Testicular cavernous hemangioma masquerading as testicular malignancy.

Cavernous hemangiomas are benign tumors of vascular origin that can develop in any part of the body. However, its occurrence in the testis is rare. To the best of our knowledge, we are reporting the first case of a patient with cavernous hemangioma with concern for an extracapsular extension on ultrasound imaging.

Impact of radiation on the incidence and management of ureteroenteric strictures: a contemporary single center analysis.

BACKGROUND: Ureteroenteric stricture incidence has been reported as high as 20% after urinary diversion. Many patients have undergone prior radiotherapy for prostate, urothelial, colorectal, or gynecologic malignancy. We sought to evaluate the differences between ureteroenteric stricture occurrence between patients who had radiation prior to urinary diversion and those who did not. METHODS: An IRB-approved cystectomy database was utilized to identify ureteroenteric strictures among 215 patients who underwent urinary diversion at a single academic center between 2016 and 2020. Chart abstraction was conducted to determine the presence of confirmed stricture in these patients, defined as endoscopic diagnosis or definitive imaging findings. Strictures due to malignant ureteral recurrence were excluded (3 patients). Statistical analysis was performed using chi squared test, t-test, and Wilcoxon Rank-Sum Test, logistic regression, and Kaplan-Meier analysis of stricture by cancer type. RESULTS: 65 patients had radiation prior to urinary diversion; 150 patients did not have a history of radiation therapy. Benign ureteroenteric stricture rate was 5.3% (8/150) in the non-radiated cohort and 23% (15/65) in the radiated cohort (p = < 0.001). Initial management of stricture was percutaneous nephrostomy (PCN) in 78% (18/23) and the remaining 22% (5/23) were managed with primary retrograde ureteral stent placement. Long term management included ureteral reimplantation in 30.4% (7/23). CONCLUSIONS: Our study demonstrates a significant increase in rate of ureteroenteric strictures in radiated patients as compared to non-radiated patients. The insult of radiation on the ureteral microvascular supply is likely implicated in the cause of these strictures. Further study is needed to optimize surgical approach such as utilization of fluorescence angiography for open and robotic approaches.

Differences in Patient-Reported Outcomes That Are Most Frequently Detected in Randomized Controlled Trials in Patients With Solid Tumors: A Pooled Analysis of 229 Trials.

OBJECTIVES: Patient-reported outcome (PRO) measurements used in cancer research can assess a number of health domains. Our primary objective was to investigate which broad types of PRO domains (namely, functional health, symptoms, and global quality of life [QoL]) most frequently yielded significant differences between treatments in randomized controlled trials (RCTs). METHODS: A total of 229 RCTs published between January 2004 and February 2019, conducted on patients diagnosed with the most common solid malignancies and assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, were considered. Studies were identified systematically using literature searches in key electronic databases. Unlike other PRO measurements typically used in RCTs, the scoring algorithm of the multidimensional EORTC QLQ-C30 allowed us to clearly distinguish the 3 broad types of PRO domains. RESULTS: In total, 134 RCTs (58.5%) reported statistically significant differences between treatment arms for at least 1 of the QLQ-C30 domains. Most frequently, differences were reported for 2 or all 3 broad types of PRO domains (78 of 134 trials; 58.2%). In particular, 35 trials (26.1%) found significant differences for symptoms, functional health, and global QoL, 24 trials (17.9%) for symptoms and functional health, 11 trials (8.2%) for functional health and global QoL, and 8 trials (6.0%) for symptoms and global QoL. The likelihood of finding a statistically significant difference between treatment arms was not associated with key study characteristics, such as study design (ie, open-label vs blinded trials) and industry support. CONCLUSIONS: Our findings emphasize the importance of a multidimensional PRO assessment to most comprehensively capture the overall burden of therapy from the patients' standpoint.

Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder.

