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Aims/hypothesis: The aim of this study was to test the effectiveness of a structured strength and balance training intervention in improving health-related quality of life (HRQoL) and functional status in individuals with diabetic peripheral neuropathy (DPN)., Methods: The study was a single-blind parallel-group randomised controlled trial comparing 2 months of once-weekly home-based strength and balance training against standard medical therapy. Participants were patients with physician-diagnosed type 2 diabetes and neuropathy recruited from five public sector institutions in Singapore between July 2014 and October 2017. Participants were block-randomised to intervention or control arms. Outcomes were assessed at baseline, 2 months and 6 months by a trained assessor blinded to group assignment. Primary outcomes were change in physical component summary (PCS) score of SF-36v2 (a 36-item generic HRQoL instrument that has been validated for use in Singapore) and EQ-5D-5L index score (derived from a five-item generic HRQoL instrument [EQ-5D-5L]) over 6 months. Secondary outcomes were change in functional status (timed up-and-go [TUG], five times sit-to-stand [FTSTS], functional reach, static balance, ankle muscle strength and knee range of motion) and balance confidence over 6 months. Mean differences in scores between groups were compared using mixed models., Results: Of the 143 participants randomised (intervention, n = 70; control, n = 73), 67 participants were included in each arm for the final intention-to-treat analysis. The two groups were similar, except in terms of sex. There were no significant differences between groups on the primary outcomes of PCS score (mean difference [MD] 1.56 [95% CI -1.75, 4.87]; p = 0.355) and EQ-5D-5L index score (MD 0.02 [95% CI -0.01, 0.06]; p = 0.175). There were significant improvements in TUG test performance (MD -1.14 [95% CI -2.18, -0.1] s; p = 0.032), FTSTS test performance (MD -1.31 [95% CI -2.12, -0.51] s; p = 0.001), ankle muscle strength (MD 4.18 [95% CI 0.4, 7.92] N; p = 0.031), knee range of motion (MD 6.82 [95% CI 2.87, 10.78]°; p = 0.001) and balance confidence score (MD 6.17 [95% CI 1.89, 10.44]; p = 0.005). No adverse events due to study participation or study intervention were reported., Conclusions/interpretation: Short-term structured strength and balance training did not influence HRQoL but produced sustained improvements in functional status and balance confidence at 6 months. More intensive interventions may be needed to influence HRQoL in these individuals. However, this intervention may be a useful treatment option for individuals with DPN to reduce the risk of falls and injuries., Trial Registration: ClinicalTrials.gov NCT02115932 FUNDING: This work was supported by the National Medical Research Council, Singapore.

Aims/hypothesis: The involvement of chronic inflammation in albuminuria and renal function was investigated in a cross-sectional study of 320 type 2 diabetic Chinese patients from the Singapore Diabetes Cohort Study., Methods: Plasma levels of TNF-alpha and its two cellular receptors and of IL-6 and C-reactive protein (CRP) were measured. A composite TNF-alpha score was extracted using principal component analysis. Multiple linear regression analysis was implemented to evaluate the relationship between log( e ) (ln) albumin:creatinine ratio (ACR) and estimated GFR (eGFR) with the inflammatory variables and other clinical covariates. A Bonferroni correction was applied based on the total number of variables entered into regression analyses., Results: ln ACR was significantly associated with TNF-alpha score independently of eGFR even after a Bonferroni correction. TNF-alpha score was also significantly associated with eGFR independently of ln ACR even after correction for multiple testing. These findings were similar when the individual molecules of the TNF-alpha system were analysed separately instead of using the composite TNF-alpha score. No association was observed for IL-6 and CRP with either renal trait. Diabetes duration was a significant predictor for ln ACR but not eGFR. Conversely, age was significantly associated with eGFR but not ln ACR., Conclusions/interpretation: Activation of the TNF-alpha system may potentially exert independent effects on ln ACR and eGFR in type 2 diabetes. Because of the study design, one may also consider the possibility that changes in these renal traits may conversely be responsible for such an inflammatory response.

Aims/hypothesis: The aim of the study was to determine whether the risk of ischaemic heart disease (IHD) associated with diabetes mellitus differs between ethnic groups., Methods: Registry linkage was used to identify IHD events in 5707 Chinese, Malay and Asian Indian participants from three cross-sectional studies conducted in Singapore between the years 1984 and 1995. The study provided a median of 10.2 years of follow-up with 240 IHD events experienced. We assessed the interaction between diabetes mellitus and ethnicity in relation to the risk of IHD events using Cox proportional hazards regression., Results: Diabetes mellitus was more common in Asian Indians. Furthermore, diabetes mellitus was associated with a greater risk of IHD in Asian Indians. The hazard ratio when comparing diabetes mellitus with non-diabetes mellitus was 6.41 (95% CI 5.77-7.12) in Asian Indians and 3.07 (95% CI 1.86-5.06) in Chinese (p = 0.009 for interaction). Differences in the levels of established IHD risk factors among diabetics from the three ethnic groups did not appear to explain the differences in IHD risk., Conclusions/interpretation: Asian Indians are more susceptible to the development of diabetes mellitus than Chinese and Malays. When Asian Indians do develop diabetes mellitus, the risk of IHD is higher than for Chinese and Malays. Consequently, the prevention of diabetes mellitus amongst this ethnic group is particularly important for the prevention of IHD in Asia, especially given the size of the population at risk. Elucidation of the reasons for these ethnic differences may help us understand the pathogenesis of IHD in those with diabetes mellitus.

Aims/hypothesis: The ACE insertion/deletion polymorphism has been examined for association with diabetic nephropathy over the past decade with conflicting results. To clarify this situation, we conducted a comprehensive meta-analysis encompassing all relevant studies that were published between 1994 and 2004 and investigated this potential genetic association., Methods: A total of 14,727 subjects from 47 studies was included in this meta-analysis. Cases (n=8,663) were type 1 or 2 diabetic subjects with incipient (microalbuminuria) or advanced diabetic nephropathy (proteinuria, chronic renal failure, end-stage renal disease). Control subjects (n=6,064) were predominantly normoalbuminuric., Results: No obvious publication bias was detected. Using a minimal-case definition based on incipient diabetic nephropathy, subjects with the II genotype had a 22% lower risk of diabetic nephropathy than carriers of the D allele (pooled odds ratio [OR]=0.78, 95% CI=0.69-0.88). While there was a reduced risk of diabetic nephropathy associated with the II genotype among Caucasians with either type 1 or type 2 diabetes, the association was most marked among type 2 diabetic Asians (Chinese, Japanese, Koreans) (OR=0.65, 95% CI=0. 51-0.83). This OR is significantly different from the OR of 0.90 (95% CI= 0.78-1.04) that was obtained for type 2 diabetic Caucasians (p=0.019). Using a stricter case definition based on advanced diabetic nephropathy, a comparable risk reduction of 24-32% was observed among the three subgroups, although statistical significance was reached only among Asians., Conclusions/interpretation: The results of our meta-analysis support a genetic association of the ACE Ins/Del polymorphism with diabetic nephropathy. These findings may have implications for the management of diabetic nephropathy using ACE inhibitors especially among type 2 diabetic Asians.