CME INDIA Presentation by Admin.

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Part – [2]

• Diabetes India 2022 is a platform, where clinicians, diabetes care providers, researchers and industries convene with the aim to promote, support and enhance the development of treatments for diabetes.
• The Diabetes India 2022 brings you the food for thought and stimulation for your grey cells.
• Here we present the best takeaways from the 12th World Congress of Diabetes India – Diabetes India 2022

Read Part 1 here:

Dr. Ralph A DeFronzo San Antonio, TX

• The ominous octet of hyperglycemia: decreased insulin secretion, decreased incretin effect, increased lipolysis, increased glucose reabsorption, decreased glucose uptake, neurotransmitter dysfunction, increased hepatic glucose production and increased glucagon secretion.
• The treatment of T2DM

Halting the Progression of Prediabetes to Diabetes: Myth or Reality?

Dr. Adrian Vella Rochester, MN

• Islet cell function and insulin signalling are the primary regulators of glucose metabolism in humans.
• Abnormal glucagon suppression is an early change in the pathogenesis of type 2 diabetes.
• To date, no therapy clearly changes the natural history of prediabetes progression.
• As such if treatment is to be undertaken, there needs to be a careful appraisal of the risk vs. benefits.

New Insights

HFpEF: Role of the Diabetologist in Tackling a Multidisciplinary Problem

Dr. Eberhard Standl, Germany

• The pathophysiology of type 2 diabetes and cardiorenal metabolic syndrome have the same cluster complications such as insulin resistance, dysmetabolism, low-grade inflammation, oxidative stress, etc. These factors are driving the progression of type 2 diabetes and in turn affect the kidney and heart.
• Hence, the role of a diabetologist in this multidisciplinary paradigm starts with an assuring diagnosis of heart failure.
• Assuring that the patient complies with the recommended cardiologic therapy (β-blockers, diuretics, statins and antithrombotic).
• Based on the patient history, diabetologists should address an appropriate cardio-metabolic approach including appropriate glucose-lowering therapy, a suitable exercise regimen, etc.
• Lastly, he/she should co-operate with cardiologists/nephrologists to reduce the risk of CV and renal outcomes

Glucose Variability and Its Implications

Dr. Tsvetalina Tankova, Bulgaria

• Unpredictable fluctuations in blood glucose levels make it difficult to optimize insulin doses and reach desired glycemic targets.
• Glucose variability is a strong predictor of hypoglycemia leading to poor glucose control; increased risk of diabetes burden and poor compliance.
• Glycemic variability seems to have more deleterious effects than sustained hyperglycemia on endothelial function and oxidative stress and thus in the development of diabetic complications.
• HbA1c is the gold standard for the assessment of glycemic control, yet it has a lot of limitations.
• Glucose variability evaluated from CGM data should be considered in the overall clinical representation of glycemic control. Time in range has been shown to be associated with complications in both type 1 and type 2 diabetes.

Glycemic Management in Patients with CKD

Dr. Guillermo Umpierrez, USA

• Overall, 80% of CKD cases are undiagnosed in diabetes patients with 6-time more probability of death by CVD than advance to ESRD and dialysis.
• The clinical diagnosis of diabetic kidney disease in a patient with diabetes is based on the reduced kidney function or presence of albuminuria with diabetic retinopathy and/or type 1 diabetes for more than 10 years.
• However, in the absence of any sign or symptom of the primary cause of kidney damage, most patients usually progress to ESRD.
• Management approaches to diabetes and reducing the progression of CKD is multifactorial such as BP-lowering, treatment of dyslipidemia, RAAS and SNS blockade, glycemic control, SGLT2 inhibitors and other medications. The EMPA-Reg, CANVAS and DECLARE trials showed that empagliflozin, canagliflozin and dapagliflozin were associated with slower progression of kidney disease and clinically proven fewer renal events in comparison to placebo in standard care.