Inverted urothelial papilloma (IUP) and urothelial papilloma (UP) are rare urothelial neoplasms that typically follow a benign clinical course. Oncogenic mutations in FGFR3, HRAS, and the TERT promoter have been reported in these entities but no comprehensive molecular analysis has been performed. We sought to characterize the genomic landscape of IUP and UP using whole-exome and targeted next-generation sequencing. In IUP, 10 of 11 tumors harbored oncogenic hotspot mutations in HRAS and the remaining tumor had an oncogenic KRAS mutation. None of the IUP tumors harbored TERT promoter or FGFR3 mutations. In UP, 8 of 11 tumors had oncogenic KRAS mutations and two had oncogenic HRAS mutations. One UP tumor had oncogenic mutations in FGFR3, PIK3CA, and the TERT promoter, and arose in a patient with recurrent non-invasive papillary urothelial carcinomas. In contrast to urothelial carcinoma, the APOBEC mutational signature was not present in any IUP and UP tumors, and oncogenic alterations in chromatin remodeling genes were uncommon in both IUP and UP. The current study suggests that IUP and UP are driven primarily by RAS pathway activation and lack the more common genomic features of urothelial cancers. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Minnelide Inhibits Androgen Dependent, Castration Resistant Prostate Cancer Growth by Decreasing Expression of Androgen Receptor Full Length and Splice Variants.

BACKGROUND: With almost 30,000 deaths per year, prostate cancer is the second-leading cause of cancer-related death in men. Androgen Deprivation Therapy (ADT) has been the corner stone of prostate cancer treatment for decades. However, despite an initial response of prostate cancer to ADT, this eventually fails and the tumors recur, resulting in Castration Resistant Prostate Cancer (CRPC). Triptolide, a diterpene triepoxide, has been tested for its anti-tumor properties in a number of cancers for over a decade. Owing to its poor solubility in aqueous medium, its clinical application had been limited. To circumvent this problem, we have synthesized a water-soluble pro-drug of triptolide, Minnelide, that is currently being evaluated in a Phase 1 clinical trial against gastrointestinal tumors. In the current study, we assessed the therapeutic potential of Minnelide and its active compound triptolide against androgen dependent prostate cancer both in vitro as well as in vivo. METHODS: Cell viability was measured by a MTT based assay after treating prostate cancer cells with multiple doses of triptolide. Apoptotic cell death was measured using a caspase 3/7 activity. Androgen Receptor (AR) promoter-binding activity was evaluated by using luciferase reporter assay. For evaluating the effect in vivo, 22Rv1 cells were implanted subcutaneously in animals, following which, treatment was started with 0.21 mg/kg Minnelide. RESULTS: Our study showed that treatment with triptolide induced apoptotic cell death in CRPC cells. Triptolide treatment inhibited AR transcriptional activity and decreased the expression of AR and its splice variants both at the mRNA and the protein level. Our studies show that triptolide inhibits nuclear translocation of Sp1, resulting in its decreased transcriptional activity leading to downregulation of AR and its splice variants in prostate cancer cells. In vivo, Minnelide (0.21 mg/kg) regressed subcutaneous tumors derived from CRPC 22RV1 at our study endpoint. Our animal studies further confirmed that Minnelide was more efficacious than the standard of care therapies, Docetaxel and Enzalutamide. CONCLUSION: Our study indicates that Minnelide is very effective as a therapeutic option against CRPC at a dose that is currently tolerated by patients in the ongoing clinical trials. Prostate 77: 584-596, 2017. © 2017 Wiley Periodicals, Inc.

Non-muscle invasive bladder cancer risk stratification.

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) comprises about 70% of all newly diagnosed bladder cancer, and includes tumors with stage Ta, T1 and carcinoma in situ (CIS.) Since, NMIBC patients with progression to muscle-invasive disease tend to have worse prognosis than with patients with primary muscle-invasive disease, there is a need to significantly improve risk stratification and earlier definitive treatment for high-risk NMIBC. MATERIALS AND METHODS: A detailed Medline search was performed to identify all publications on the topic of prognostic factors and risk predictions for superficial bladder cancer/NMIBC. The manuscripts were reviewed to identify variables that could predict recurrence and progression. RESULTS: The most important prognostic factor for progression is grade of tumor. T category, tumor size, number of tumors, concurrent CIS, intravesical therapy, response to bacillus Calmette-Guerin at 3- or 6-month follow-up, prior recurrence rate, age, gender, lymphovascular invasion and depth of lamina propria invasion are other important clinical and pathological parameters to predict recurrence and progression in patients with NMIBC. The European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Club UrológicoEspañol de Tratamiento Oncológico (CUETO) risk tables are the two best-established predictive models for recurrence and progression risk calculation, although they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Molecular biomarkers such as Ki-67, FGFR3 and p53 appear to be promising in predicting recurrence and progression but need further validation prior to using them in clinical practice. CONCLUSION: EORTC and CUETO risk tables are the two best-established models to predict recurrence and progression in patients with NMIBC though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Future research should focus on enhancing the predictive accuracy of risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi-institutional cohorts.

