Bone mineral density (BMD) serves as a key diagnostic tool for assessing fracture risk and managing osteoporosis. However, its interpretation in individuals with diabetes poses unique challenges. Type 1 diabetes (T1DM) is often linked to reduced BMD and a heightened fracture risk, influenced by poor bone quality and microarchitectural deficiencies. In contrast, Type 2 diabetes (T2DM) typically shows normal or even elevated BMD, yet patients remain at an increased risk of fractures due to altered bone strength and quality.

Standard BMD assessments may underestimate fracture risk in diabetes, necessitating complementary approaches like the trabecular bone score (TBS) or modifications to fracture risk prediction models. Additionally, the effects of diabetes treatments on bone health warrant careful consideration, with some therapies potentially influencing BMD and fracture outcomes.

Understanding the complex interplay between diabetes and skeletal health is crucial for accurate diagnosis and effective management. Tailored strategies that account for these unique considerations can improve fracture prevention and overall skeletal outcomes in patients with diabetes.

With age and menopause, there are significant differential changes in skeletal mass, lean mass, and fat mass. Sarcopenia, characterized by a decline in skeletal mass and function, whether physiologically or secondary to pathological states, not only predisposes individuals to osteoporosis and fragility fractures but also to several metabolic disorders. The dual-energy X-ray absorptiometry (DXA) body composition analysis provides a quantitative measurement of skeletal mass. Total body lean mass (LM) and appendicular lean mass (ALM) are the main parameters obtained through DXA to assess lean mass.

The skeletal mass index (SMI) and the appendicular skeletal mass index (ASMI), corrected for the allometric differences in body size, provide an accurate estimate of muscle mass independent of body size. Skeletal mass assessment by DXA is the recommended diagnostic test for quantification of muscle mass in the evaluation of sarcopenia. By providing an objective understanding of muscle mass, these muscle indices promise diagnostic and prognostic implications in various pathological states.

Previous studies have demonstrated that in certain medical conditions, fragility fractures tend to occur even at bone mineral density (BMD) levels that are in the non-osteoporotic range. This warrants the assessment of other factors beyond BMD that might confer an increased propensity to fracture. Trabecular bone score assesses the microarchitecture of the lumbar spine and may find utility in diabetes. Vertebral fracture assessment gives information about prevalent vertebral fractures. Hip structural analysis (HSA) is also performed by the DXA scanner and evaluates different variables pertaining to proximal hip geometry such as the cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), and the buckling ratio (BR) at each of three sites namely the narrow neck (NN), the inter-trochanteric region (IT) and the femoral shaft (FS).

Although current consensus guidelines do not advocate the routine assessment of HSA in the evaluation of bone health, it may confer additional benefit to conventional BMD assessment in conditions such as type 2 diabetes mellitus and in cases where fragility fractures are encountered even in the presence of non-osteoporotic BMD. Bone Strain Index (BSI) is another novel DXA-based tool that was recently developed to further assess bone health. This has been based on a finite element analysis of grey scale images of density distribution of the femoral and lumbar spine scans obtained from a DXA scanner. Preliminary studies assessing the utility of Bone Strain Index in predicting fragility fractures have been promising.

This review will focus on the technical details and utility of the HSA and BSI beyond conventional BMD assessment.

There is an increasing prevalence of obesity and lifestyle disorders across the globe. There is a deeper understanding of the different obesity phenotypes coupled with a rapid outburst of highly effective anti-obesity medications. These factors necessitate greater use of body composition analysis in clinical practice. It provides an insight into the body's nutritional status and functional capacity.

For many years, a two-compartment model has been used wherein the entire body is categorized as fat mass and fat-free mass. Fat-free mass comprises water, organs, bone, and muscle mass. The clinical utilization of body composition assessment helps to diagnose normal weight obesity, visceral adiposity, sarcopenia, and disorders like lipodystrophy.

Many techniques are used to assess body composition, ranging from simple indirect measures such as anthropometric indices to sophisticated direct volumetric methods. All the methods involve some assumption regarding the density of body tissues, concentrations of water, and the interrelationship of various body components such as muscle, fat, and bone in healthy individuals.

Factors such as feasibility, cost, technical skill, level of accuracy, participant burden, radiation exposure, assessment time, validation in a given population, and availability of reference data have to be considered while choosing a suitable method. This review article describes the different body composition methods, their utility in clinical practice, and the associated fallacies.

References:
Kapoor N. et al. Understanding body composition analysis in obesity management. Journal of the Association of Physicians of India 2025.

The diabetes prevalence in India stands at 9.3% according to 2018 and is rising at a fast rate. A well-functioning pancreas preserves glucose homeostasis and prevents diabetes. Glucose homeostasis is maintained by secretion of insulin from pancreatic beta cells that lowers blood glucose after a meal. Although mechanisms behind secretion of insulin have been studied for years a clear subcellular view on secretion had remained elusive. My talk will focus on molecular drivers that show subcellular changes in diabetes in both the young and the older people. We have been pursuing high-resolution microscopy approaches to understand the islet environment to understand the functional changes brought about by these molecular drivers. This can provide novel insights into islet dysfunction during diabetes at multiple levels such as single cells of islet, whole islet, islet cell interactions and pancreas functioning.

Total pancreatectomy with islet auto transplantation (TP-IAT) is a procedure considered in select adults and children with chronic pancreatitis where medical, endoscopic or surgical therapies are unsuitable and in whom debilitating pain is an indication for total pancreatectomy. In these patients, irreversible damage to the pancreas leads to progression to exocrine and eventual endocrine insufficiency. Genetic causes are associated with a long-term risk of malignancy.

Following pancreatectomy, islets are extracted from the removed pancreas and auto transplanted back into the patient (usually into the liver) to significantly reduce the risk of complete insulin deficiency and diabetes post pancreatectomy.

Fibrocalculous Pancreatic Diabetes (FCPD) is a form of secondary diabetes that causes significant exocrine and endocrine pancreatic dysfunction and is unique to tropical populations, including India. While its clinical course is distinguished by recurrent abdominal pain, steatorrhea, brittle diabetes with reduced occurrences of ketosis/ketoacidosis, and an enhanced risk of pancreatic adenocarcinomas, precise metabolic characterization remains challenging. Though beta-cell destruction leading to insulin deficiency remains the key component, other metabolic regulators like hepatic and peripheral insulin resistance, and the role of glucagon, have increasingly become important to understand disease progression.

Further, exploration of the endocrine-exocrine crosstalk and the contribution of the incretin axes to the endocrine milieu of FCPD can provide novel mechanistic insights. State-of-the-art dynamic studies conducted at CMC Vellore in recent years have provided a unique, integrated viewpoint of the key metabolic alterations in FCPD, while suggesting a possible role of gut-derived glucagon as a major driver of glycaemic fluctuations.

Further research into these less explored facets of FCPD, as well as elucidating the impact of genetic mutations on the metabolic fluxes, could prove to be crucial in the proper understanding of this enigmatic form of secondary diabetes.

Exogenous insulin administration is currently the only treatment available for patients with type-1 diabetes, but it is not a cure. Long-term complications associated with the disease may be preventable with a treatment strategy that can provide better blood glucose control. The transplantation of isolated human islets provides the potential to restore endogenous insulin production and reestablish normoglycemia. Clinical islet transplantation can be considered one of the safest and least invasive transplant procedures.

Significant progress has been made in the outcomes of clinical islet cell transplantation, reflecting improvements in non-diabetogenic immunosuppression and preparation of sufficient quantities of highly viable islets for transplantation. Islet transplantation represents a potential cure for patients with type-1 diabetes.

