was derived from 24 beta cell dysfunction-related single nucleotide polymorphisms, with lower and upper 25 percentiles defined as low and high genetic risk. Glycaemic progression was defined as requirement for sustained insulin therapy. RESULTS: 388 participants in cross-sectional and 128 in prospective sub-study experienced glycaemic progression. Young onset age (T2D diagnosis below 40 year-old) was associated with high risk of glycaemic progression as compared to usual-onset counterparts (adjusted OR 1.64 [95% CI 1.14-2.36], and 2.92 [95% CI 1.76-4.87] in cross-sectional and prospective sub-study, respectively). As compared to those with intermediate risk, a low GRS was associated with lower risk for glycaemic progression (adjusted OR 0.72 [95% CI 0.49-1.06], and 0.51 [95% CI 0.29-0.90]) whereas a high GRS was not significantly associated with glycaemic progression. Notably, the association of young-onset T2D with high risk of glycaemic progression was independent of known clinical risk factors and beta cell dysfunction GRS (P interaction > 0.10). CONCLUSION: Young onset age and low genetic risk of beta cell dysfunction are independently associated with risk of glycaemic progression. Our data do not support that genetic risk modulates the risk of glycaemic progression in individuals with young-onset T2D.

Zinc-α2-glycoprotein is associated with non-albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4-year follow-up.

AIM: To investigate the association between baseline plasma zinc-α2-glycoprotein and non-albuminuric chronic kidney disease progression in type 2 diabetes. METHODS: Adults with normoalbuminuria at entry (n=341; age 57±10 years, 52% men) were analysed. Chronic kidney disease progression was defined as a decrease in chronic kidney disease stage and a decline of ≥25% in estimated GFR from baseline. Baseline plasma zinc-α2-glycoprotein levels were quantified by immunoassay, and analysed either as a continuous variable or by tertiles in Cox proportional hazards models. Model discrimination was assessed using Harrell's C-index. A sensitivity analysis was performed on a subset of individuals who maintained normoalbuminuria during follow-up. RESULTS: Chronic kidney disease progression occurred in 54 participants (16%). Zinc-α2-glycoprotein levels were elevated in chronic kidney disease progressors (P = 0.011), and more progressors were assigned to the higher zinc-α2-glycoprotein tertile than non-progressors. In the unadjusted Cox model, zinc-α2-glycoprotein, both as a continuous variable (hazard ratio 1.72, 95% CI 1.08-2.75) and tertile 3 (vs tertile 1; hazard ratio 2.14, 95% CI 1.10-4.17), predicted chronic kidney disease progression. The association persisted after multivariable adjustment. The C-index of the Cox model increased significantly after incorporation of zinc-α2-glycoprotein into a base model comprising renin-angiotensin system antagonist usage. Sensitivity analysis showed that zinc-α2-glycoprotein independently predicted chronic kidney disease progression among individuals who maintained normoalbuminuria during follow-up. CONCLUSIONS: Plasma zinc-α2-glycoprotein is associated with chronic kidney disease progression, and may serve as a useful early biomarker for predicting non-albuminuric chronic kidney disease progression in type 2 diabetes.

Attitudes and perception of influenza vaccines among older people in Singapore: A qualitative study.

BACKGROUND: Despite recommendations for influenza vaccination of people aged 65 and above, uptake rate of influenza vaccines remains low. This study aims to understand barriers and motivators behind older adult's decision on influenza vaccination. METHODS: Face to face interviews with participants aged 65 and above were conducted and audio recorded in Geylang polyclinic in Singapore. Thematic content analysis was used to organise the data. RESULTS: 15 older adults were interviewed, aged between 66 and 85 years old. 6 were vaccine refusers, 3 defaulters and 6 acceptors. A perceived lack of vulnerability, fear of side effects, and trivialisation of influenza were common reasons for not taking the vaccine. Encouragement from family and friends, travel and previous positive vaccination experiences were motivators for getting vaccinated. Healthcare workers played a role in influencing many of the participants' decision-making. Common misconceptions included vaccines considered as necessary only before travel and as a cure rather than prevention. Most participants exhibited ambivalence, giving reasons both for and against vaccine uptake. DISCUSSION: Most older adults do not perceive influenza as a potentially serious disease nor trust in influenza vaccines' efficacy. Misconceptions played a significant role in vaccine decline. Novel findings include the importance of the family unit in decision making, prioritization of chronic health problems over vaccination and misconception that vaccines are only needed when travelling out of country. Healthcare workers and family members appear to be important influencers in the decision making of older adults and should be actively engaged in future health promotion initiatives.

