Prevalence of cardiac abnormalities and heart failure in unselected out-patients with type 2 diabetes mellitus and associated clinical factors: Real-world evidence from an Indian registry.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is known to be associated with development of left ventricular (LV) dysfunction and heart failure (HF). The study aimed to determine the prevalence of LV dysfunction and HF in unselected out-patients with T2DM with no previous cardiac history and to correlate LV dysfunction and HF with demographic and comorbid characteristics. METHODS: This cross-sectional study conducted at 27 centers in India captured demographic and clinical data through electronic case record forms. B-type natriuretic peptide of >105 pg/mL was used to diagnose HF and two-dimensional echocardiography was used to assess LV dysfunction. RESULTS: Of the 615 patients, 54.3 % (n = 334) were males; mean age was 57.4 ± 10.48 years. More than one-third of the patients had T2DM duration of >10 years (n = 238; 38.7 %), with hypertension as the most prevalent comorbidity (n = 372, 78.6 %). Approximately 61.3 % of the patients had LV hypertrophy. The mean LV mass was 135.0 ± 56.16 g (95 % CI 130.28, 139.70). The prevalence of any type of LV dysfunction, including systolic or diastolic dysfunction and HF was 55 % (95 % CI 51.0, 59.0) and 10 % (95 % CI 7.0, 12.0), respectively. A negligible but statistically significant correlation was observed between LV dysfunction and T2DM duration (p = 0.011), alongside HF and age (p < 0.0001). CONCLUSION: Real-world data from this registry from India demonstrates a substantial burden of LV dysfunction and HF in individuals with T2DM in India. It is imperative to formulate strategies for early identification of LV dysfunction in individuals with T2DM for prevention and consequent management of HF.

Genital Infections with Sodium Glucose Cotransporter-2 Inhibitors: Occurrence and Management in Patients with Type 2 Diabetes Mellitus.

Diabetes is a metabolic disorder characterized by hyperglycemia and is associated with several comorbidities and complications. Genital infection is one such complication that is often associated with diabetes mellitus (DM). Even though abnormalities in immune system, high urine glucose, and bladder dysfunction are important contributors for the increased risk of genitourinary symptoms, yet the possible role of pharmacologically induced glucosuria cannot be completely overlooked in such patients. There are various classes of medications to control blood glucose levels. A new therapeutic option to manage hyperglycemia is to increase renal glucose excretion by inhibiting sodium-glucose cotransporter-2 (SGLT2) glucose transport proteins. SGLT2 inhibitors (SGLT2i) represent a novel class of oral antidiabetic drugs which are associated with drug-induced glucosuria. Currently, canagliflozin, dapagliflozin, and empagliflozin are the three SGLT2i approved for therapy in Type 2 DM (T2DM). Safety studies with these three SGLT2i have reported events of mild-moderate genital infections in patients on SGLT2i therapy. However, most of the reported infections responded to standard treatment. Apart from SGLT2i, factors including personal hygiene, menopause, and circumcision might have a possible role in reported events of genital infections among T2DM patients on SGLT2i therapy. The present review identifies the occurrence of genital infections in diabetic patients on SGLT2i therapy, factors affecting the incidence of genital infections, and management strategies in patients with T2DM on SGLT2i therapy.

A Study to derive distribution of carotid intima media thickness and to determine its COrrelation with cardiovascular Risk factors in asymptomatic nationwidE Indian population (SCORE-India).

BACKGROUND: There is presently no data to describe normal distribution of carotid intima-media thickness (CIMT), an established measure of subclinical atherosclerosis, in Indian subjects. METHODS: In this multi-centric study, 1229 subjects with age ≥30 years and no previous cardiovascular disease (CVD) underwent CVD risk factor assessment and CIMT measurement. Mean far wall common carotid artery IMT was measured on both sides and averaged. RESULTS: Mean age of the subjects was 48.0±12.0 years and 54.2% were men. CIMT measurement was feasible in 1157 subjects. Mean, median and 75th percentile values of CIMT for different age-groups were derived for men and women separately. There was a progressive increase in CIMT with increasing age (P<0.001) and men had higher CIMT values than women (0.608±0.12mm vs. 0.579±0.11mm, P<0.001). The CIMT values were also higher in diabetics (0.635±0.10mm) and hypertensives (0.624±0.10mm) as compared to non-diabetics (0.589±0.12mm, P<0.001) and non-hypertensives (0.592±0.12, P 0.02) respectively. Among continuous variables, age, systolic blood pressure and fasting blood glucose had strong to modest correlation with CIMT (Pearson's r 0.524, 0.282 and 0.192 respectively, all P values <0.001), whereas body mass index, diastolic blood pressure and serum triglycerides exhibited weak but still statistically significant relationship (Pearson's r 0.069, P 0.019; Pearson's r 0.065, P 0.026; and Pearson's r 0.094, P 0.001, respectively). CONCLUSIONS: This is the first study to provide age- and gender-specific distribution of CIMT in Indian subjects free from CVD. This information should help facilitate further research and clinical work involving CIMT in India.

