Glycated haemoglobin trajectories and one-year risk of potentially avoidable hospitalisations among adult patients with type 2 diabetes from specialist outpatient clinics of a tertiary hospital: A cohort study.

AIM: To evaluate the association between trajectories of glycated haemoglobin (HbA1c) and potentially avoidable hospitalisations (PAH). METHODS: We performed a cohort study in a tertiary hospital in Singapore among adult type 2 diabetes patients with ≥ 3 HbA1c tests over two years. Then, we followed up for one year after the last HbA1c reading to determine the PAH outcome. Glycaemic control was analysed by (1) HbA1c trajectories through group-based trajectory modelling, and (2) mean HbA1c. PAH was defined using the Agency of Healthcare Research and Quality criteria, categorising as overall, diabetes, acute, and chronic-composites. RESULTS: A total of 14,923 patients (mean age: 62.9 ± 12.8 years; 55.2% men) were included. Four HbA1c trajectories were observed; low-stable (n = 9854, 66.0%), moderate-stable (n = 3125, 20.9%), high-decrease (n = 1017, 6.8%) and high-persistent (n = 927, 6.2%). Compared to the low-stable trajectory, one-year risk ratio (RR) and 95% confidence interval (CI), respectively for moderate-stable, high-decrease and high-persistent trajectories were as follows: (1) overall PAH: 1.15 (1.00-1.31), 1.53 (1.31-1.80), 1.96 (1.58-2.43); (2) diabetes PAH: 1.30 (1.04-1.64), 1.98 (1.55-2.53), 2.24 (1.59-3.15); (3) acute PAH: 1.14 (0.90-1.44), 1.29 (0.95-1.77), 1.75 (1.17-2.62); and (4) chronic PAH: 1.21 (1.02-1.43), 1.62 (1.34-1.97), 2.14 (1.67-2.75). Mean HbA1c was significantly associated with overall and chronic-composites of PAH whilst evidence of a non-linear relationship with diabetes-composite of PAH was noted. CONCLUSION: Patients with high-decrease trajectory had a risk lower than those with persistently-high HbA1c, highlighting that a greater risk of hospitalisation conferred by poor glycaemic control is potentially reversible. Determining HbA1c trajectories could help to identify the high-risk individuals for targeted and intensive management to improve care and reduce hospitalisations.

Diabetic foot in primary and tertiary (DEFINITE) Care: A health services innovation in coordination of diabetic foot ulcer (DFU) Care within a healthcare cluster - 18-month results from an observational population health cohort study.

Diabetic Foot in Primary and Tertiary (DEFINITE) Care is an inter-institutional and multi-disciplinary team (MDT) health systems innovation programme at a healthcare cluster in Singapore. We aim to achieve coordinated MDT care across primary and tertiary care for patients with diabetic foot ulcers (DFU), within our public healthcare cluster - an integrated network of seven primary care polyclinics and two acute care tertiary hospitals (1700-bed and 800-bed) with a total catchment population of 2.2 million residents. Results from prospective DEFINITE Care is referenced against a retrospective 2013-2017 cohort, which was previously published. Cardiovascular profile of the study population is compared against the same population's profile in the preceding 12 months. Between June 2020 and December 2021, there were 3475 unique patients with DFU with mean age at 65.9 years, 61.2% male, mean baseline HbA1c at 8.3% with mean diabetes duration at 13.3 years, mean diabetes complication severity index (DCSI) at 5.6 and mean Charlson Comorbidity Index (CCI) at 6.8. In the 12-months preceding enrolment to DEFINITE Care, 35.5% had surgical foot debridement, 21.2% had minor lower extremity amputation (LEA), 7.5% had major LEA whilst 16.8% had revascularisation procedures. At 18-months after the implementation of DEFINITE Care programme, the absolute minor and major amputation rates were 8.7% (n = 302) and 5.1% (n = 176), respectively, equating to a minor and major LEA per 100000 population at 13.7 and 8.0, respectively. This represents an 80% reduction in minor amputation rates (P < .001) and a 35% reduction in major amputation rates (P = .005) when referenced against a retrospective 2013-2017 cohort, which had minor and major LEA per 100000 population at 68.9 and 12.4, respectively. As compared to the preceding 12 months, there was also a significant improvement in cardiovascular profile (glycemic and lipid control) within the DEFINITE population, with improved mean HbAc1 (7.9% from 8.4%, P < .001), low-density lipoprotein (LDL) levels (2.1 mmol/L from 2.2, P < .001), total cholesterol (3.9 mmol/L from 4.1, P < .001) and triglycerides levels (1.6 mmol/L from 1.8, P = .002). Multivariate analysis revealed a history of minor amputation in the preceding 12 months to be an independent predictor for major and minor amputation within the study period of 18 months (Hazard Ratio 3.4 and 1.8, respectively, P < .001). In conclusion, within DEFINITE care, 18-month data showed a significant reduction of minor and major LEA rates, with improved medical optimisation and cardiovascular profile within the study population.

