Time to reposition sulfonylureas in type 2 diabetes management in Indian context: A pragmatic practical approach.

Sulfonylureas (SU) continue to be a vital therapeutic category of oral hypoglycemic agents (OHAs) for the management of type 2 diabetes mellitus (T2DM). Physicians consider modern SU (gliclazide and glimepiride) as "safe and smart" choices for T2DM management. The presence of multiple international guidelines and scarcity of a national guideline may contribute to the challenges faced by few physicians in choosing the right therapeutic strategy. The role of SU in diabetes management is explicit, and the present consensus aims to emphasize the benefits and reposition SU in India. This pragmatic, practical approach aims to define expert recommendations for the physicians to improve caregivers' knowledge of the management of T2DM, leading to superior patient outcomes.

Sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus without established cardiovascular disease: Do they have a role in primary prevention?

Most guidelines and cardiovascular outcome trials (CVOTs) focus on secondary prevention of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Patients with T2DM without established CVD (eCVD) also form a critical cohort, for whom primary prevention with timely pharmacological and non-pharmacological interventions can effectively prevent or delay the onset of CVD. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated a promising role for primary prevention of CVD in CVOTs and real-world studies. The 2019 American College of Cardiology/American Heart Association guidelines on primary prevention of CVD recommend SGLT2i as one of the add-on treatment options to metformin for adults with T2DM and glycated hemoglobin >7% who have cardiovascular (CV) risk factors. The outcomes with maximal response to SGLT2i use in primary prevention are hospitalization for heart failure and chronic kidney disease. The cardiorenal benefits with SGLT2i are attributed to pleiotropic effects on CV risk factors, and interference with glucose and sodium handling in kidneys, independent of their glycemic benefits. Results therefore support a role for SGLT2i not only in patients with T2DM and eCVD but also in patients with T2DM without eCVD. This review examines the evidence for potential role of SGLT2i for primary prevention of CVD in T2DM.

Evidence-based recommendations for insulin intensification strategies after basal insulin in type 2 diabetes.

Over the time due to progressive nature of diabetes, proactive intensification of the existing insulin therapy becomes imminent as it minimizes patients' exposure to chronic hypo/hyperglycaemia and reduces weight gain while achieving individualized glycaemic targets. This review focuses on the strength of evidence behind various options for intensification, primarily the insulins as also the GLP-1 analogues. The recommendations presented here are meant to serve as a guide for the physician managing type 2 diabetes patients requiring insulin intensification upon failing of basal insulin therapy.

Evaluation Series on Safety and Efficacy of Nutritional Supplements in Newly Diagnosed Hyperglycemia: A Placebo-Controlled, Randomized Study.

BACKGROUND: Diabetes is endemic with developing economies contributing to the bulk of this pandemic. Despite the evidence of incremental benefit of glycemic control starting early in life, acceptance of and adherence to modern medications remain suboptimal. AIMS: To determine the hemoglobin A1c (HbA1c)-lowering efficacy and safety of nutritional supplement, PreCrea(®), in adult Indians with newly diagnosed hyperglycemia. MATERIALS AND METHODS: Double-blind, randomized study conducted in six diabetes centers in India. A total of 193 treatment-naïve subjects with newly diagnosed hyperglycemia and fasting plasma glucose (FPG) >100 mg/dL were randomized into either PreCrea(®) 600 mg (n = 90) or matched placebo (n = 89) capsules twice daily, along with lifestyle modification, for 12 weeks. The main outcomes were changes in HbA1c and FPG levels, attainment of the American Diabetes Association (ADA)-defined goals for HbA1c, and clinical and biochemical measures of safety. RESULTS: At 12 weeks, mean HbA1c in PreCrea(®) group reduced by 0.91% compared with 0.08% increase in the placebo group (P < .001). The reductions in the mean FPG at week 4 (P < .001) and week 12 (P = 0.04) were significant compared to the baseline. ADA goal of HbA1c <7% increased from 15.5% at the baseline to 35.6% at week 12 in PreCrea(®) subjects. Clinical safety and biochemical safety did not change. Hypoglycemia and weight gain were not observed with PreCrea(®). CONCLUSIONS: Nearly 1% point reduction in HbA1c at week 12 with PreCrea(®) is comparable with most first-line glucose-lowering drugs. The safety and tolerability of PreCrea(®) highlights its potential as a first-line therapy in newly detected hyperglycemia.

