Pre-therapeutic Biomarkers for Ranibizumab Therapy among Type 2 Diabetic Patients with Diabetic Macular Edema.

SIGNIFICANCE: A differential outcome in randomized controlled trials of anti-vascular endothelial growth factor (anti-VEGF) therapy, including ranibizumab, for diabetic macular edema is a major dilemma for planning, optimizing, and managing clinical usage. The variable outcome of the therapeutics necessitates the importance of finding a predictive biomarker for anti-VEGF therapy to improve subject selection. PURPOSE: Our study correlates the baseline pro- and anti-VEGF isoforms and its three receptors (VEGFReceptor1, VEGFReceptor2, and VEGFReceptor3) for circulatory candidate protein molecules among diabetic patients with macular edema, with the clinical outcome of ranibizumab therapy. METHODS: This study included 86 individuals who were anti-VEGF naive at the time of ascertainment but have completed the standardized therapy regimen of the clinic. Plasma proteins for pro- and anti-VEGF isoforms and its three receptors were determined in replicate by an enzyme-linked immunosorbent assay. RESULTS: The study demonstrated that 56 (65.12%) individuals benefited from the therapy in terms of letter gain (Snellen chart). Baseline plasma soluble VEGF receptor 2 (sVEGFR-2) was significantly higher among responders (65.10 pg/mL; 95% confidence interval, 55.41 to 74.80 pg/mL) compared with nonresponders (46.38 pg/mL; 95% confidence interval, 38.69 to 54.07 pg/mL; PFDR = .03). Diffuse diabetic macular edema with proliferative diabetic retinopathy increases the risk of nonresponse to the therapy by 3.03-fold (PFDR = .04). CONCLUSIONS: The present study postulates that diffuse diabetic macular edema with proliferative diabetic retinopathy and baseline circulatory soluble VEGF receptor 2 may be potential candidates as therapy-stratifying markers for ranibizumab treatment among patients with diabetic macular edema.

Distribution of hypertension subtypes in a hill tribe of Mizoram, Northeast India.

OBJECTIVE: Hypertension is a potential risk factor for cardiovascular diseases. With increasing age there is differential rise of systolic and diastolic blood pressure leading to development of various hypertension subtypes which have its own clinical implications. Present study assessed distribution and risk factors of hypertensive subtypes in the hill tribe of Mizoram. METHODS: The present study was a community-based cross-sectional study carried out in Aizawl, Mizoram representing both rural (fourteen villages) and urban (six wards) population and which were selected by PPS method. Individuals aged 18 years and above providing informed verbal consent were included for collection of sociodemographic and clinical data including blood pressure. Of the total 12,313 subjects (Urban: 5853, Rural: 6460) & (Male: 5459, Female: 6854) surveyed, 549 hypertensive subjects who were under antihypertensive treatment were excluded. Hypertension subtype was defined as per standard guidelines. RESULTS: Out of 11,764 study individuals, 88.03% (CI: 87.43-88.61) were normotensive and 11.97% (CI: 11.39-12.57) individuals were hypertensive. Prevalence of ISH, IDH and SDH were 241(2.05%), 403 (3.43%) and 764 (6.49%) respectively. Older age, unmarried participants, physical inactivity and obesity are found to be associated with ISH. Male gender, older age, higher educational status, physical inactivity, consumption of extra salt, alcohol consumption, use of tuibur and high BMI were significantly associated with SDH. CONCLUSIONS: The overall prevalence of hypertension with its subtypes specifically isolated systolic hypertension are low in this hill tribe of Mizoram. It is the right time for initiating intervention programme to modify the risk factors associated with hypertension.

An information, education and communication module to reduce dietary salt intake and blood pressure among tea garden workers of Assam.

OBJECTIVE: High salt diet increases blood pressure. Tea garden workers (TGW) of Assam, India have high (60.8%) prevalence of hypertension (HTN), which may be due to consumption of extra salt (salt as side dish) and salted tea at work place and home. The present study evaluated an information, education and communication (IEC) module to reduce salt intake and blood pressure among TGW. METHODS: Two tea gardens (usual care and intervention) were selected at random covering a total population of 13,458. The IEC module consisting of poster display, leaflets, health rally, documentary show, individual and group discussion was introduced in the intervention garden targeting study participants, health care providers, key stake holders, school children and teachers. IEC intervention was continued for one year. Participants from usual care and intervention were followed at three monthly intervals and BP and other information were compared after one year. RESULTS: A total of 393 study participants (Non intervention: 194; intervention: 199) were included. After one year of follow up, consumption of extra salt was reduced significantly in the intervention participants (66.3 vs. 45.5%, p=0.000). Intention to treat analysis revealed significant reduction in systolic [-6.4 (-8.6 to -4.2)] and diastolic [-6.9 (-8.1 to -5.7)] blood pressure after one year. Prevalence of HTN was reduced significantly (52.5 vs. 40.0%, p=0.02) among them. CONCLUSIONS: Our IEC module created awareness about risk of hypertension associated with high salt intake and could reduce dietary salt intake and BP.

Salt-sensitive phenotypes: A community-based exploratory study from northeastern India.

