Association of Vitamin D Deficiency and Vitamin D Receptor Gene Polymorphisms with Type 1 Diabetes Risk: A South Indian Familial Study

Objective: Vitamin D is a potent immune modulator and is associated with autoimmune diseases, including type 1 diabetes (T1D). The vitamin D levels and its receptor gene polymorphisms together in T1D are not yet investigated in the South Indian population. The present study focused on exploring the significance of vitamin D levels and vitamin D receptor (VDR) gene polymorphisms with the risk of developing T1D in the South Indian population. Methods: Patients with T1D and unaffected first-degree relatives (FDRs) were included in this study. Genotyping of VDR polymorphisms at four different loci (FokI- F/f, BsmI- B/b, TaqI- T/t, and ApaI- A/a) was assessed through the amplification refractive mutation system-polymerase chain reaction method. Serum vitamin D levels were measured in 98 T1D patients and 75 age- and sex-matched siblings. Results: A total of 120 patients with T1D and 214 FDRs were included. Vitamin D deficiency (VDD) was observed in a higher proportion of T1D patients than in controls (52% vs. 32%; p<0.03). The frequency of the FokI-FF genotype was significantly higher [odds ratio (OR)=1.66; p<0.03] in T1D patients conferring a susceptible association with the disease. Nevertheless, the increased frequency of heterozygous Ff genotype (OR=0.57; p<0.02) among controls may confer a protective association with T1D. Furthermore, the transmission disequilibrium test revealed over-transmission of ApaI-A (T: U=15/5; p<0.006) and BsmI-B alleles (T: U=17/5; p<0.01) and under-transmission of BsmI-b/ApaI-a/TaqI-T haplotype (T: U=5.4/14.4; p=0.04) from parents to T1D patients. Conclusion: The present study concludes that VDD is the major contributing risk factor to T1D development in the South Indian population. Furthermore, the FokI-FF genotype, BsmI-B, and ApaI-A alleles were positively associated with T1D. In contrast, the FokI-Ff genotype and BsmI-b/ApaI-a/TaqI-T haplotype were negatively associated with T1D.

Evaluation of HLA-G 14bp Ins/Del and +3142 C/G Polymorphisms in Type 1 Diabetes among South Indian Population.

Background: Type 1 diabetes (T1D) is a multifactorial autoimmune disease, involving strong genetic components with familial predisposition. Human leukocyte antigen-G (HLA-G) is a non-classical HLA-class I molecule having several immunomodulatory functions. Polymorphisms in HLA-G are associated with several autoimmune diseases including T1D. This study aims to evaluate the association of HLA-G 14bp Ins/Del and +3142 C/G polymorphisms with T1D among the South Indian population. Methods: The study was performed in a cohort of 123 T1D patients along with their 51 siblings and 126 parents. The association and linkage of HLA-G 14bp Ins/Del and +3142 C/G polymorphisms with T1D were analysed, and transmission disequilibrium test (TDT) was performed. Results: Significantly increased frequencies of HLA-G 14bp Del/Del genotype (OR = 2.16, pc = 0.0302) and Del allele (OR = 1.71, pc = 0.0398) were observed in female patients compared to parents. Higher frequencies of DelDel/GG combined genotype (OR = 4.45, pc = 0.0049) and Del/G haplotype (OR = 2.91, pc = 0.0277) were observed in female patients compared to parents. TDT also revealed over-transmission of Del/G haplotype (25T vs 7UT; P = 0.0015) and a strong linkage disequilibrium between the studied polymorphisms. Conclusion: This familial study shows the association of HLA-G 3'UTR 14bp Ins/Del polymorphism with the risk of T1D among the South Indian population, especially in females.

Expert Opinion by Clinicians on the Use of Insulin Therapy in People with Hepatic Impairment.

