Cardiovascular risk in newly diagnosed type 2 diabetes patients in India.

BACKGROUND: Type 2 diabetes mellitus (T2DM) worldwide continues to increase, in particular in India. Early T2DM diagnosis followed by appropriate management will result in more cardiovascular event free life years. However, knowledge of the cardiovascular profile of newly diagnosed T2DM patients is still limited. The aim of this study was to understand the extent of cardiovascular disease (CVD) risk of newly diagnosed T2DM patients in India. METHODS: A cross sectional observational study was conducted to evaluate clinical laboratory and socio-demographic parameters of 5,080 newly diagnosed T2DM patients (48.3 ± 12.8 years of age; 36.7% female). In addition, we determined their cardiovascular risk according to the guidelines of the Lipid Association of India (LAI) and the criteria of the QRISK3 score. RESULTS: Of the newly T2DM diagnosed patients in India 2,007(39.5%) were classified as "High risk" and 3,073 (60.5%) were classified as "Very high risk" based on LAI criteria. On average, patients had 1.7 ± 0.9 major atherosclerotic cardiovascular disease (ASCVD) risk factors. Low HDL-C value was the most frequent major risk (2,823; 55.6%) followed by high age (2,502; 49.3%), hypertension (2,141; 42.1%), smoking/tobacco use (1,078; 21.2%) and chronic kidney disease stage 3b or higher (568; 11.2%). In addition, 4,192 (82.5%) patients appeared to have at least one cholesterol abnormality and, if the latest LAI recommendations are applied, 96.5% (4,902) presented with lipid values above recommended targets. Based on the QRISK3 calculation Indian diabetes patients had an average CVD risk of 15.3 ± 12.3%, (12.2 ± 10.1 vs. 17.1 ± 13.5 [p<0.001] for females and males, respectively). CONCLUSIONS: Newly diagnosed Indian T2DM patients are at high ASCVD risk. Our data therefore support the notion that further extension of nationwide ASCVD risk identification programs and prevention strategies to reduce the occurrence of cardiovascular diseases are warranted.

Effect of Gliclazide or Gliclazide plus Metformin Combination on Glycemic Control in Patients with T2DM in India: A Real-World, Retrospective, Longitudinal, Observational Study from Electronic Medical Records.

BACKGROUND: The efficacy of gliclazide has been reported in clinical trials in India. However, real-world data on the effectiveness of gliclazide in India is unavailable. OBJECTIVE: To provide real-world evidence regarding the effectiveness of gliclazide or gliclazide + metformin fixed-dose combination or separate medications, used either as monotherapy or as the latest add-on to other antihyperglycemic agents in reducing glycated hemoglobin (HbA1c) levels in Indian patients with type 2 diabetes mellitus (T2DM). METHODS: Electronic medical record data of adult patients who were diagnosed with T2DM who were newly initiated on or had been prescribed gliclazide or gliclazide + metformin combination for < 30 days as monotherapy or as add-on therapy to other antihyperglycemic agents, and had HbA1c ≥ 6.5% were retrospectively analyzed. Mean change in HbA1c from baseline was the primary endpoint. Secondary endpoints were assessment of dosages and formulations of gliclazide or gliclazide + metformin prescribed in the HbA1c spectrum and antihyperglycemic agents to which gliclazide or gliclazide + metformin was added as an adjunct. Readings were obtained before initiating gliclazide or gliclazide + metformin and after at least 90 days of treatment with gliclazide or gliclazide + metformin. RESULTS: Included patients (n = 498) were categorized into gliclazide only (n = 66), gliclazide + metformin only (n = 179), gliclazide add-on (n = 169), and gliclazide + metformin add-on (n = 84) groups. Mean (95% confidence interval [CI]) change in HbA1c among patients with baseline HbA1c > 7% was - 0.8% (- 1.26, - 0.34) in gliclazide only group; - 1.6% (- 1.89, - 1.31; p < 0.001) in gliclazide + metformin group; - 1.2% (- 1.50, - 0.90; p < 0.001) in add-on gliclazide group; and - 1.4% (- 1.75, - 1.05; p < 0.001) in add-on gliclazide + metformin group. Gliclazide once daily was the most prescribed regimen in the gliclazide only group (72.7%), with 60 mg being the most prescribed modified-release dose (62.5%). Gliclazide + metformin twice daily was the most prescribed regimen in the gliclazide + metformin group (69.3%) with 80 mg + 500 mg being the most prescribed immediate-release dose (62.9%). Gliclazide and gliclazide + metformin were most added as an adjunct to existing prescriptions of biguanides (83.4%) or insulin (64.3%), respectively. CONCLUSION: Gliclazide or gliclazide + metformin prescribed as mono- or add-on therapy during routine clinical practice effectively reduced HbA1c in Indian patients with T2DM, thus validating the use of gliclazide and gliclazide + metformin for managing T2DM in India.