Consensus Statement on Management of Post-Prandial Hyperglycemia in Clinical Practice in India.

Postprandial hyperglycemia (PPHG) is a detrimental factor in the evolution of diabetes related complications. Numerous studies have established the role of PPHG in development of atherosclerosis and associated cardiovascular conditions. It is seen that management of PPHG can be more troublesome than fasting plasma glucose (FPG). Currently, there are various strategies both monitoring as well as therapeutic to control PPHG but there is no uniformity in practicing these strategies. In the absence of any standard guidelines, widespread variations in the management of PPHG are observed among physicians and diabetologists. The objective of this document is to set forth uniform guidelines to manage PPHG. This will not only result in optimal management and prevention of long term complications of diabetes but also better co-ordination and collaboration among the care providers. Moreover, an Indian perspective that can take into consideration the issues relevant to Indian patient pool will be effective. An expert committee comprising of prominent physicians and researchers associated with diabetes care provided their inputs to provide a basic platform for the formulations of guidelines. Their inputs were supplemented by extensive literature search to collect the relevant evidences. An initial draft was prepared which was reviewed by the core committee. Inputs from other experts were also sought and an initial guideline version was formulated that was presented in a conference, discussed and debated among experts. The guidelines on PPHG were then finalized and published.

Myocardial injury in coronary artery bypass grafting: On-pump versus off-pump comparison by measuring heart-type fatty-acid-binding protein release.

This prospective study uses heart-type fatty-acid-binding protein (hFABP) and creatine kinase-MB (CK-MB) release to compare myocardial injury in on-pump versus off-pump coronary artery bypass grafting (CABG). Fifty patients were randomly assigned to on-pump or off-pump CABG. The hFABP and CK-MB concentrations were measured in serial venous blood samples drawn before heparinization in both groups and after aortic unclamping at 1, 2, 4, 8, 24, 48, and 72 hours in the on-pump group. In the off-pump group, samples were taken after the last distal anastomosis at the same time intervals as in the on-pump group. The total amount of hFABP and CK-MB released was significantly higher in the on-pump than in the off-pump group (hFABP = 100.43 +/- 77.63 vs 3.94 +/- 0.36 ng/mL, P < 0.0001; CK-MB = 33.33 +/- 3.81 vs 28.65 +/- 3.91 log units, P < 0.001). In all patients, hFABP levels peaked as early as 1 hour after declamping (on-pump group) or 2 hours after the last distal anastomosis (off-pump group), whereas CK-MB peaked only at 4 hours after declamping (on-pump group) or 24 hours after the last distal anastomosis (off-pump group). The lower release of hFABP and CK-MB in the off-pump CABG group indicates that on-pump CABG with cardioplegic arrest causes more myocardial damage than does off-pump CABG. Heart-type fatty-acid-binding protein is a more rapid marker of perioperative myocardial damage, peaks earlier than CK-MB, and may predict the requirement for intensive monitoring for postoperative myocardial infarction.

Evaluation of Epsilon amino-caproic acid (EACA) and autologous blood as blood conservation strategies in patients undergoing cardiac surgery.

BACKGROUND: To evaluate the effects of autologous blood and Epsilon amino-caproic acid on intra-operative and post-operative blood loss and homologous blood product requirements in patients undergoing cardiac surgery. METHODS: Patients were randomly allocated to two groups of 30 each. In the Epsilon amino-caproic acid (EACA) group, the drug was administered in a loading dose of 100 mg/kg before skin incision followed by an infusion of 1/5 th the loading dose hourly and terminated 3 h after heparin neutralization. In the autologous transfusion (AT) group, 10% of the calculated whole blood volume was collected intra-operatively before cardiopulmonary bypass and re-infused after its termination. RESULTS: Haemoglobin values were comparable pre-operatively, on cardiopulmonary bypass, off cardiopulmonary bypass and post-operatively on day two in both groups. Intra-operative blood loss was not significantly different (643.3+/-129.14 ml in group EACA versus 710+/-145.5 ml in group AT, p = 0.66). Although the chest drainage was more in group AT during 0-3 h (71.3+/-54.3 ml versus 112.6+/-79.3.6 ml, p = 0.006) it was comparable amongst in the first 24 h (231.1+/-98.3 ml in group AT versus 235+/-101.4 ml in group EACA, p = 0.88). Homologous blood product requirements were similar in both groups. CONCLUSION: Autologous blood is as efficacious as Epsilon amino-caproic acid for blood conservation in cardiac surgery.