People with type 2 diabetes mellitus (T2DM) have a higher risk of developing chronic liver disease (CLD) and its complications. T2DM, obesity, and insulin resistance are all strongly associated with nonalcoholic fatty liver disease (NAFLD). Conversely, people suffering from cirrhosis have reduced glucose tolerance in approximately 60% of cases, diabetes in 20% of cases, and insulin-mediated glucose clearance is lowered by 50% as compared with those who do not have cirrhosis. An exploratory review was conducted using existing published evidence from clinical studies on dosing and titrations of individual insulin formulations in people with CLD to optimize insulin dosage titration for minimizing hypoglycemia risk.pThis article discusses current hyperglycemia treatment techniques for patients with CLD as well as the consensus recommendations on insulin use in special populations with T2DM and hepatic impairment. Based on available evidence and expert diabetologists' recommendations, careful insulin dose titration, customized glycemic targets, and frequent glucose screening are recommended for optimal glycemic management without hypoglycemia in CLD. Long-acting insulin should be avoided or used when short-acting insulin fails to provide adequate glycemic control with raised fasting blood sugar levels. While the patient's glucose profile is being evaluated, the prandial insulin dose can be lowered by 25% initially. The dose can be titrated based on the patient's postprandial glycemic expression and whether their food intake meets the Child-Pugh scores A and B categories. Titrating premixed insulins is difficult for patients in class C since their appetite and overall health are constantly compromised and in flux.

Association of Killer Cell Immunoglobulin-Like Receptors and Their HLA-Ligands with Type 1 Diabetes Among South Indian Population.

BACKGROUND: Type 1 diabetes (T1D) is a multifactorial autoimmune disease, involving strong genetic components with familial predisposition. Killer cell immunoglobulin-like receptors (KIRs) found on the surface of NK cells have ligands of human leukocyte antigen (HLA) class I that are associated with T1D. The present study evaluates the influence of KIR genes and their HLA-ligands in the aetiology of T1D among the South Indian population. METHODS: A total of 125 T1D patients, along with their parents (n = 126) and siblings (n = 52) were recruited. PCR-based genotyping was performed for KIR genes and HLA class I ligands. The gene frequencies were compared between patients and siblings/parents. Linkage-disequilibrium (LD) analysis was performed to assess the genetic association between KIR gene pairs. RESULTS: The results show significant differences in HLA-ligands of KIR genes between patients and parents. The HLA-C1C1 homozygosity was found to be a predisposing risk factor, and HLA-C1C2 heterozygosity was protective towards T1D along with either the activating KIR2DS2 or inhibitory KIRs 2DL1, 2DL2, 2DL3. However, the frequency of inhibitory KIR3DL1 significantly increased in the presence of HLA-B Bw4 Ile80 in parents when compared to patients showing a protective effect on T1D. Two pairs of KIR genes, 2DS4-3DL1 and 2DS1-2DL5, showed strong LD in patients, siblings and parents. CONCLUSION: The KIR-HLA ligand combinations have a significant effect on T1D aetiology among the South Indian population. This study defines a pattern for family-based association studies with genotypic information about KIR genes and their HLA-ligands, providing the first evidence towards T1D among the South Indian population.

Understanding Patients' Willingness to Pay for Biphasic Insulin Aspart 30/70 in a Pen Device for Type 2 Diabetes Treatment in an Out-of-Pocket Payment Market.

OBJECTIVE: Our objective was to investigate willingness to pay (WTP) for biphasic insulin aspart 30/70 (BIAsp 30) in patients with type 2 diabetes mellitus (T2DM) in India. METHODS: A multicenter, prospective, non-interventional, preference study was conducted that assessed WTP for BIAsp 30 in an insulin pen (FlexPen® or Penfill® device) in patients in India with T2DM previously treated with biphasic human insulin (BHI) in vials and believed to be able to pay for treatment. The primary endpoint was the proportion of patients willing to continue to pay for BIAsp 30 after 12 weeks' treatment. Secondary endpoints included the change from baseline in treatment and device satisfaction and patient preferences for treatment attributes as assessed by a nested discrete-choice experiment. RESULTS: Overall, 54.9% (n = 277/505) of participants were male; the mean age was 56.4 years; diabetes duration was 10.9 years; 63.8% had a body mass index ≥ 25 kg/m2; > 75% had an annual household income > 150,000 Indian rupees (INR). After 12 weeks' treatment, 96.4% of patients were willing to pay for BIAsp 30. Mean treatment and device satisfaction significantly improved from baseline (p < 0.0001). Patients were willing to pay INR3576 (95% confidence interval [CI] 2755-4398) for improved glycemic control, INR688 (95% CI 383-994) for a device upgrade (vial/syringe to an insulin pen), or INR327 (95% CI 95-560) to avoid major hypoglycemia. Patients would need to be compensated INR44 (95% CI 56-32) per minor hypoglycemic event. CONCLUSIONS: In India, patients with T2DM previously treated with BHI were willing to pay for BIAsp 30 in an insulin pen. Furthermore, treatment and device satisfaction improved after this therapeutic switch. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03374774.