The exocrine pancreas produces digestive enzymes essential for nutrient breakdown. Pancreatic exocrine insufficiency (PEI) arises from reduced acinar cell mass, flow obstruction, low duodenal pH, or insufficient pancreatic stimulation. PEI adversely affects nutritional status and complicates diabetes management. Diagnosing PEI is challenging due to the limitations of available tests. Fecal elastase-1 is the most commonly used test for PEI.

Pancreatic enzyme replacement therapy (PERT) remains the cornerstone of PEI management. An ideal enzyme preparation should mix well with meals, resist gastric inactivation, empty with nutrients, and release enzymes in the duodenum. Global societies differ on the ideal dose of PERT for an individual. It is generally accepted to administer 500 units of lipase/kg with major meals and half the dose with snacks. PERT is costly, and the cost of medication poses a significant challenge in the management of PEI.

This presentation will discuss how differences in pancreatic islet cell function or mass may contribute to the heterogeneity of diabetes and be involved in the pathogenesis of all forms of diabetes. This presentation will discuss the multi-modal analysis of gene and protein expression and islet cell function in type 1 and type 2 diabetes using human pancreatic tissue and islets procured during organ donation. Some of these studies are part of the NIH-funded Human Pancreas Analysis Program (HPAP).

This presentation will also discuss pancreatic size by MRI in individuals with type 1 diabetes and how pancreatic endocrine and exocrine compartments communicate.

Neonatal Diabetes Mellitus (NDM) represents a group of rare monogenic disorders that present with hyperglycemia and insulin deficiency, typically in the first 6 months. Almost all cases of diabetes before 6 months of age, and a proportion of those between 6-12 months, are of monogenic etiology.

Pointers to a diagnosis of NDM according to age group are summarized below: 

NDM was first described in 1995. Mutations in KCNJ11 and ABCC8 genes were identified as implicated in etiology in the years 2004 and 2006. The entity and its recognition as distinct from Type 1 diabetes, and in some cases amenable to treatment with oral sulfonylureas, is just about two decades old. At present, mutations in >30 different genes that regulate the development or function of the pancreas or insulin action have been identified as causative for NDM.

In data from a large international database, mutations were identified in approximately 80% of children with neonatal diabetes. Activating mutations in KCNJ11 and ABCC8 genes accounted for about 40% in non-consanguineous cohorts, while in consanguineous cohorts, these accounted for about 12%, with mutations in the EIF2AK3 gene being the most common.

NDM can be transient or permanent. Transient NDM (TNDM) typically presents within the first few days of life and resolves within the first few weeks to months. However, it may recur with features mimicking T2DM in adolescence or during pregnancy. In >70% of cases, TNDM is caused by overexpression of the 6q24 imprinted chromosomal region. Management is with insulin.

Roughly half the permanent NDM (PNDM) cases are caused by defects in the ATP-sensitive K channel in the pancreatic beta cells channel and are responsive to oral sulfonylureas, while the rest are managed with insulin only. Several syndromic forms of NDM such as Wolcott Rallison syndrome, Rogers, and Wolfram syndrome are known and should be suspected in infants with syndromic features.

Early molecular diagnosis has an important role in identifying babies likely to respond to oral sulfonylureas, preempting the development of syndromic features such as hepatic or renal tubular dysfunction, and predicting the risk and performing antenatal diagnosis in subsequent pregnancies.

Lipodystrophy syndromes share a common clinical and body fat compartmentalization phenotype with metabolic syndrome (MetS) in South Asians. In monogenic congenital lipodystrophies, germline mutations in any one of a group of genes enriching molecular pathways of adipocyte development (adipogenesis) and fat storage result in partial or complete adipose tissue deficiency, ectopic fat deposition, and severe metabolic dysfunction. Their underlying genetic mutations and the consequent pathophysiology are well deciphered.

On the contrary, Type 2 Diabetes (T2D) and MetS are complex genetic traits, and their pathophysiology is still partly understood. However, they share a common molecular mechanism with congenital lipodystrophies, which includes:

• 1) In South Asians, the “lipodystrophy partial polygenic score” identified by GWAS shows a strong association with T2D and GDM.
• 2) Transcriptomic analysis of diabetics reveals differentially expressed genes converging on adipogenesis and lipid metabolism.
• 3) The majority of lipodystrophy genes are downregulated in T2D and MetS individuals, and their degree of expression shows association with T2D, MetS, and HOMA-IR.
• 4) Individualization of MetS individuals is possible based on the expression of 10-12 lipodystrophy genes.

These findings suggest that T2D and MetS can be considered as a group of “functional lipodystrophy syndromes” in South Asians.

There exists significant heterogeneity of diabetes across the world’s diverse population, and our current understanding of the pathophysiology of diabetes and the contributions of multiple metabolic pathways, especially for Type 2 diabetes, are not captured in the current definition of diabetes. The rationale for the focus on heterogeneity of diabetes to improve classification stems from the fact that the field is evolving toward more precise diagnostic, preventive, and management strategies for diabetes and its complications (i.e., precision medicine).

Today’s evidence, however, suggests that multiple etiologic and pathogenic processes lead to both type 1 and type 2 diabetes, reflecting significant heterogeneity in factors associated with initiation, progression, and clinical presentation of each disorder of glucose homeostasis. In addition, the current classification fails to recognize what is currently defined as “atypical” diabetes.

Heterogeneity of diabetes continues through the life-course of an individual, with modification of prognosis risk (e.g., diabetic complications) altered by genetics, life experience, comorbidities, and therapy. Understanding the sources of heterogeneity in diabetes will likely improve diagnosis, prevention, treatment, and prediction of complications in both the medical and public health settings. The presentation will inform on data to date that will help inform progress in understanding the heterogeneity of diabetes and will suggest a proposed roadmap for future research in type 2 diabetes heterogeneity.

With advancements in sequencing technology, we have established targeted next-generation sequencing (NGS) panels for Maturity-Onset Diabetes of the Young (MODY) and monogenic diabetes (30 genes) as well as a comprehensive Young Onset Diabetes (YODI) panel covering 62 genes for clinical diagnostics. Screening 709 samples for MODY/monogenic diabetes and 194 for the extended YODI panel, we identified variants (Pathogenic/Likely Pathogenic/Variants of Uncertain Significance [VUS]) in 14 MODY genes, with a positive predictive value (PPV) >50 observed in 26.6% of MODY cases and 25.85% for PPV <50.

YODI panel screening revealed 21% variant positivity in patients with PPV >50 and 8.84% in PPV <50, underscoring the utility of extended panels for patients with higher PPV. Syndromic diabetes screening uncovered a novel WFS1 founder mutation and heterozygous variants in young-onset diabetes, supporting WFS1 inclusion in first-tier screening. Additionally, we report novel variants in LRBA, TRMT10A, IL2RA, APPL1, and PTF1A, marking their first documented implications in monogenic diabetes in India.

Monogenic diabetes refers to single gene defects causing diabetes and is sub-classified into Maturity Onset Diabetes of the Young (MODY), which presents in youth and adults by 30 years of age, and Neonatal Diabetes Mellitus (NDM), which presents before 6-12 months of age. Of all the monogenic diabetes genes, pancreatic β-cell genes such as Hepatocyte Nuclear Factor 1α (HNF1A), Hepatocyte Nuclear Factor 4α (HNF4A), ATP-Binding Cassette, sub-family C, member 8 (ABCC8), and Potassium channel, inwardly rectifying subfamily J member 11 (KCNJ11) are the most crucial. Missense variations in these genes cause MODY and NDM.

We have previously identified a number of missense variants in these genes, of which 60% are of unknown functional consequences and are therefore clinically unactionable. In order to understand if the variations have clinical impact, a number of bioinformatics analyses are being carried out. These analyses help in predicting the nature of the variants, but the validation of these predictions comes from functional characterization through experimental pipelines. In my talk, I will be presenting some of the results we have obtained through functional characterization of the variants.

