Sodium-glucose Cotransporter-2 Inhibitors in Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Patients with Type 2 Diabetes Mellitus: A Meta-analysis.

BACKGROUND: The available evidence was systematically reviewed to evaluate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) on cardiovascular (CV) and renal outcomes in people with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors (MRF), with or without heart failure (HF), and per estimated glomerular filtration rate (eGFR) rate at baseline. METHODS: We comprehensively searched three electronic databases to retrieve publications up to 30th November 2019, which were screened for inclusion. The data extracted for the outcomes according to baseline ASCVD, HF, and eGFR levels were meta-analyzed using fixed effects model. RESULTS: Of the 735 screened citations, 15 primary and secondary publications from five CV or renal outcome trials were included. SGLT2is reduced the risk of CV death or hospitalization for HF (HHF), HHF alone, and composite renal-specific outcome, irrespective of ASCVD and HF at baseline. The three-point major adverse cardiovascular events (3P-MACE) risk was reduced by 14% (p<0.001) in patients with ASCVD and by 10% (p = 0.018) in those without baseline HF compared with their counterparts. SGLT2is significantly reduced the risk of MACE (18%) in patients with mild kidney dysfunction (eGFR within the range of 60-<90 mL/min/1.73 m2 and <60 mL/min/1.73 m2 ). CONCLUSION: SGLT2is are effective for both secondary and primary prevention of composite CV outcomes, and secondary prevention of MACE. The upcoming evidence may strengthen the primary prevention benefits of SGLT2is.

Consensus on "Basal insulin in the management of Type 2 Diabetes: Which, When and How?"

INTRODUCTION: Type 2 diabetes mellitus (T2DM) has attained epidemic proportions and continues to increase despite the availability of a number of oral antidiabetic medications and major advances made in insulin delivery since its discovery nearly a hundred years ago. One, amongst many other reasons responsible for the inability to achieve adequate glycaemic control in a substantial proportion of T2DM patients is the delayed initiation and inappropriate intensification of insulin treatment. Appropriate initiation and intensification of insulin is critical for the successful achievement of tight glycaemic control. OBJECTIVE: To provide simple and easily implementable guidelines to primary care physicians on basal insulin initiation and intensification, along with use of basal insulin in special situations (hepatic failure, renal failure and gestational diabetes mellitus). METHODS: Each consensus statement on basal insulin initiation, intensification and use of basal insulin in special situations was evaluated for dosing and titration based on established guidelines, data from approved pack inserts, prescribing information or summary of product characteristics for each insulin type, and published scientific literature. These evaluations were then factored into the national context based not only on the clinical experience of the expert committee representatives' but also based on the common therapeutic practices followed in India to successfully achieve optimal glucose control. RESULTS: Recommendations on initiation and intensification of basal insulin, and its use in special situations, have been developed. The key recommendations are to initiate basal insulin when 2 or 3 oral antidiabetic medications fail to achieve target glycaemic control, or in symptomatic patients with glycated haemoglobin value greater than 9%. Depending upon patient characteristics, any of the four available basal insulins [Neutral protamine Hagedorn (NPH), Glargine (IGlar), Detemir (IDet), Degludec (IDeg)] can be used. However, IDeg has a longer duration of action, comparatively lesser hypoglycaemia (both overall and nocturnal) and more flexibility in administration timing compared to IGlar) and IDet. Inability to maintain glycaemic control should lead to prompt intensification of basal insulin treatment by adding mealtime insulin, consisting of one to three injections of either rapid-acting insulin analog or regular insulin; depending upon patient characteristics, intensification can also be achieved by transition from basal insulin to twice daily premixed insulin analogs/premixed human insulin/insulin co-formulations. IDeg/IDet can be used in all grades of renal and hepatic impairment; and IDet has been approved for use in gestational diabetes mellitus. CONCLUSIONS: We hope that these consensus based recommendations shall be a useful reference tool for health care practitioners and help them in initiating and intensifying insulin therapy in T2DM patients in order to achieve optimal glycaemic control.

The effect of the different waves of COVID-19 pandemic on the outcome of diabetic foot ulcers.