Effect of a multicomponent intervention on achievement and improvements in quality-of-care indices among people with Type 2 diabetes in South Asia: the CARRS trial.

AIMS: To evaluate whether and what combinations of diabetes quality metrics were achieved in a multicentre trial in South Asia evaluating a multicomponent quality improvement intervention that included non-physician care coordinators to promote adherence and clinical decision-support software to enhance physician practices, in comparision with usual care. METHODS: Using data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) trial, we evaluated the proportions of trial participants achieving specific and combinations of five diabetes care targets (HbA1c <53 mmol/mol [7%], blood pressure <130/80 mmHg, LDL cholesterol <2.6 mmol/L, non-smoking status, and aspirin use). Additionally, we examined the proportions of participants achieving the following risk factor improvements from baseline: ≥11-mmol/mol (1%) reduction in HbA1c , ≥10-mmHg reduction in systolic blood pressure, and/or ≥0.26-mmol/l reduction in LDL cholesterol. RESULTS: Baseline characteristics were similar in the intervention and usual care arms. Overall, 12.3%, 29.4%, 36.5%, 19.5% and 2.2% of participants in the intervention group and 16.2%, 38.3%, 31.6%, 11.3% and 0.8% of participants in the usual care group achieved any one, two, three, four or five targets, respectively. We noted sizeable improvements in HbA1c , blood pressure and cholesterol, and found that participants in the intervention group were twice as likely to achieve improvements in all three indices at 12 months that were sustained over 28 months of the study [relative risk 2.1 (95% CI 1.5,2.8) and 1.8 (95% CI 1.5,2.3), respectively]. CONCLUSIONS: The intervention was associated with significantly higher achievement of and greater improvements in composite diabetes quality care goals. However, among these higher-risk participants, very small proportions achieved the complete group of targets, which suggests that achievement of multiple quality-of-care goals is challenging and that other methods may be needed in closing care gaps.

Consensus on Use of Insulins in Gestational Diabetes.

INTRODUCTION: Gestational Diabetes Mellitus (GDM), diabetes diagnosed during pregnancy is associated with maternal (caesarean delivery, hypoglycaemia, hyperbilirubinaemia, shoulder dystocia, pre-term delivery and birth trauma) and fetal (Hyperbilirubinaemia in offspring, Neonatal hypoglycaemia, Macrosomia) complications. Despite, insulin being the standard treatment for GDM cases, there is no existing comprehensive consensus update on use of insulin in Indian patients with GDM. OBJECTIVE: To provide simple and easily implementable guidelines to healthcare physicians on use of insulin in GDM. METHODS: Each consensus based on indications, choice of insulin regimen , titration and insulin therapy during intrapartum and postpartum was presented based on established guidelines and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives' patient-physician experience in their clinical practice and common therapeutic practices followed in India for successful GDM management. RESULTS: Recommendations based on use of insulin in GDM has been developed. The key recommendations are:to monitor fasting plasma glucose (FPG) and 2-hour post prandial glucose PPG levels and the glycaemic targets are: FPG < 95 mg/dL and 2-hour PPG < 120 mg/dL, short-and intermediate acting human insulin are the first choice of insulin regimens, rapid-acting (Insulin Aspart or Lispro) may be considered, use basal/intermediate acting insulin at bedtime, if FPG>110 mg/dL. During intrapartum, start IV insulin infusion with hourly glucose monitoring. Those women who require insulin < 20 U over 24 hours prior to labor may not need interpartum use of insulin infusion and Insulin dosing is stopped after birth and capillary glucose monitoring for 24-48 hours. CONCLUSIONS: We hope that the consensus based recommendations mentioned in this paper will be a useful reference tool for healthcare practitioners to achieve glycaemic targets in GDM patients.

Association of Physicians of India: Position Statement on Role of Chirally Pure Molecules in Clinical Practice.