Study of efficacy and safety of losartan (losar) in Asian Indian hypertensives.

Although there has been widespread dissemination of knowledge about hypertension, it remains poorly treated in most populations. Systemic hypertension is associated with increased risk for coronary artery disease, stroke, nephrosclerosis, peripheral vascular disease, etc. The treatment of hypertension includes non-pharmacological measures and the specific drug therapy. Losartan potassium is an orally active, non-peptide angiotensin II receptor antagonist. It is the first of this new class of drugs introduced for clinical use in hypertension. Data was obtained of 347 patients from 140 general physicians. The study revealed that losartan potassium is used in the treatment of mild to moderate hypertension with excellent to good response in 98.8% of the cases. Mild adverse reactions were reported in 5.8% of the cases. None of the adverse reactions were severe enough which required discontinuation of therapy or needed hospitalisation. Thus, the present postmarketing surveillance study confirms the safety and efficacy of losartan potassium in Indian population.

Functional characterization of antibodies against heparin-platelet factor 4 complex in heparin-induced thrombocytopenia patients in Asian-Indians: relevance to inflammatory markers.

Occurrence of heparin-induced thrombocytopenia (HIT) was investigated for 33 Indian patients undergoing cardiovascular surgery who received unfractionated heparin (UFH). Platelet counts were performed prior to the initiation of UFH therapy and 5-16 days post therapy. Heparin-induced platelet aggregation, C-serotonin release assay, and enzyme-linked immmunosorbent assay (ELISA) tests were performed in all the patients to detect the antibodies formed against the complex of heparin and platelet factor 4 (HPF4). Levels of inflammatory markers/mediators such as CD40 ligand (CD40L) and C-reactive protein (CRP) were also measured in the patient plasmas utilizing ELISA tests. Based on clinical observations and laboratory diagnoses, five patients (15%) were considered to have confirmed HIT. Despite wide variations in the titers of inflammatory markers, patients who tested ELISA-positive for HPF4 antibodies showed markedly elevated levels of both soluble CD40L and C-reactive protein. Most strikingly, the C-serotonin release assay-positive patients showed up to a 10-fold increase in the level of CD40L. It is concluded that approximately 15% Asian-Indian patients receiving UFH during cardiovascular surgery develop functional HPF4 antibodies, which are associated with the increased levels of inflammatory markers/mediators in this catastrophic HIT syndrome.

Characteristics of gestational diabetic mothers and their babies in an Indian diabetes clinic.