AIMS: COVID-19 pandemic has massively impacted human health. We studied the effect of COVID-19 on outcome of Diabetic foot ulcers (DFUs). OBJECTIVES AND METHODS: We recruited 483 people with DFUs from June 2020 to April 2022 (pandemic) together with a matched group of 226 people with DFU from March 2019 to March 2020 (pre-pandemic). Primary endpoint was outcome of ulcers-healed or amputation (major/minor). It was sub-analysed into 3 waves of COVID-19. Secondary endpoint was healing of individual types of DFUs. Basic anthropometric data included site and type of ulcer (ischemic or neuropathic), duration, presence or absence of infection and Wagner's grading of DFUs was collected for all patients. Diagnosis of peripheral neuropathy was done by monofilament testing and peripheral arterial disease by handheld Doppler and ankle brachial index (ABI). Standardized treatment protocol was provided. All patients were monitored for 6 months. RESULTS: In the pandemic group 323 (66.9%) patients in whom ulcers healed, 70 (14.5%) underwent minor amputation, 11 (2.2%) major amputation, 29 (6%) were lost to follow up, 22 (4.6%) were not healed. Rate of healing of DFU was higher (66.9% vs 53.5%) and rate of amputation was lower (16.7% vs 23.4%) in the pandemic group than in the pre-pandemic group (P = 0.001 and 0.037 respectively). Rate of healing in first, second and third wave was 65.4%, 75.2%, 58.3% respectively (P = 0.001). Neuropathic ulcers though less prevalent (49.8% vs 57.8%) in the first two waves than in the third wave, healing was better (79.3% vs 75.6%) in the first two waves than in the third wave (P = 0.085 and 0.488 respectively). Similarly, amputation rates in ischemic and neuro-ischemic ulcers were greater in the third wave than first two waves (46.7% vs 15.7%, P = 0.049). CONCLUSION: During the COVID-19 pandemic, healing of neuropathic ulcers was better, especially in the first and second waves and travel restriction may have accounted for this. However, worsening of ischemic and neuro-ischemic ulcers was observed with more amputation in these two groups. Conversely, in the third wave withdrawal of lockdown led to worsening of DFUs resulting in less healing and more amputation.

Rifampicin in the Treatment of Refractory Diabetic Foot Ulcer and Diabetic Foot Osteomyelitis-an Observational Study.

INTRODUCTION: Refractory diabetic foot ulcer (rDFU) and osteomyelitis (diabetic foot osteomyelitis [DFO]) are a major problem in people with diabetes. Often resulting from multidrug-resistant polymicrobial infection, these may result in amputation or nonhealing ulcers. In this nonrandomized open-label study, we looked at the outcome of treatment with rifampicin in patients with nonhealing diabetic foot ulcers. MATERIAL AND METHODS: Patients with DFUs (n = 67, n = 55 with DFO) unresponsive to conventional antimicrobial therapy for >3 months (rDFU) were taken as the study group. All patients received rifampicin for a minimum of 3 months (maximum 6 months if DUFs did not heal after 3 months) in addition to standard antibiotics and compared with similar kind of DFUs (n = 68, n = 55 DFO) who formed the control group, treated with conventional antimicrobial therapy. Patients were followed up for 12 months. Healing of DFU at 6 months and amputation were primary endpoints of the study. RESULTS: In total, 43 patients (64.2%) in the rifampicin group healed at 3 months and another 4 patients healed when rifampicin was continued for 6 months (n = 47, 70.1%). In the control group, 11 patients healed at 3 months (16.2%) and 25 patients healed at 6 months (36.8%). In total, 14 patients (20.9%) in the study group and 29 patients (42.6%) in the control group had to undergo minor amputation. Comparison between the rate of healing at 3 and 6 months and minor amputation between the study group and control group showed statistically significant results (P ≤ .00001, <.00001, and .008, respectively). In total, 6 and 8 patients despite healing of the primary ulcer had a subsequent recurrence of ulcer in the rifampicin and control group, respectively. CONCLUSION: Rifampicin used in conjunction with other standard poly-microbial therapy in refractory complex diabetic foot ulcer unresponsive to standard antimicrobial therapy, can significantly improve wound healing as well as decrease the need for amputation in addition to standard of care.