Anthropometrics indices of obesity, and all-cause and cardiovascular disease-related mortality, in an Asian cohort with type 2 diabetes mellitus.

AIM: The study investigated the relationship of general (body mass index [BMI]) and central (waist circumference [WC]; waist-hip ratio [WHipR]; waist-height ratio [WHeightR]) adiposity with all-cause and cardiovascular disease (CVD)-related mortality in an Asian population with diabetes. METHODS: A total of 13,278 participants with type 2 diabetes mellitus (T2DM) recruited from public-sector primary-care and specialist outpatients clinics in Singapore were followed-up for a median duration of 2.9 years, during which time there were 524 deaths. Cox proportional-hazards regression and competing-risk models were used to obtain hazard ratios (HRs) for anthropometric variables of all-cause and CVD-related mortality. RESULTS: After adjusting for BMI, the highest quintiles of WC, WHipR and WHeightR were all positively associated with mortality compared with the lowest quintiles, with WHeightR exhibiting the largest effect sizes [all-cause mortality HR: 2.13, 95% confidence interval (CI): 1.33-3.42; CVD-related mortality HR: 3.42, 95% CI: 1.62-7.19]. Being overweight but not obese (BMI:≥23.0 but<27.5kg/m(2)) was associated with a decreased risk of CVD-related mortality in those aged≥65 years (HR: 0.47, 95% CI: 0.29-0.75), but not in those aged<65 years (HR: 1.11, 95% CI: 0.49-2.50). CONCLUSION: Overweight, but not obesity, was associated with a reduction in risk of mortality. This was seen in T2DM patients aged≥65 years, but not in those younger than this. At the same BMI, having higher central-obesity indices such as WC, WHipR and WHeightR also increased the risk of mortality.

High normal albuminuria is independently associated with aortic stiffness in patients with Type 2 diabetes.

BACKGROUND: High normal albuminuria is associated with higher cardiovascular risk in patients with diabetes. Increased aortic stiffness is an established risk factor of vascular events. However, the relationship between albuminuria within the normal range (0-30 mg/g) and aortic stiffness in patients with Type 2 diabetes is unknown. METHODS: A total of 614 normoalbuminuric subjects with Type 2 diabetes with spot urinary albumin:creatinine ratio ≤ 30 mg/g and estimated glomerular filtration rate ≥ 60 ml min⁻¹ 1.73 m⁻² were included in the study. Aortic stiffness was assessed by carotid-femoral pulse wave velocity. RESULTS: Pulse wave velocity increased progressively with the increase of albumin:creatinine ratio within the normoalbuminuric range (0-30 mg/g). Only 2.6% of the subjects with an albumin:creatinine ratio in the lowest quartile (0.7-3.4 mg/g) were classified as having aortic stiffness (pulse wave velocity ≥12 m/s). In contrast, the proportion of subjects with aortic stiffness increased significantly with the increase of albumin:creatinine ratio level (11.0%, 10.4% and 13.6% in albumin:creatinine ratio quartiles 2, 3 and 4, respectively, P = 0.008). A logistic regression model revealed that the odds of having aortic stiffness were increased by 56% with a 1-SD increase of log albumin:creatinine ratio after adjustment for age, gender, duration of diabetes, HbA1c , blood pressure, HDL and LDL cholesterol, estimated glomerular filtration rate, BMI, usage of renin-angiotensin system antagonists, statins and insulin. CONCLUSIONS: High normal albuminuria is associated with aortic stiffness in patients with Type 2 diabetes, which may in part explain their increased cardiovascular risk.

Validity and reliability of a self-reported measure of medication adherence in patients with Type 2 diabetes mellitus in Singapore.

