Association of major candidate protein biomarkers and long-term diabetic kidney disease progression among Asians with young-onset type 2 diabetes mellitus.

AIMS: We aim to determine the association of seven major candidate protein biomarkers and diabetic kidney disease (DKD) progression among Asians with young-onset type 2 diabetes mellitus (T2DM). METHODS: 824 T2DM patients (onset ≤ 40 years old) were classified as DKD progressors based on yearly estimated glomerular filtration rate (eGFR) decline of >3 ml/min/1.73 m2 or >40 % from baseline. Plasma leucine-rich α-2-glycoprotein 1 (pLRG1), tumor necrosis factor-receptor 1 (pTNF-R1), pigment epithelium-derived factor (pPEDF), urinary α-1-microglobulin (uA1M), kidney injury molecular 1 (uKIM-1), haptoglobin (uHP) and uromodulin (uUMOD) were measured using enzyme-linked immunoassays. RESULTS: Over 5.7 years of follow-up, 25.2 % of patients were DKD progressors. Elevated levels of pLRG1, pTNF-R1, pPEDF, uA1M, uKIM-1 and uHP were associated with DKD progression. The association between pTNF-R1 levels and DKD progression persisted after adjusting for clinical covariates (OR 1.84, 95 %CI 1.44-2.34, p < 0.001). The effects of pTNF-R1 were partially mediated through hyperglycemia (8 %) and albuminuria (10 %). Inclusion of pTNF-R1 in a clinical variable-based model improved the area under the receiver operating characteristics curve for predicting DKD progression by 0.02, from 0.72 (95 %CI 0.68-0.76) to 0.74 (95 %CI 0.70-0.78), p = 0.099. CONCLUSIONS: Among seven major candidate proteins, pTNF-R1, partially mediated through hyperglycemia and albuminuria, robustly predicted DKD progression among Asians with young-onset T2DM.

Foot care behaviours and associated factors among patients with type 2 diabetes: A cross-sectional study.

Background: As numerous studies highlighted the importance of maintaining proper foot care (FC) behaviours among individuals with diabetes to prevent complications, we sought to assess FC behaviours among patients with diabetes and to identify the factors associated with the practice of diabetic FC. Methods: We used a cross-sectional design and collected data through self-reported questionnaires administered to a sample of 586 patients from five medical centres. We conducted descriptive and inferential analyses to explore the relationships between potential risk and protective factors and FC behaviours. Results: Overall, 429 individuals (73.2%) had good FC behaviours, while 157 (26.8%) displayed poor FC behaviours. Furthermore, we identified eight influencing factors on FC behaviours, including smoking status, the availability of a caregiver, the presence of diabetic foot ulcers, amputation history, FC knowledge, subjective norms in diabetes self-care behaviour, diabetes-related stress, and quality of life index values. The logistic regression analysis showed that current smokers were 60% less likely to practice good FC compared to non-smokers (odds ratio (OR) = 0.40; 95%; confidence interval (CI) = 0.22-0.73). Having a caregiver decreased the likelihood of practicing good FC by 50% (OR = 0.52; 95% CI = 0.33-0.84), while having diabetic foot ulcers doubled it (OR = 2.65; 95% CI = 1.26-5.54). Additionally, more FC knowledge increased the likelihood by 20% (OR = 1.21; 95% CI = 1.10-1.33), and higher diabetes-related stress increased it by 1.03 times (OR = 1.03; 95% CI = 1.02-1.05). Conclusions: Our findings underscore the interplay of various factors influencing FC behaviours among individuals with diabetes and call for targeted interventions and tailored strategies to improve FC practices in this vulnerable population.

Proteomics profiling and association with cardiorenal complications in type 2 diabetes subtypes in Asian population.

