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Aims: This real-world observational clinical programme evaluated short and medium-term effects of intermittent flash glucose monitoring on HbA1c, glycaemic variability and lifestyle behavioural changes., Methods: Two first-generation Libre flash glucose monitoring sensors were provided 3-4 months apart with a food, activity diary, user evaluation survey and treatment modification after each sensor wear. T-tests were used to compare glucose variables within each sensor (week 1 vs. week 2) and between sensors (1st sensor vs. 2nd sensor). EasyGV software was used to calculate glycaemic variability., Results: From 42 type 1 diabetes and 120 type 2 diabetes participants, there was no statistically significant change in mean HbA1c for participants with type 1 diabetes at 3-4 months after the 1st sensor but there was a statistically significant HbA1c reduction for participants with type 2 diabetes [-4 mmol/mol (-0.4%), p = 0.008], despite no statistically significant differences in carbohydrate intake, exercise frequency and duration. Greater reduction was seen in those with baseline HbA1c> 86 mmol/mol (10%) in both type 1 [-12 mmol/mol (-1.1%), p = 0.009] and type 2 diabetes [-11 mmol/mol (-1.0%), p = 0.001). Both type 1 and type 2 diabetes showed improvements in Glucose Management Indicator and percentage time-above-range when comparing week 1 versus week 2 of the same sensor. Higher scan frequency resulted in improved glycaemic parameters and certain measures of glycaemic variability. The majority of participants (85%) agreed that flash glucose monitoring is a useful device but only 60% were keen to use it for daily monitoring., Conclusion: Constant feedback from flash glucose monitoring improves glycaemic parameters within the first week of wear. Intermittent use 3-4 months apart resulted in greater improvements for those with higher baseline HbA1c., (© 2021 Diabetes UK.)

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., (© 2020 Diabetes UK.)

Aim: To characterize haemoglobin A1c (HbA1c) trajectories and examine their associations with chronic kidney disease (CKD) progression., Methods: This was a prospective cohort study on 770 patients with type 2 diabetes mellitus (T2DM) attending a diabetes centre in 2002-2017. Group-based trajectory modelling was used to identify HbA1c trajectories. Cox proportional hazards models were used to examine association between the trajectories and CKD progression which was defined as deterioration across the Kidney Disease: Improving Global Outcomes estimated glomerular filtration rate categories with ≥25% drop from baseline., Results: We identified four HbA1c trajectories: 'near-optimal stable' (49.1%), 'moderate stable' (37.9%), 'moderate-increasing' (6.0%) and 'high-decreasing' (7.0%). Over a median follow-up period of 4.6 years (interquartile range 2.5-5.6), CKD progression occurred in 35.6% of patients. The risk of CKD progression was significantly higher in the moderate-increasing with adjusted hazard ratios (HR) 2.23 (95% confidence interval (CI) 1.09-4.57). After additional adjustment for mean HbA1c, the association between the moderate-increasing subgroup and CKD progression remained significant at HR 3.07 (95% CI 1.08-8.77)., Conclusion: Moderate-increasing HbA1c trajectory is associated with renal disease progression in patients with T2DM, independent of mean HbA1c. The deleterious effects of deteriorating HbA1c trajectory highlight the importance of achieving sustained good glycaemic control in diabetes management., (© 2018 Asian Pacific Society of Nephrology.)

Aim: We aim to examine difference in incremental direct medical costs between non-progressive and progressive chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) in Singapore., Methods: This was a prospective study on 676 patients with T2DM attending a diabetes centre in a regional hospital. Annual direct medical costs were extracted from the administrative database. Ordinary least squares regression was used to estimate contribution of CKD progression to annual costs, adjusting for demographics and baseline clinical covariates., Results: Over mean follow-up period of 2.8 ± 0.4 years, 266 (39.3%) had CKD progression. The excess total follow-up medical costs from baseline was S$4243 higher in progressors compared to non-progressors (P = 0.002). The mean cost differential between the two groups increased from S$2799 in Stages G1-G2 to S$11180 in Stage G4. Inpatient cost accounted for 63.4% of total cost of progression. When stratified by glomerular filtration rate stages, the respective total mean annual costs at stages glomerular filtration rate Stages G3a-G3b and G4 were S$3290 (132%; P = 0.001) and S$4416 (135%; P = 0.011) higher post-progression., Conclusion: Chronic kidney disease progression in T2DM is associated with high medical costs. The cost of progression is higher with higher severity of CKD stage at baseline and could be largely driven by inpatient admission., (© 2018 Asian Pacific Society of Nephrology.)

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 m 2 ), 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., (© 2016 Asian Pacific Society of Nephrology.)