Chirally pure molecules or enantiomers are non-superimposable mirror images of each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure molecules (single enantiomers) are important in the field of drug discovery as the drug targets such as enzymes and receptors are enantioselective in nature. Clinical studies have demonstrated that chirally pure drugs exhibit different pharmacokinetic and metabolic profiles, reduced adverse events, improved safety profiles and similar therapeutic activity at lowered drug dosage as compared with the racemate in many therapeutic areas. However, since there is a low level of awareness on the advantages of chirally pure molecules among clinicians, pharmacists and patients in India, the Association of Physicians of India (API) developed this position statement to increase awareness on the concept of chirality and the associated advantages of using chirally pure drugs in certain therapeutic areas to maximize patient outcomes. This includes the clinical evidence associated with single enantiomers such as S-metoprolol, S-amlodipine, esomeprazole, escitalopram, levobupivacaine, cisatracurium, S-etodolac, dexketoprofen, levofloxacin in terms of efficacy and safety as compared with their racemates. In addition, the API also provides some tactical recommendations for clinicians, pharmacists, patients, regulatory body and pharmaceutical companies to increase awareness on chirally pure drugs and puts forth the need for expedited availability of chirally pure drugs in the Indian market.

Translating structure to clinical properties of an ideal basal insulin.

There is a need for ideal basal insulin which can overcome the unmet need of a truly once daily insulin, with a flat peakless profile. Useful for all types of patients Insulin degludec is next generation insulin with a unique mode of protraction of forming soluble multi-hexamers and slow continuous absorption giving it a flat profile compared to the existing basal insulin. In patients with type 1 diabetes or with type 2 diabetes, at steady-state, the mean terminal half-life of insulin degludec was 25 hours, i.e., approximately twice as long as for insulin glargine (half-life of 12.1 hours). In once-daily dosing regimen it reaches steady state after approximately 3 days. The duration of action of insulin degludec was estimated to be beyond 42 hours in euglycaemic clamp studies and this gives the unique opportunity of flexible time dosing which is not an available option with the existing basal insulin. The glucose-lowering effect is evenly distributed across a 24-hour dosing interval with insulin degludec having 4 times lower variability than insulin glargine. This is an important attribute given the narrow therapeutic window of insulin and the goal of achieving night time and inter-prandial glycaemic control without increasing the risk for hypoglycaemia, a goal that is challenging given the variability of absorption and lower PK half-lives of current basal insulin products. The combination of the ultra-long, flat and stable profile with an improved hour-to-hour and day-to-day variability could present an improved risk-benefit trade-off with the lower risk of hypoglycaemia, allowing for targeting improved levels of glycaemic control.

Renal histology in diabetic nephropathy: A novel perspective.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease all over the world. India has a high incidence and prevalence of diabetes and >30% have nephropathy. Recently, a histological classification has been proposed. This study analyzed the renal histology in 114 diabetic patients with renal dysfunction. Nearly 75% of patients had DN. Fifty five (63.95%) were males. Mean duration of diabetes was 7.04 ± 4.9 years. Mean serum creatinine in study group was 5.2 ± 2.9 mg/dl, with mean estimated glomerular filtration rate of 23.43 ± 21.48 ml/min/1.732 m(2). Forty eight patients (55.81%) had diabetic retinopathy (DR); prevalence of DR was more in patients who had diabetes for > 10 years than patients who had diabetes for <6 years (P = 0.022). The most common histological class was Class IV observed in 37 (43.02. %) cases, Class III DN in 24 (27.90%) cases, Class IIa and Class IIb in 11 (12.79%) cases each and Class I DN in 3 (3.48%) cases. Higher histological class was associated with higher proteinuria, lower glomerular filtration rate (P < 0.001) and was more likely to be associated with retinopathy (P = 0.012) and hypertension (P = 0.0003) but did not correlate with duration of diabetes (P = 0.85). There was a poor correlation between retinopathy and DN. Biopsy helps to stage the renal lesions in diabetics with renal dysfunction.

Acarbose improves glycemic control and reduces body weight: Subanalysis data of South Asia region.

Alpha-glucosidase inhibitors (AGIs) are widely used especially in Asian countries as a treatment option for type 2 diabetes patients with high postprandial glycaemia. However, data from South Asia region is very limited. In order to examine the effect of AGI in real-life setting, 10 PMS/NIS from all over the world from the launch of acarbose to date were pooled in one database and exploratory analysis was performed for glycemic parameters and weight. In total 62,905 patients were pooled from 21 countries and regions. Mean follow up (± SD) was 12.2 ± 4.8 weeks (range 0.1-108.9). From South Asia region (India and Pakistan), 8,738 Asian patients were enrolled. Mean PPG decreased from 240.0 and 261.1 mg/dl at baseline by 70.26 ± 65.10 and 82.96 ± 56.59 mg/dl at the last visit in total and South Asian populations, respectively (n = 53,883; n = 7,991, P < 0.0001 for both). Mean FPG decreased from 171.6 and 176.5 mg/dl at baseline by 38.48 ± 47.83 and 49.59 ± 41.41 mg/dl at the last visit in total and South Asian populations, respectively (n = 56,672; n = 7,837, P < 0.0001 for both). Mean HbA1c decreased from 8.4 and 8.4% at baseline by 1.11 ± 1.31% and 0.91 ± 0.93% at the last visit in total and South Asian populations, respectively (n = 38,843; n = 2,343, P < 0.0001 for both). Mean relative reduction of body weight (BW) was 1.40 ± 3.28% and 1.10 ± 3.39% at the last visit for mean baseline BW 73.6 and 74.2 kg in total and South Asian populations, respectively (n = 54,760; n = 7,718, P < 0.0001 for both). Consistent with RCT meta-analyses, post-hoc analysis of real-life data showed acarbose treatment improved glycaemic control and reduced the BW. Acarbose treatment in real life setting showed significant reductions in all glycemic parameters and BW in Asian patients from South Asia region.