Safety of Insulin Degludec/Insulin Aspart in Patients with Diabetes Mellitus over a Period of 1 Year during Routine Clinical Care in India: SMART (Study of Management of Diabetes with Ryzodeg™ Treatment).

This post-authorization study was conducted to evaluate the safety of insulin degludec/insulin aspart (IDegAsp) in adult patients with diabetes mellitus (DM) during routine clinical care under a real-world setting in India. Eligible patients received IDegAsp for a minimum of 12 months during routine clinical management. Data were collected at 0, 3, 6, and 12 months. In total, 1029 adult patients with DM were included; 65.2% (n = 671) were men; mean age was 55.0 ± 12.2 years, and the mean duration of diabetes mellitus was 10.8 ± 7.4 years. Thirty adverse events were reported in 23 patients (2.2%) during the follow-up: two adverse events in two patients were serious with fatal outcomes, which were unrelated to IDegAsp use. At baseline, there were 176 confirmed hypoglycemic events in 67 (6.7%) patients while they were on their previous treatment options. At 12 months of treatment with IDegAsp, 11 confirmed hypoglycemic events were reported in 11 (1.1%) patients since the previous visit; there were no reported episodes of severe hypoglycemia. Mean glycosylated hemoglobin value reduced from 9.5% ± 1.8% at baseline to 7.7% ± 1.1% at 12 months. This study showed the safety of IDegAsp in patients with diabetes mellitus over a period of 1 year during routine clinical care.

Teneligliptin Real-World Effectiveness Assessment in Patients with Type 2 Diabetes Mellitus in India: A Retrospective Analysis (TREAT-INDIA 2).

INTRODUCTION: Teneligliptin is an antidiabetic medication that has been approved for the management of type 2 diabetes mellitus (T2DM) in Japan, South Korea and India. It is one of the most commonly prescribed antihyperglycaemic agents. The aim of this study was to assess the effectiveness of teneligliptin in improving glycemic control amongst Indian patients with T2DM in a real-world setting. METHODS: This was a retrospective observational study in which a predesigned structured proforma was used to collect information from hospital records of 18 medical centres across India. All participating centres were established primary care hospitals with adequate record keeping, a pre-determined condition in the study design. Data were collected during the period of January 2019 to June 2019. Data extracted from patient records, including glycaemic parameters, concomitant drugs, drug dosage and duration, were collated. The effectiveness of teneligliptin was assessed by analyzing the mean change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG) and post-prandial plasma glucose (PPG) at 12 weeks after initiation of teneligliptin. RESULTS: Data from 10,623 patients were available for analysis. The mean age of the enrolled patients was 51.86 ± 11.76 years. At 12 weeks after initiation of teneligliptin as monotherapy or add-on to other medications (combination therapy), the patients showed a signficant decrease from baseline in mean HbA1c, FPG and PPG. Mean HbA1c dropped from 8.66 ± 1.15% at baseline to 7.67 ± 1.28% at 12 weeks (71 ± 12.6 to 60 ± 14 mmol/mol), with a difference of - 0.99% (95% confidence interval [CI] 0.96-1.02) or - 10.8 (95% CI 10.5-11.1) mmol/mol (p < 0.0001). The mean reductions in FPG and PPG were 43.12 mg/dL (2.39 mmol/L) and 87.73 mg/dL (4.87 mmol/L) (both p < 0.0001) respectively. HbA1c (%) reductions with teneligliptin when used as add-on to metformin, add-on to metformin + sulfonylurea combination and add-on to metformin + sulfonylurea + alpha glucosidase inhibitor combination were 0.76% (8.3 mmol/mol), 1.24% (13.6 mmol/mol) and 1.04% (11.4 mmol/mol), respectively. Teneligliptin also significantly reduced HbA1c (1.13% or 12.4 mmol/mol, p < 0.0001) in patients with impaired renal function, without worsening the estimated glomerular filtration rate. Teneligliptin consistently reduced HbA1c across all three age categories tested-by 1% (10.9 mmol/mol) in patients aged < 60 years, by 1.15% (12.6 mmol/mol) in patients aged 60-75 years and by 0.88% (9.6 mmol/mol) in patients aged > 75 years. CONCLUSION: Teneligliptin significantly improved glycaemic parameters in Indian patients with T2DM when prescribed either as monotherapy or as an add-on to one or more other commonly prescribed antihyperglycaemic agents.