Primary Neuroendocrine Prostate Cancer with Penile Metastasis.

Supplemental material is available for this article.

India Ink Tattooing of Ureteroenteric Anastomoses.

While upper tract access through the insensate conduit following urinary diversion takes less time and incurs fewer costs than percutaneous kidney access does for the treatment of ureter and kidney pathology, endoscopic ureteroenteric anastomoses (UEA) identification can be difficult. We injected India Ink into the bowel mucosa near the UEA during ileal conduit diversion (IC) to determine the safety and feasibility of ink tattooing. Patients undergoing IC were prospectively randomized to receive ink or normal saline (NS) injections. The injections were placed 1 cm from UEA in a triangular configuration, and loopogram exams and looposcopy were performed to identify reflux (UR), UEA, the tattooing site and strictures in 10 and 11 patients randomized with respect to ink and NS injections, respectively. Ink patients were older (72 vs. 61 years old, p = 0.04) and had a higher Charlson Comorbidity Index (5 vs. 2, p = 0.01). Looposcopy was performed in three ink and four NS patients. Visualization of UEA was achieved in 100% of the ink and 75% of the NS patients (p = 0.26). The ink ureteroenteric anastomotic stricture (UEAS) rate was higher (N = 3 vs. N = 1) and six patients vs. one patients underwent surgery, respectively, for UEAS (p = 0.31). The study was halted early due to safety concerns. Our pilot study demonstrates that ink can be well visualized following injection near UEA during IC. However, the ink cohort had more UEAS than previously cited in the literature and our prior institutional UEAS rate of 6%. While this study sample is small, the higher incidence of UEAS after ink injection led us to question the utility and safety of ink injection following IC.

Association of [-2]proPSA with biopsy reclassification during active surveillance for prostate cancer.

PURPOSE: Previous studies have suggested an association between [-2]proPSA expression and prostate cancer detection. Less is known about the usefulness of this marker in following patients with prostate cancer on active surveillance. Thus, we examined the relationship between [-2]proPSA and biopsy results in men enrolled in an active surveillance program. MATERIALS AND METHODS: In 167 men from our institutional active surveillance program we used Cox proportional hazards models to examine the relationship between [-2]proPSA and annual surveillance biopsy results. The outcome of interest was biopsy reclassification (Gleason score 7 or greater, more than 2 positive biopsy cores or more than 50% involvement of any core with cancer). We also examined the association of biopsy results with total prostate specific antigen, %fPSA, [-2]proPSA/%fPSA and the Beckman Coulter Prostate Health Index phi ([-2]proPSA/free prostate specific antigen) × (total prostate specific antigen)(½)). RESULTS: While on active surveillance (median time from diagnosis 4.3 years), 63 (37.7%) men demonstrated biopsy reclassification based on the previously mentioned criteria, including 28 (16.7%) of whom had reclassification based on Gleason score upgrading (Gleason score 7 or greater). Baseline and longitudinal %fPSA, %[-2]proPSA, [-2]proPSA/%fPSA and phi measurements were significantly associated with biopsy reclassification, and %[-2]proPSA and phi provided the greatest predictive accuracy for high grade cancer. CONCLUSIONS: In men on active surveillance, measures based on [-2]proPSA such as phi appear to provide improved prediction of biopsy reclassification during followup. Additional validation is warranted to determine whether clinically useful thresholds can be defined, and to better characterize the role of %[-2]proPSA and phi in conjunction with other markers in monitoring patients enrolled in active surveillance.

A rare presentation of unilateral periureteral renal lymphangiomatosis.

Renal lymphangiomatosis is a rare developmental malformation of the perirenal lymphatic system. We report a unique case with unilateral massive periureteral involvement in addition to intrarenal and peripelvic lymphangiomatosis. Although this is a rare entity, it should be considered in patients with peripelvic or periureteric cystic lesions as it may affect appropriate management and follow-up. This case report reviews the imaging features of this entity and a comprehensive literature review and discussion about the entity will be provided.

Prediction of patient-specific risk and percentile cohort risk of pathological stage outcome using continuous prostate-specific antigen measurement, clinical stage and biopsy Gleason score.