Having devoted many years of preparation, execution, and analysis to your research study, you naturally want to share your findings in the most impactful way. How do you convince an editor at a “high-impact” journal to publish your paper?

In this session, Zoë Mullan, Editor-in-Chief of The Lancet Global Health, will share insights into how such editors make decisions about papers, the key elements they are looking for, and some other tips for success. There will be plenty of time for questions on any aspect of the academic publishing process in this interactive presentation.

People with type 1 diabetes mellitus on insulin face various challenges daily to keep their blood glucose levels in the desirable target range. Traditional insulin delivery methods include basal-bolus insulin or continuous subcutaneous insulin infusions. Traditional glucose monitoring uses self-monitored or continuous glucose monitoring systems (CGMS). The insulin doses are adjusted manually based on glucose monitoring, carbohydrate counting, and subsequent meal-related insulin dosing, as well as modification of diet and insulin to adjust for variable lifestyle habits like exercise. These factors make them prone to high glucose variability, hypoglycemic episodes, the need for frequent glucose monitoring, and calculation of insulin doses, diabetic distress, and poor quality of life for both the individual and caregivers. Despite these challenges, less than 25% of patients in various studies achieve a target HbA1c < 7%.

By integrating the blood glucose data from the continuous glucose monitoring system and using an algorithm to decide insulin delivery with an insulin pump, these automated insulin delivery systems (AID) have revolutionized the management of type 1 diabetes.

Insulin pumps, combined with continuous glucose monitoring (CGM), provide an integrated system to maintain tight glycemic control in a safe and uninterrupted fashion, while minimizing hypoglycemic events. Recent advances have allowed for various features in insulin pumps, such as low glucose suspend, predictive low glucose suspend, hybrid closed-loop systems, and advanced hybrid closed-loop systems, all aimed at better mimicking endogenous insulin secretion and glucose level regulation.

Automated insulin delivery (AID) systems, also known as closed-loop (CL) systems, are strongly recommended for youth with diabetes in order to improve time in range (TIR) by minimizing hypoglycemia and hyperglycemia, enhancing person-reported outcomes, and reducing the burden of care, especially overnight. With hybrid closed-loop (HCL) systems, insulin delivery is adjusted based on sensor glucose values. Therefore, differentiating between "manual or user-initiated" and "automated insulin delivery" is more meaningful than the classic categorization of insulin delivery as either basal or bolus.

System targets are set using either a treat-to-target approach (with a single target glucose) or a treat-to-range approach. The FDA has approved the use of the T:slim X2 pump with Control-IQ or Basal-IQ technology (Tandem Diabetes Care), Omnipod 5 (Insulet) for children ≥6 years, and MiniMed 670G (Medtronic) for children ≥2 years. The AID available in India is the Medtronic 780G. When using these insulin pump/CGM systems in "auto" mode, the system automatically delivers mini-boluses (or no bolus) of rapidly acting insulin every five minutes based on CGM results and the target glucose.

Advanced hybrid closed-loop systems also provide automatic correction insulin doses. It is recommended that patients avoid making too many changes or attempting to "game" the system, as the machine learning will help improve control over time. While the "hybrid" closed-loop devices still require the user to count carbohydrates for meal-time bolus delivery, more automated systems (such as the iLet ACE pump) require only qualitative descriptions of carbohydrate intake.

Clinical outcomes after AID use over 3-6 months include sustained improvement in glycemic control, both in terms of HbA1c and Time in Range, with reduced episodes of hypoglycemia and improved quality of life. Ongoing developments in delivery algorithms, with or without glucagon, will provide further layers of regulation for automated insulin pumps.

More than 2 decades after its introduction in India, the use of Insulin pump therapy is increasing. The published data shows its benefits such as lower rates of hypoglycemia, superior glycemic control, and increased quality of life. Despite recent advances in our understanding and treatment of diabetes, the burden remains vast and is expected to increase rapidly, especially in resource-limited countries such as India.

Automated Insulin Delivery represents a milestone on the road to insulin independence in type 1 diabetes, and its benefits in other types of diabetes are emerging. Case studies are useful in understanding the challenges and solutions to overcome in the clinical management of insulin pump therapy users in India. They can help to develop or optimize clinical pathways for diabetes management. Case studies are helpful in identifying the benefits of insulin pump in areas with limited evidence.

Current management of type 1 diabetes mellitus (T1DM) is aimed at achieving insulin replacement as close to physiological insulin secretion as possible. The hybrid close loop (HCL) technology is an important step in this direction. The term ‘hybrid’ is used since only basal insulin delivery is automated at present.

The automated insulin delivery (AID) system consists of a continuous glucose monitoring (CGM) device to measure interstitial glucose, a control algorithm to process the information from the CGM, and an insulin pump to administer insulin doses.

Some of the commonly used algorithms are:

• PID control (Proportional Integrative Differential) (Medtronic 670G, 780G)
• MPC (Model Predictive Control) (Tandem control IQ, Insulet Omnipod 5)
• Fuzzy logic (Medtronic 780G)

Mathematically, all algorithms calculate an infusion rate as a function of time and changing glucose values. The differences between the algorithms are in the way various parameters are taken into account and the extent to which predictive glucose values are calculated.

The ongoing challenges include limitations of subcutaneous insulin delivery, adjustment to meals, and daily life situations. There is a need for better comparative studies between various algorithms.

Intrauterine adversity, such as undernutrition during critical periods of fetal growth, results in permanent metabolic programming of organ systems (Barker hypothesis). Alterations such as postnatal excessive weight gain in these individuals amplify the programmed risks of later metabolic diseases, including Type 2 diabetes. Insulin resistance plays a key role in the development of metabolic syndrome. Adiposity, especially visceral adiposity, is the most significant factor contributing to insulin resistance.

Prematurity is associated with both intrauterine and early postnatal adversity. Reduced insulin sensitivity (SI) and increased visceral adiposity have been demonstrated in individuals born preterm, from early childhood to mid-adulthood. This suggests two discrete programming effects linked to prematurity: an isolated reduction in insulin sensitivity and an increased risk of later obesity. Increased adiposity has also been observed in the term-born offspring of preterm parents, suggesting epigenetic changes affecting two generations.

Thus, prematurity not only affects the health of an individual throughout their life but also influences the health of subsequent generations.

Atypical lean diabetes is recognized in individuals with low BMI and/or a history of childhood malnutrition. In an Afro-Caribbean cohort of children with Severe Acute Malnutrition (SAM), those with marasmus weighed 300g less at birth and were more wasted at the time of hospitalization compared to those with kwashiorkor.

As adults, glucose intolerance was more common among marasmus survivors (Ms) than kwashiorkor survivors (Ks), age/sex/BMI-matched controls, and birth weight-matched controls. Marasmus survivors had lower beta-cell secretion and oral disposition index but showed similar insulin sensitivity and clearance compared to kwashiorkor survivors and controls.

Beta-cell dysfunction in marasmus survivors may predispose them to the development of lean diabetes.

Developmental programming provides a conceptual framework explaining multiple organ dysfunctions and co-morbidities in T2D. We recently showed that low birthweight (LBW), a proxy of the intrauterine environment, is not only associated with increased T2D prevalence, but also with increased T2D incidence, which is independent of yet additive to genetics and obesity.

We also showed that LBW is associated with a significantly earlier T2D onset, less obesity, and less family history of T2D. Despite this, LBW is associated with a more severe T2D disease course with more hypertension and overall co-morbidities, including a significantly increased risk of cardiovascular disease in T2D.