Efficacy and Safety of Remogliflozin Etabonate, a New Sodium Glucose Co-Transporter-2 Inhibitor, in Patients with Type 2 Diabetes Mellitus: A 24-Week, Randomized, Double-Blind, Active-Controlled Trial.

BACKGROUND: Metformin is the first-line treatment for type 2 diabetes mellitus (T2DM), but many patients either cannot tolerate it or cannot achieve glycemic control with metformin alone, so treatment with other glucose-lowering agents in combination with metformin is frequently required. Remogliflozin etabonate, a novel agent, is an orally bioavailable prodrug of remogliflozin, which is a potent and selective sodium-glucose co-transporter-2 inhibitor. OBJECTIVE: Our objective was to evaluate the efficacy and safety of remogliflozin etabonate compared with dapagliflozin in subjects with T2DM in whom a stable dose of metformin as monotherapy was providing inadequate glycemic control. METHODS: A 24-week randomized, double-blind, double-dummy, active-controlled, three-arm, parallel-group, multicenter, phase III study was conducted in India. Patients aged ≥ 18 and ≤ 65 years diagnosed with T2DM, receiving metformin ≥ 1500 mg/day, and with glycated hemoglobin (HbA1c) levels ≥ 7 to ≤ 10% at screening were randomized into three groups. Every patient received metformin ≥ 1500 mg and either remogliflozin etabonate 100 mg twice daily (BID) (group 1, n = 225) or remogliflozin etabonate 250 mg BID (group 2, n = 241) or dapagliflozin 10 mg once daily (QD) in the morning and placebo QD in the evening (group 3, n = 146). The patients were followed-up at weeks 1 and 4 and at 4-week intervals thereafter until week 24. The endpoints included mean change in HbA1c (primary endpoint, noninferiority margin = 0.35), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), bodyweight, blood pressure, and fasting lipids. Treatment-emergent adverse events (TEAEs), safety laboratory values, electrocardiogram, and vital signs were evaluated. RESULTS: Of 612 randomized patients, 167 (group 1), 175 (group 2), and 103 (group 3) patients with comparable baseline characteristics completed the study. Mean change ± standard error (SE) in HbA1c from baseline to week 24 was - 0.72 ± 0.09, - 0.77 ± 0.09, and - 0.58 ± 0.12% in groups 1, 2, and 3, respectively. The difference in mean HbA1c of group 1 versus group 3 (- 0.14%, 90% confidence interval [CI] - 0.38 to 0.10) and group 2 versus group 3 (- 0.19%; 90% CI - 0.42 to 0.05) was noninferior to that in group 3 (p < 0.001). No significant difference was found between group 1 or group 2 and group 3 in change in FPG, PPG, and bodyweight. The overall incidence of TEAEs was comparable across study groups (group 1 = 32.6%, group 2 = 34.4%, group 3 = 29.5%), including adverse events (AEs) of special interest (hypoglycemic events, urinary tract infection, genital fungal infection). Most TEAEs were mild to moderate in intensity, and no severe AEs were reported. CONCLUSION: This study demonstrated the noninferiority of remogliflozin etabonate 100 and 250 mg compared with dapagliflozin, from the first analysis of an initial 612 patients. Remogliflozin etabonate therefore may be considered an effective and well-tolerated alternative treatment option for glycemic control in T2DM. TRIAL REGISTRATION: CTRI/2017/07/009121.

Association of CTLA-4 and CD28 Gene Polymorphisms with Type 1 Diabetes in South Indian Population.

Each functional gene illustrates the complexity of genetic predisposition to disease; however, it is difficult to bring out these traits with reference to autoimmune diseases like type 1 diabetes (T1D). To find out the genetic contribution of CTLA-4 + 49A/G, CTLA-4 -318C/T and CD28 + 17T/C polymorphisms toward T1D, the present study was performed with 124 T1D patients, 54 siblings and 125 parents including 39 trios in South Indian population. The association and linkage of CTLA-4 + 49A/G, CTLA-4 -318C/T and CD28 + 17T/C polymorphisms with T1D were analyzed and transmission disequilibrium test was performed. CTLA-4 G allele carrying genotypes (GG+AG) showed a higher risk association and can be considered as susceptible to develop T1D among patients with age at diagnosis from 0 to 10 years as compared to siblings (OR = 2.9; pc = 0.047) and parents (OR = 2.7; pc = 0.036). On the other hand, a strong protection against the disease (age at diagnosis; 0-10 years) was observed with CTLA-4 + 49AA genotype (OR = 0.37; pc = 0.036) and combined AA/CC genotype (OR = 0.31; pc = 0.034) of CTLA-4 + 49A/G and CTLA-4 -318C/T polymorphisms. However, a significant association was not observed between CTLA-4 -318C/T and CD28 + 17T/C polymorphisms and T1D. This family-based study reports a strong association between possible genotypes of CTLA-4 gene polymorphism and T1D in South Indian population, particularly in younger individuals.