OBJECTIVES: • To develop a '2010 Partin Nomogram' with total prostate-specific antigen (tPSA) as a continuous biomarker, in light of the fact that the current 2007 Partin Tables restrict the application of tPSA as a non-continuous biomarker by creating 'groups' for risk stratification with tPSA levels (ng/mL) of 0-2.5, 2.6-4.0, 4.1-6.0, 6.1-10.0 and >10.0. • To use a 'predictiveness curve' to calculate the percentile risk of a patient among the cohort. PATIENTS AND METHODS: • In all, 5730 and 1646 patients were treated with radical prostatectomy (without neoadjuvant therapy) between 2000 and 2005 at the Johns Hopkins Hospital (JHH) and University Clinic Hamburg-Eppendorf (UCHE), respectively. • Multinomial logistic regression analysis was performed to create a model for predicting the risk of the four non-ordered pathological stages, i.e. organ-confined disease (OC), extraprostatic extension (EPE), and seminal vesicle (SV+) and lymph node (LN+) involvement. • Patient-specific risk was modelled as a function of the B-spline basis of tPSA (with knots at the first, second and third quartiles), clinical stage (T1c, T2a, and T2b/T2c) and biopsy Gleason score (5-6, 3 + 4 = 7, 4 + 3 = 7, 8-10). RESULTS: • The '2010 Partin Nomogram' calculates patient-specific absolute risk for all four pathological outcomes (OC, EPE, SV+, LN+) given a patient's preoperative clinical stage, tPSA and biopsy Gleason score. • While having similar performance in terms of calibration and discriminatory power, this new model provides a more accurate prediction of patients' pathological stage than the 2007 Partin Tables model. • The use of 'predictiveness curves' has also made it possible to obtain the percentile risk of a patient among the cohort and to gauge the impact of risk thresholds for making decisions regarding radical prostatectomy. CONCLUSION: • The '2010 Partin Nomogram' using tPSA as a continuous biomarker together with the corresponding 'predictiveness curve' will help clinicians and patients to make improved treatment decisions.

Nuclear roundness variance predicts prostate cancer progression, metastasis, and death: A prospective evaluation with up to 25 years of follow-up after radical prostatectomy.

BACKGROUND: Nuclear structure is often altered in cancer due to spatial rearrangements of chromatin organization via activation of oncogenes and other chromatin remodeling genes. Therefore, we evaluated the prognostic value of nuclear roundness variance (NRV) for prostate cancer (PCa) progression, metastasis and PCa-specific death free survivals in a cohort of 116 men after radical prostatectomy (RP). METHOD: NRV was calculated for each case using the variance of the nuclear roundness from approximately 150 nuclei captured at a magnification of 2,440x for each case in 1992-1993. $${\rm Nuclear}\,{\rm roundness} = {{{\rm Radius}({\rm circumference})} \over {{\rm radius}({\rm area})}} = {R \over r} = {{P/2\pi } \over {\sqrt {A/\pi } }}$$ NRV data were merged with clinical, pathologic, and follow-up data for all patients in 2009. Cox proportional hazards regression and Kaplan-Meier plots were employed to analyze the data. RESULTS: Median follow-up time after RP for all patients was 19 years (range: 1-25 years, mean: 17 years), with approximately 92% (107/116), 71% (82/116), and 47% (55/116) patients having >or=10, 15, and 20 years of follow-up, respectively. NRV was the most significant parameter for prediction of all three outcomes and its concordance-index (C-Index) increased from progression (0.7080) to metastasis (0.7332) to PCa-specific death (0.8090) free survival predictions. Of note, NRV C-Index was significantly higher compared to Gleason Score C-Index for metastasis (0.7332 vs. 0.6046; P = 0.027) and PCa-specific death (0.8090 vs. 0.6336; P = 0.004) free survival predictions. However, the difference between NRV and Gleason Score C-Indexes was not statistically significant for progression free survival prediction (0.7080 vs. 0.6463; P = 0.106). CONCLUSION: NRV is valuable nuclear structural feature that exceeds Gleason score to predict an aggressive phenotype of PCa.

DNA content in the diagnostic biopsy for benign-adjacent and cancer-tissue areas predicts the need for treatment in men with T1c prostate cancer undergoing surveillance in an expectant management programme.