Metabolic effects of brown fat in transitioning from hyperthyroidism to euthyroidism.

OBJECTIVE: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. DESIGN: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. RESULTS: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). CONCLUSION: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.

Psychometric properties of the thyroid-specific quality of life questionnaire ThyPRO in Singaporean patients with Graves' disease.

BACKGROUND: Graves' disease is the most common cause of hyperthyroidism. It results in accelerated tissue metabolism with multi-organ involvement ranging from cardiovascular to neuropsychological function. This results in a negative impact on the quality of life (QOL) of the individual patient. We aim to evaluate the psychometric properties of ThyPRO, a Thyroid-related Patient Reported Outcome questionnaire, and validate its use in our multi-ethnic Asian patients with Graves' hyperthyroidism. METHODS: Forty-seven consecutive Graves' hyperthyroidism patients answered the ThyPRO questionnaire at baseline and at 4 months after treatment initiation. Data were recorded for thyroid related symptoms and signs, thyroid function tests and thyroid volume. We analyzed the internal consistency using Cronbach's alpha, construct validity by evaluating relationship between clinical variables and ThyPRO scales, ceiling and floor effects, and responsiveness of ThyPRO to treatment based on Cohen's effect size. RESULTS: Correlations between individual scale scores and free thyroxine concentrations were moderate and statistically significant: 0.21-0.64 (p <  0.05). There was high internal consistency between the items in this instrument, Cronbach's alpha > 0.7 for all scales. ThyPRO was responsive to the changes in QOL after treatment (Effect Size: 0.20-0.77) in 9 of the 14 scales including the hyperthyroid symptoms and psychosocial scales (Tiredness, Cognitive complaints, Anxiety, Emotional susceptibility, Impact on Social, Daily and Sex life). CONCLUSION: This study provides evidence that ThyPRO has satisfactory measurement properties in hyperthyroid Graves' disease patients in Singapore population with the potential to complement clinical care.

Efficacy and Safety of Use of the Fasting Algorithm for Singaporeans With Type 2 Diabetes (FAST) During Ramadan: A Prospective, Multicenter, Randomized Controlled Trial.

PURPOSE: We aimed to evaluate the efficacy and safety of use of the Fasting Algorithm for Singaporeans with Type 2 Diabetes (FAST) during Ramadan. METHODS: We performed a prospective, multicenter, randomized controlled trial. The inclusion criteria were age ≥21 years, baseline glycated hemoglobin (HbA1c) level ≤9.5%, and intention to fast for ≥10 days during Ramadan. Exclusion criteria included baseline estimated glomerular filtration rate <30 mL/min, diabetes-related hospitalization, and short-term corticosteroid therapy. Participants were randomized to intervention (use of FAST) or control (usual care without FAST) groups. Efficacy outcomes were HbA1c level and fasting blood glucose and postprandial glucose changes, and the safety outcome was incidence of major or minor hypoglycemia during the Ramadan period. Glycemic variability and diabetes distress were also investigated. Linear mixed models were constructed to assess changes. RESULTS: A total of 97 participants were randomized (intervention: n = 46, control: n = 51). The HbA1c improvement during Ramadan was 4 times greater in the intervention group (-0.4%) than in the control group (-0.1%) (P = .049). The mean fasting blood glucose level decreased in the intervention group (-3.6 mg/dL) and increased in the control group (+20.9 mg/dL) (P = .034). The mean postprandial glucose level showed greater improvement in the intervention group (-16.4 mg/dL) compared to the control group (-2.3 mg/dL). There were more minor hypoglycemic events based on self-monitered blood glucose readings in the control group (intervention: 4, control: 6; P = .744). Glycemic variability was not significantly different between the 2 groups (P = .284). No between-group differences in diabetes distress were observed (P = .479). CONCLUSIONS: Our findings emphasize the importance of efficacious, safe, and culturally tailored epistemic tools for diabetes management.

Impact of Timing Between Insulin Administration and Meal Consumption on Glycemic Fluctuation and Outcomes in Hospitalized Patients With Type 2 Diabetes.