Efficacy and safety of three-times-daily versus twice-daily biphasic insulin aspart 30 in patients with type 2 diabetes mellitus inadequately controlled with basal insulin combined with oral antidiabetic drugs.

AIMS: To compare the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) administered three times daily (TID) vs. twice daily (BID), plus metformin, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on basal insulin ± 1 oral antidiabetic drug (OAD). METHODS: Randomised, multinational, open-label, treat-to-target trial. Subjects inadequately controlled (HbA1c 7.5-10.0%) on basal insulin and metformin ±â€¯1 OAD were randomised to BIAsp30 TID (n = 220) or BIAsp30 BID (n = 217). Primary endpoint was change from baseline in HbA1c after 24 weeks of treatment. RESULTS: Most (400/437, 91.5%) subjects completed the trial. The majority (276/400 [69.0%]) were from the China region. After 24 weeks, HbA1c decreased comparably in both BIAsp 30 groups (-1.7% vs. -1.6% [-19 vs. -18 mmol/mol], for TID and BID dosing, respectively; estimated treatment difference: -0.09% [-0.23; 0.06]95% CI, -1 mmol/mol [-3; 1], p = 0.26). Safety profiles, including number of subjects experiencing hypoglycaemia, were similar. CONCLUSIONS: BIAsp 30 administered either TID or BID with metformin was a safe and effective option when intensifying treatment after failure of basal insulin and OADs in patients with T2DM. Adding a third injection at lunchtime may be preferable if HbA1c remains above target, if the lunchtime meal is the largest meal of the day, or if persistent postprandial hyperglycaemia after lunch is observed. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT02582242.

SLC30A8 Gene rs13266634 C/T Polymorphism in Children with Type 1 Diabetes in Tamil Nadu, India

Objective: Zinc transporter 8 (ZnT8) is a multi-transmembrane protein situated in the insulin secretory granule of the islets of ß-cells and is identified as a novel auto-antigen in type 1 diabetes (T1D). The gene coding for ZnT8, solute carrier family 30 member 8 (SLC30A8) is located on chromosome 8q24.11. This study aimed to identify the association of SLC30A8 rs13266634 C/T gene polymorphism with T1D in a sample of T1D children in Tamil Nadu, India. Methods: The family based study was conducted in 121 T1D patients and 214 of their family members as controls. The SLC30A8 gene rs13266634 C/T polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism. Results: No significant differences were observed in either allele (odds ratio: 0.92; confidence interval: 0.33-2.58; p=0.88) and genotype (CC: p=0.74; CT: p=0.82; TT: p=0.80) frequencies of rs13266634 C/T between T1D patients and controls. Transmission disequilibrium test has identified over-transmission of mutant T allele from parents to affected children (T: U=9:7) without statistical significance. Metaanalysis on the overall effects of rs13266634 C allele frequency was not different (p=0.10 and Pheterogeneity=0.99) in T1D patients as compared to the controls. Conclusion: The present study along with the meta-analysis does not show any substantial association of the rs13266634 C/T polymorphism with T1D development in this population.

Quality of Hypertension Management in Type 2 Diabetes in India: A Multisite Prescription Audit.