STUDY TYPE: Prognosis (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To assess the DNA content in benign-adjacent and cancer-tissue areas of a diagnostic biopsy, to predict which patients would subsequently develop an unfavourable biopsy necessitating treatment for prostate cancer in the expectant management (EM) programme. PATIENTS AND METHODS: Of 71 patients who had benign-adjacent and cancer-tissue areas of diagnostic biopsies available, 39 developed unfavourable biopsies (Gleason score > or =7, Gleason pattern 4/5, three or more cores positive for cancer, >50% of any core involved with cancer), while 32 maintained favourable biopsies on annual surveillance examination (median follow-up 3.7 years). DNA content was measured on Feulgen-stained biopsy sections using an automatic imaging system (AutoCyte(TM), TriPath Imaging Inc, Burlington, NC, USA). Cox proportional-hazard regression and Kaplan-Meier plots were used to identify significant predictors for unfavourable biopsy conversion. RESULTS: Univariately, DNA content measurements i.e. an excess of optical density (OD) in the benign-adjacent tissuer area, and the sd of the OD in the cancer tissue were significant, with a hazard ratio and 95% confidence interval of 2.58 (1.17-5.68; P = 0.019) and 5.36 (1.89-15.24; P = 0.002), respectively, for predicting unfavourable biopsy conversion that required intervention. Also, several other DNA content measurements in benign-adjacent and cancer-tissue areas showed a trend to statistical significance. Further, benign-adjacent excess of OD (3.12, 1.4-6.95; P = 0.005) and cancer sd of OD (5.88, 2.06-16.82; P = 0.001) remained significant in the multivariate model to predict unfavourable biopsy conversion. Patients with benign-adjacent excess of OD > 25.0 and cancer sd of OD of >4.0 had the highest risk for unfavourable biopsy conversion (P < 0.001). CONCLUSIONS: DNA content measurements in the benign-adjacent and cancer-tissue areas appear to be useful for predicting unfavourable biopsy conversion (a recommendation for intervention) on annual surveillance examinations in the EM programme.

Valproic acid causes dose- and time-dependent changes in nuclear structure in prostate cancer cells in vitro and in vivo.

Histone deacetylase inhibitors such as valproic acid (VPA) are promising anticancer agents that change the acetylation status of histones and loosen the chromatin structure. We assessed nuclear structure changes induced by VPA in prostate cancer LNCaP, CWR22R, DU145, and PC3 cell lines and xenografts and their potential use as a biomarker of treatment. In vitro tissue microarrays consisted of prostate cancer cell lines treated for 3, 7, or 14 days with 0, 0.6, or 1.2 mmol/L VPA. In vivo tissue microarrays consisted of cores from prostate cancer xenografts from nude mice treated for 30 days with 0.2% or 0.4% VPA in drinking water. Digital images of at least 200 Feulgen DNA-stained nuclei were captured using the Nikon CoolScope and nuclear alterations were measured. With a set of seven most frequently significant nuclear alterations (determined by univariate logistic regression analysis), control and VPA treatment nuclei were compared in vitro and in vivo. Depending on the cell line, area under the curve-receiver operating characteristics ranged between 0.6 and 0.9 and were dose- and time-dependent both in vitro and in vivo. Also, VPA treatment caused significant nuclear alterations in normal drug-filtering organs (liver and kidney tissue). In vitro and in vivo VPA treatment of prostate cancer cell lines results in significant dose- and time-dependent changes in nuclear structure. Further, VPA induces nuclear structural changes in normal liver and kidney tissue, which likely reflects a natural physiologic response. Therefore, nuclear structural alterations may serve as a biomarker for histone deacetylase inhibitor treatment.

Germ Cell Tumor Molecular Heterogeneity Revealed Through Analysis of Primary and Metastasis Pairs.