Background: Salt sensitivity is known to increase the risk of cardiovascular diseases in both normotensive and hypertensive subjects. The population in the northeastern region of India consumes excess dietary salt but their saltsensitive phenotype is not known. Methods: We did a community-based exploratory study using volunteers in the northeastern region of India to determine salt-sensitive (SS) and salt-resistant (SR) phenotypes. A total of 374 (206 normotensive and 168 hypertensive) subjects who gave informed consent were stabilized for salt with 7 days of a low-salt (2.9 g/day) diet followed by 7 days of a high-salt (15.2 g/day) diet. SS was defined as an increase of mean arterial blood pressure ≥9 mmHg after a high-salt diet. Results: We noted an increase in systolic blood pressure of 9.3 mmHg in normotensive subjects and 10.7 mmHg in hypertensive subjects, with a modest effect on diastolic blood pressure (6.9 mmHg in normotensive and 8.2 mmHg in hypertensive subjects) after a high-salt diet. Salt-sensitive phenotype was present in 40.8% of normotensive and 47.6% of hypertensive subjects. Resistance to introduction of high salt was observed in 43.7% of normotensive and 33.9% of hypertensive subjects. Consumption of extra salt (adjusted OR 1.99, 95% CI 1.25-3.18) was independently associated with salt sensitivity. Conclusion: Salt sensitivity was found in a large proportion of normotensive and hypertensive subjects. Restriction of salt intake could be an effective intervention to control hypertension among salt-sensitive subjects.

Pro- and antiangiogenic VEGF and its receptor status for the severity of diabetic retinopathy.

PURPOSE: Alteration of pro- and antiangiogenic homeostasis of vascular endothelial growth factor (VEGF) isoforms in patients with hyperglycemia seems crucial but substantially unexplored at least quantitatively for diabetic retinopathy (DR). Therefore, in the present study we aimed to estimate the difference between the pro- (VEGF165a) and antiangiogenic (VEGF165b) VEGF isoforms and its soluble receptors for severity of DR. METHODS: The study included 123 participants (diabetic retinopathy: 81, diabetic control: 20, non-diabetic control: 22) from the Regional Institute of Ophthalmology, Kolkata. The protein levels of VEGF165a (proangiogenic), VEGF165b (antiangiogenic), VEGF receptor 1 (VEGFR1), VEGFR2, and VEGFR3 in plasma were determined with enzyme-linked immunosorbent assay (ELISA). RESULTS: An imbalance in VEGF homeostasis, a statistically significant concomitant increase (p<0.0001) in the level of VEGF165a and a decrease in the level of VEGF165b, was observed with the severity of the disease. Increased differences between VEGF165a and VEGF165b i.e. VEGF165a-b concomitantly increased statistically significantly with the severity of the disease (p<0.0001), patients with diffuse diabetic macular edema (DME) with proliferative DR (PDR) had the highest imbalance. The plasma soluble form of VEGFR2 concentration consistently increased statistically significantly with the severity of the disease (p<0.0001). CONCLUSIONS: The increased difference or imbalance between the pro- (VEGF165a) and antiangiogenic (VEGF165b) homeostasis of the VEGF isoforms, seems crucial for an adverse prognosis of DR and may be a better explanatory marker compared with either VEGF isoform.

Insertion/Insertion Genotype of Angiotensin I-Converting-Enzyme Gene Predicts Risk of Myocardial Infarction in North East India.

Myocardial infarction (MI) is common in India and the disease occurs at a relatively younger age. We wanted to look for association of Angiotensin I-converting enzyme (ACE) gene with MI in North East India. We also wanted to examine possible environmental interaction of ACE gene with established cardiovascular risk factors in causation of MI. In the study carried out in Assam Medical College, 200 consecutive confirmed cases of MI were recruited. Equal numbers of age- and sex-matched control subjects from hospital workers and patients attending the hospital for diseases unrelated to cardiovascular disease were enrolled. Structured questionnaires were used to note demographic and clinical factors. Cardiovascular risk factors were determined from history, physical examination and biochemical investigations. ACE insertion/deletion (I/D) polymorphism was determined by PCR method. Interaction of ACE gene with other risk factors was noted. The study identified ACE II genotype (odds ratio = 3.02; 95% CI 1.40-6.51), smoking, hypertension, diabetes and serum triglyceride > 150 mg/dl as independent risk factors for MI. ACE II genotype showed greater risk in non-smokers, non-hypertensives, non-diabetics and in subjects with LDL-C < 130 mg/dl. Low HDL cholesterol enhanced the genetic risk. Subjects with ACE II genotype have an independent risk of developing MI, specially in low cardiovascular risk subjects.

Glutathione S-transferase M1 and T1 gene polymorphisms and risk of hypertension in tea garden workers of North-East India.

AIMS: Polymorphisms of genes encoding phase II metabolic enzymes, for example, glutathione S-transferase, have been linked with hypertension. The present study aimed at finding out the association between GSTM1 and GSTT1 polymorphism and hypertension in a population from North-East India. MATERIALS AND METHODS: We carried out a case-control study in tea garden workers of Assam. A total of 223 hypertensive cases and 236 normotensive control subjects were recruited with a record of socio-demographic information, blood pressure, and anthropometric data. Fasting venous blood samples from all subjects were obtained and subjected to DNA extraction and polymerase chain reaction to detect polymorphism of the GSTM1 and GSTT1 genes. RESULTS: The null genotype was prevalent in 38.1% and 28.1% of the study participants (cases and controls) for GSTM1 and GSTT1 genes, respectively. Hypertensive subjects had a significantly higher prevalence of the GSTM1 null genotype (43% vs. 33.5%, than normotensive control subjects, p=0.035). Association between the GSTM1 null genotype and hypertension was significant in younger subjects. Tobacco users with the GSTT1 null genotype were at an increased risk for hypertension. CONCLUSION: The knowledge of GSTM1 and GSTT1 variant status will be useful to predict the risk of hypertension in a population.