BACKGROUND AND OBJECTIVE: Renin-angiotensin system (RAS) blockers (angiotensin converting enzyme inhibitors ACEI, angiotensin receptor blockers, ARB) are preferred drugs to control hypertension among diabetic patients. To determine frequency of RAS blocker use in hypertensive patients with type 2 diabetes, we performed a multisite study in India. METHODS: We evaluated physician prescriptions in consecutive patients with type 2 diabetes at 9 sites in India. Details of socio-demographic characteristics, clinical findings and prescription medicines were obtained. Descriptive statistics are reported. RESULTS: Hypertension treatment details were available in 8056 of 8699 diabetic patients (4829 men, 3227 women). No hypertension was in 3300 (40.9%), hypertension in 3625 (45.0%), and hypertension with vascular disease in 1131 (14.0%). In diabetics with no hypertension, hypertension, and hypertension with vascular disease, respectively, prescriptions of antihypertensive drugs was: RAS blockers in 19.4, 48.2 and 58.1%, beta-blockers in 4.8, 31.6 and 38.8%, calcium channel blockers in 0.4, 27.4 and 14.3% and diuretics in 0.6, 36.4 and 17.1%. ACEIs were prescribed more frequently than ARB's in hypertensive diabetics (60.7 vs 39.2%) as well as in diabetics with vascular disease (58.6 vs 41.4%). In diabetics with hypertension (n=3625) prescription of one, two or three antihypertensive drugs was 49.8%, 33.7% and 3.5% while statins were prescribed in 54.1%. CONCLUSION: Use of RAS blockers (ACEI or ARB) in uncomplicated as well as complicated hypertensive patients with type 2 diabetes is sub-optimal. Most of the patients are on one drug and prescription of ≥3 drugs are rare. Statins are prescribed in only a half.

Dose Modification of Antidiabetic Agents in Patients with Type 2 Diabetes Mellitus and Heart Failure.

Heart failure is the most common comorbidity of diabetes. The incidence of heart failure in patients with diabetes is about 9%-22%, which is four times higher Than that in patients without diabetes. Heart failure and diabetes are collectively associated with increased morbidity and mortality compared to either condition alone. Several epidemiological studies have demonstrated an increased risk of heart failure in patients with diabetes; moreover, poor glycemic control accounts for the increased risk of heart failure. At present, several oral (metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, etc.) as well as injectable (insulins, glucagon-like peptide 1 receptor agonists) antidiabetic agents are available. However, optimal treatment strategy to achieve adequate glycemic control in patients with type 2 diabetes mellitus (T2DM) and heart failure has not been well studied. In the view of rising prevalence of heart failure in patients with diabetes mellitus, clinicians need to understand the potential implications of antidiabetic agents in patients with heart failure. A group of experts from across India were involved in a consensus meeting in Pondicherry during the National Insulin Summit in November 2015. They evaluated agents currently available for the treatment of diabetes looking at existing scientific evidence relevant to each class of therapy. In addition, the existing guidelines and prescribing literature available with all these agents were also reviewed. Findings from the expert evaluations were then factored into the national context incorporating personal experience and common clinical practices in India. The purpose of this consensus document is to assist the clinicians while treating patients with T2DM and heart failure.

Consensus on Initiation and Intensification of Premix Insulin in Type 2 Diabetes Management.

INTRODUCTION: Premix insulin is the most commonly used insulin preparation in India. The first Indian premix guidelines were developed in 2009 and thereafter were updated in 2013. There is a need to revisit the Indian premix insulin guidelines, in view of emerging evidence and introduction of newer co-formulations. OBJECTIVE: The present consensus has been developed to evaluate available premix formulations, examine existing evidence related to premix formulations, and evolve consensus statement of recommendations on the topic. METHODS: A meeting of experts from across India was conducted at Chennai in July 2016. The expert committee evaluated each premix insulin regimen with reference to 1) Current recommendations by various guidelines, 2) Approved pack inserts and 3) Published scientific literature. The information was debated and discussed within the expert group committee, to arrive at seven consensus-based recommendations for initiation and intensification with premix insulin. RESULTS: Recommendations based on consensus on initiation and intensification of premix insulin in type 2 diabetes mellitus (T2DM) management were developed for the following situations. 1) Initiation of premix insulin co-formulation at diagnosis, 2) Initiation of once daily (OD) premix insulin/co-formulation, 3) Initiation of twice daily (BID) premix insulin/co-formulation 4) Intensification with BID and thrice daily (TID) premix insulin/co-formulation. Three recommendations pertained to the use of premix insulin in other forms of diabetes, or in specific situations: 5) Use of premix insulin in gestational diabetes mellitus 6) Use of premix insulin in type 1 Diabetes Mellitus (T1DM) 7) Premix insulin use during Ramadan. CONCLUSIONS: In the setting of high carbohydrate consumption in India, or in patients with predominant post prandial hyperglycemia, premix insulin/co-formulation can offer effective and convenient glycemic control. This paper will help healthcare practitioners initiate and intensify premix insulin effectively.

Evaluation of statin prescriptions in type 2 diabetes: India Heart Watch-2.