Diabetes Treatment in an Elderly Patient

Dr. Florian Toti, Albania

• Patients have different requirements depending on their diabetes status.
• Many choices exist to individualize treatment.
•  Reinforce healthy lifestyle, treat blood sugar, lipids and BP.
• Avoid using medications to achieve HbA1c < 7.5% in most adults ≥65 years old; moderate control is generally better.
• There is no evidence that using medications to achieve tight glycemic control in most older adults with type 2 diabetes is beneficial.
• Tight control has been consistently shown to produce higher rates of hyperglycemia in older adults.

SGLT2 Inhibitors – Organ Benefits, with Emphasis on CKD and Heart Failure

Dr. Jiten Vora, UK

• SGLT2 inhibitor therapy is recommended for all diabetes patients, irrespective of the subtypes and sometimes for patients without a diabetes diagnosis for organ protection.
• CKD progression is a major risk among diabetes patients, with more than 50% having lost kidney functions to an extent.
• SGLT2 inhibitors produces a protective effect at all stages of renal disease, from prevention of development and progression to nephropathy and ESRD, as well as renal death. From the perspective of CV failure, it improves CV outcomes (composite primary endpoint of CV death or HHF) in patients with or without pre-existing HFrEF, diabetes, CKD and different types of background HFrEF medical therapy.
• Several studies have also proven the positive effect of SGLT2 inhibitors in HFrEF, predominantly in cases of HHF such as CANVAS program, VERTIS program, DECLARE-TIMI 58, etc

Responders and Nonresponders to SGLT2 Inhibitors and GLP-1 Receptor Agonists: Possible Mechanisms and Opportunities

Dr. Leszek Czupryniak, Poland

• Aspects of the mechanisms of GLP-1RA-induced weight loss: – Weight loss induced by caloric restrictions leads to a compensatory reduction in energy expenditure; Weight loss induced by semaglutide only transiently did so: energy expenditure returned to baseline levels within a week.
• The possible mechanism for (non)-responding to GLP1RAs are GLP-1 receptor genetic polymorphism, various degrees of receptor response to GLP-1, adaptations in basal metabolic rate, varied CND response to hypothalamus stimulation, early vs. late responders, duration of the history of obesity and increased vs. decreased patient’s motivation to lifestyle modification.
• The possible mechanism for (non)-responders to SGLT2 inhibitors is compensatory hyperphagia-varied degree, adaptations in basal metabolic rate and complex hormonal changes due to calorie loss with urine.
• Clinical questions that remain unanswered are: Successful identification of early and late and nonresponders – clinical criteria; Giving up medications in non (late?) responders vs. intensifying therapy; Combination therapy – in whom, in what sequence

Effects of Lipid-lowering Drugs and Types of Statins on SARS-CoV-2 Infection and Severity in Diabetes

Dr. Michel P. Hermans, UK

• Since the beginning of the COVID-19 pandemic, diabetes is considered a risk factor for severe COVID-19. There is no evidence that having diabetes increases the risk of contracting COVID-19.
• The two major risk factors for T2DM onset and severe COVID-19 are the same, i.e., age and obesity.
• Factors predisposing to infection and/or severe disease are subject to generalizations that do not take into account the type of diabetes. ‹ A study was conducted to document the phenotype before infection with SARS-CoV-2 and with severe COVID-19 – In a T2DMT1DM cohort; In T2DM and T1DM subgroups.
• The conclusions of the study were: Infected (T2DM + T1DM) patients less often on statins; Infected T2DM less often on statins (-10%) – [More often on atorvastatin (+39%), Less often on rosuvastatin (-24%)]; No difference in statins use between infected and noninfected T1DM – Nonsignificant higher use of atorvastatin among infected T1DM; Similar % of severe COVID-19 on statins compared to nonsevere – Same SED of statin in severe vs. nonsevere, Nondifferent % of HIS in severe vs. nonsevere; Severe COVID-19 >2 times more R/atorvastatin (+238%); Nonsevere forms >4 times more R/rosuvastatin (+434%); Ezetimibe ± statins much lower (-57%) in severe COVID-19, as was the combination of [any statin + ezetimibe] (-69%).

Multidisciplinary Management of Diabetic Foot Ulcers: Can We Do it Better?