Alpha-glucosidase inhibitor, acarbose, improves glycamic control and reduces body weight in type 2 diabetes: Findings on indian patients from the pooled data analysis.

Alpha-glucosidase inhibitors are widely used especially in Asian countries as a treatment option for type 2 diabetes patients with high postprandial glycemia (PPG). The higher carbohydrate in the Indian diets lead to greater prandial glycemic excursion, increased glucosidase, and incretin activity in the gut and may need special therapeutic strategies to tackle these glucose peaks. This is the subgroup analysis of Indian subjects who participated in the GlucoVIP study that investigated the effectiveness and tolerability of acarbose as add-on or monotherapy in a range of patients with type 2 diabetes mellitus. A total of 1996 Indian patients were included in the effectiveness analysis. After 12.5 weeks (mean), the mean change in 2-hour PPG from baseline was -74.4 mg/dl, mean HbA1c decreased by -1.0%, and mean fasting blood glucose decreased by -37.9 mg/dl. The efficacy of acarbose was rated "very good" or "good" in 91.1% of patients, and tolerability as "very good" or "good" in 88.0% of patients. The results of this observational study suggest that acarbose was effective and well tolerated in the Indian patients with T2DM.

Initiation of insulin aspart to Indian subjects on OADs show significant improvement in glycaemic outcomes: the A1chieve observational study.

The prevalence of diabetes is increasing worldwide and India stands second next only to china. The management of diabetes in real life settings needs to be evaluated for deriving better management practices. A1chieve observational study evaluated the use of modern insulin in real life settings. This was a 24-week, international, prospective, multicenter, non-interventional, observational study of people with type 2 diabetes. India recruited with 20,554 subjects and a total of 1815 patients were enrolled to receive insulin aspart as bolus insulin therapy of whom 1450 (79.9%) were insulin naïve and 365 (20.1%) were insulin users. At the end of 24 weeks, only one SAE was reported in this study and overall hypoglycemia events per patient year decreased from 2.49 (348 episodes) to 0.17 (20 episodes). There were no major hypoglycemic episodes reported in either insulin naive or insulin treated subjects. There was a significant improvement in the HbA(1c) values from the baseline in both insulin naive and insulin users. The mean HbA(1c) value was reduced from 9.5 to 7.4 (p < 0.001) for insulin naïve subjects and from 9.2 to 7.7 (p < 0.001) in insulin experienced subjects. Fasting plasma glucose values decreased by 70 mg/dL and 50 mg/dL in insulin naive and insulin experienced, respectively and the difference from baseline was statistically significant (P < 0.001). The post prandial glucose value was also significantly (p < 0.001) reduced by 105 mg/dL for insulin naïve subjects and 55 mg/dL for insulin experienced subjects. The composite end point was achieved by 46.6% of insulin naive and 38.1% of insulin-experienced subjects. The study concluded with good HbA(1c) reduction along with lower incidence of hypoglycemia and better health related quality of life outcomes in both in insulin naive and insulin experienced subjects who used insulin aspart as bolus insulin treatment.

Recommendations for insulin initiation based on ethnicity.

Even in a developed country like USA, substantial number of subjects with type 2 diabetes fail to achieve adequate glycemic control despite the availability of several groups of anti-diabetic medications targeting multiple pathophysiological features of type 2 diabetes. Are we treating our type 2 diabetes subjects appropriately? To aid practicing clinicians various professional bodies like American Diabetes Association (ADA), European Association for Study of Diabetes (EASD), Canadian Diabetes Association (CDA), etc. regularly publish clinical practice guidelines and consensus statements. Since racial and ethnic differences in insulin resistance, dietary pattern, glucose metabolism, genetic variation are known phenomena, it would be interesting to evaluate the aptness of these guidelines from ethnopharmacy perspective. We postulate that certain ethnic characteristics of populations will decide the best form of insulin therapy rather than blanket recommendations on starting every patient on basal insulin.