BACKGROUND: Contemporary treatment guidelines advise statin use in all patients with diabetes for reducing coronary risk. Use of statins in patients with type 2 diabetes has not been reported from India. METHODS: We performed a multisite (n=9) registry-based study among internists (n=3), diabetologists (n=3), and endocrinologists (n=3) across India to determine prescriptions of statins in patients with type 2 diabetes. Demographic and clinical details were obtained and prescriptions were audited for various medications with a focus on statins. Details of type of statin and dosage form (low, moderate, and high) were obtained. Patients were divided into categories based on presence of cardiovascular risk into low (no risk factors, n=1506), medium (≥1 risk factor, n=5425), and high (with vascular disease, n=1769). Descriptive statistics are presented. RESULTS: Prescription details were available in 8699 (men 5292, women 3407). Statins were prescribed in 55.2% and fibrates in 9.2%. Statin prescription was significantly greater among diabetologists (64.4%) compared with internists (n=53.3%) and endocrinologists (46.8%; p<0.001). Atorvastatin was prescribed in 74.1%, rosuvastatin in 29.2%, and others in 3.0%. Statin prescriptions were lower in women (52.1%) versus men (57.2%; p<0.001) and in patients aged <40 years (34.3%), versus those aged 40-49 (49.7%), 50-59 (60.1%), and ≥60 years (62.2%; p<0.001). Low-dose statins were prescribed in 1.9%, moderate dose in 85.4%, and high dose in 12.7%. Statin prescriptions were greater in the high-risk group (58.0%) compared with those in the medium-risk (53.8%) and low-risk (56.8%) groups (p <0.001). High-dose statin prescriptions were similar in the high-risk (14.5%), medium-risk (11.8%), and low-risk (13.5%) groups (p=0.31). CONCLUSIONS: Statins are prescribed in only half of the clinic-based patients in India with type 2 diabetes. Prescription of high-dose statins is very low.

Prevalence of diabetes and cardiovascular risk factors in middle-class urban participants in India.

OBJECTIVES: To determine the prevalence of diabetes and awareness, treatment and control of cardiovascular risk factors in population-based participants in India. METHODS: A study was conducted in 11 cities in different regions of India using cluster sampling. Participants were evaluated for demographic, biophysical, and biochemical risk factors. 6198 participants were recruited, and in 5359 participants (86.4%, men 55%), details of diabetes (known or fasting glucose >126 mg/dL), hypertension (known or blood pressure >140/>90 mm Hg), hypercholesterolemia (cholesterol >200 mg/dL), low high-density lipoprotein (HDL) cholesterol (men <40, women <50 mg/dL), hypertriglyceridemia (>150 mg/dL), and smoking/tobacco use were available. Details of awareness, treatment, and control of hypertension and hypercholesterolemia were also obtained. RESULTS: The age-adjusted prevalence (%) of diabetes was 15.7 (95% CI 14.8 to 16.6; men 16.7, women 14.4) and that of impaired fasting glucose was 17.8 (16.8 to 18.7; men 17.7, women 18.0). In participants with diabetes, 27.6% were undiagnosed, drug treatment was in 54.1% and control (fasting glucose ≤130 mg/dL) in 39.6%. Among participants with diabetes versus those without, prevalence of hypertension was 73.1 (67.2 to 75.0) vs 26.5 (25.2 to 27.8), hypercholesterolemia 41.4 (38.3 to 44.5) vs 14.7 (13.7 to 15.7), hypertriglyceridemia 71.0 (68.1 to 73.8) vs 30.2 (28.8 to 31.5), low HDL cholesterol 78.5 (75.9 to 80.1) vs 37.1 (35.7 to 38.5), and smoking/smokeless tobacco use in 26.6 (23.8 to 29.4) vs 14.4 (13.4 to 15.4; p<0.001). Awareness, treatment, and control, respectively, of hypertension were 79.9%, 48.7%, and 40.7% and those of hypercholesterolemia were 61.0%, 19.1%, and 45.9%, respectively. CONCLUSIONS: In the urban Indian middle class, more than a quarter of patients with diabetes are undiagnosed and the status of control is low. Cardiovascular risk factors-hypertension, hypercholesterolemia, low HDL cholesterol, hypertriglyceridemia, and smoking/smokeless tobacco use-are highly prevalent. There is low awareness, treatment, and control of hypertension and hypercholesterolemia in patients with diabetes.

Normotension, prehypertension, and hypertension in urban middle-class subjects in India: prevalence, awareness, treatment, and control.