AIM: Among multi-ethnic Asians, type 2 diabetes (T2D) clustered in three subtypes; mild obesity-related diabetes (MOD), mild age-related diabetes with insulin insufficiency (MARD-II) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII) had differential cardio-renal complication risk. We assessed the proteomic profiles to identify subtype specific biomarkers and its association with diabetes complications. METHODS: 1448 plasma proteins at baseline were measured and compared across the T2D subtypes. Multivariable cox regression was used to assess associations between significant proteomics features and cardio-renal complications. RESULTS: Among 645 T2D participants (SIRD-RII [19%], MOD [45%], MARD-II [36%]), 295 proteins expression differed significantly across the groups. These proteins were enriched in cell adhesion, neurogenesis and inflammatory response processes. In SIRD-RII group, ADH4, ACY1, THOP1, IGFBP2, NEFL, ENTPD2, CALB1, HAO1, CTSV, ITGAV, SCLY, EDA2R, ERBB2 proteins significantly associated with progressive CKD and LILRA5 protein with incident heart failure (HF). In MOD group, TAFA5, RSPO3, EDA2R proteins significantly associated with incident HF. In MARD-II group, FABP4 protein significantly associated with progressive CKD and PTPRN2 protein with major adverse cardiovascular events. Genetically determined NEFL and CALB1 were associated with kidney function decline. CONCLUSIONS: Each T2D subtype has unique proteomics signature and association with clinical outcomes and underlying mechanisms.

Strategies to prevent cardiovascular disease in Singapore: A call to action from Singapore Heart Foundation, Singapore Cardiac Society and Chapter of Cardiologists of the Academy of Medicine, Singapore.

Introduction: In 2022, the Minister for Health of Singapore launched Healthier SG, a national strategy in championing the shift towards a population health approach. Method: The Singapore Heart Foundation conducted a series of roundtable discussions, also attended by representatives of the Singapore Cardiac Society and the Chapter of Cardiologists of the Academy of Medicine Singapore. During the meetings, the authors formulated interventions supportive of Healthier SG that specifically aimed to uplift the state of cardiovascular (CV) preventive care in Singapore. Results: In line with Healthier SG, the authors propose a 3-pronged approach ("Healthier Heart SG") to augment the success of Healthier SG in achieving good CV outcomes. This proposal includes the following components: (1) a call to update the standards of care in addressing the 5 main modifiable risk factors of cardiovascular disease (CVD); (2) patient education through cooperation between healthcare professionals and community partners for a whole-of-system approach; and (3) support for integrated care, including access to cardiac rehabilitation in the community, improved referral processes and access to nutrition/dietetics counselling and tobacco cessation, optimal use of information technology, and continued CV research. Conclusion: Healthier Heart SG would bring the standards of care and CV care delivery in Singapore closer to achieving the vision of proactive prevention of CVD and CV morbidity and mortality. This can only be achieved through the concerted efforts of healthcare professionals, policymakers and community partners, coupled with the cooperation of community members.

Short-term Weight Trajectory of Severely Obese Individuals With and Without Pathogenic Satiety-Regulation Melanocortin 3/4 Receptor (MC3/4R) Mutations From a Multi-ethnic Asian Large Bariatric Surgery Program.

The melanocortin (3 or 4) receptor (MC3/4R) is involved in regulating satiety and body weight. Therefore, pathogenic mutation in MC3/4R is associated with severe obesity, for which bariatric surgery is one of the treatment options. However, there is limited data on whether individuals with MC3/4R mutation will have differential weight response to surgery, especially among the Asian populations-the epi-center of the evolving global obesity epidemic. From our large prospective Obesity-Metabolism & Intervention Cohort Study (OMICS; N = 654, recruited between 2007 and 2022), 5 individuals with pathogenic MC3/4R mutations ("case") were identified using candidate-genes panel next-generation sequencing (Illumina iSeq). These subjects were carefully propensity score-matched (baseline body mass index [BMI], age, sex, ethnicity, proportion with diabetes, type of bariatric surgery) in a 1:4 ratio to other controls. We performed linear mixed model analysis (for repeated measurements) to compare their longitudinal weight trajectories (percentage total weight loss, %TWL) over 12 months. The 5 cases with MC3/4R mutations were 48 ± 11 years, BMI 40.8 ± 11.2 kg/m2, 60% with diabetes, and all males. Their weight at baseline (pre-op), and 6 months and 12 months after surgery were 120 ± 38, 100 ± 31, and 101 ± 30 kg, respectively. Compared with propensity score-matched controls (N = 20), linear mixed model analysis suggested no difference in surgically induced %TWL (ß coefficient = -5.8 ± 3.7, P = .13) over 12 months between the groups. Therefore, we conclude that rare pathogenic MC3/4R mutations do not significantly modify weight change (%TWL) in response to bariatric surgery.