Apart from malnutrition, infections during pregnancy can contribute to developmental programming and the emergence of multiple organ dysfunctions and co-morbidities in adulthood.

Research has shown that placental malaria exposure is associated with lower birth weight compared to non-exposed individuals, as well as subtle glycaemic dysfunction observed both in the fasting state and when subjected to an oral glucose tolerance test in young adults.

While no significant differences were found in glycolytic skeletal muscle myosin heavy chain sub-types or enzymatic activities between exposed and non-exposed individuals, the mild elevations in plasma glucose levels due to placental malaria exposure may be attributed to compromised insulin secretion rather than insulin resistance.

Conventionally, diabetes and other non-communicable diseases are thought to have genetic susceptibility and be precipitated by lifestyle factors. Over the last 50 years, research has highlighted the role of intrauterine epigenetic programming which is influenced by maternal nutrition, diabetes, stress, and endocrine disruptors. The association of birth weight with the risk of subsequent diabetes is U-shaped. Rapid post-natal catch-up growth in low birthweight babies is an additional risk factor.

India is the world’s double capital of low-birth-weight babies and type 2 diabetes. The small and thin Indian babies are more adipose compared to the European babies and show higher levels of biomarkers for diabetes risk in the cord blood. Improving fetal growth and body composition by improving maternal nutrition and glycemia is expected to curtail the rising epidemic of type 2 diabetes. Such primordial prevention will be more of a community action rather than in the clinics.

The developmental origins of health and disease (DOHaD) framework emphasizes the profound impact of early-life nutrition on long-term metabolic health. Severe acute malnutrition (SAM), particularly with non-oedematous wasting, induces lasting epigenetic, hormonal, and physiological changes, thereby increasing the risk of metabolic disorders such as type 2 diabetes.

This presentation will examine the connection between SAM and diabetes, drawing on evidence from longitudinal and mechanistic studies, while also discussing the clinical implications. Early nutritional insults significantly shape health trajectories across the lifespan, making targeted interventions during critical developmental windows essential. However, there remains a limitation of data regarding effective strategies.

A register of all insulin-requiring diabetes patients, both rural and urban, in two Ethiopian health zones was used to study the disease in this resource-poor setting. The annual incidence was found to be twice as high in men as in women and peaked at the age of 25-29 years. Urban incidence was five times higher than that in the surrounding rural areas.

Most patients had a very low BMI, and the majority were from impoverished backgrounds. The typical insulin-requiring patient in Ethiopia is an impoverished, young adult male with severe symptoms requiring insulin, a phenotype that contrasts with the typical presentations seen in the West.

Diabetes mellitus is a highly heterogeneous metabolic disorder of which the classification has changed as knowledge about its clinical and pathophysiological features has evolved. There are many forms of atypical diabetes which do not fit into the definition of type 1 and type 2 diabetes.

There is no standardized definition and nomenclature in the literature to describe “lean diabetes” which occurs in people with low BMI, whose diagnosis is made around the third decade with low total body fats, absence of islet auto-antibodies, and decreased insulin sensitivity. The lack of consensus on the naming and classification of diabetes occurring in abnormally thin young people may overestimate type 1 DM prevalence in areas with limited diagnostic resources and may result in inappropriate management of this subset of individuals with “lean diabetes.”

In addition to analyzing macro-level data on diabetes, such as epidemiological numbers, there is a need to focus on caring for individual patients. Thus, it is crucial to combine epidemiological data collection with community health-based approaches.

The mobile clinic-based rural diabetes program of the Chellaram Diabetes Institute (an urban tertiary care diabetes center) is an attempt to address this in several stages. In the first stage, a large number of people with type 2 diabetes were screened and provided basic lifestyle advice. In the second project, a quasi-experimental study compared community health worker-directed care in a cluster of villages to a comparator group. This led to the final project, where community health worker-supported diabetes care was continued in rural India.

These projects provided insights into the burden of diabetes, obesity, and gestational diabetes, as well as how community-level care can be delivered by collaborating with the government and local health authorities at both the village and district levels.

Person-centred care means care that is respectful of, and responsive to, the individual’s preferences, needs, and values. Responsible person-centred care implies that healthcare professionals ensure the individual receives the right information, in an easily understandable manner, so that informed decisions can be made.

Pragmatic person-centred care is an advanced construct, reflective of available resources and restrictions, regulating care in a rational, realistic, and renewable manner, ensuring optimal results. Person-centred care is essential for sustained diabetes management. This approach involves the person with diabetes, the public, peers, physicians, other professionals, policymakers, and planners, all working together to ensure the best care.

A focus on empathic conversation, "therapy by the ear," resource management, and teamwork helps foster a person-centred ethos in diabetes care. This approach can also be extended to include family- and community-centred care, ensuring broader support for the individual.

Non-communicable diseases (NCDs), especially diabetes, are a major global health challenge, disproportionately affecting low- and middle-income countries. Prevention efforts in developing countries emphasize cost-effective strategies such as lifestyle modification, community mobilization, and mHealth initiatives.

Programs leveraging cultural and religious platforms, like those in Bangladesh, have demonstrated success in promoting healthy behaviours. Collaborative approaches involving policymakers, healthcare providers, and religious leaders are essential to establish sustainable interventions.

While pharmacological prevention may benefit high-risk individuals, the focus remains on public health education and community engagement. National policies and global partnerships are critical to reducing the growing burden of diabetes and NCDs, ensuring long-term health improvements.

The landscape of diabetes in sub-Saharan Africa is undergoing a dramatic shift, with the disease becoming a major public health threat. It is probable that the unique genetic makeup of sub-Saharan African populations, coupled with rapid population growth and rising life expectancy, are contributing to the escalating burden of diabetes in the region.

Approximately 11.1% of individuals in this region present with a unique underweight (BMI ≤ 18.5 kg/m²), nonautoimmune phenotype, with absent visceral adiposity, reduced late-phase insulin secretion, and greater insulin deficiency, which represents a lean diabetes pattern. This clinical picture is evolving into the classic obese, insulin-resistant phenotype, suggesting the probable existence of hybrid phenotypes.

The complexity of diabetes in sub-Saharan Africa necessitates a comprehensive approach to care. This includes early detection, appropriate diagnosis, and timely initiation of effective treatment, while also addressing underlying socioeconomic factors, such as poverty and food insecurity, to reduce the escalating health burden.

There is increasing recognition of the heterogeneity of diabetes and the existence of atypical forms, including diabetes diagnosed in lean adults. Much less is known about the incidence, prevalence, phenotypes, and cost-effective treatment strategies for these atypical forms, particularly in settings where antibody, C-peptide, and genetic testing is limited.

Defining atypical diabetes is challenging, but it is clear that some populations are at higher risk, particularly certain ethnic groups in rural areas, often with a history of malnutrition.

This talk will attempt to summarize the existing knowledge on the socio-demographic characteristics of people with atypical lean diabetes, shedding light on this emerging but under-studied aspect of diabetes care.

Despite the rising diabetes epidemic and record-high forced displacement globally—both predominantly affecting lower- and middle-income countries—diabetes care is not routinely included in humanitarian health interventions and is poorly coordinated. Diabetes services provided by humanitarian organizations vary widely, lacking standardized minimum requirements or operating procedures for crisis settings.

UN agencies are increasingly advocating for the integration of non-communicable disease care in emergency responses. This presentation will outline key challenges in delivering diabetes care in humanitarian settings and highlight ongoing initiatives to improve continuity and quality of care in emergencies.

In sub-Saharan Africa, diabetes presents with diverse phenotypic variations influenced by regional differences in genetics, diet, and socio-economic factors. This presentation will explore the unique manifestations of type 1, type 2, Malnutrition Related Diabetes Mellitus (MRDM), and Ketosis prone diabetes in African populations.