AIMS: A reliable and valid measure is essential for the assessment of medication adherence. Until now, no patient-reported medication adherence measure has been validated in Singapore. The aim of this study was to validate a modified 4-item Morisky-Green-Levine Medication Adherence Scale in patients with Type 2 diabetes in Singapore. METHODS: A cross-sectional survey was conducted in a sample of outpatients with Type 2 diabetes in Singapore from September to December in 2009. Respondents completed either an English or Chinese version of the modified 4-item Morisky-Green-Levine Medication Adherence Scale. The scale scores ranged from 0 to 4, with higher scores indicating better medication adherence. Reliability was assessed using Cronbach's alpha. Content validity was assessed by expert review. Construct validity was examined using factor analysis and hypothesis testing. RESULTS: Of the 294 respondents who completed the modified Morisky-Green-Levine Medication Adherence Scale, 13.3, 21.4, 35.7 and 29.6% had a score of 0-1, 2, 3 and 4, respectively. The internal consistency of the scale was moderate (Cronbach's alpha = 0.62). Principal component analysis showed that the four items loaded onto one factor (eigenvalue = 1.95). Respondents with higher scores were older (P < 0.001), had lower HbA(1c) levels (P < 0.001) and had better adherence to physician-recommended diet (P < 0.001) and physical exercise (P = 0.02). CONCLUSIONS: The psychometric properties of the modified Morisky-Green-Levine Medication Adherence Scale were less than satisfactory. A ceiling effect was observed. The scale may not be an adequate measure to assess medication adherence in patients with Type 2 diabetes in Singapore. Future research could target refining the scale and investigating its use in other patient populations.

Health-related quality of life and glycaemic control in patients with Type 2 diabetes mellitus in Singapore.

AIMS: To investigate the health-related quality of life of patients with diabetes mellitus in Singapore and its associations with diabetes-related characteristics and glycaemic control. METHODS: An interviewer-administered, cross-sectional survey was conducted in a sample of 301 adult diabetes patients under primary care. The survey questionnaire included both a generic health-related quality of life measure, the Euroqol 5-D and a diabetes-specific instrument, the Audit of Diabetes-dependent Quality of Life. Patients' most recent HbA(1c) values were extracted from their medical records. RESULTS: After excluding patients who lacked the 90-day HbA(1c) test result, the final number of responses analysed was 282. Pain/discomfort was the most common complaint among the five Euroqol 5-D domains (by 28.0% of the respondents). Lack of freedom to eat was the Audit of Diabetes-dependent Quality of Life domain with the greatest negative average weighted impact (= -3.8, on a scale of -9 to 3). A significant association was observed between Audit of Diabetes-dependent Quality of Life average weighted impact and both duration of diabetes and use of insulin. A negative correlation was found between health-related quality of life and HbA(1c) values in both health-related quality of life measures (both r=-0.2, P=0.001). CONCLUSIONS: Patients with diabetes in primary-care settings frequently reported problems with pain/discomfort and restrictions in diet. Poorer health-related quality of life was found to be associated with higher HbA(1c) values. The chronicity of diabetes and insulin therapy may have a negative impact on patients' diabetes-related health-related quality of life. This study indicates the importance of achieving better disease management to improve the health-related quality of life of patients with diabetes.

Perceptions of insulin therapy amongst Asian patients with diabetes in Singapore.

AIMS: The objective of this study was to determine the prevalence of insulin refusal amongst Singaporean patients with Type 2 diabetes mellitus, to compare perceptions regarding insulin therapy use between patients who were willing to use insulin and those who were not and to identify demographic factors that might predict insulin refusal. METHODS: A cross-sectional interviewer-administered survey incorporating demographic variables and 17 perceptions regarding insulin use (14 negative and three positive) was conducted among a sample of 265 patients attending a public primary healthcare centre. RESULTS: Seven of every 10 patients expressed unwillingness to use insulin therapy (70.6%). The greatest differences in perceptions between patients willing to use insulin therapy and those who were not included fear of not being able to inject insulin correctly (47.4 vs. 70.6%), fear of pain (44.9 vs. 65.8%), belief that insulin therapy would make it difficult to fulfil responsibilities at work and home (46.2 vs. 66.8%) and belief that insulin therapy improved diabetes control (82.1 vs. 58.3%). A tertiary level of education was associated with willingness to use insulin (odds ratio 3.3, confidence interval 1.8-6.1), and significant differences in perceptions were present in patients with different educational levels. CONCLUSIONS: Insulin refusal is an important problem amongst our patients with Type 2 diabetes mellitus. Findings of this study suggest that interventions aimed at increasing insulin therapy use should focus on injection-related concerns, perceived lifestyle adaptations and correction of misconceptions. Different interventions may also be required for patients of different educational groups.