Associations of non-invasive indices of liver steatosis and fibrosis with progressive kidney impairment in adults with type 2 diabetes.

AIMS: Longitudinal data linking non-alcoholic fatty liver disease to kidney dysfunction in type 2 diabetes (T2D) are limited. This study evaluated the associations of non-invasive indices of liver steatosis and liver fibrosis with kidney impairment, and the mediatory role of the pro-angiogenic factor leucine-rich α-2 glycoprotein 1 (LRG1). METHODS: T2D adults (n = 2057) were followed for a mean period of 6.1 ± 1.6 years. Baseline liver steatosis [(hepatic steatosis index (HSI) and Zhejiang University index (ZJU)] and liver fibrosis [aspartate transaminase/alanine transaminase ratio (AAR) and BARD] indices derived from composite scoring systems were calculated. Plasma LRG1 levels were quantified using immunoassay. The study outcomes were progressive kidney function decline defined as estimated glomerular filtration rate (eGFR) decline of ≥ 40% and albuminuria progression defined as an increase in albuminuria category. RESULTS: Cross-sectionally, liver steatosis and liver fibrosis indices were associated with increased albuminuria (urinary albumin/creatinine ratio ≥ 30 µg/mg) and reduced renal function (eGFR < 60 mL/min/1.73 m2) after covariate adjustment, respectively. Approximately 32% of the participants experienced progressive kidney function decline, while 38% had albuminuria worsening over time. Longitudinal analysis revealed that baseline AAR (hazard ratio: 1.56; 95% CI 1.15-2.11) and BARD (hazard ratio: 1.16, 95% CI 1.04-1.28) predicted progressive kidney function decline, partly mediated by LRG1. In contrast, liver steatosis (HSI and ZJU) but not liver fibrosis (AAR and BARD) indices were independently associated with albuminuria progression. CONCLUSIONS: Increased liver steatosis scores were associated with albuminuria deterioration. Conversely, liver fibrosis indices may be associated with progressive kidney function decline, potentially driven by increased inflammation and angiogenesis.

Association of Baseline Triglyceride-Glucose Index with Poor Glycemic Control and Diabetes Remission After Metabolic Surgery.

PURPOSE: The utility of insulin resistance (IR) as a predictor of diabetes remission after metabolic surgery is not well-defined. We assessed the association of baseline surrogate IR indices including triglyceride-glucose (TyG) index and homeostatic model assessment for IR (HOMA-IR) with glycemic control and diabetes remission after metabolic surgery. MATERIALS AND METHODS: Patients with type 2 diabetes scheduled for metabolic surgery were recruited at a single-center (n = 149; age: 44 ± 10 years, 47.7% men, body mass index: 41.5 ± 7.5 kg/m2), and followed-up for 12 months postoperatively. The relationships between the IR indices and poor glycemic control (HbA1c ≥ 7%) at baseline or complete diabetes remission (HbA1c < 6% without glucose-lowering medications at 12 months) post-surgery were examined. RESULTS: Elevated TyG index was associated with poor glycemic control cross-sectionally. Compared with non-remitters, lower baseline TyG index levels were observed in individuals with complete diabetes remission after surgery (P = 0.012); whereas HOMA-IR was not significantly different. Consistently, the proportion of diabetes non-remitters (compared to remitters) increased with increasing TyG tertiles from 1 to 3 (P = 0.015). Both TyG index (relative risk = 0.62, 95% CI = 0.42-0.91, P = 0.014) and TyG tertile 1 (relative risk = 1.99, 95% CI = 1.25-3.24, P = 0.003) independently predicted diabetes remission. The TyG index identified diabetes remission with an area under the curve of 0.68. The optimal TyG threshold was 9.41, yielding a sensitivity of 69.6%, specificity of 60.9%, positive predictive value of 64.0%, and negative predictive value of 66.7%. CONCLUSION: TyG index, previously suggested to predominantly reflect muscle IR, outperforms HOMA-IR as an IR indicator associated with glycemic control and diabetes remission after metabolic surgery.