Regional differences highlighting the impact of obesity, hypertension, and insulin management will be discussed. The clinical implications of these variations, emphasizing a tailored approach to management, will be highlighted. Understanding these phenotypic variations is key to improved diagnosis, management, and ultimate outcomes for people with diabetes in sub-Saharan Africa.

Type 2 diabetes is highly heterogeneous, yet current treatment often relies on the average effects of interventions seen in clinical trials. A precision medicine approach aims to select the optimal treatment based on a patient's individual characteristics, in order to maximize treatment response and minimize side effects.

In this session, Dr. Angus Jones will explore precision approaches to diabetes treatment, focusing on glucose-lowering therapies. He will discuss why treatment responses differ across patients and how routine and non-routine measures can be used to target treatments for better outcomes.

Dr. Jones will also address the strengths and limitations of patient subgrouping techniques, such as clustering (widely reported in recent studies), and compare them to alternative approaches that rely on continuous prediction of individual outcomes.

The global heterogeneity of diabetes is becoming more apparent, including individuals with a BMI <18.5 kg/m² who exhibit an atypical phenotype distinct from both Type 1 and Type 2 diabetes. This unique form of diabetes is characterized by a history of chronic malnutrition into adulthood, resistance to ketosis, and low C-peptide levels.

While the exact pathophysiological mechanisms underlying this form of diabetes are still not fully understood, malnutrition appears to interfere with the normal development of pancreatic beta cells, leading to impaired insulin secretion.

Dr. Meredith Hawkins will discuss the potential pathophysiologic mechanisms for this perplexing condition and emphasize the need for further research to better understand the relationship between malnutrition and the development of this diabetes phenotype.

From a perspective of diabetes in the young, wherein those who have a BMI less than 18.5kg/m2, there are several clinical disorders which are relevant beyond type 1 (or slowly evolving immune-mediated diabetes in the young), which are often neglected in terms of diagnosis. A clinically operational algorithm is critical to ensure that treatment is implemented appropriately.

Fibrocalcific pancreatic diabetes mellitus is a disorder in tropical countries that must be ruled out, where the symptoms of malabsorption need not necessarily be that florid, and pancreatic imaging is best undertaken with a CT scan of the abdomen. Other genetic causes for hypoplastic pancreas should also be considered.

Patients who lack autoimmune markers for type 1 diabetes and are ketosis-resistant should have certain forms of monogenic beta-cell disorders, such as HNF1Beta variants, investigated. Wolfram-like syndrome should also be considered. A comprehensive evaluation with a broad next-generation sequencing panel is vital for diagnosis, where phenotypic features need not necessarily be classical.

HIV-induced lipodystrophy should be considered in those with the disorder as a potential cause of diabetes. Genetic causes for lipodystrophy are relatively less common, but in these subjects, elevated C-peptide levels, hepatic steatosis, and characteristic body composition findings on DXA scans, supplemented by next-generation sequencing, are helpful in diagnosing these conditions.

Finally, atypical lean diabetes (malnutrition-modulated diabetes) should be considered, particularly in patients from lower socio-economic communities in tropical countries, after ruling out all other conditions in a systematic fashion.

Recently the WHO has pointed out a tripling of diabetes prevalence worldwide. 80% of people living with diabetes come from Southeast Asia. The diabetes pathophysiology varies compared to other regions in the world. The IDF is very keen to better understand determinants of lean diabetes pathophysiology as a mandatory basis for better diagnostic and prevention approaches, as well as advanced treatment strategies.

To implement new strategies, a community of colleagues who are passionate about improving the quality of diabetes care is absolutely necessary. The IDF fellowship programme will be the melting pot for the implementation of innovative and advanced diabetes strategies.

The prevalence of diabetes is increasing around the globe. Among South Asians, the increase in diabetes prevalence is alarming, and there is a rise in diabetes complications causing significant health and economic impact. Several biological and lifestyle factors are unique among South Asians, predisposing them to an increased chance of developing diabetes.

It is crucial to understand the pathophysiology and genetics of risk factors and associated complications of diabetes in South Asians. South Asians have an increased incidence of visceral adiposity and thus insulin resistance and impaired β-cell function, leading to an increased diabetes risk.

Some environmental factors, such as urbanization across Asia, leading to decreased physical activity, increased intake of dietary fats and processed foods, a fast-food culture, increased mental stress, and migration to more affluent countries, multiply the effects of insulin resistance and abdominal obesity.

Prevention of diabetes and its complications should be the primary focus due to the great economic and health burden of diabetes and its complications in South Asians.

Type 2 Diabetes (T2D) is a chronic disorder marked by disturbances in both carbohydrate and lipid metabolism. It exhibits heterogeneity, with well-documented defects in insulin action, insulin secretion, and hepatic de novo lipogenesis (DNL). In a physiological state, insulin suppresses gluconeogenesis in the liver and encourages de novo lipogenesis, facilitating the storage of carbohydrates.

Insulin resistance, a hallmark of T2D, leads to increased circulating free fatty acids, which reach the liver, where they promote non-suppressible gluconeogenesis and elevated hepatic glucose output. As insulin resistance progresses or insulin secretion decreases, there is reduced peripheral glucose uptake, which increases substrate availability for DNL.

Hepatic de novo lipogenesis involves the conversion of acetyl-CoA to fatty acids, which are then stored as triglycerides in the liver. This process, under normal circumstances, is tightly regulated to balance fatty acid synthesis and oxidation. However, when DNL becomes aberrant, it can contribute to chronic conditions like metabolic-associated fatty liver disease (MASLD), obesity, and Type 2 Diabetes.

Dr. Jayapaul's talk will delve into how diet intersects with these metabolic processes, contributing to insulin secretion, sensitivity, and the dysregulation of hepatic DNL, and discuss its implications for managing and preventing Type 2 Diabetes.

Dietary habits among Bengali-speaking communities, including those in Bangladesh, West Bengal, and the diaspora, have significant implications for diabetes management. These populations traditionally consume diets rich in rice, fish, lentils, and seasonal vegetables. However, there is also a high intake of sweets and fried foods, which contribute to the growing diabetes prevalence.

In rural areas, diets are predominantly composed of fresh, unprocessed ingredients, but urban areas have seen a shift towards refined and processed foods, raising the risks of diabetes and other metabolic disorders.

Key challenges include the overconsumption of carbohydrates, low fiber intake, and a cultural resistance to changing traditional dietary practices. Despite these obstacles, Shahjada Selim will discuss the potential for promoting low-glycemic alternatives, balanced diets, and culturally sensitive education. These strategies could help improve diabetes management within Bengali-speaking communities while still respecting and honoring traditional dietary customs.

Dietary diversity is a key contributor to proper nutrition, but in Nepal, the traditional diet is centered around Dal-Bhaat-Tarkari, a meal consisting primarily of lentils, rice, and vegetables, which forms the staple food across the country. Unlike India, where flatbreads like naan or roti are widely consumed, Nepalese cuisine does not focus on such items, which leads to different nutritional patterns and health outcomes.

One of the significant barriers to healthy dietary habits in Nepal includes perceived dietary restrictions, which can create emotional and social discomfort for individuals with diabetes. Additionally, meals are often high in carbohydrates, and the limited variety in food choices and preparation methods further complicates the management of diabetes.

The dietary patterns in India present a unique "double burden of malnutrition," where some populations still experience undernutrition, while others face rising rates of obesity and non-communicable diseases. Dr. Robin Maskey will explore how Nepal’s diet compares to that of India, particularly in terms of its impact on health, diabetes, and overall nutrition. His presentation will provide insights into dietary practices and propose potential solutions to address these public health challenges.