AIMS AND OBJECTIVES: To compare clinical and metabolic features of mothers with gestational diabetes (GDM) and their offspring with those in non-diabetic pregnancies at the King Edward Memorial Hospital, Pune, India. MATERIALS AND METHODS: Antenatal information was obtained from hospital records. GDM was diagnosed by 75 g OGTT (Oral Glucose Tolerance Test) in clinically high-risk women. Anthropometric measurements of mother and the babies were recorded within 24h of delivery and a maternal blood sample collected for hematological and biochemical measurements. RESULTS: Between the period Jan 1998 to December 2003,265 women with gestational diabetes were treated in our Unit. Forty nine percent had first-degree relatives with diabetes. Compared to non-diabetic mothers (n=215) GDM mothers were older (29.0 vs. 26.0y, p<0.001), more obese (body mass index- BMI 26.0 vs. 22.0 kg/m2, p<0.001), centrally obese (Waist hip ratio-WHR 0.89 vs 0.86, p<0.001), adipose (sum of 4 skinfolds 98.4 vs. 61.4 mm, p<0.001) and had higher blood pressure (127/80 vs. 122/70 mmHg, p<0.001). GDM mothers had higher concentrations of plasma triglycerides (195.0 vs. 153.0 mg/dl, p<0.01); blood hemoglobin (11.7 vs 10.9 g/dl, p<0.001) and higher platelet count but lower concentration of HDL cholesterol and albumin. Sixty percent GDM mothers and 34% of non-diabetic mothers were delivered by caesarean-section, 23% of GDM mothers delivered pre term (<37 wk). Despite the smaller gestation, babies of GDM mothers were heavier (BW 2950.0 vs. 2824.0g, p<0.001, adjusted for gender), longer (48.9 vs. 48.0 cm, p<0.01) and more adipose (sum of 2 skinfolds 10.5 vs. 8.5 mm). Only 5% of babies born to GDM mothers weighed > 4000 g but 30% were >90th centile of birth weight of babies born to non-diabetic mothers. Babies of GDM mothers suffered higher neonatal morbidity. CONCLUSIONS: GDM mothers in urban India are more obese and more adipose than non-diabetic mothers, frequently have a family history of diabetes and show metabolic features of insulin resistance syndrome, suggesting high cardiovascular risk. Neonates of GDM mothers are heavier, longer and more adipose than those born to non-diabetic mothers, and suffer higher neonatal morbidity.

Dose comparison of tranexamic acid in pediatric cardiac surgery.

To compare different doses of tranexamic acid, 150 consecutive children with congenital cyanotic heart disease were randomly assigned to one of 5 groups of 30 each. Group A served as a control. Group B received 50 mg.kg(-1) of tranexamic acid at induction of anesthesia. Group C received 10 mg.kg(-1) at induction followed by an infusion of 1 mg.kg(-1).h(-1). Group D had 10 mg.kg(-1) at induction, 10 mg.kg(-1) on bypass, and 10 mg.kg(-1) after protamine. Group E had 20 mg.kg(-1) at induction and again after protamine. The control group had the longest sternal closure time, the greatest blood loss in the first 24 hours, and the highest requirements for blood and blood products. Among the 4 groups given tranexamic acid, group D (triple dose) had the best results, followed by group E (double dose). Group B (single dose) had the worst results among the groups receiving tranexamic acid.

Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery.

OBJECTIVE: This study compared the efficacy of aminocaproic acid and tranexamic acid in reducing postoperative blood loss, as well as blood and blood product requirements in children with cyanotic congenital heart disease. DESIGN: A prospective randomized study. SETTING: Cardiac center of a tertiary care, referral hospital. PARTICIPANTS: One hundred fifty children in the age group of 2 months to 14.5 years with cyanotic congenital heart disease undergoing corrective surgery on cardiopulmonary bypass (CPB). INTERVENTIONS: Patients were randomized into 3 groups. Group A was given aminocaproic acid in a dose of 100 mg/kg after anesthetic induction, 100 mg/kg on CPB and 100 mg/kg after protamine. Group T was given tranexamic acid, 10 mg/kg, after anesthetic induction, 10 mg/kg on CPB, and 10 mg/kg after protamine. Group C was the control group. MAIN RESULT: Control group had the longest sternal closure time, maximum blood loss at 24 hours, and maximum requirements of blood and blood products. Among the 2 groups given antifibrinolytics, there was no significant difference in postoperative blood loss, blood and product requirement, and reexploration rates. CONCLUSION: Aminocaproic acid and tranexamic acid are equally effective in reducing postoperative blood loss, as well as blood and blood product requirements in children with cyanotic heart disease undergoing corrective surgery as compared with the control group.

Laboratory diagnosis of heparin-induced thrombocytopenia in Asian Indians as investigated with functional and immunologic methods.