Chylomicronemia through a burr hole: A case report.

Chylomicronemia has either a monogenic or multifactorial origin. Multifactorial chylomicronemia is the more common form and is due to the interaction of genetic predisposition and secondary factors such as obesity, diabetes, unhealthy diet, and medications. We report a case of a 38-year-old man who was diagnosed with multifactorial chylomicronemia following presentation with a subarachnoid hemorrhage requiring emergency surgery through a burr hole; lactescent cerebrospinal fluid mixed with blood was observed through the burr hole. The serum triglyceride concentration was 52⋅4 mmol/L with a detectable triglyceride concentration in the cerebrospinal fluid. Rapid weight gain leading to obesity and related unfavorable lifestyle factors were identified as key secondary causes of chylomicronemia. Gene testing revealed a homozygous variant in APOA5 and a heterozygous common variant in GPIHBP1. Accompanied with secondary causes, the interactions of gene and environmental conditions contribute to chylomicronemia. With aggressive medical treatment including excess weight loss, healthy diet, cessation of alcohol, and combination of anti-lipemic medications, normal plasma triglyceride levels were achieved.

A real-world study on SGLT2 inhibitors and diabetic kidney disease progression.

Background: Randomized controlled trials have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, real-world data on CKD progression and the development of end-stage kidney disease (ESKD) remains scarce. Our aim was to study renal outcomes of people with diabetic kidney disease (DKD) using SGLT2is in a highly prevalent DKD population. Methods: Between 2016 and 2019 we recruited T2DM patients in the renal and diabetic clinics in a regional hospital in Singapore. Patients prescribed SGLT2is were compared with those on standard anti-diabetic and renoprotective treatment. The outcome measures were CKD progression [a ≥25% decrease from baseline and worsening of estimated glomerular filtration rate (eGFR) categories according to the Kidney Disease: Improving Global Outcomes guidelines] and ESKD (eGFR <15 mL/min/1.73 m2). Results: We analysed a total of 4446 subjects; 1598 were on SGLT2is. There was a significant reduction in CKD progression {hazard ratio [HR] 0.60 [95% confidence interval (CI) 0.49-0.74]} with SGLT2is. The HR for eGFR ≥45 mL/min/1.73 m2 and 15-44 mL/min/1.73 m2 was 0.60 (95% CI 0.47-0.76) and 0.43 (95% CI 0.23-0.66), respectively. There was also a reduction in risk for developing ESKD for the entire cohort [HR 0.33 (95% CI 0.17-0.65)] and eGFR 15-44 mL/min/1.73 m2 [HR 0.24 (95% CI 0.09-0.66)]. Compared with canagliflozin and dapagliflozin, empagliflozin showed a sustained risk reduction of renal outcomes across CKD stages 1-4. Conclusions: This real-world study demonstrates the benefits of SGLT2is on CKD progression and ESKD. The effect is more pronounced in moderate to advanced CKD patients.

