Tavintharan Subramaniam

Early Retinal Arteriolar Changes and Peripheral Neuropathy in Diabetes

OBJECTIVE To examine the association between early retinal arteriolar abnormalities and diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS Data from 608 people (aged 40–80 years) with diabetes from the population-based Singapore Malay Eye Study were analyzed. Participants underwent binocular two-field digital retinal photography and quantitative sensory testing. DPN was defined as an abnormal response to a monofilament or neurothesiometer test. Quantitative changes of retinal vascular caliber and arteriolar bifurcation geometry were measured using a computer-based program. Qualitative retinal signs of retinopathy and retinal arteriolar wall signs were graded by standardized methods. RESULTS DPN was present in 155 people (25.5%). After adjusting for age, sex, diabetes duration, HbA1c, cardiovascular risk factors, antihypertensive medication use, and peripheral arterial disease, people with suboptimal arteriolar caliber (odds ratio 1.94 [95% CI 1.22–3.10]), larger arteriolar branching coefficient (1.58 [1.03–2.42]), diabetic retinopathy (1.82 [1.20–2.75]), and focal arteriolar narrowing (2.92 [1.48–5.76]) were more likely to have DPN. Participants with a greater number of retinal microvascular signs were more likely to have DPN than those without retinal changes (6.11 [2.11–17.71] for two or more signs and 3.47 [1.18–10.21] for one sign compared with none). CONCLUSIONS Individuals with diabetes with early retinal arteriolar abnormalities are more likely to have DPN, independent of hyperglycemia and major vascular risk factors. These data support the hypothesis that early microvascular dysfunction, evident in the retina, is an independent risk factor for DPN.

Distribution of ankle—brachial index and the risk factors of peripheral artery disease in a multi-ethnic Asian population:

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis and is associated with increased cardiovascular morbidity and mortality. We describe the prevalence and risk factors of PAD in a multi-ethnic Asian population (Chinese, Malays and Indians) in Singapore. The Singapore Prospective Study Program recruited 4132 individuals between 2004 and 2006 in which the ankle—brachial index (ABI) was measured using the Smartdop™ 20EX bi-directional blood flow detector. PAD was defined as ≤ 0.9 and a high ABI > 1.4, with ABI 1.11—1.20 as reference. The mean age (SD) of individuals in the study was 49.9 (11.8) years, with 51.8% females. PAD was present in 4.3% of the population and a high ABI (> 1.4) was rare. Malays and Indians had a higher risk (especially in females). Compared to those with an ABI between 1.11 and 1.20, those with PAD were more likely to be of Malay and Indian ethnicity, female sex, with higher systolic blood pressure and pulse pressure, with increased prevalence of diabetes mellitus, hypertension, albuminuria and renal impairment, and with a past history of stroke. In conclusion, in this large multi-ethnic Asian population, we document the distribution and risk factor associations for PAD. PAD shows an ethnic distribution similar to that of coronary artery disease in Singapore, with differences in sex distribution. Apart from traditional vascular risk factors, pulse pressure, renal impairment and a past history of stroke are important determinants of PAD.

Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients

Introduction: The aging-suppression gene α-klotho is potentially reno-protective. Animal studies suggest that angiotensin II may be a negative regulator of α-klotho expression. Therefore, we hypothesize that renin–angiotensin system antagonism may increase α-klotho secretion in type 2 diabetes (T2DM). Subjects and methods: In this post-hoc analysis of a randomized crossover study, 33 T2DM subjects with albuminuria received either 50 mg of losartan or 20 mg of quinapril (both 50% maximal dose) daily for 4 weeks with 4-week wash-out period in between. Results: Our data showed that losartan, but not quinapril, significantly increased circulating α-klotho level by an average of 23% (from 542 pg/ml to 668 pg/ml, p=0.001). Linear regression revealed that, besides different mode of treatment, increment in plasma α-klotho was associated with decrement in urine albumin/creatinine ratio (β=-0.263, p=0.029). Conclusions: The angiotensin receptor blocker losartan increases circulating α-klotho in T2DM with albuminuria. The clinical significance of this rise in α-klotho associated with losartan intervention deserves further investigation.