OBJECTIVE: We conducted a multisite study to determine the prevalence and determinants of normotension, prehypertension, and hypertension, and awareness, treatment, and control of hypertension among urban middle-class subjects in India. METHODS: We evaluated 6,106 middle-class urban subjects (men 3,371; women, 2,735; response rate, 62%) in 11 cities for sociodemographic and biological factors. The subjects were classified as having normotension (BP < 120/80), prehypertension (BP 120-139/80-89), and hypertension (documented or BP ≥ 140/90). The prevalence of other cardiovascular risk factors was determined and associations evaluated through logistic regression analysis. RESULTS: The age-adjusted prevalences in men and women of normotension were 26.7% and 39.1%, of prehypertension 40.2% and 30.1%, and of hypertension 32.5% and 30.4%, respectively. The prevalence of normotension declined with age whereas that of hypertension increased (P-trend < 0.01). A significant association of normotension was found with younger age, low dietary fat intake, lower use of tobacco, and low obesity (P < 0.05). The prevalence of hypercholesterolemia, diabetes, and metabolic syndrome was higher in the groups with prehypertension and hypertension than in the group with normotension (age-adjusted odds ratios (ORs) 2.0-5.0, P < 0.001). The prevalences in men and women, respectively, of two or more risk factors were 11.1% and 6.4% in the group with normotension, 25.1% and 23.3% in the group with prehypertension, and 38.3% and 39.1% in the group with hypertension (P < 0.01). Awareness of hypertension in the study population was in 55.3%; 36.5% of the hypertensive group were receiving treatment for hypertension, and 28.2% of this group had a controlled BP (< 140/90 mm Hg). CONCLUSIONS: The study found a low prevalence of normotension and high prevalence of hypertension in middle-class urban Asian Indians. Significant associations of hypertension were found with age, dietary fat, consumption of fruits and vegetables, smoking, and obesity. Normotensive individuals had a lower prevalence of cardiometabolic risk factors than did members of the prehypertensive or hypertensive groups. Half of the hypertensive group were aware of having hypertension, a third were receiving treatment for it, and quarter had a controlled BP.

Association of educational, occupational and socioeconomic status with cardiovascular risk factors in Asian Indians: a cross-sectional study.

BACKGROUND: To determine correlation of multiple parameters of socioeconomic status with cardiovascular risk factors in India. METHODS: The study was performed at eleven cities using cluster sampling. Subjects (n = 6198, men 3426, women 2772) were evaluated for socioeconomic, demographic, biophysical and biochemical factors. They were classified into low, medium and high socioeconomic groups based on educational level (<10, 10-15 and >15 yr formal education), occupational class and socioeconomic scale. Risk factor differences were evaluated using multivariate logistic regression. RESULTS: Age-adjusted prevalence (%) of risk factors in men and women was overweight or obesity in 41.1 and 45.2, obesity 8.3 and 15.8, high waist circumference 35.7 and 57.5, high waist-hip ratio 69.0 and 83.8, hypertension 32.5 and 30.4, hypercholesterolemia 24.8 and 25.3, low HDL cholesterol 34.1 and 35.1, high triglycerides 41.2 and 31.5, diabetes 16.7 and 14.4 and metabolic syndrome in 32.2 and 40.4 percent. Lifestyle factors were smoking 12.0 and 0.5, other tobacco use 12.7 and 6.3, high fat intake 51.2 and 48.2, low fruits/vegetables intake 25.3 and 28.9, and physical inactivity in 38.8 and 46.1%. Prevalence of > = 3 risk factors was significantly greater in low (28.0%) vs. middle (23.9%) or high (22.1%) educational groups (p<0.01). In low vs. high educational groups there was greater prevalence of high waist-hip ratio (odds ratio 2.18, confidence interval 1.65-2.71), low HDL cholesterol (1.51, 1.27-1.80), hypertriglyceridemia (1.16, 0.99-1.37), smoking/tobacco use (3.27, 2.66-4.01), and low physical activity (1.15, 0.97-1.37); and lower prevalence of high fat diet (0.47, 0.38-0.57),overweight/obesity (0.68, 0.58-0.80) and hypercholesterolemia (0.79, 0.66-0.94). Similar associations were observed with occupational and socioeconomic status. CONCLUSIONS: Low educational, occupational and socioeconomic status Asian Indians have greater prevalence of truncal obesity, low HDL cholesterol, hypertriglyceridemia, smoking or tobacco use and low physical activity and clustering of > = 3 major cardiovascular risk factors.