Ethnic-Specific Type 2 Diabetes Risk Factor PAX4 R192H Is Associated with Attention-Specific Cognitive Impairment in Chinese with Type 2 Diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been shown to increase the risks of cognitive decline and dementia. Paired box gene 4 (PAX4), a transcription factor for beta cell development and function, has recently been implicated in pathways intersecting Alzheimer's disease and T2DM. OBJECTIVE: In this report, we evaluated the association of the ethnic-specific PAX4 R192H variant, a T2DM risk factor for East Asians which contributes to earlier diabetes onset, and cognitive function of Chinese T2DM patients. METHODS: 590 Chinese patients aged 45-86 from the SMART2D study were genotyped for PAX4 R192H variation using Illumina OmniExpress-24 Array. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) which had been validated in the Singapore population was administered to assess five cognitive domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Multiple linear regression was used to assess the association of the R192H risk allele and cognitive domains. RESULTS: Patients with two PAX4 R192H risk alleles showed significantly lower attention index score (ß= -8.46, 95% CI [-13.71, -3.21], p = 0.002) than patients with wild-type alleles after adjusting for age, gender, diabetes onset age, HbA1c, body-mass index, renal function, lipid profiles, systolic blood pressure, metformin usage, smoking history, education level, Geriatric Depression Scale score, and presence of APOEɛ4 allele. CONCLUSION: Ethnic-specific R192H variation in PAX4 is associated with attention-specific cognitive impairment in Chinese with T2DM. Pending further validation studies, determining PAX4 R192H genotype may be helpful for early risk assessment of early-onset T2DM and cognitive impairment to improve diabetes care.

MODY5 Hepatocyte Nuclear Factor 1ß (HNF1ß)-Associated Nephropathy: experience from a regional monogenic diabetes referral centre in Singapore.

From our monogenic diabetes registry set-up at a secondary-care diabetes center, we identified a nontrivial subpopulation (~15%) of maturity-onset diabetes of the young (MODY) among people with young-onset diabetes. In this report, we describe the diagnostic caveats, clinical features and long-term renal-trajectory of people with HNF1B mutations (HNF1B-MODY). Between 2013 and 2020, we received 267 referrals to evaluate MODY from endocrinologists in both public and private practice. Every participant was subjected to a previously reported structured evaluation process, high-throughput nucleotide sequencing and gene-dosage analysis. Out of 40 individuals with confirmed MODY, 4 (10%) had HNF1B-MODY (harboring either a HNF1B whole-gene deletion or duplication). Postsequencing follow-up biochemical and radiological evaluations revealed the known HNF1B-MODY associated systemic-features, such as transaminitis and structural renal-lesions. These anomalies could have been missed without prior knowledge of the nucleotide-sequencing results. Interestingly, preliminary longitudinal observation (up to 15 years) suggested possibly 2 distinct patterns of renal-deterioration (albuminuric vs. nonalbuminuric chronic kidney disease). Monogenic diabetes like HNF1B-MODY may be missed among young-onset diabetes in a resource-limited routine-care clinic. Collaboration with a MODY-evaluation center may fill the care-gap. The long-term renal-trajectories of HNF1B-MODY will require further studies by dedicated registries and international consortium.

The role of pulse pressure in navigating the paradigm of chronic kidney disease progression in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Arterial stiffness is a risk factor for chronic kidney disease progression (CKD). Pulse pressure is a surrogate marker of arterial stiffness. It is unclear if pulse pressure predicts CKD progression in type 2 diabetes mellitus. METHODS: This was prospective study involving 1494 patients with estimated glomerular filtration rate (eGFR) ≥ 15 ml/min/1.73 m2. Carotid-femoral pulse wave velocity was measured using applanation tonometry. Pulse pressure was calculated as difference between systolic and diastolic blood pressures. CKD progression was defined as worsening of eGFR categories (stage 1, ≥ 90 ml/min/1.73 m2; stage 2, 60-89 ml/min/1.73 m2; stage 3a, 45-59 ml/min/1.73 m2; stage 3b, 30-44 ml/min/1.73 m2; stage 4; 15-29 ml/min/1.73 m2; and stage 5, < 15 ml/min/1.73 m2) with ≥ 25% decrease in eGFR from baseline. RESULTS: After follow-up of up to 6 years, CKD progression occurred in 33.5% of subjects. Subjects in 2nd, 3rd and 4th quartiles of peripheral pulse pressure experienced higher risk of CKD progression with unadjusted hazard ratios (HRs) 1.55 [95% confidence interval (CI) 1.13-2.11; p = 0.006], 2.58 (1.93-3.45; p < 0.001) and 3.41 (2.58-4.52; p < 0.001). In the fully adjusted model, the association for 2nd, 3rd and 4th quartiles remained with HRs 1.40 (1.02-1.93; p = 0.038), 1.87 (1.37-2.56; p < 0.001) and 1.75 (1.25-2.44; p = 0.001) respectively. Similarly, 2nd, 3rd and 4th quartiles of aortic pulse pressure were associated with higher hazards of CKD progression with HRs 1.73 (1.25-2.40; p = 0.001), 1.65 (1.18-2.29; p = 0.003) and 1.81 (1.26-2.60; p = 0.001). Increasing urinary albumin-to-creatinine ratio accounted for 44.0% of the association between peripheral pulse pressure and CKD progression. CONCLUSIONS: Individuals with high pulse pressure were more susceptible to deterioration of renal function. Pulse pressure could potentially be incorporated in clinical practice as an inexpensive and readily available biomarker of renal decline in type 2 diabetes mellitus. Graphic abstract.