Pleiotropic effects of statins.

Statins or 3-hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors not only prevents the synthesis of cholesterol biosynthesis but also inhibits the synthesis of essential isoprenoid intermediates such as farnesyl pyrophosphate, geranylgeranyl pyrophosphate, isopentanyl adenosine, dolichols and polyisoprenoid side chains of ubiquinone, heme A, and nuclear lamins. These isoprenoid intermediates are required for activation of various intracellular/signaling proteins- small guanosine triphosphate bound protein Ras and Ras-like proteins like Rho, Rab, Rac, Ral, or Rap which plays an indispensible role in multiple cellular processes. Reduction of circulating isoprenoids intermediates as a result of HMG CoA reductase inhibition by statins prevents activation of these signalling proteins. Hence, the multiple effects of statins such as antiinflammatory effects, antioxidant effects, antiproliferative and immunomodulatory effects, plaque stability, normalization of sympathetic outflow, and prevention of platelet aggregation are due to reduction of circulating isoprenoids and hence inactivation of signalling proteins. These multiple lipid-independent effects of statins termed as statin pleiotropy would potentially open floodgates for research in multiple treatment domains catching attentions of researchers and clinician across the globe.

An observational, cross-sectional study to assess the prevalence of chronic kidney disease in type 2 diabetes patients in India (START -India).

OBJECTIVE: The primary objective of this study is to estimate the prevalence of chronic kidney disease (CKD) among type 2 diabetes mellitus (T2DM) patients in India. MATERIALS AND METHODS: This cross-sectional, observational, epidemiological, multi-center, study is enrolling T2DM patients of either gender aged 30 years or above. This study aimed to enroll a total of 3000 T2DM patients at 30 participating hospitals/clinics across India and the data from a planned interim analysis of 1500 patients are presented here. The primary endpoint of the study is to estimate proportion of T2DM patients with CKD (glomerular filtration rate [GFR] <60 ml/min/1.73 m(2) or albumin creatinine ratio [ACR] ≥30 mg/g or ≥3 mg/mmol or both). Routine treatment, as administered by the treating physician, was continued without any study specific intervention. Patients' data pertaining to demographic characteristics, medical history, current medication and physical examination were recorded. The blood/plasma and urine samples, were collected for estimation of hemoglobin A1c, microalbuminuria, serum creatinine, urine creatinine, and routine urine analysis. ACR was calculated from urine creatinine and albumin while GFR was estimated by using a modification of diet in the renal disease equation. RESULTS: Study recruited 1500 patients from 18 centers across India. The study population included 840 (56.05%) males. Mean age, body mass index and systolic blood pressure were 55.1 years, 27.4 kg/m(2) and 134.5 mmHg respectively. The mean duration of diabetes was 102.2 months. History of co-morbid diseases such as dyslipidemia, hypertension, microvascular complications and macrovascular complications was present in 657 (43.8%), 655 (43.7%), 268 (17.9%) and 104 (6.93%), respectively. This interim analysis revealed that about 46% of the T2DM patients had CKD (urinary albumin creatinine ratio (UACR) ≥30 mg/g and/or estimated GFR [eGFR] <60 mL/min/1.73 m(2)). The renal dysfunction as per eGFR criteria (<60 mL/min/1.73 m(2)) was reported in about 23% while as per UACR criteria (≥30 mg/g) it was reported in about 35% patients. CONCLUSION: This interim analysis results suggests that over 40% of T2DM patients have CKD. Despite this high number of T2DM patients with CKD, eGFR analysis shows there are almost 80% of T2DM patients still have reasonably good renal function (eGFR above 60 ml/min), which ensures less restrictions in selecting oral anti-diabetic drugs. Full study results from Start-India study will provide detail insights into the occurrence of CKD in patients with T2DM in India.

Prevalence of dyslipidemia in adult Indian diabetic patients: A cross sectional study (SOLID).

