Androgens regulate the immune/inflammatory response and cell survival pathways in rat ventral prostate epithelial cells.

A major hurdle in understanding the role of androgens is the heterogeneity of androgen receptor (AR) expression in the prostate. Because the majority of prostate cancer arises from the AR-positive secretory luminal epithelial cells, identifying the androgen-mediated pathways in the prostate epithelium is of great significance to understanding their role in prostate pathogenesis. To meet this objective, the current study was designed to identify immediate-early genes expressed in response to the synthetic androgen R1881 in cultured rat ventral prostate epithelial cells. Rat ventral prostate epithelial cells, purified from 20-d-old rats, were cultured, and the presence of AR and the response to androgen were established. The cells were then treated with R1881 for 2 and 12 h to capture immediate-early genes in an Affymetrix-based gene chip platform. A total of 66 nonredundant genes were identified that were responsive to R1881. The functional androgen response elements were identified in the proximal promoter to determine possible molecular mechanism. Cluster analysis identified five distinct signatures of R1881-induced genes. Pathway analysis suggested that R1881 primarily influences cell proliferation/differentiation and inflammatory/immune response pathways. Androgens appear to regulate cell renewal by regulating differentiation, cell proliferation, and apoptosis. Two mutually exclusive inflammatory response pathways were observed. The interferon pathway was up-regulated, and the ILs were down-regulated. The data identified novel androgen-regulated genes (e.g. Id1, Id3, IL-6, IGF-binding protein-2 and -3, and JunB). The loss of androgen regulation of these genes can have important consequences for cellular transformation and transition to androgen-independent growth and survival.

SOD1 Gene +35A/C (exon3/intron3) Polymorphism in Type 2 Diabetes Mellitus among South Indian Population.

Superoxide dismutase is an antioxidant enzyme that is involved in defence mechanisms against oxidative stress. Cu/Zn SOD is a variant that is located in exon3/intron3 boundary. The aim of the present study was to investigate whether the Cu/Zn SOD (+35A/C) gene polymorphism is associated with the susceptibility to type 2 diabetes mellitus among south Indian population. The study included patients with type 2 diabetes mellitus (n = 100) and healthy controls (n = 75). DNA was isolated from the blood and genotyping of Cu/Zn SOD gene polymorphism was done by polymerase chain reaction based restriction fragment length polymorphism method. Occurrence of different genotypes and normal (A) and mutant (C) allele frequencies were determined. The frequency of the three genotypes of the total subjects was as follows: homozygous wild-type A/A (95%), heterozygous genotype A/C (3%), and homozygous mutant C/C (2%). The mutant (C) allele and the mutant genotypes (AC/CC) were found to be completely absent among the patients with type 2 diabetes mellitus. Absence of mutant genotype (CC) shows that the Cu/Zn SOD gene polymorphism may not be associated with the susceptibility to type 2 diabetes mellitus among south Indian population.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Tamil Nadu cohort of the A1chieve study.

BACKGROUND: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. MATERIALS AND METHODS: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Tamil Nadu, India. RESULTS: A total of 2221 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 1707), insulin detemir (n = 270), insulin aspart (n = 85), basal insulin plus insulin aspart (n = 79) and other insulin combinations (n = 80). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 9.2%) and insulin user (mean HbA1c: 9.2%) groups. After 24 weeks of treatment, both the groups showed improvement in HbA1c (insulin naïve: -1.7%, insulin users: -1.7%). SADRs including major hypoglycaemic events did not occur in any of the study patients. CONCLUSION: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Physicians' perceptions of a national consensus guideline on insulin therapy: Data from the IMPACT study.

INTRODUCTION: The effectiveness and impact of the Indian insulin guideline in clinical practice was evaluated by the Improving Management Practices and Clinical Outcomes in Type 2 Diabetes (IMPACT) Study. The study also evaluated the participating physicians' perceptions on the use of IIG versus RCP for management of diabetes. MATERIALS AND METHOD: This 26 week multicenter, open label, randomized, prospective study aimed to evaluate effectiveness of Indian insulin guideline (IIG) versus routine clinical practice (RCP) in patients with type 2 diabetes (T2D). RESULTS: Out of 426 physicians who completed the physicians' perception questionnaire, 189 (44.4%) felt that it was "easy" to initiate insulin in their patients using IIG. Cost of therapy (52.3%), followed by poor adherence (40.3%), and lack of motivation among physicians (40.4%) were the most important reasons cited for delay in initiation of insulin therapy. Two hundred and thirty three (54.7%) physicians felt that insulin titration was made "easy" in their patients using IIG, while 104 (24.4%) had a neutral approach. A total of 222 physicians (52.1%) felt it was "convenient" applying IIG in their practice, and 239 (67.8%) physicians felt "satisfied" with using IIG for achieving the targeted HbA1c <7%. One hundred and seventy seven (41.5%) physicians felt that there was scope for improving the IIG further by simplifying and revising the titration charts [117 (27.5%)]. CONCLUSION: Primary care physicians in India have perceived the IIG to be easy algorithm to initiate and titrate insulin therapy. These results will encourage the use and facilitate future revision of the guideline.