BACKGROUND: The effect of time interval from insulin injection to meal consumption ("insulin-meal") on glycemic fluctuation and outcomes is not well understood. OBJECTIVE: This study aims to investigate the impact of coordinated versus mismatched insulin-meal administration on glycemic fluctuation and outcomes among hospitalized patients with type 2 diabetes (T2D). METHODS: Hospitalized patients with T2D who received at least 1 dose of insulin as part of sliding scale regimen were included. Data such as capillary blood glucose values and insulin-meal time intervals were collected. RESULTS: A total of 215 patients with 840 insulin-meal encounters were eligible for the study. Compared to the insulin-meal mismatch group (n = 206), the coordinated insulin-meal administration group (n = 9) had lower mean glycemic fluctuation (6.5 [2.6] mmol/L vs 5.6 [2.5] mmol/L or 117 [47] mg/dL vs 100 [45] mg/dL). Encounters with the insulin-meal time interval of 30 to 45 minutes (n = 172) were associated with the lowest percentage of severe hyperglycemia occurrences (13%) as compared to encounters with time interval of 0 to 29 minutes (n = 280, 15%) and more than 45 minutes (n = 246, 16%). CONCLUSION: Coordinated insulin-meal administration was associated with lower glycemic fluctuation among hospitalized patients with T2D.

Development of a Collaborative Algorithm for the Management of Type 2 Diabetes during Ramadan: An Anchor on Empowerment.

Empowerment plays significant roles in the complex management of type 2 diabetes. International guidelines have provided recommendations on management of Muslims who fast during Ramadan. However, there remains a lack of patient-centered epistemic tool to empower healthcare providers and patients in managing diabetes during Ramadan. This study discussed the development and evaluation of such tool. The collaborative algorithm was developed with reference to the nominal group technique by a board-certified clinical pharmacist and discussed with endocrinologists, nurses, and family physicians. The empowerment component of the algorithm was developed based on the Basic Psychological Needs Theory. The algorithm was evaluated through a randomized controlled trial. Glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial glucose (PPG) levels and safety profiles in terms of hypoglycemic events were assessed. The collaborative algorithm was developed with four components: screening, education, dose modification by healthcare provider, and dose adjustment by patient. A total of 62 individuals were recruited, with 30 and 32 randomized into the intervention and control groups, respectively. The mean age was 58.4 years, with majority being females (67.7%). There was a reduction in mean HbA1c from 7.9% ± 0.9% to 7.5% ± 0.8% (P < 0.001) in the intervention group, while no significant difference was observed in the control group (P = 0.270). FPG (P < 0.001) and PPG (P = 0.002) also improved significantly in the intervention group. There were no major hypoglycemic events and minor hypoglycemia comparable between both groups (P = 0.465). The collaborative algorithm incorporated empowerment and promoted shared decision-making in diabetes management, hence promoting safe and effective fasting.

Medication adherence and glycemic control among newly diagnosed diabetes patients.

BACKGROUND: Poor medication adherence can have negative consequences for the patients, the provider, the physician, and the sustainability of the healthcare system. To our knowledge, the association between medication adherence and glycemic control among newly diagnosed diabetes patients has not been studied. This study aims to bridge the gap. METHOD: This is a retrospective cohort study of 2463 patients managed in the National Healthcare Group in Singapore with newly diagnosed diabetes. Patients were followed up for the first two years from their first medication dispensed for measuring medication adherence, proportion of days covered (PDC); and for another three years for investigating outcomes of glycemic control, emergency department visit, and hospitalization. Multivariable regressions were performed to study the association between medication adherence and the outcomes as well as the risk factors of poor adherence. RESULTS: The prevalence of medication adherence (PDC≥80%) was 65.0% (95% CI 63.1% to 66.9%) among newly diagnosed diabetes patients in Singapore. Male, Indian, or patients without hypertension or dyslipidemia were associated with poorer medication adherence. The HbA1c level of poor adherent patients (PDC <40%) increased by 0.4 (95% CI 0.2 to 0.5) over the two years, and they were also more likely to have hospitalization (OR 2.6,95% CI 1.7 to 3.8) or emergency department visit (OR 2.4,95% CI 1.7 to 3.4) compared with the fully adherent patients (PDC=100%). CONCLUSIONS: The medication adherence in the early stage of diabetes is important for maximizing the effectiveness of pharmaceutical therapy. Health policies or interventions targeting the improvement of medication adherence among newly diagnosed diabetes patients are in need.

Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus.

Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. Herein, we present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus (T2DM) patients using small blood volumes (fingerprick ~100 µL). The developed inertial microfluidics technology enables single-step neutrophil isolation (>90% purity) without immuno-labeling and sorted neutrophils are used to characterize their rolling behavior on E-selectin, a critical step in leukocyte recruitment during inflammation. The integrated microfluidics testing methodology facilitates high throughput single-cell quantification of neutrophil rolling to detect subtle differences in speed distribution. Higher rolling speed was observed in T2DM patients (P < 0.01) which strongly correlated with neutrophil activation, rolling ligand P-selectin glycoprotein ligand 1 (PSGL-1) expression, as well as established cardiovascular risk factors (cholesterol, high-sensitive C-reactive protein (CRP) and HbA1c). Rolling phenotype can be modulated by common disease risk modifiers (metformin and pravastatin). Receiver operating characteristics (ROC) and principal component analysis (PCA) revealed neutrophil rolling as an important functional phenotype in T2DM diagnostics. These results suggest a new point-of-care testing methodology, and neutrophil rolling speed as a functional biomarker for rapid profiling of dysmetabolic subjects in clinical and patient-oriented settings.