Objective: A substantial proportion of diabetic nephropathy individuals are non-albuminuric. Using a proteomic approach, we searched for novel urinary biomarkers., Methods: We studied three groups (n = 6 per group) of males with Type 2 diabetes: (1) normal renal function; (2) classical diabetic nephropathy (urinary albumin-creatinine ratio > 1000 mg/g and glomerular filtration rate < 60 ml/min.1.73 m(2) ) and (3) non-albuminuric diabetic nephropathy (glomerular filtration rate < 60 ml/min.1.73 m(2) and urinary albumin-creatinine ratio < 30 mg/g). We used two-dimensional fluorescence differential gel electrophoresis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry peptide identification and western blot validation in the study., Results: Sixty protein spots were differentially abundant between the non-albuminuric and macro-albuminuric subjects (> 2.5-fold, P < 0.05). In the non-albuminuric subjects, in addition to previously reported α(1) -microglobulin, the next most interesting spot (upregulated 3.44-fold, P = 0.0026) was human zinc-α(2) -glycoprotein, a novel adipose-cytokine associated with glomerular injury. This was confirmed by western blot and replicated in female diabetic nephropathy subjects., Conclusions: From our preliminary results, human zinc-α(2) -glycoprotein may be a novel urinary biomarker for non-albuminuric diabetic nephropathy., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Aim: Individuals with diabetes and prediabetes are at risk of vascular injury. However, the exact mechanisms are unclear. The mitochondria mobile electron carrier coenzyme Q(10) (CoQ(10)) is a potent lipophilic antioxidant. We hypothesize that oxidative stress, detectable as changes in plasma CoQ(10) concentrations and composition, plays an important role in vascular disease in diabetes., Methods: We measured plasma CoQ(10) concentrations (including reduced ubiquinol and oxidized ubiquinone subfractions) in 60 subjects with normal glucose tolerance [NGT; fasting plasma glucose (FPG) < 5.5 mmol/l], 63 with impaired fasting glucose (IFG; FPG 5.6-6.9 mmol/l) and 69 with Type 2 diabetes (DM; FPG > 6.9 mmol/l)., Results: In men and women, the total CoQ(10)/total cholesterol ratio was reduced in DM (mean +/-sd) [male (M) 0.09 +/- 0.04; female (F) 0.07 +/- 0.04] compared with NGT (0.29 +/- 0.08; 0.21 +/- 0.07) and IFG (0.27 +/- 0.07; 0.23 +/- 0.07) (DM vs. NGT and IFG P = 0.001). A stepwise reduction in the plasma ubiquinol fraction (ubiquinol/total CoQ10) was observed from NGT (M 0.93 +/- 0.06; F 0.95 +/- 0.06) compared with IFG (0.43 +/- 0.25; 0.41 +/- 0.15) and DM (0.24 +/- 0.11; F 0.29 +/- 0.16) (DM vs. IFG vs. NGT P = 0.001). In contrast, the plasma ubiquinone/ubiquinol ratio increased from NGT (M 0.08 +/- 0.07, F 0.06 +/- 0.08) to IFG (2.14 +/- 1.84, 1.75 +/- 1.04) to DM (4.77 +/- 4.88, 3.81 +/- 3.71) (DM vs. IFG vs. NGT P = 0.001). These differences remained after adjusting for age, body mass index and FPG., Conclusions: The change in CoQ(10) with increasing FPG concentration suggests an increase in oxidative burden, already evident in the prediabetic IFG individuals. This increase in oxidative stress might contribute to the increased risk of vascular disease.

Objective: Genetic determinants are important in diabetic nephropathy (DN). Oxidative stress has also emerged as an important pathogenic factor in DN and vascular NADH oxidase is a major source of reactive oxygen species (ROS). Previous small studies reported a strong but contradictory association between functional genetic variation of p22(phox), an important subcomponent of NADH oxidase, and DN. We investigated the association between two common functional single nucleotide polymorphisms (SNPs) (-930 A > G and +242 C > T) and DN in a much larger group of Chinese patients with Type 2 diabetes mellitus (T2DM)., Research Design and Methods: Case-control study of Chinese subjects with long-standing T2DM (> 10 years). Cases (n = 306) were subjects with a spot urinary albumin : creatinine ratio (ACR) of > 113 mg/mmol or elevated serum creatinine. Control subjects (n = 306) had ACR < 3.3 mg/mmol and normal serum creatinine. Genotyping was carried out by standard PCR and restriction fragment length polymorphism analysis., Results: Gender distribution, age, duration of diabetes and HbA(1c) were similar in cases and control subjects. Distribution of genotypes in the control subjects for both SNPs was consistent with the Hardy-Weinberg equilibrium. Distribution of genotypes did not differ significantly between cases and control subjects for both polymorphisms-+2424C > T: cases CC 84.6%, CT 15.0%, TT 0.4% and control subjects CC 87.6%, CT 11.8%, TT 0.6% (P = 0.45); -930 A > G: cases AA 40.5%, AG 41.8%, GG 17.7% and control subjects AA 38.2%, AG 49.0%, GG 12.8% (P = 0.12). Distribution of alleles was also similar-+2424 C > T: cases C 92.2%, T 7.8% and control subjects C 93.5%, T 6.5% (P = 0.66); -930 A > G cases A 61.4%, G 38.6% and control subjects A 62.7%, G 37.3% (P = 0.38). We estimated that our study has approximately 80% power to detect a relative risk of 1.65 (for +242 C > T) and 1.35 (for -930 A > G) conferred by the minor allele, respectively., Conclusions: In contrast with previous small studies, our data suggest that these SNPs do not confer significantly increased susceptibility to DN secondary to T2DM in Chinese subjects.