Ramadan fasting is a significant spiritual practice for Muslims, involving fasting every day for one month, between dawn and sunset. Managing diabetes during this period presents unique challenges due to changes in meal timing, sleep patterns, and increased glucose variability. The International Diabetes Federation (IDF) and the Diabetes and Ramadan (DAR) International Alliance have developed recommendations to guide diabetes management during Ramadan.

The main goal of the Ramadan Nutrition Plan is to ensure that individuals with diabetes consume an adequate amount of calories, with balanced proportions of macronutrients, during the non-fasting periods to prevent hypoglycemia during fasting. This plan emphasizes individualized calorie intake, with 1500–2000 kcal/day for women and 1800–2200 kcal/day for men to maintain weight. For weight loss, reduced targets are recommended. Meals should consist of 40–50% low glycemic index carbohydrates, 20–30% protein from lean sources (poultry, fish, and legumes), and 30–35% fats, prioritizing unsaturated fats and limiting saturated fats to less than 7% of total calories.

It is encouraged to consume carbohydrates from vegetables (both cooked and raw), whole fruits, yogurt, milk, and dairy products. Sugary foods, processed grains (such as wheat flour, corn, white rice, and potatoes) should be avoided or minimized. Maintaining adequate hydration by drinking water and non-sweetened beverages at, or between, the two main meals is essential. Sugary drinks, syrups, canned juices, or fresh juices with added sugar should be avoided. The consumption of caffeinated drinks (coffee, tea, and cola) should also be minimized, as they can lead to dehydration.

The Suhoor (pre-dawn meal) should be nutrient-dense and hydrating, while Iftar (the breaking of the fast) should consist of controlled portions to prevent hyperglycemia. The caloric distribution should ideally be 30–40% at Suhoor, 40–50% at Iftar, and 10–20% for snacks, ensuring a balance that minimizes glycemic fluctuations and promotes satiety.

Structured education is essential for safe fasting, including dietary advice, recognizing hypoglycemia and hyperglycemia symptoms, and knowing when to break the fast. Collaborative planning between patients and healthcare providers ensures informed decision-making and tailored care. Ramadan-focused programs have demonstrated significant benefits in improving outcomes for individuals with diabetes who fast.

The first 1000 days of life have a profound impact on childhood and adult potential. Evidence from two Vellore birth cohorts has highlighted several critical findings related to child development, nutrition, and cognition:

- Child development revealed a declining trend during the first 3 years, influenced by both stunting and underweight, despite controlling for socioeconomic status (SES).

- Anemia was found in more than 50% of children at both 7 and 15 months, with the latter being linked to iron deficiency.

- Chronic lead toxicity was associated with cognitive function at 2 years, while chronic iron deficiency affected cognition at 5 years.

- 45% of the cohort was stunted at 2 years, with 80% catching up in stature by 9 years.

- Children who were always stunted had lower cognitive scores (5 points, 0.3 SD) compared to those who were never stunted.

- A double burden of malnutrition was observed between 7-9 years of age, indicating both undernutrition and overnutrition.

- Children who were always stunted had smaller total brain volumes, with the most affected areas being those responsible for networking and connecting, such as the basal ganglia, cerebellum, and corpus callosum.

- Secular trends showed better growth parameters in the latter cohort, suggesting improvements over time.

- Dietary surveys conducted during early childhood revealed that over 30% of children consumed unhealthy foods and sweetened beverages, with poor dietary diversity in those under 2 years of age.

The Asian Indian Phenotype is a unique ancestral specific phenotype, also described as a ‘partial lipodystrophy phenotype’ with restricted adipogenesis, that predisposes Indians to a greater risk of insulin resistance, dyslipidemia, and type 2 diabetes mellitus. Recent genetic studies in our lab that have included human adipose tissue expression studies of common diabetogenic genes have helped understand the pathogenetic links between the Asian Indian phenotype, postprandial lipid metabolism, and type 2 diabetes risk.

We showed that adipose tissue expression of several of these genes also involved in adipogenesis is altered in Indians, resulting in impaired adipogenesis and a lowered capacity to handle high energy (high fat/high carbohydrate) intakes associated with inadequate trapping of triglycerides following a meal. The consequent postprandial hypertriglyceridemia leads to excess fat deposition and acceleration of the twin cycles in liver and pancreas, resulting in insulin resistance, reversible beta cell dysfunction, and type 2 diabetes.

Gestational diabetes mellitus (GDM) is a metabolic disorder marked by elevated glucose levels during pregnancy, which poses risks to both maternal and fetal health. The onset of GDM is influenced by genetic factors, inflammatory pathways, lifestyle choices, and non-genetic variables.

The intricate relationship between genetics and GDM onset is evident, with specific genes such as SLC30A8, CDKAL1, TCF7L2, IRS1, and GCK showing polymorphisms strongly associated with an increased risk of GDM. Additionally, histone alterations and other epigenetic changes, such as DNA methylation, regulate gene expression throughout pregnancy and play a key role in GDM development.

Pregnant women with diabetes may experience beta cell dysfunction due to mutations or rare variants in genes related to Maturity Onset Diabetes of the Young (MODY), which could account for up to 5% of GDM cases identified in routine screening. Distinguishing between MODY and GDM is crucial for appropriate management, as MODY is associated with hyperinsulinemic hypoglycemia in newborns.

In a study conducted at CMC Vellore, 50 subjects were screened for variants in a panel of 13 MODY-related genes using Next Generation Sequencing (NGS). The results showed that 18% (9/50) were positive for either definite, likely pathogenic, or uncertain MODY variants. The majority of these variants were found in subjects with an autosomal dominant family history, including 5 women with pre-GDM and 4 with overt GDM.

Identified variants included HNF1A Ser3Cys, PDX1 Glu224Lys, His94Gln, NEUROD1 Glu59Gln, Phe318Ser, INS Gly44Arg, GCK, ABCC8 Arg620Cys, and BLK Val418Met. Additionally, three of the seven offspring screened were positive for the identified variants.

A GWAS study by researchers from the University of Helsinki identified nine novel genetic regions associated with GDM, bringing the total number of chromosomal regions linked to the condition to 13. This highlights the multifactorial nature of GDM, with connections to Type 2 Diabetes Mellitus (T2DM), while also showing that GDM has its own unique genetic basis.

Despite GDM's status as a significant global health issue, more research is needed to uncover its molecular causes.

EAT HEALTHY - BE ACTIVE - THINK POSITIVE

Metformin, a biguanide antihyperglycemic agent, is increasingly being used during pregnancy to manage gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS). Unlike insulin, metformin offers the advantages of oral administration, cost-effectiveness, and fewer risks of hypoglycemia.

The primary mechanism of metformin is to reduce hepatic glucose production and enhance peripheral glucose uptake. Clinical studies have shown that metformin effectively controls maternal blood glucose levels and reduces excessive gestational weight gain. Moreover, it has been associated with lower risks of macrosomia and neonatal hypoglycemia when compared to insulin.

Although metformin crosses the placenta, current evidence suggests that it does not cause significant teratogenic effects. However, concerns about its long-term impact on offspring metabolism remain. Ongoing research is exploring its potential role in preventing preeclampsia and improving outcomes in obese pregnant women.

Despite the promising results, individualized risk-benefit assessments and close monitoring are essential for the safe and effective use of metformin during pregnancy. Further longitudinal studies are required to fully establish its safety profile and optimize its use.