The haptoglobin 2-2 genotype is associated with inflammation and carotid artery intima-media thickness.

The haptoglobin 2-2 genotype is associated with atherosclerosis in type 2 diabetes mellitus. We examined the associations of the haptoglobin 2-2 genotype with C-reactive protein (high-sensitivity C-reactive protein) and carotid artery intima-media thickness, adjusting for age, gender, ethnicity, type 2 diabetes mellitus, smoking status, body mass index, blood pressure, glycated haemoglobin, non-high-density lipoprotein cholesterol and medications via logistic multivariate regression in 200 subjects (160 type 2 diabetes mellitus versus 40 healthy individuals). The prevalence of the haptoglobin 2-2 genotype was 58% (115/200), higher in the Indians than in Chinese (72% versus 45%, p = 0.001). Multivariate analysis showed that the haptoglobin 2-2 genotype was associated with high-sensitivity C-reactive protein [mean: 3.5 ± 3.9 versus 2.2 ± 2.6 mg/L (non-haptoglobin 2-2), p < 0.001], haptoglobin concentration [mean: 116.9 ± 54.4.0 versus 147.2 ± 54.5 mg/dL (non-haptoglobin 2-2), p < 0.001] and average carotid artery intima-media thickness (multiplied by 10) [6.15 ± 1.22 versus 5.98 ± 1.20 mm (non-haptoglobin 2-2), p = 0.013]. This pilot study shows an association of the haptoglobin 2-2 genotype with low-grade inflammation, haptoglobin concentration and carotid artery intima-media thickness in multi-ethnic Singapore.

A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: The DIMENSION trial.

We sought to determine if vitamin D supplementation, to target 25(OH)D concentrations of 30-40 ng/mL, improves endothelial function in Singapore's multi-ethnic type 2 diabetes mellitus population. We randomised 64 type 2 diabetes mellitus patients with hypovitaminosis D to cholecalciferol 4000 International Unit/matching placebo [baseline 25(OH)D < 20 ng/mL] or cholecalciferol 2000 International Unit/matching placebo [baseline 25(OH)D: 20-30 ng/mL] daily for 16 weeks with a down titration at 8 weeks if 25(OH)D > 30 ng/mL. Endothelial function was assessed by peripheral tonometry (reactive hyperaemia index-endothelial peripheral arterial tonometry) and vascular biomarkers: E-selectin, von-Willebrand factor and high-sensitivity C-reactive protein. We compared the change from baseline parameters in the two groups using Student's t-test or Kruskal-Wallis test. A log-normal multivariate regression analysis was used to adjust for relevant baseline variables. The median reactive hyperaemia index in the vitamin D group increased from 0.65 (interquartile range: 0.42) to 0.73 (interquartile range: 0.36), whereas it decreased from 0.73 (interquartile range: 0.65) to 0.65 (interquartile range: 0.38) (p = 0.02) in the placebo group. After adjustment for baseline variables, the change was not statistically significant for reactive hyperaemia index (p = 0.07) and for other vascular biomarkers (p > 0.05). Targeted vitamin D supplementation for 16 weeks resulted in a small but non-significant improvement in endothelial function in a type 2 diabetes mellitus cohort.

Evaluating the Effect of Ramadan Fasting on Muslim Patients with Diabetes in relation to Use of Medication and Lifestyle Patterns: A Prospective Study.

Objectives. This study aimed to examine the effect of Ramadan fasting on HbA1c in Muslim patients with type 2 diabetes. The incidence of hypoglycemia and glycemic changes in relation to the adjustment of doses of antidiabetic agents, diet, and physical activity during Ramadan was also evaluated. Methods. This was a prospective study conducted in an outpatient endocrine clinic. A set of questionnaires was administered to Muslim patients with diabetes who fasted for ≥10 days. Those who were hospitalized for diabetic ketoacidosis or severe hypoglycemia a month prior to Ramadan or were given short-term corticosteroid therapy were excluded. The patients' responses and clinical outcomes from the clinic database were collected before, during, and after Ramadan. Results. A total of 153 participants completed the study. The mean HbA1c improved from 8.9% before Ramadan to 8.6% during Ramadan (P < 0.05). Although diet and physical activity did not contribute to changes in glycemia, a significant improvement in HbA1c was observed in patients who had adjustments made to their doses of antidiabetic agents during Ramadan (P < 0.001). In addition, their rate of hypoglycemia was minimal. Conclusions. Ramadan fasting appeared to improve glycemic control, especially in those whose doses of antidiabetic agents were adjusted during Ramadan.