CONTEXT: India leads the world with largest number of diabetic patients and is often referred to as the diabetes capital of the world. Diabetic dyslipidemia in India is one of the main cause for Coronary Artery Disease (CAD) mortality. Although diabetes continues to be a major lifestyle condition in India, there is a lack of studies in India on whether dyslipidemia in Indian diabetics is being adequately controlled. Our study provides critical insights into the insights into proportion of diabetes patients achieving lipid goal in India. AIMS: The primary objective of our study was to assess the control of dyslipidemia in the Indian diabetic population treated with lipid lowering drugs (LLDs), as per American Diabetes Association (ADA) 2010 guidelines. SETTINGS AND DESIGN: The study was carried out in a real world Indian clinical setting involving 178 sites. This is a multicenter, noninterventional, and cross-sectional observational study. MATERIALS AND METHODS: A total of 5400 adult subjects with established type-2 diabetes mellitus (T2DM) and dyslipidemia were recruited for the study. Patients in the study were on LLD at a stable dose for at least last 3 months before the designated study visit. Routine lipid profile tests were conducted for all patients. STATISTICAL ANALYSIS USED: Descriptive statistics was used to analyze qualitative and discrete variables. Chi-square test and t-test were conducted to assess the existence of statistically significant association between the variables. RESULTS: A total of 5400 patients with T2DM from 178 centers across India were recruited. Out of the total population, 56.75% (N = 3065) of them were males. Primary end-point of low-density lipoprotein cholesterol (LDL-C) level below ADA 2010 target was achieved in a total of 48.74% (N = 2632) patients. Gender was significantly associated with lipid levels and age was significantly (P < 0.05) correlated with all lipid levels. Control rates of other lipid parameters like high-density lipoprotein cholesterol, triglyceride, and total cholesterol in the study were 60.48% (N = 3236), 57.54% (N = 3107), and 92.24% (N = 4981) respectively. Among those with overt cardiovascular disease (CVD), target LDL-C level of < 70 mg/dL was achieved in 22.87% (70 out of 306) patients. The LDL-C levels of 49.03% (N = 1768) patients who were on statin therapy were within target levels, while 53.46% (N = 634) patients who were on statin and their combinations with other LLDs had their LDL-C levels within the stipulated range. CONCLUSIONS: This study has reveled that dyslipidemia control in Indian T2DM patients is very poor with almost half of them not reaching their LDL -C goal. Dyslipidemia being one of the main risk factors for CVD in T2DM patients there is a need to treat dyslipidemia aggressively to reduce risk of future CV events.

Plaque regression and plaque stabilisation in cardiovascular diseases.

Atherosclerosis is characterized by formation of plaques on the inner walls of arteries that threatens to become the leading cause of death worldwide via its sequelae of myocardial infarction and stroke. Endothelial dysfunction leads to cholesterol uptake and accumulation of inflammatory markers within the plaque. The stability of a plaque eventually depends on the balance between vascular smooth muscle cells that stabilize it and the inflammatory cells like macrophages and T lymphocytes that make it prone to rupture. The current approach to manage atherosclerosis focuses on the treatment of a ruptured plaque and efforts have been made to reduce the risk of plaque rupture by identifying vulnerable plaques and treating them before they precipitate into clinical events. New diagnostic approaches such as IVUS and CIMT ultrasound are now being preferred over traditional coronary angiography because of their better accuracy in measuring plaque volume rather than the level of stenosis caused. The present review highlights the literature available on two prevalent approaches to manage a vulnerable plaque, namely, plaque stabilization and plaque regression, and their validation through various treatment modalities in recent plaque management studies. Plaque stabilization focuses on stabilizing the content of plaque and strengthening the overlying endothelium, while plaque regression focuses on the overall reduction in plaque volume and to reverse the arterial endothelium to its normal functional state. Although earlier studies contemplated the practicality of plaque regression and focused greatly on stabilization of a vulnerable plaque, our review indicated that, aided by the use of superior diagnostics tools, more intensive lipid modifying therapies have resulted in actual plaque regression.

LIPITENSION: Interplay between dyslipidemia and hypertension.

The burden of cardiovascular disease (CVD) is increasing worldwide. The increase in the burden is a major concern in developing countries like India. It is well-established that hypertension and dyslipidemia are the two major contributing risk factors for CVD. Various epidemiological studies have shown the prevalence of the co-existence of hypertension and dyslipidemia, in the range of 15 to 31%. The co-existence of the two risk factors has more than an additive adverse impact on the vascular endothelium, which results in enhanced atherosclerosis, leading to CVD. This review emphasizes on the 'co-existence and interplay of dyslipidemia and hypertension'. The authors have termed the co-existence as, 'LIPITENSION'. The term LIPITENSION may help clinicians in easy identification and aggressive management of the two conditions together, ultimately preventing future cardiovascular events.