Practical aspects of usage of insulin in India: Descriptive review and key recommendations.

BACKGROUND AND AIMS: Insulin therapy is an integral part of diabetes management. However, reliable and easily accessible information on a number of basic facts concerning insulin therapy, including storage of insulin, managing insulin therapy during travel, nuances of insulin use while driving, and dose adjustments during sick days is lacking. This document aims to make readily available, reliable, and easy to implement information on these essential but relatively less discussed aspects of insulin therapy. METHOD: Literature search was performed using PubMed and Cochrane Library from inception till 1st of July 2019. The relevant topics were reviewed by a panel of 5 specialists and 23 contributing physicians and endocrinologists, who had assembled at Bengaluru, India for the 13th National Insulin Summit. After a thorough review of the literature, and following detailed discussions, the committee arrived at these recommendations. RESULTS: Unopened vials and cartridges of insulin should be stored at 2 °C-8 °C in a refrigerator and protected from direct sunlight. For opened vials and in-use cartridges, manufacturer's instructions must be followed at all times. While traveling by air, dose adjustments are required only when flying across more than five time zones in the east or west directions. Insulin therapy should not be omitted or stopped during an acute illness; rather the doses need careful adjustments based on self-monitoring of blood glucose. CONCLUSION: Recommendations and guidelines, covering many common aspects of insulin therapy are readily available. This consensus document aims to make recommendations for those essential aspects of insulin therapy that are crucial for its success but are relatively less known and less discussed.

Assessing prevalence and predictors of depression in Type 2 Diabetes Mellitus (DM) patients - The DEPDIAB study.

OBJECTIVES: Depression is common in diabetes and has significant impact on health outcomes. Suicidal ideation also forms a part of the spectrum of diabetes and coexistent depression. To assess the predictors of depression as well as its prevalence in Type 2 Diabetes Mellitus (T2DM) patients, we conducted a cross sectional study entitled "DEPression in DIABetes" (DEPDIAB). MATERIAL AND METHODS: A cohort of consecutive 1371 T2DM patients from Eastern India suffering from diabetes greater than 1 year was assessed in a cross- sectional survey in 9 different hospitals and medical polyclinics in Kolkata, India for depression by administering the 9-item PHQ - 9 and Beck depression scales. Socioeconomic status was assessed by the "Revised Kuppuswamy and B G Prasad socio-economic scales for 2016", a validated scoring system for assessing the socioeconomic status of Indian patients. RESULTS: In our study 836 patients (60.9%) were male and 535 (39.02%) were female. 56 patients (4.1%) met the criteria for major depression and 494 patients (36.16%) for minor depression. No sign of depression was found in 816 patients (59.74%). Depression was strongly associated with younger age (18-40 years vs. >60 years) [OR-2.09; 95% CI 1.11-3.96], female sex [OR-1.31; 95% CI 1.11-2.01], low socioeconomic status [OR-2.69; 95% CI 1.34-3.79], poor compliance [OR- 5.05; 95% CI 2.79-8.13], hypoglycemia [OR 1.466; 95% CI 1.076-1.999] and difficulty in managing day-to-day activities [OR- 4.648; 95% CI 3.450-6.262] Suicidal ideation was detected in 201 patients (14.8%). Among patients who had repeated attacks of hypoglycemia (>1 episode per month), 22% experienced suicidal ideation. This was significantly higher than in patients who had not suffered from hypoglycemia (12%) (p < 0.0001). Patients with HbA1C of 7% or lower experienced statistically significantly lesser suicidal ideation than patients with a higher HbA1C (12% vs. 16.8% {p = 0.016}). Suicidal ideation did not correlate withbody mass index (BMI), fasting plasma glucose (FPG) or insulin usage. CONCLUSIONS: We found a high prevalence of depression in T2DM patients in Eastern India. Younger age, female sex, lower socio-economic status, poor compliance, hypoglycemia, and difficulty in managing day to day activities emerged as significant predictors of depression in this study. Recurrent episodes of hypoglycemia were an independent risk factor for suicidal ideation in patients with depression. Depression was not significantly associated with co morbidities associated with T2D and surprisingly insulin usage was not associated with increased depression.

Testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism -an Integrated Diabetes and Endocrine Academy (IDEA) consensus guideline.

BACKGROUND: Though testosterone replacement therapy in men with organic hypogonadism is established, its role in men with type 2 diabetes mellitus (T2DM) and functional hypogonadism is unclear. METHODS: Thirteen experts addressed ten topic-specific questions after an in-depth review of literature, where all relevant issues were critically evaluated. RESULTS: Ten recommendations concerning diagnosis and management of men with T2DM and functional hypogonadism have been put forward. CONCLUSION: Routine measurement of serum testosterone in all, and inappropriate replacement of testosterone in asymptomatic T2DM men with functional hypogonadism and borderline low serum testosterone values, is not recommended.

Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician's perspective.

BACKGROUND AND AIMS: Interest in corticosteroid therapy in COVID-19 has been rekindled after the results from Randomized Evaluation of COVid-19 thERapY (RECOVERY) Trial. However, the World health Organization has not recommended corticosteroid in the treatment of COVID-19. We sought to conduct a systematic review on the role of corticosteroid in the management of patients of COVID-19. METHODS: A systematic electronic search of PubMed, Cochrane and MedRxiv database using specific keywords was made up till June 17, 2020. Full text of all the original articles with supplementary appendix that fulfilled the inclusion criteria were retrieved and a detailed analysis of results were represented. RESULTS: Of the 5 studies (4 retrospective studies and 1 quasi-prospective study) conducted for evaluating the role of corticosteroids, 3 studies have shown benefit, while 2 studies shown no benefit and there was a suggestion of significant harm in critical cases in one sub-study. RECOVERY trial is the only randomized controlled trial that has shown a significant reduction of death by 35% in ventilated patients and by 20% amongst patients on supplemental oxygen therapy with the dexamethasone, although no benefit was observed in mild cases. CONCLUSIONS: While the results from retrospective studies are heterogenous and difficult to infer of a definitive protective benefit with corticosteroids, RECOVERY trial found a significantly better outcome with dexamethasone, mostly in severe cases. Nonetheless, more studies are needed to replicate the outcome shown in RECOVERY trial for a substantial conclusion.

Consensus statement on insulin therapy in chronic kidney disease.

INTRODUCTION: Diabetes mellitus (DM) is one of the leading causes of chronic kidney disease (CKD) which eventually leads to insulin resistance and decreased insulin degradation. In patients with diabetic kidney disease (DKD), the overall insulin requirement declines which necessitates the reassessment for individualization, adjustment and titration of insulin doses depending on the severity of kidney disease. OBJECTIVE: To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens in patients with DKD. METHODS: Each insulin regimen (basal, prandial, premix and basal-bolus) was presented and evaluated for dosing and titration based on data from approved medical literatures on chronic kidney disease. These evaluations were then factored into the national context based on the expert committee representatives' and key opinion leaders' clinical experience and common therapeutic practices followed in India. RESULTS: Recommendations based on dosing and titration of insulins has been developed. Moreover, the consensus group also recommended the strategy for dose estimation of insulin, optimal glycaemic targets and self-monitoring in patients with DKD. CONCLUSION: The consensus based recommendations will be a useful reference tool for health care practitioners to initiate, optimise and intensify insulin therapy in patients with DKD.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Kolkata cohort of the A1chieve study.

BACKGROUND: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. MATERIALS AND METHODS: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Kolkata, India. RESULTS: A total of 576 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 417), insulin detemir (n = 70), insulin aspart (n = 55), basal insulin plus insulin aspart (n = 19) and other insulin combinations (n = 15). At baseline, glycaemic control was poor for both insulin naïve (mean HbA1c: 8.3%) and insulin user (mean HbA1c: 8.6%) groups. After 24 weeks of treatment, both the groups showed improvement in HbA1c (insulin naïve: -1.3%, insulin users: -1.4%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. CONCLUSION: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Physiotherapists' perceptions of their role in the rehabilitation management of individuals with obesity.