Dr. Z. G. Abbas, Tanzania

• There is an urgent need to reassess care pathways pertaining to diabetic foot ulcer (DFU) management in our health systems, as we sense the overall gravity of this diagnosis is underestimated.
• The concomitant lack of prevention, insufficient early detection and often inadequate management of ulcers often lead to eventually high morbidity and mortality. ‹ The multidisciplinary diabetic foot clinic has proven to be a unique forum to provide urgent treatment of infection and ischemia with rapid access to laboratory, radiological and inpatient facilities.
• The multidisciplinary team especially those able to address glycemic control, local wound management, vascular disease and infection are associated with a reduction in the risk of major amputation for patients with severe diabetic foot.
• One-step, MDT-led diabetic foot clinic benefits patients and improves outcomes related to the avoidance of hospital admissions, limb salvage procedures and minor amputations, although, we recognize that time and education are needed to see its full effects

Latent Autoimmune Diabetes in Adults

Dr. Sanjay Reddy, Bengaluru

• Latent autoimmune diabetes in adults (LADA), dubbed type 1.5D may account for 2% to 12% of all cases of diabetes in the adult population.
• LADA is a form of diabetes mellitus that has characteristic manifestations similar to both T2D and T1D. Early diagnosis is paramount to inhibiting appropriate treatment and preventing complications.
• New insight into the pathophysiology of LADA explained the slow progression of β-cell destruction.
• Insulin, DPP-4 inhibitors alone or in combination with thiazolidinediones, and GLP-1 receptor inhibitors have shown promising results in controlling glycemic levels and preserving β-cell functions.

Dr. Kamlakar Tripathy, Varanasi

Early Combination Therapy for the Treatment of T2DM

Prevention is the best

Update on Diabetes Prevention

Dr. Anil Kumar Virmani, Jamshedpur, Jharkhand

• Awareness and education of all (right from schools) are very important. Strategies to screen for prediabetes and assessment of individual risk factors are the need of the hour.
• Prediabetes needs to be further classified for risk stratification – Not all patients behave similarly.
• All patients with prediabetes should be counseled for intensive lifestyle modification.
• Clustering of prediabetes is a novel and emerging concept.
• Recognizing the heterogeneity of treatment effects, metformin therapy should also be limited to individuals who are at the highest risk and most likely to benefit, including those who are younger, more obese, more hyperglycemic or who have histories of GDM and cluster 3 and 5.
• Looking beyond guidelines – Pioglitazone and SGLT2 inhibitors, appear to be of immense benefit in clusters 3, 5 and 6.

Promises and Pitfalls of Remission of Diabetes

Dr. Sujoy Majumdar, Kolkata

• The term used to describe a sustained metabolic improvement in T2DM to nearly normal levels should be remission of diabetes and not a reversal of diabetes mellitus.
• Remission should be defined as a return of HbA1c to 6.5% that occurs spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering pharmacotherapy.
• When HbA1c is determined to be an unreliable marker of chronic glycemic control, FPG < 126 mg/dL or eA1c < 6.5% calculated from CGM values can be used as alternate criteria.
• Testing of HbA1c to document a remission should be performed just prior to an intervention and no sooner than 3 months after initiation of the intervention and withdrawal of any glucose-lowering pharmacotherapy.
• Subsequent testing to determine long-term maintenance of remission should be done at least yearly thereafter, together with the testing routinely recommended for potential complications of diabetes. Reversal of diabetes remains a distant goal to date.

Point of View

Is There a Current Place for Sulfonylureas in Diabetes Management?