Heparin-induced thrombocytopenia (HIT) was looked for in 33 Indian patients undergoing cardiovascular surgery who received unfractionated heparin (UFH). Platelet counts were performed before the initiation of UFH therapy and 5 to 16 days after administration of the therapy. A decrease in patients' platelet count > 35% of the baseline value or < 100,000/microL was considered to be suggestive of HIT syndrome. Heparin-induced platelet aggregation (HIPA) and enzyme-linked immunosorbent assay (ELISA) tests were performed in all the patients to detect antibodies against heparin/PF4 complex. Thrombocytopenia was found to be present in 10 (30%) patients. Of these, two patients were found to be positive as detected by HIPA and ELISA tests. These two patients were considered to have classic HIT syndrome. One of these had bleeding while the other was asymptomatic. Among the 23 non-thrombocytopenic patients and controls, HIT antibodies were not detectable by HIPA test in all but absent by ELISA in only 21 of them. Two of 23 non-thrombocytopenic patients had positive results on the ELISA test. Because the latter had negative test results on HIPA, they were considered to be false-positive results. Thus, HIT syndrome develops in approximately 6% of Indian patients treated with UFH.

A comparison of aminocaproic acid and tranexamic acid in adult cardiac surgery.

We compared Aminocaproic acid with tranexamic acid, prospectively in 120 patients undergoing coronary artery bypass surgery on cardiopulmonary bypass. Patients were assigned to one of the 3 groups. Group A (n=40) did not receive any drug and acted as the control group. Group B (n=4) received aminocaproic acid 100 mg/kg each at anaesthetic induction, on bypass and after protamine reversal of heparin. group C (n=40) received tranexamic acid 10 mg/kg each at anaesthetic induction, on bypass and after protamine reversal of heparin. Postoperative blood loss at 24 hours, blood and blood product usage, and re-exploration rates were recorded, and tests for coagulation were performed at 6 hours postoperatively. It was found that blood loss in group A at 24 hours (780+/-120 mL) was significantly greater than Group B (360+/-90 mL) and Group C (215+/-70 mL). Plasma and platelet concentrate use in Group A (215+/-30 mL and 150+/-30 mL) was greater than Group B (190+/-20 mL and 75+/-30 mL) and Group C (185+/-20 mL and 80+/-30 mL). Re- explorations in Group A, 8/40 (20%) were greater than Group B, 2/40 (5%) and Group C, 2/40 (5%). Coagulation tests revealed better preservation of fibrinogen and lower levels of fibrin degradation products, in group B and C. These two groups were however statistically indistinguishable in respect to all the parameters studied, when compared with each other. It was concluded that both the antifibrinolytic agents in the doses studied were equally effective in reducing postoperative blood loss, blood and blood products usage and re-exploration rates. Coagulation parameters were better preserved as compared to the control group.

A comparative study of release of interleukin-6 and tumour necrosis factor during normothermic and hypothermic cardiopulmonary bypass.

The institution of cardiopulmonary bypass generates many pro-inflammatory cytokines and several clinical variables, including temperature, have been shown to influence cytokine release during and after cardiopulmonary bypass. The release of tumour necrosis factor and interleukin-6 are the best predictors of post-cardiopulmonary bypass related morbidity. Their release during normothermic and hypothermic cardiopulmonary bypass and the correlation with clinical parameters of organ injury was studied. This prospective study was carried out in 52 adult patients, scheduled for cardiac surgery, exposed to normothermic and 27 to hypothermic cardiopulmonary bypass. Samples for estimation of tumour necrosis factor and interleukin-6 were collected preoperatively, 1 hour and 24 hours post cardiopulmonary bypass and analysed by ELISA. Haemodynamic parameters and respiratory parameters were noted and lung injury scores calculated. Interleukin-6 levels were raised in both the groups at 1 hour and 24 hours post cardiopulmonary bypass and the response was higher in the normothermic group. Tumour necrosis factor response was, however, similar in both the groups, with a rise at 1 hour returning back to baseline by 24 hours post cardiopulmonary bypass. The normothermic group had a better respiratory index in the postoperative period, early extubation was possible, had better clinical haemodynamics, a shorter cardiopulmonary bypass time and had reduced requirement of defibrillation after the release of aortic cross clamp. We conclude that the release of interleukin-6 was thermo-dependent but did not correlate with the clinical signs of organ injury. Tumour necrosis factor levels were significantly raised after the cardiopulmonary bypass but the rise was not thermo-dependent.