The objective of this study was to explore the potential role of serum chemerin, a proinflammatory adipokine, in identifying dysglycemic PCOS and its association with various adiposity markers, including BMI, body fat percentage, and waist circumference (WC). The study involved 93 PCOS participants and 33 healthy controls, classified based on fasting and 2-hour plasma glucose levels (2hPGPG) and glycated hemoglobin A1c (HbA1c) levels into normoglycemic (n=34), dysglycemic (n=33), and type 2 diabetes (T2D, n=26).

The results revealed that metabolic syndrome was present in 9.7% of the PCOS group, and significant differences in waist circumference, body fat percentage, 2hPGPG, and HbA1c levels were noted between the T2D group and other groups. Serum chemerin levels were significantly higher in the PCOS group compared to controls (P < 0.001), with total body fat percentage, 2hPGPG, HbA1c, and the TG/HDL-c ratio showing a positive correlation with chemerin levels. A noteworthy observation was that 2hPGPG levels were higher in PCOS subjects with increased body fat percentage.

The study further categorized participants based on waist circumference and BMI. Significant differences in 2hPGPG levels were found only in PCOS subjects with T2D. Chemerin levels were significantly higher in PCOS subjects with dysglycemia, and these higher levels were associated with increased WC and the presence of T2D. However, BMI did not show significant differences in chemerin levels. These findings suggest that WC and body fat percentage are more closely associated with metabolic abnormalities in PCOS than BMI, and chemerin may serve as a potential biomarker for metabolic dysfunction, particularly in cases with central obesity or T2D.

Serum chemerin levels also correlated negatively with HOMA-2β. The study found that a serum chemerin cutoff level of greater than 309.3 ng/mL could distinguish PCOS individuals with dysglycemia from those without, with a sensitivity of 85.71% and specificity of 89.47%. The Cohen kappa test showed a substantial agreement (P < 0.001) between the chemerin cutoff and 2hPGPG levels greater than 200 mg/dL.

In conclusion, elevated serum chemerin levels reliably identify PCOS individuals with dysglycemia. Chemerin levels were higher in subjects with more adiposity, defined by body fat percentage and WC, particularly in those with T2D. BMI was not able to distinguish subjects in terms of adiposity. Further longitudinal studies with larger sample sizes are required to confirm this association.

Gestational diabetes (GDM) is characterized by glucose intolerance first detected during pregnancy. Traditionally, GDM was diagnosed between 24 and 28 weeks of pregnancy, but more recently, it is being diagnosed earlier in the first trimester, known as ‘Early GDM’ or eGDM. Typically, GDM is diagnosed using an oral glucose tolerance test (OGTT), which can be challenging to conduct. In the Stratification of Risk of Diabetes in Early Pregnancy (STRiDE) study, it was demonstrated that using HbA1c as the initial screening test for GDM could help avoid nearly 50% of OGTTs.

The prevalence of early GDM varies significantly depending on the criteria used, with the highest rates observed in South Asians. Women with eGDM present with a unique metabolic profile, which suggests worse beta-cell dysfunction compared to late-onset GDM. This condition is linked to a higher occurrence of adverse pregnancy outcomes, increased incidence of postpartum dysglycemia, and a greater need for insulin during pregnancy.

The Treatment Of Booking Gestational Diabetes Mellitus (ToBOGM) study, a randomized controlled trial, highlighted the benefits of early intervention in women with eGDM, showing improved neonatal outcomes for those who received early treatment. The findings from this study underscore the importance of early identification and management of GDM to improve maternal and fetal health.

Women with a history of gestational diabetes mellitus (GDM) have a nearly 10 times higher risk of developing type 2 diabetes mellitus (T2DM) compared to age-matched healthy controls. This heightened risk varies based on the degree of dysglycemia and clinical status during pregnancy. In South Asia, particularly in India, women with prior GDM face an even higher conversion rate to T2DM, often occurring within a few years after childbirth.

Given this increased risk, it is crucial to identify risk factors and associations in South Asian women with prior GDM, improve screening for diabetes postpartum, and explore relevant strategies to prevent or delay the progression to diabetes in this population. Initial evidence suggests that simple lifestyle interventions may not be sufficient for diabetes prevention in these women. More intensive approaches, such as family-focused interventions and potential preventive drug therapies, may need to be explored to mitigate the risk of T2DM in this high-risk group.

Obesity in women of reproductive age is a major public health challenge both globally and in India. The NFHS 5 data has shown that nearly one out of four women is obese, and the prevalence has risen since the last survey. Multiple risk factors have been identified as potential drivers of the obesity epidemic in women.

The greater challenge arises when women enter pregnancy either overweight or obese. This could potentially lead to a host of pregnancy complications and seriously impact the health of the offspring. Complications include miscarriages, birth defects, gestational diabetes, hypertensive disorders, thromboembolism, big baby, operative deliveries, and anesthesia complications. Offspring outcomes could include neonatal feeding difficulties, neurodevelopmental issues, and future cardiometabolic risk.

Preconception care and optimizing weight is the low-hanging fruit. However, addressing the health of adolescent girls and young women months to years before their reproductive journey is probably needed as a public health strategy.

Charcot neuro-osteoarthropathy (CN) is a condition frequently observed in diabetic patients with neuropathy, though it can occur in various other conditions such as leprosy, syringomyelia, and alcoholism. Acute CN typically presents with redness, swelling, and increased temperature in the affected foot. If not diagnosed and treated promptly, the condition can progress to chronic stages with bony deformities, joint dislocations, fractures, and the development of a rocker-bottom foot.

Diagnosing acute CN in diabetic patients requires a high degree of suspicion, as the symptoms often resemble those of cellulitis, deep venous thrombosis, or osteomyelitis. Key diagnostic clues include foot swelling with local inflammatory signs and the presence of neuropathy. Infrared thermometry is a useful tool in diagnosing CN, with a temperature difference of more than 2ºC between the affected and unaffected foot supporting the diagnosis. Radiological imaging is essential for confirming CN, with an X-ray being the initial investigation of choice. Magnetic resonance imaging (MRI) may be used for detailed assessment in the early stages of CN.

The gold standard treatment for active CN is a knee-high, non-walking, fiberglass total contact cast (TCC). Although various medical therapies have been explored to shorten the time to remission, no consistent success has been demonstrated.

The World Health Organization estimates that every 30 seconds, a leg is lost somewhere in the world because of diabetes. Surgical offloading is a procedure to relieve mechanical stress from a specific foot region. It is ideal for patients with pre-ulcerative changes or early complicated ulcers, especially in the forefoot and hindfoot regions.

The pathophysiology includes a triad of neuropathy, ischemia, and limited joint mobility. The various procedures involved in surgical offloading include Achilles tendon lengthening, metatarsal head resection, osteotomy, arthroplasty, exostectomy, external fixation, flexor tendon transfer or tenotomy, and tissue fillers such as silicone or fat.

The International Working Group in Diabetic Foot Guidelines 2019 also recommends that a person with diabetes and a neuropathic plantar digital ulcer consider using surgical offloading techniques to promote healing if non-surgical offloading treatment fails.

Diabetic foot is one of the most serious complications of diabetes, which is one of the largest global public health problems. In India, the magnitude of this complication has increased significantly, and it also remains one of the most common causes of hospitalization, imposing a significant burden on our healthcare system.

IWGDF guidelines (2023) recommend identifying at-risk feet as one of the essential elements for the prevention of foot ulcers. The recognition of high-risk feet involves one or more of the following criteria: loss of protective sensation (LOPS), absence of pedal pulses, severe foot deformity, history of foot ulcer or pre-ulcerative callus, and limited joint mobility of the foot.

Simple tools like monofilament and tuning fork can be used to assess peripheral neuropathy. Hence, there is a need for early screening and comprehensive examination of the feet to prevent diabetic foot infections.