Dr. Anuj Maheshwari, Lucknow, Uttar Pradesh

• The availability of new drug classes has sparked a debate regarding the utility and viability of SUs as a therapeutic option with views on CV risks and hypoglycemia. However, this may hold true for older SUs due to their non-selective mechanisms of action.
• Sulfonylurea has reigned over the other antidiabetic agents in diabetes management for over 40 years. The development of modern SUs that do not block ischemic preconditioning has rendered the University Group Diabetes Program (UGDP) controversy moot and preserved a place for SUs in the treatment of type 2 diabetes. Modern SUs are proven to be effective, safe and well-tolerated in various clinical situations. Sulfonylurea, when compared to the other oral antidiabetic agents (OADs) has the highest efficacy in reducing HbA1c levels by up to 2%, moderate risk of hypoglycemia, neutral CV event and a cost-effect therapy.
• Sulfonylureas are also reported as the most cost-effective therapy compared to other OADs. There have been several key studies advocating the superiority of SU, namely, the UKPDS trial which reported that intensive glucose therapy with the SU has reduced the risk of microvascular complications
•  In a 10-year follow-up study of the trial, it was determined that SU maintained a risk reduction in microvascular, macrovascular and myocardial infarctions up to 9%. Similarly, the ADVANCE trial and ADVANCE-ON echoed the same results with the added benefit of renal outcomes. The trial showed that intensive glucose control strategically reduced HbA1c by 6.5% thereby reducing the risk of renal failure and nephropathy by 11% and 21%, respectively.
• TOSCA.IT and CAROLINA trial established the status of SU as an OAD with a safe CV profile with similar risk reduction in 3P-Mace and 3P-Mace with hospitalization.
• Meanwhile, CAROLINA study reassured that the use of SU leads to weight gain in the initial therapy, yet it is stabilized over the long-term, especially with glimepiride. Also, the use of SU with metformin was reported to have negated the weight gain and hypoglycemia.
• In cases of elderly patients, people in Ramadan or patients diagnosed with CKD, gliclazide was a choice for reducing the risk of secondary failure and Hb1Ac. Hence, it can be confirmed that SU is an effective second-line agent for glycemic control for type 2 diabetes. The renaissance of SUs therapy might ensure that it remains the drug of choice for uncontrolled diabetes in the future with enough room for flexibility.

Timely Intervention in T2DM: Focus on SGLT2-DPP-4 Inhibitor Combinations

Dr. A. G. Unnikrishnan, Pune

• The sequential treatment approach is often compounded by substantial clinical inertia to timely treatment intensification. Substantial clinical inertia exists at each sequential intensification step.
• At HbA1c 8.0% to 8.5%, HbA1c-lowering is slightly greater with DPP-4 inhibitors than with SGLT2 inhibitors as an add-on to metformin.
• SGLT2 inhibitors are associated with larger HbA1c levels.
• DPP-4 inhibitors moderate the risk of genitourinary tract infections associated with SGLT2 inhibitors.
• In cases of HbA1c ≥8.0%, dual DPP-4 inhibitors-SGLT2 inhibitors add-on therapy to metformin should be considered to help more patients achieve glycemic targets.
• Real-world evidence with empagliflozin and linagliptin FDC conducted across India involving 1,232 T2D patients showed a significant reduction in HbA1c, FPG, PPG, weight and BP.

Mechanism of β-cell Dysfunction in T2DM

Dr. Om Lakhani, Ahmedabad

• Over 50% of β-cell function is lost at the time of diagnosis along with a 4-5% reduction every year in T2D patients.
• Beta-cell impairment is the key to the pathogenesis of T2D.
• In comparison to the insulin resistance in a prediabetic patient, diabetic patients have both insulin resistance and β-cell dysfunction as insulin secretion is a cumulative factor of β-cell mass and its function.
• Preservation of β-cell is the key to preventing progression from prediabetes to T2D and further disease progression in T2D patients itself.

What Future Treatments are on the Horizon for NAFLD?

Dr. Shalini Jaggi, New Delhi

• One in five individuals globally are estimated to have nonalcoholic fatty liver disease (NAFLD). Its prevalence is strongly associated with obesity and metabolic disorders; however, evidence is mounting among nonobese individuals. ‹ Whilst bland steatosis itself is not harmful, it lays the foundation for the development of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma.
• The complex and heterogeneous nature of NAFLD challenges the quest to find the holy grail of treatments.
• So far treatments are generally aimed at directly ameliorating either one of the hallmark characteristics driving NAFLD (steatosis, inflammation and fibrosis) or the gut microbiome.
• The NAFLD treatment landscape is rapidly evolving as a consequence of our growing understanding of its underpinning mechanisms. Treatments aimed at ameliorating not one, but multiple, features of the condition hold great promise. Several treatments have been tested in clinical trials, and whilst some promising results have been obtained, most have failed to deliver the desired outcome.
• Increasing appreciation of the heterogeneity of NAFLD will enable us to develop more personalized therapies. Whilst the holy grail has not yet been found; step by step, its quest is ongoing and getting closer to the discovery of successful NAFLD treatments.