Refractory rickets in the tropics.

Rickets is an important problem in children. The majority of rickets in children is due to deficiency of calcium, phosphorus or vitamin D. However, rickets may also be a feature of renal diseases, e.g. renal tubular acidosis, hypophosphatemic rickets or rickets associated with renal insufficiency. The treatment varies with etiology and hence complete workup is essential before initiating therapy.

Baseline characteristics of the Indian cohort from the IMPROVE study: a multinational, observational study of biphasic insulin aspart 30 treatment for type 2 diabetes.

INTRODUCTION: The IMPROVE study is an openlabel, nonrandomized, observational study aimed at determining the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) treatment in subjects with type 2 diabetes from 11 countries. Here, we report the baseline data of the Indian cohort. METHODS: All subjects with type 2 diabetes requiring insulin and considered suitable for BIAsp 30 therapy based on their physician's clinical judgment were eligible to enter the study. The data recorded at baseline included demographic characteristics, detailed medical histories, physician-cited reasons for starting BIAsp 30 treatment, and the chosen dosage regimens. RESULTS: The Indian cohort included 17,995 subjects with diabetes. Poor glycemic control (glycated hemoglobin [HbA(1c)], 8.7%-9.6%) was observed at baseline in all four geographical zones (North, South, East, and West) and prestudy treatment groups (no therapy, only oral antidiabetic drug [OAD], OAD +/- insulin, and OAD +/- insulin +/- BIAsp 30). Prevalence of both micro- and macrovascular complications was high, also reflecting poor glycemic control. Improving HbA(1c) and fasting and postprandial blood glucose levels were the most common reasons for starting BIAsp 30 therapy. The subjects were prescribed a mean BIAsp 30 dose of approximately 24 IU, and a twice-daily regimen was employed in almost 80% of subjects. CONCLUSION: The baseline results of the IMPROVE study Indian cohort confirm the poor glycemic control and the delayed initiation and/or inadequacy of treatment in subjects with type 2 diabetes. These results also highlight the need for timely and appropriately intensive insulin-based therapy.

Cerebral salt wasting syndrome in a patient with a pituitary adenoma.

Cerebral salt wasting syndrome (CSWS) is often an unrecognized cause of hyponatremia that occurs in the setting of intracranial lesions. It is important to differentiate CSWS from the syndrome of inappropriate ADH secretion, as this would alter the management of hyponatremia. We describe a case of CSWS that occurred in association with a non-functioning pituitary adenoma.

Hypertension in diabetes.

Diabetes mellitus and hypertension are both major public health problems in our country, which co-exist frequently resulting in significant morbidity and mortality. The reported prevalence of hypertension in diabetes varies widely but is probably 1.5-2 times higher than that reported in the general population. In type 2 diabetics many are hypertensives at the time of diagnosis, while in type 1 diabetes, hypertension is predominantly associated with the development of nephropathy. Hypertension in diabetes is due to several pathophysiological mechanisms which include increased volume expansion, altered sodium homeostasis, increased peripheral vascular resistance, hyperinsulinaemia, insulin resistance, etc. The presence of hypertension in diabetic patients increases the mortality 4-5 folds, largely through coronary artery disease and stroke. It may also be an aetiological factor in the development of nephropathy and retinopathy. Treatment of hypertension in a diabetic has considerable therapeutic advantages and should be carried out vigorously. Lifestyle modifications have a useful role in the treatment of mild hypertension and have a beneficial effect on other cardiovascular risk factors. The choice of antihypertensive agents should be based on their potential impact on the metabolic abnormalities observed in diabetics. Amongst the currently available antihypertensive agents, ACE inhibitors and calcium channel blockers are the favoured agents.

Neurological emergencies--diabetes management.

Diabetes can affect the nervous system in several ways. Of all the neurological complications of diabetes, peripheral neuropathy is by far the commonest and has been extensively studied. The involvement of central nervous system can be in several forms. The underlying damage may be due to involvement of the large and small cerebral blood vessels as also due to metabolic derangement caused by prolonged hypoglycemia, anoxia or ketoacidosis. The neurological emergencies that occur in diabetes can be: 1) atherothrombotic and lacunar strokes; 2) convulsive disorder in the setting of both hypo and hyperglycemia; 3) coma; 4) cranial neuropathies; and 5) acute proximal muscle weakness. In patients with diabetes, atherothrombotic stroke is associated with poor outcome. Hyperglycemia at the time of stroke is an important risk factor for an adverse outcome than chronic stable diabetic state. Proper management of diabetes in these acute situations is crucial for a better outcome of the underlying disease process.