Improving management practices and clinical outcomes in type 2 diabetes study: Prevalence of complications in people with type 2 diabetes in India.

INTRODUCTION: Diabetes is the fourth leading cause of disease-related death and almost 80% of diabetes-related deaths occur in developing countries. Optimal glycemic control, in particular HbA1c level less than 7% with effective management of dyslipidemia and hypertension can reduce development of diabetes-related complications. Delay in initiating/or optimizing appropriate anti-diabetic therapy including insulin could be a possible cause of the increase in complications. METHOD: Improving management practices and clinical outcomes in type 2 diabetes (IMPACT) was a prospective, open-label, 26-week, comparative, multi-center study to compare efficacy and safety of the Indian insulin guideline (IIG) group versus routine clinical practice (RCP) group in type 2 diabetes patients. A total of 20,653 subjects from 885 centers across India were enrolled. RESULTS: A total of 4695 patients (22.7%) (IIG, 4113 [22.6%]; RCP, 582 [23.5%]) had macrovascular complications and 8640 patients (41.8%) (IIG, 7486 [41.2%]; RCP, 1154 [46.6%]) had microvascular complications. Of 4695 patients with macrovascular complications, 2850 patients (60.7%) had coronary heart disease followed by 1457 patients (31.0%) with peripheral vascular disease. Of all the microvascular complications recorded, 5627 patients (65.1%) had peripheral neuropathy followed by 3313 patients (38.3%) with retinopathy. CONCLUSION: The rates of complications were high in patients with type 2 diabetes at the time of being initiated on insulin therapy in India.

Baseline results indicate poor glycemic control and delay in initiation and optimization of insulin therapy: results from the improving management practices and clinical outcomes in type 2 diabetes study.

INTRODUCTION: Improving management practices and clinical outcomes in type 2 diabetes (IMPACT), was a prospective, open-label, 26- week, comparative, multi-center study to compare efficacy and safety of the Indian insulin guideline (IIG) group versus routine clinical practice (RCP) group in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 20,653 patients from 885 centers across India were enrolled and treated with premixed insulin therapy as per IIG or routine care. RESULTS: Most of the participating centers (81.7%) reported following a diabetes guideline in their practice routinely but only 20.4% targeted HbA1c <7%. Very few of the physicians (2.7%) reported that most of their patients (>75%) achieved an HbA1c <7%. Most of the physicians (39.8%) also agreed that only 10-25% of the patients agree to start insulin therapy at the first counseling. Mean duration of diabetes before initiating insulin in patients using oral anti-diabetic drugs (OADs) was 7 years, indicating a delay in initiating insulin therapy. The difference in mean daily dose of insulin at initiation vs. at 26 weeks was only 0.8 U (25.8 ± 11.3 at initiation compared to 26.6 ± 9.5, respectively, p = ns) suggesting lack of treatment optimization. Weekly titration till achieving HbA1c <7% was done in 51.1% of the patients and only 8.9% performed self-titration. CONCLUSION: Baseline glycemic control in these patients was poor and reflects a delay in initiating insulin therapy. Data also reflect a lack of optimization of insulin doses.

Endothelial nitric oxide synthase gene polymorphism (G894T) and diabetes mellitus (type II) among South Indians.

The objective of the study is to find out whether the endothelial nitric oxide synthase (eNOS) G894T single-nucleotide polymorphism is associated with type 2 diabetes mellitus in South Indian (Tamil) population. A total number of 260 subjects comprising 100 type 2 diabetic mellitus patients and 160 healthy individuals with no documented history of diabetes were included for the study. DNA was isolated, and eNOS G894T genotyping was performed using the polymerase chain reaction followed by restriction enzyme analysis using Ban II. The genotype distribution in patients and controls were compatible with the Hardy-Weinberg expectations (P > 0.05). Odds ratio indicates that the occurrence of mutant genotype (GT/TT) was 7.2 times (95% CI = 4.09-12.71) more frequent in the cases than in controls. Thus, the present study demonstrates that there is an association of endothelial nitric oxide synthase gene (G894T) polymorphism with diabetes mellitus among South Indians.