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Heidelberg, Australia

Uma Jyothi K.,Indian Statistical Institute | Jayaraj M.,Indian Statistical Institute | Subburaj K.S.,Indian Statistical Institute | Prasad K.J.,Endocrine Center | And 3 more authors.

We attempt to evaluate the nature of association of TCF7L2 gene variants with T2DM, for the first time in the population of Hyderabad, which is considered to be diabetic capital of India. It is a case-control study of the three SNPs of TCF7L2, rs7903146, rs12255372 and rs11196205, genotyped on Sequenom Massarray platform, in a sample of 758 patients and 621 controls. The risk allele frequency of the three SNPs was found to be significantly higher in the T2DM cases than controls, implicating susceptibility for diabetes (p<0.01). The greatest risk of developing the disease was conferred by rs7903146. Further, the logistic regression of genotypes of each SNP under log additive model, and the haplotypes constituted by at least one of the three risk alleles also show significantly greater risk of developing T2DM when compared to the wild type haplotype. Further, BMI and WHR emerge as significant covariates with confounding effects. The strong association of the TCF7L2 SNPs with T2DM is consistent with the findings among other Indian and Non-Indian populations, suggesting universal phenomena of its association across ethnic groups globally, both within and outside the Indian subcontinent, albeit the functional relevance of these SNPs needs yet to be established. © 2013 Uma Jyothi et al. Source

Miyakawa M.,Endocrine Center
Nihon rinsho. Japanese journal of clinical medicine

Recently, thyroid nodules are found frequently when other imaging test was performed, and selection of diagnostic methods and its handling have become a problem clinically. Although it is possible to differentiate the malignant tumor from benign one using B-mode ultrasound, it can be obtained more detailed information in combination of other modalities such as color Doppler and tissue elasticity imaging (elastography). The malignant B-mode findings are irregular shape, indistinct border, hypoechoic and inhomogeneous internal echo, and fine calcification. CT/MRI is useful to evaluate the extention of thyroid cancer to adjacent organs beyond the thyroid capsule. It is also useful to evaluate distant metastases to lung or brain of thyroid cancer. In nuclear medicine, 125I scintigraphy is used to measure thyroid uptake rate, 131I scintigraphy is used to investigate the distant metastasis of thyroid cancer. It is necessary to be careful that some false-positive cases exist in 18FDG-PET. Source

MacIsaac R.J.,University of Melbourne | MacIsaac R.J.,Endocrine Center | Jerums G.,University of Melbourne
Current Opinion in Nephrology and Hypertension

Purpose of review: Historically, for people at risk of developing diabetic chronic kidney disease (CKD), an initial increase in albumin excretion rate (AER) has been linked to a subsequent decline in glomerular filtration rate (GFR). We review recent findings that suggest that in some people with diabetic CKD there is an uncoupling of progressive increases in AER and declining GFR. Recent findings: Approximately 20% of people with type 2 diabetes develop at least stage 3 CKD, defined as an estimated GFR (eGFR) less than 60 ml/min/1.73 m, after accounting for the use of renin-angiotensin system blockers, while remaining normoalbuminuric. A recent analysis from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study has shown that 24% of people with type 1 diabetes reached an eGFR threshold of less than 60 ml/min/1.73 m that was not associated with a rise in albuminuria to the microalbuminuria or macroalbuminuria range. This discordance between changes in GFR and AER has resulted in a search for new markers that identify people with diabetes who are at risk of declining GFR independent of progressive increases in AER. Summary: The conventional paradigm of kidney disease in people with diabetes has been challenged. Changes in AER and GFR are being increasingly recognized as complementary rather than obligatory manifestations of diabetic CKD. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Kommoju U.J.,Indian Statistical Institute | Maruda J.,Indian Statistical Institute | Kadarkarai Samy S.,Indian Statistical Institute | Irgam K.,Indian Statistical Institute | And 2 more authors.
Journal of Diabetes

Background: We attempted to validate earlier findings on the nature of the association of the IRS1, CAPN10, and PPARG genes with type 2 diabetes mellitus (T2DM) in the high-risk population of Hyderabad, India. Methods: A sample of 1379 subjects (758 T2DM patients, 621 controls) was genotyped for single nucleotide polymorphisms (SNPs) of the IRS1 (rs1801278), CAPN10 (rs3792267, rs5030952), and PPARG (rs1801282) genes. Results: The allele and genotype frequencies of IRS1 (rs1801278) and CAPN10 (rs3792267) SNPs differed significantly between the patient and control groups. Logistic regression analysis suggested a significant association of these two SNPs (P≤0.007) with T2DM and the strength of association did not alter when adjusted for age, gender, body mass index, and the waist:hip ratio as covariates. The same two SNPs showed significant association in multivariate logistic regression analyses, even after Bonferroni correction for multiple testing, suggesting an independent nature of the role of these genes in the manifestation of T2DM in our population. Conclusions: We replicated the significant association of rs1801278 and rs3792267 SNPs of the IRS1 and CAPN10 genes with T2DM in the population of Hyderabad. Despite the known biological significance of the PPARG gene and a sufficient statistical power of the present study, we could not replicate the association of PPARG with T2DM in our high-risk population. Given the vast ethnic, geographic, and genetic heterogeneity of the Indian population, many more studies are needed covering the ethnic and geographic heterogeneity of India to enable identification of an Indian-specific profile of genes associated with T2DM. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd. Source

Teng J.,St. Vincents Hospital | Dwyer K.M.,St. Vincents Hospital | Hill P.,University of Melbourne | See E.,St. Vincents Hospital | And 6 more authors.

The spectrum of renal disease in patients with diabetes encompasses both diabetic kidney disease (including albuminuric and non-albuminuric phenotypes) and non-diabetic kidney disease. Diabetic kidney disease can manifest as varying degrees of renal insufficiency and albuminuria, with heterogeneity in histology reported on renal biopsy. For patients with diabetes and proteinuria, the finding of non-diabetic kidney disease alone or superimposed on the changes of diabetic nephropathy is increasingly reported. It is important to identify non-diabetic kidney disease as some forms are treatable, sometimes leading to remission. Clinical indications for a heightened suspicion of non-diabetic kidney disease and hence consideration for renal biopsy in patients with diabetes and nephropathy include absence of diabetic retinopathy, short duration of diabetes, atypical chronology, presence of haematuria or other systemic disease, and the nephrotic syndrome. Summary at a Glance This review article highlights the heterogeneity of renal disease in patients with diabetes. The spectrum of renal disease in patients with diabetes encompasses both diabetic kidney disease (including albuminuric and non-albuminuric phenotypes) and non-diabetic kidney disease which can be independent or superimposed on albuminuric diabetic kidney disease. It is important to identifying non-diabetic kidney disease because it is potentially reversible. The clinical features suggestive of non-diabetic kidney disease, which should prompt consideration of renal biopsy, are discussed. © 2014 Asian Pacific Society of Nephrology. Source

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