PURPOSE: Although primary germ cell tumors (GCTs) have been extensively characterized, molecular analysis of metastatic sites has been limited. We performed whole-exome sequencing and targeted next-generation sequencing on paired primary and metastatic GCT samples in a patient cohort enriched for cisplatin-resistant disease. PATIENTS AND METHODS: Tissue sequencing was performed on 100 tumor specimens from 50 patients with metastatic GCT, and sequencing of plasma cell-free DNA was performed for a subset of patients. RESULTS: The mutational landscape of primary and metastatic pairs from GCT patients was highly discordant (68% of all somatic mutations were discordant). Whereas genome duplication was common and highly concordant between primary and metastatic samples, only 25% of primary-metastasis pairs had ≥ 50% concordance at the level of DNA copy number alterations (CNAs). Evolutionary-based analyses revealed that most mutations arose after CNAs at the respective loci in both primary and metastatic samples, with oncogenic mutations enriched in the set of early-occurring mutations versus variants of unknown significance (VUSs). TP53 pathway alterations were identified in nine cisplatin-resistant patients and had the highest degree of concordance in primary and metastatic specimens, consistent with their association with this treatment-resistant phenotype. CONCLUSION: Analysis of paired primary and metastatic GCT specimens revealed significant molecular heterogeneity for both CNAs and somatic mutations. Among loci demonstrating serial genetic evolution, most somatic mutations arose after CNAs, but oncogenic mutations were enriched in the set of early-occurring mutations as compared with VUSs. Alterations in TP53 were clonal when present and shared among primary-metastasis pairs.

South Asian diets and insulin resistance.

A role of dietary nutrients in relation to insulin resistance has been suggested but conclusive evidence in human beings is lacking. Asian Indians and South Asians are prone to develop insulin resistance and the metabolic syndrome. In the present paper, data pertaining to nutrient intake, insulin resistance and cardiovascular risk factors in Asian Indians and South Asians have been reviewed. In these populations, several dietary imbalances have been reported: low intake of MUFA, n-3 PUFA and fibre, and high intake of fats, saturated fats, carbohydrates and trans-fatty acids (mostly related to the widespread use of Vanaspati, a hydrogenated oil). Some data suggest that these nutrient imbalances are associated with insulin resistance, dyslipidaemia and subclinical inflammation in South Asians. Specifically, in children and young individuals, a high intake of n-6 PUFA is correlated with fasting hyperinsulinaemia, and in adults, high-carbohydrate meal consumption was reported to cause hyperinsulinaemia, postprandial hyperglycaemia and hypertriacylglycerolaemia. Dietary supplementation with n-3 PUFA leads to an improved lipid profile but not insulin sensitivity. Inadequate maternal nutrition in pregnancy, low birth weight and childhood 'catch-up' obesity may be important for the development of the metabolic syndrome and diabetes. Even in rural populations, who usually consume traditional frugal diets, there is an increasing prevalence of cardiovascular risk factors and the metabolic syndrome due to changes in diets and lifestyle. Nationwide community intervention programmes aimed at creating awareness about the consequences of unhealthy food choices and replacing them by healthy food choices are urgently needed in urban and rural populations in India, other countries in South Asia and in migrant South Asians.

Diet & insulin resistance: a review & Asian Indian perspective.

Insulin resistance is associated with type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). These abnormalities have been aggravated because of imbalanced and excess nutrition in developed countries, and rapid nutritional and lifestyle transition occurring in developing countries. This review presents evidence linking dietary nutrients with insulin resistance and its metabolic correlates, and also describes these issues from a Asian Indians and South Asian perspective. Despite possible influences from genetic and perinatal factors, diet and physical activity are likely to have greater and often overriding influence in pathogenesis of the insulin resistance, the metabolic syndrome, and T2DM. In animal studies, a link has been established between dietary nutrients and insulin resistance. However, in human studies evidence is not as strong as in animals. Data suggest that dietary omega-3 polyunsaturated fatty acids (PUFAs) improve lipid profile and may have beneficial effect on insulin resistance. Dietary saturated fatty acids intake is positively associated with insulin resistance. Also, low glycaemic index foods and whole grain intake decrease insulin resistance. Importantly, high carbohydrate diets increase plasma triglycerides, cause hyperinsulinaemia and decreases low-density lipoprotein cholesterol. Among micronutrients, high magnesium and calcium intake have been reported to decrease insulin resistance. High intake of dietary carbohydrate and omega-6 PUFAs, low intake of omega-3 PUFAs and fiber, and high omega -6/omega-3 PUFAs ratio have been reported in South Asians. Our recent investigations have shown that increased dietary omega-6 PUFAs and saturated fat intake are significantly associated with fasting hyperinsulinaemia and sub-clinical inflammation, respectively. Such imbalanced diets contribute to high prevalence of insulin resistance, the metabolic syndrome and T2DM in South Asians and Asian Indians.