Long-Term Observation of a Man With Severe Obesity and Undiagnosed Monogenic Diabetes Serendipitously Treated With Metabolic Surgery.

A 43-year-old man, with severe obesity (43 kg/m2) and diabetes (presumed as type 2 diabetes [T2D]), underwent vertical sleeve gastrectomy in 2009 and Roux-en-Y gastric bypass in 2013. Recently, whole exome sequencing (conducted to search for monogenic obesity) serendipitously revealed that the individual harbored a heterozygous glucokinase (GCK) variant p.(Arg422Leu) that was bioinformatically strongly predicted to be likely pathogenic. Therefore, he is likely to have concomitant maturity-onset diabetes of the young (MODY) type 2 (GCK-MODY). A retrospective evaluation of the clinical data showed that the subject was diagnosed with T2D (given his severe obesity) in 2005 and was treated with oral antidiabetic monotherapy. His hyperglycemia was mostly mild (HbA1c [hemoglobin] < 8.1%), consistent with that of MODY2, despite severe obesity. After vertical sleeve gastrectomy, complete diabetes remission (HbA1c <6.0% and fasting plasma glucose <5.6 mmol/L without use of antidiabetic medication) was achieved. The percentage of maximum body weight loss attained after surgery was 23.6%. Euglycemia was maintained during the subsequent decade, up to the last follow-up in 2019, without any sign of hypoglycemia. In conclusion, we report a decade-long clinical experience of a man with severe obesity and diabetes likely due to the coexistence of GCK-MODY and T2D, serendipitously treated with metabolic surgery. Interestingly, metabolic surgery was effective and safe for him.

Metabolic Surgery Diabetes Remission (MDR) Score: a New Preoperative Scoring System for Predicting Type 2 Diabetes Remission at 1 Year After Metabolic Surgery in the Singapore Multi-ethnic Asian Setting.

PURPOSE: The utility of available scoring systems for type 2 diabetes (T2D) remission prediction after metabolic surgery has not been defined in a multi-ethnic Asian population like Singapore. We sought to assess the predictive performance of the Asia-developed ABCD scoring system for T2D remission after metabolic surgery, and develop a new algorithm to improve prediction. MATERIALS AND METHODS: We conducted a retrospective analysis of adults with T2D who underwent either Roux-en-Y gastric bypass or sleeve gastrectomy between 2007 and 2018, and followed for 1 year postoperatively (n = 114, mean age 46 ± 9 years, 48.2% men, body mass index 40.1 ± 6.6 kg/m2). The primary outcome was complete T2D remission defined as HbA1c < 6% without the use of anti-diabetic medication at 1 year after surgery. RESULTS: Complete T2D remission was observed in 47.4% of subjects at 1 year post-surgery. Stepwise logistic regression identified preoperative age, T2D duration, HbA1c, and ß-cell function (estimated by the homeostasis model) as predictors of complete T2D remission. Based on these four variables, we constructed a new 10-point scoring system named Metabolic surgery Diabetes Remission (MDR) score. Compared with ABCD, MDR produced fewer misclassifications at the mid-high scores, achieving a predictive accuracy of 71-100% at 6 points and above. In addition, MDR achieved a higher area under the receiver operating characteristic curve than ABCD for the primary outcome (0.79 versus 0.67, P = 0.007). CONCLUSION: MDR may serve as a useful clinical scoring system for predicting short-term T2D remission after metabolic surgery in Singapore's multi-ethnic Asian cohort.