PURPOSE: To examine physiotherapists' perceptions of their role in the rehabilitation management of individuals with obesity. METHODS: A Web-based survey was conducted in 2008. Participants were recruited through the Canadian Physiotherapy Association (CPA) via electronic communication and were eligible if they had entry level to practice qualifications and were residents of Canada. The online questionnaire consisted of 61 statements pertaining to potential PT roles, barriers, and learning needs, developed using the framework of CPA's position statement on obesity. Frequencies were computed for all Likert-scale response items on the questionnaire. RESULTS: A total of 851 physiotherapists, representative of CPA membership, participated in the study. There was strong agreement that physiotherapists have a role to play in the management of clients who are obese through exercise interventions (96%), mobility training (97%), and cardiorespiratory programmes for impairments associated with obesity (95%). Respondents were less clear about their role in the assessment of body fat or patients' weight loss. Lack of client motivation was identified as a barrier to treatment. CONCLUSION: Physiotherapists were clear that they see their role as largely focused on exercise and education to treat conditions associated with obesity. These are important components but do not by themselves constitute an overall management plan.Purpose: To examine physiotherapists' perceptions of their role in the rehabilitation management of individuals with obesity. Methods: A Web-based survey was conducted in 2008. Participants were recruited through the Canadian Physiotherapy Association (CPA) via electronic communication and were eligible if they had entry level to practice qualifications and were residents of Canada. The online questionnaire consisted of 61 statements pertaining to potential PT roles, barriers, and learning needs, developed using the framework of CPA's position statement on obesity. Frequencies were computed for all Likert-scale response items on the questionnaire. Results: A total of 851 physiotherapists, representative of CPA membership, participated in the study. There was strong agreement that physiotherapists have a role to play in the management of clients who are obese through exercise interventions (96%), mobility training (97%), and cardiorespiratory programmes for impairments associated with obesity (95%). Respondents were less clear about their role in the assessment of body fat or patients' weight loss. Lack of client motivation was identified as a barrier to treatment. Conclusion: Physiotherapists were clear that they see their role as largely focused on exercise and education to treat conditions associated with obesity. These are important components but do not by themselves constitute an overall management plan.

RÉSUMÉ Objectif : Examiner les perceptions qu'ont les physiothérapeutes de leur rôle dans la gestion de la réadaptation des personnes souffrant d'obésité. Méthode : Un sondage par Internet a été réalisé en 2008. Les participants ont été recrutés par l'intermédiaire de l'Association canadienne de physiothérapie (ACP) par communication électronique. Pour être admissibles, ils devaient posséder les compétences de base nécessaires à la pratique de la physiothérapie et être résidents du Canada. Le questionnaire en ligne qui leur a été soumis comportait 61 affirmations relatives au rôle potentiel des physiothérapeutes, aux obstacles et aux besoins de formation en pratique. Ces affirmations ont été préparées à partir des grandes lignes de l'énoncé de position de l'ACP en matière d'obésité. Les fréquences ont été calculées pour toutes les réponses du questionnaire recueillies à l'aide de l'échelle de Likert. Résultats : Au total, 851 physiothérapeutes représentatifs des membres de l'ACP ont participé à l'étude. Les répondants se sont dits fortement en accord avec le fait que les physiothérapeutes ont un rôle à jouer dans la gestion des clients obèses, par des interventions en matière d'exercices (96 %), par de l'entraînement à la mobilité (97 %) et par des programmes cardiorespiratoires pour faire face aux incapacités associées à l'obésité (95 %). Les répondants n'étaient pas aussi clairs quant à leur rôle dans l'évaluation du gras corporel ou de la perte de poids des patients. La motivation des clients a été citée comme un obstacle au traitement. Conclusion : Les physiothérapeutes perçoivent clairement leur rôle comme celui de professionnels centrés sur l'exercice et l'éducation pour le traitement de problèmes associés à l'obésité. Ces résultats semblent indiquer que leur rôle constitue une composante importante mais incomplète d'un plan de gestion global de l'obésité.