Are We Missing Evidence-based Practice in Diabetes?

Dr. Benny Negalur, Thane, Maharashtra

• If we all agree on best practices based on data and research – we can reduce unnecessary care, save money and push people into pathways to yield better results.
• Scientific discovery in recent years has led to important advances in our understanding of the mechanisms that may underlie type 2 diabetes.
• Interventions to increase exercise, reduce weight and control elevated glycemia, BP, and cholesterol levels demonstrated a significant decrease in morbidity and mortality. Many barriers to the adoption of evidence into clinical care at the community level exist. Diabetes translational issues are diverse and complicated. No single best practice is appropriate for all patients and practitioners. Tailoring to patients and customizing to settings is necessary.
• Real-world translation requires flexibility to deal with pragmatic issues such as provider time constraints, reimbursement and system problems.

Beta-cell Preservation: Myth or Fact?

Dr. Vijay Negalur Thane, Maharashtra

• Prolonged hyperglycemia leads to oxidative stress, endoplasmic reticulum (ER) stress, hypoxic stress and cytokine induction leading to β-cell compensation, stress and later failure and de-differentiation.
• Beta-cell identity is fragile, but islet identity is stable: islet cells share chromatin structure and methylome. Other than hormone genes, they represent flexibility and plasticity states rather than stable subtypes.
• FoxO1 plays an important role in the de-differentiation and re-differentiation of β cells.
• Reprogramming of other cell types to β cells is a possibility and can be a potential treatment option for diabetes in the future. Glucagon-like peptide 1 (GLP-1), SGLT2 inhibitors, thiazolidinediones, metformin and intensive insulin therapy offer β-cell protection and preservation.

Effect of Remogliflozin on Glycemic Variability:

Prof. (Dr.) Jayant Kumar Panda, Cuttack

“REMIT-GV Trial”

• In monitoring, glycemic variability is proven as a very accurate measure in accessing glycemic control.
• Remogliflozin is the latest SGLT2 inhibitor with a very attractive profile.
• REMIT-GV trial shows round the clock good glycemic control with remogliflozin.
• We can use this molecule for the overall benefit of our patients including cardiac and renal outcomes.

Insulin

Breaking Barriers of Insulin Initiation in Tune with Indian Patient Needs

Dr. Krishna Seshadri, Chennai

Relevance of Remix Insulin in Indian Practice

Dr. Rakesh Sahay, Hyderabad

• A significant contribution from PPG even at higher HbA1c in the Indian population as compared to Caucasians.
• Premix insulins are simple to start with a single injection with effective HbA1c control targeting both PPG and FPG.
• Patients uncontrolled on 2 or more OADs with flexible lifestyles can be started on premix insulin and the dose can be titrated on a weekly basis.
• Premix insulin provides convenience and simplicity at initiation, titration and intensification. Premix insulin provides both convenience and efficacy to the patient and contributes a long way to achieving the patient’s glycemic target.

Gen 2.0 Basal Insulin: Leveraging Time-in-Range to Improve Patient Outcomes

Dr. Jothydev Kesavadev, Thiruvananthapuram

• Time-in-range (TIR) and GV have emerged integral in diabetes management.
• In range is the first randomized clinical trial comparing TIR and GV of the two second-generation basal insulin, in adults with T1DM.
• The trial met the primary endpoint of noninferiority of U300 glargine vs. U100 degludec with respect to TIR. The GV, hypoglycemic episodes and safety were also comparable.
• We need to adopt better, newer therapies so as to prevent microvascular complications in diabetes

Burning Topics

Androgen Deficiency in Adult Males and Diabetes

Dr. Sambit Das, Bhubaneswar

• Hypogonadism is common amongst elderly males and even higher prevalence when associated with obesity, T2DM as comorbidities.
• Optimal management should focus on symptom improvement, alleviating signs and maintaining normal testosterone levels.
• Overall bio-psychosexual health should be given importance.
• A systematic approach to history taking and individualization of management is of paramount significance.