Plasma osteoprotegerin as a biomarker of poor glycaemic control that predicts progression of albuminuria in type 2 diabetes mellitus: A 3-year longitudinal cohort study.

AIMS: Poor glycaemic control elevates the risk for vascular complications. Biomarkers for predicting susceptibility to glycaemic worsening are lacking. This 3-year prospective analysis assessed the utility of several circulating diabetes-related biomarkers for predicting loss of glycaemic control, and their contribution to albuminuria progression in type 2 diabetes mellitus (T2DM). METHODS: T2DM subjects with adequately-controlled diabetes (HbA1c < 8%) at initial recruitment were analysed (N = 859). Baseline plasma levels of osteoprotegerin (OPG), C-reactive protein (CRP), adiponectin, intercellular-cell adhesion molecule-1, and vascular-cell adhesion molecule-1 were quantified using immunoassay. Definitions for development of uncontrolled diabetes and albuminuria progression were HbA1c ≥ 8.0% and increase in albuminuria category at follow-up, respectively. RESULTS: At follow-up, 185 subjects developed uncontrolled diabetes. Higher baseline CRP and OPG levels were observed in the high-risk individuals, and predicted increased risk for developing uncontrolled diabetes. OPG, but not CRP, was associated with albuminuria progression after multivariable adjustment. The relationship was attenuated following adjustment for development of uncontrolled diabetes, which emerged as a significant associate. Mediation analysis revealed that loss of glycaemic control explained 64.5% of the relationship between OPG and albuminuria progression. CONCLUSIONS: OPG outperformed other diabetes-related biomarkers to be a potentially useful biomarker for predicting loss of glycaemic control and its associated albuminuria deterioration.

Efficacy of self-monitoring of blood glucose versus retrospective continuous glucose monitoring in improving glycaemic control in diabetic kidney disease patients.

AIMS: Patients with diabetic kidney disease (DKD) on anti-diabetic agents, are at greater risk of glycemic variations, both hypoglycemia and hyperglycemia. We aimed to compare glycemic control (using HbA1c) and hypoglycemia incidence in patients with Stage 3 DKD (eGFR 30-60 mL/min per 1.73 m2 ), receiving retrospective CGM-guided anti-diabetic therapy versus self-monitoring of blood glucose (SMBG) over 3 months. METHODS: Thirty patients with HbA1c >8% were randomized to 6-day retrospective CGM or SMBG. In the CGM group, CGM was worn at the beginning and 6 weeks. HbA1c, assessment of hypoglycaemia events (self-reported and BG < 4 mmol/L from CGM/SMBG data) and medication adjustment were performed at baseline and 3 months. All patients received education on hypoglycaemia avoidance. RESULTS: Fourteen patients were allocated to CGM and 16 to SMBG. Mean (±SD) eGFR was 42.9 ± 10.3 mL/min. Majority (86.7%) of patients had diabetes duration >10 years and on insulin therapy (90%). HbA1c improved significantly from baseline 9.9 ± 1.2 to 9.0 ± 1.5% (P < 0.001) at 3 months, with no difference between CGM (9.8 ± 1.2 to 8.8 ± 1.8%, P = 0.009) or SMBG (9.9 ± 1.3 to 9.1 ± 1.1%, P = 0.007) groups (P = 0.869 between groups). In the CGM group, percentage duration in hyperglycaemia (BG > 10 mmol/L) reduced from baseline 65.4 ± 22.4% to 54.6 ± 23.6% (P = 0.033) at 6 weeks, with a non-significant rise in percentage duration in hypoglycaemia from 1.2 ± 2.2% to 4.0 ± 7.0% (P = 0.176). There was no difference in self-reported and documented hypoglycaemia events. CONCLUSION: In a pilot study of DKD patients, short-term episodic use of CGM reduced time spent in hyperglycaemia range without significantly increasing time-exposure to hypoglycaemia. However, both CGM and SMBG were equally effective in improving glycaemic control.