The effect of long‐term glycemic variability on estimated glomerular filtration rate decline among patients with type 2 diabetes mellitus – insights from the Diabetic Nephropathy Cohort in Singapore

In the present study, we examined the association between HbA1c variability and renal disease progression based on estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes mellitus (T2DM) in Singapore.

Adiponectin Gene Polymorphisms and Type 2 Diabetes among Singaporean Chinese Adults

Background: Adiponectin is the most abundant circulating adipokine in human that regulates insulin actions. Association of adiponectin gene variations with type 2 diabetes (T2DM) has been reported albeit predominantly in non-Asian populations. Additionally, proof of variant functionality beyond statistical association is often unavailable. We studied six common (minor allele frequency ≥0.05) adiponectin single nucleotide polymorphisms (SNPs) in Singaporean Chinese adults with follow-up functional genetic experiments. Methods: In a case-control study (N=588), genotyping of six common adiponectin haplotype tagging SNPs [-3964A>G(rs822396), +45T>G(rs2241766), 276C>A(rs1501299), 973G>A(rs3774262), 4551G>C(rs1063539) and 5852G>A(rs6444175)] was performed using Taqman genotyping assay. Allele-dependent differential efficiency of mRNA expression was tested with quantitative real time PCR using human subcutaneous and omental adipose tissues. Results: Distributions of genotypes for all SNPs among controls were consistent with Hardy-Weinberg Equilibrium. Single locus, genotyped-based analysis suggested borderline significant ( P=0.07) association between an exon2 coding-synonymous +45T>G(rs2241766) and T2DM. We demonstrated that the relative mRNA expression of adiponectin gene was ~80% lower among carriers of minor G allele in human subcutaneous adipose tissue (N=43, p G(rs2241766) and T2DM among Singaporean Chinese adults. Functional experiments in both human subcutaneous and omental adipose tissue suggested that polymorphisms in +45T>G(rs2241766) may be associated with differential allelic expression.

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

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.

Ethnic disparities in relationship of obesity indices and telomere length in Asians with type 2 diabetes

Obesity and shorter telomeres increase the risk for diabetes complications and mortality. However, the relationship between obesity and telomere length in diverse Asian populations with type 2 diabetes (T2D) is not well understood. This study examined the association of baseline and changes in obesity indices with telomere length in multiethnic Asian populations with T2D.

Medical Costs Associated with Chronic Kidney Disease Progression in an Asian Population with Type 2 Diabetes Mellitus: Chronic Kidney Disease Progression and Medical Costs

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.

Long Term Outcomes of Patients With Type 2 Diabetes Attending a Multidisciplinary Diabetes Kidney Disease Clinic

The best model of care to retard diabetic kidney disease (DKD) in the clinic is underexplored. In this study we investigated the long‐term renal outcomes of a joint endocrinologist–nephrologist clinic.

The role of triglyceride glucose index in development of Type 2 diabetes mellitus

AIMS Triglyceride-Glucose (TyG) is an emerging surrogate indicator of insulin resistance. We explored the role of TyG in development of Type 2 Diabetes Mellitus (T2DM) and elucidated the mechanism for the relationship. METHODS 4109 subjects without baseline T2DM participated in a community screening programme in 2013-2016. TyG was calculated as Ln[fasting triglyceride level (mg/dl) × fasting plasma glucose (FPG) (mg/dl)/2]. Outcome was T2DM defined as FPG ≥ 7.0 mmol/l; current treatment with anti-diabetes medication; and/or self-reported diabetes on follow-up screening. We used Cox proportion-hazard model to assess risk of T2DM by TyG quartiles at baseline. Binary mediation analysis was performed to examine extent of mediation by TyG between Body Mass Index (BMI) and T2DM development. RESULTS After 5734.23 person-years of follow-up, T2DM developed in 117 subjects with an incidence of 20.40/1000 person-years. Risk of T2DM incidence was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG (adjusted HR 1.79(95%CI 0.80-3.99), 2.54 (1.18-5.49) and 4.68(2.19-10.01), Ptrend < 0.001) across TyG quartiles. TyG accounted for 35.1% of association between BMI and T2DM development, having adjusted for potential cofounders (p < 0.001). CONCLUSIONS TyG is potentially useful for predicting T2DM in clinical practice. It is a potential mediator of association between BMI and T2DM development.