Diabetes and Bone Health

Dr. Ganapathi Bantwal, Bengaluru

• In T1DM, a lack of osteoanabolic pancreatic hormones, including insulin, prevents the accrual of an adequate peak bone mass.
• In T2DM, frequent falls combined with impaired bone quality cause fragility fractures even when bone mass remains normal.
• After repletion of calcium and vitamin D, most osteoporosis drugs can be used, but associated comorbidities should be considered and glitazones should be avoided in postmenopausal women.

Getting Basics Right in Improving Outcomes for People with Diabetes

Dr. Sunil Kota Berhampur, Odisha

• Vascular complications are common in patients with type 1 and 2 diabetes.
• Annual screening for retinopathy with retinal eye exams, for nephropathy with urine albumin-to-creatinine ratio and neuropathy with physical examination allows early identification and appropriate interventions; these may delay progression or intensity.
• Metabolic control of glucose levels. Blood pressure with a combination of lifestyle interventions and pharmacological therapy (including insulin) can prevent the onset or delay the progression of each of these diabetes-related microvascular and neuropathic complications. We need to be alert for emerging risk factors.

CKD Equivalent to High CV Risk: A Single Disease Spectrum

Dr. Arvind Gupta, Jaipur

• Chronic kidney disease (CKD) is characterized by a progressive decline in glomerular filtration rate (GFR) over many years resulting in permanent kidney failure requiring dialysis or transplantation
• The Kidney Disease Improving Global Outcomes (KDIGO) statement has defined CKD as either kidney damage or reduced estimated GFR to <60 mL/min/1.73 m² sustained for ≥3 months

• Patients with CKD carry a larger burden of comorbid cardiovascular conditions than do those without CKD, and have a significant additional burden of congestive heart failure (CHF), myocardial infarction (MI), and stroke.

Hypoglycaemia: A Major Challenge in T1DM

Dr. Pratap P. Jethwani, Rajkot

Dr. Abdul Hamid Zargar, Srinagar

Dr. L. Sreenivasa Murthy, Bangalore

Dr. Yagnik C. S, Pune: The Unique Random Thoughts

India specific Point of care test (POCT)

Dr. Vinay Dhandhania, Ranchi

CME INDIA Tail Piece

The creator cannot be forgotten!

Dr. Shaukat Sadikot

• A true icon of the diabetes world, Dr. Sadikot was actively involved with the cause of diabetes and associated metabolic disorders in India, regionally and internationally for over 30 years.
• In his capacity as Founding President of Diabetes India, he launched many projects for the enhancement of healthcare professional education in the field of diabetes.
• During his tenure as IDF President, Dr. Sadikot oversaw the launch of the IDF School of Diabetes, the Federation’s flagship programme in support of online health
• professional education, the publication of the 7th Edition of the IDF Diabetes Atlas and the successful IDF Congress 2017 in Abu Dhabi, UAE.

Day 1 started with the inauguration, Sir and you would have been happy to see the turnout there for the “online” invoking the Almighty and lamp lighting – (very environmentally friendly sir). The dignitaries were highly accomplished and inspiring as each of them remembered your vision, your morals and also the continued legacy of the projects and need for scientific knowledge update in our field. The President of Diabetes India, Dr. Aravind Sosale sir, the Secretariat, Dr. Banshi Saboo sir, the Organizing Chairman, Dr. Sanjay Reddy, Organizing Secretary, Dr. Manoj Chawla and the Scientific chair, Dr. Jothydev Kesavadev sir, were so warm and invited delegates not only from India but across the world to attend this congress and benefit from the excellent show planned for them. Prof. Dr. Shashank R Joshi sir, our chief Guest did not fail to be there for you, even while boarding a flight to get to Goa and spoke highly of your motives. You’ll be thrilled to know the statistics on the Journal, especially as shared by Prof. Dr. Anoop Misra sir. It made us all immensely proud to realise that with his single minded dedication and focus, the quality of review and articles in our journal have up-scaled. Hats off!!! – Dr. Purvi Chawla, Mumbai.





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