Metabolic signatures and risk of type 2 diabetes in a Chinese population: an untargeted metabolomics study using both LC-MS and GC-MS.

AIMS/HYPOTHESIS: Metabolomics has provided new insight into diabetes risk assessment. In this study we characterised the human serum metabolic profiles of participants in the Singapore Chinese Health Study cohort to identify metabolic signatures associated with an increased risk of type 2 diabetes. METHODS: In this nested case-control study, baseline serum metabolite profiles were measured using LC-MS and GC-MS during a 6-year follow-up of 197 individuals with type 2 diabetes but without a history of cardiovascular disease or cancer before diabetes diagnosis, and 197 healthy controls matched by age, sex and date of blood collection. RESULTS: A total of 51 differential metabolites were identified between cases and controls. Of these, 35 were significantly associated with diabetes risk in the multivariate analysis after false discovery rate adjustment, such as increased branched-chain amino acids (leucine, isoleucine and valine), non-esterified fatty acids (palmitic acid, stearic acid, oleic acid and linoleic acid) and lysophosphatidylinositol (LPI) species (16:1, 18:1, 18:2, 20:3, 20:4 and 22:6). A combination of six metabolites including proline, glycerol, aminomalonic acid, LPI (16:1), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid and urea showed the potential to predict type 2 diabetes in at-risk individuals with high baseline HbA1c levels (≥6.5% [47.5 mmol/mol]) with an AUC of 0.935. Combined lysophosphatidylglycerol (LPG) (12:0) and LPI (16:1) also showed the potential to predict type 2 diabetes in individuals with normal baseline HbA1c levels (<6.5% [47.5 mmol/mol]; AUC = 0.781). CONCLUSIONS/INTERPRETATION: Our findings show that branched-chain amino acids and NEFA are potent predictors of diabetes development in Chinese adults. Our results also indicate the potential of lysophospholipids for predicting diabetes.

Prevalence and control of hypercholesterolaemia as defined by NCEP-ATPIII guidelines and predictors of LDL-C goal attainment in a multi-ethnic Asian population.

INTRODUCTION: Few studies in Asia have assessed the burden of hypercholesterolaemia based on the global cardiovascular risk assessment. This study determines the burden of hypercholesterolaemia in an Asian population based on the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) guidelines, and examines predictors of low-density lipoprotein cholesterol (LDL-C) goal attainment. MATERIALS AND METHODS: Five thousand and eighty-three Chinese, Malays and Asian-Indians living in Singapore were assigned to coronary heart disease (CHD)-risk category based on the NCEP-ATPIII guidelines. Awareness, treatment and control of hypercholesterolaemia based on risk- specific LDL-C goal were determined, including the use of lipid-lowering therapy (LLT). Cox-regression models were used to identify predictors of LDL-C above goal among those who were aware and unaware of hypercholesterolaemia. RESULTS: One thousand five hundred and sixty-eight (30.8%) participants were aware of hypercholesterolaemia and 877 (17.3%) were newly diagnosed (unaware). For those who were aware, 39.3% participants received LLT. Among those with 2 risk factors, only 59.7% attained LDL-C goal. The majority of them were taking statin monotherapy, and the median dose of statins was similar across all CHD risk categories. Among participants with 2 risk factors and not receiving LLT, 34.1% would require LLT. Malays or Asian-Indians, higher CHD risk category, increasing body mass index (BMI), current smoking and lower education status were associated with higher risk of LDL-C above goal. Being on LLT reduced the risk of having LDL-C above goal. CONCLUSION: The burden of hypercholesterolaemia is high in this multi-ethnic population especially those in the higher CHD risk categories, and might be partly contributed by inadequate titration of statins therapy. Raising awareness of hypercholesterolaemia, appropriate LLT initiation and titration, weight management and smoking cessation may improve LDL-C goal attainment in this population.