Diabetes-related foot ulcers (DFUs) are a significant and often overlooked complication for patients living with diabetes mellitus. Research indicates that individuals with diabetic foot ulcers frequently experience cardiovascular events and have a shorter lifespan if they undergo amputation. Therefore, the primary goal in managing DFUs is both treating the ulcers and preventing their recurrence.

In addition to wound dressings, antibiotics, and debridement, it's essential to provide offloading for patients with diabetic foot ulcers. Offloading refers to relieving pressure from the ulcer site by keeping it elevated and off the ground, which helps reduce further pressure on the plantar foot ulcers.

Due to mixed neuropathy commonly present in these patients, custom footwear is often crucial. The choice of offloading footwear should be tailored based on the location of the foot ulcer, the degree of neuropathy, and the patient's overall clinical condition.

Furthermore, patients with diabetic foot ulcers are at a higher risk for unnoticed infections and trauma, which can lead to delayed health-seeking behavior. There are also pre-ulcerative conditions that may manifest in patients with long-standing diabetes mellitus. Consequently, these patients should also be prescribed appropriate, preferably customized, foot wedges to help prevent the development of foot ulcers.

The link between Non-Alcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Mellitus (T2DM) is more complex and bidirectional than previously recognized. Recent evidence indicates that NAFLD may not only precede but also promote the onset of T2DM. The severity of NAFLD is directly correlated with the risk of developing T2DM, and conversely, the resolution of NAFLD is associated with a reduced risk of T2DM. This insight suggests that liver-focused treatments may help reduce the risk of developing T2DM.

In our recent study, we identified a novel hepatokine, S100A6, that mediates inter-organ communication between the liver and pancreas under conditions of intrahepatic lipid stress. Our findings suggest that S100A6 plays a key role in β-cell dysfunction and demise in the context of NAFLD. Neutralizing circulating S100A6 may offer a new therapeutic approach to restore β-cell function and protect against the progression of diabetes in individuals with NAFLD, opening up exciting possibilities for future treatments.

Insulin resistance (IR), along with its related conditions such as Type 2 Diabetes Mellitus (T2DM) and pre-diabetes, increases the risk of developing Alzheimer’s disease (AD) and other dementias. However, the mechanisms underlying this elevated risk are still not completely understood. Preclinical studies suggest that insulin resistance impairs mitochondrial function in brain regions that are rich in insulin receptors, leading to reduced ATP availability and increased oxidative stress. This, in turn, damages proteins in brain regions typically affected by AD.

Additionally, these abnormalities associated with insulin resistance can be alleviated through aerobic exercise and the use of metformin. In individuals with Type 1 Diabetes Mellitus (T1DM), temporary insulin deprivation impairs executive functions and cognitive performance, correlating with altered connectivity between brain regions and reduced ATP levels.

Human studies have also demonstrated that insulin resistance affects brain structure, regional connectivity, and cognitive function. Emerging data indicate that improving insulin sensitivity through interventions such as exercise training and insulin sensitizers (e.g., metformin) may help improve brain abnormalities and cognitive outcomes in individuals with insulin resistance.

Liver is a master metabolic organ as it plays a pivotal role in maintaining anabolic-catabolic balance. It is also uniquely capable of switching carbon chains (metabolites) between proteins, fats and carbohydrates depending the metabolic needs of the organism. For example, hepatic glucose and fat metabolism have emerged as key determinants of organismal physiology. However, the ability of hepatocytes to orchestrate complex metabolic processes, and in sync with whole body physiology, is intrinsically dependent upon feeding-fasting cycles. Emerging literature has clearly demonstrated that ineffective feed-fast cycles are sufficient to drive the onset and progression of metabolic deficits leading to diseases such as diabetes, obesity etc. Our work has led to the discovery of evolutionarily conserved mechanisms that govern anabolic-catabolic transitions during feed-fast cycles. Besides identifying hitherto unknown players that dictate hepatic gluconeogenesis, our studies have also provided possible therapeutic targets that may be used in the clinics.

The prevalence of diabetes in India is considerably higher and it is still increasing compared to other nations. Patients with diabetes die more often because of cardiovascular disease than other complications. The typical diabetic dyslipidemia is characterized by low HDL cholesterol, high triglycerides with mildly increased or even normal LDL. This attenuated rise in LDL is due to the more atherogenic small dense LDL particles. Genetic factors, obesity, lack of physical activity, alcohol abuse, and poorly controlled glucose levels are some of the common risk factors for dyslipidaemia.

Diabetes is a cardiovascular risk equivalent. Hence aggressive treatment of dyslipidemia is required. Non-pharmacological management of dyslipidemia is important and includes modification in diet, increase in physical activity, and efforts to reduce weight. Statins remain the mainstay of pharmacotherapy for dyslipidemia in diabetes. Due to the small dense LDL, even patients with diabetes who have normal LDL cholesterol achieve a reduction in cardiovascular risk with statin therapy.

The role of ezetimibe, bile acid sequestrants, fibrates, and niacin is less well defined because they lack CV benefits in randomized clinical trials. Many novel therapies have also emerged, such as bempedoic acid and proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors, which can be used in patients with statin intolerance or can be combined with statins for those at high cardiovascular risk who require greater LDL-C reductions.

The targets for LDL cholesterol depend upon the patient's underlying cardiovascular risk category. The use of pharmacotherapy for lowering triglycerides in patients with mild to moderate hypertriglyceridemia and diabetes is still a matter of debate. Recently, Icosapentethyl has been approved in patients with mild to moderate hypertriglyceridemia after the Reduce-It trial. Proper management of dyslipidemia is a critical component of the treatment of diabetes mellitus.

There is increasing awareness of the coexistence of Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) – formerly Non-alcoholic Fatty Liver Disease (NAFLD) or Non-Alcoholic SteatoHepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM). It is suggested that up to 65% of patients with T2DM have MASLD – with simplification of criteria (with one as opposed to two markers of metabolic dysfunction), this prevalence may be revised upwards.

There is a bidirectional relationship between diabetes and MASLD, with each impacting the outcome and the complications of the other. While there has been a long-standing debate about the need to screen and the appropriate screening tools, professional societies have updated recommendations that suggest the use of the FIB4 score, and a cut-off of 1.3 as an actionable clinical point.

We have previously shown that in a community practice setting, a third of patients with diabetes have FIB4 scores at an actionable level, with a fourth of these having significant fibrosis. The treatment algorithm of diabetes should consider the presence of MASLD in general, and fibrosis in particular, while considering anti-diabetes therapies.

Weight loss, SGLT2i, GLP1RA, dual agonists, and TZDs have an effect in reducing steatosis, hepatic inflammation, and preventing progression to fibrosis. Semaglutide (topline results) and Resemitrom have evidence that supports regression of fibrosis. Our data show that a combination of TZD and SGLT2i reduces FIB4 scores with greater significance than either treatment alone.

References:
1. En Li Cho, E. et al. Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis. Gut 72, 2138–2148 (2023).
2. Seshadri, K. G., Padhye, D., Tippisetty, S., Polisetti, S. & Gadia, S. Effects of SGLT2i and Pioglitazone on FIB-4 Index in Patients with Metabolic Dysfunction Associated Steatotic Liver Disease—A Real World Retrospective Study from India. International Journal of Clinical Metabolism and Diabetes (2024) doi:10.1177/30502071241281419.
3. American Diabetes Association Professional Practice Committee. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2025. Diabetes Care 48, S59–S85 (2025).
4. Polisetti, S., Tippisetty, S., Seshadri, K. & Reddy, S. A. IDF23-0366 Risk assessment and correlation of MAFLD and FIB4 index in patients with type 2 diabetes. Diabetes Res. Clin. Pract. 209, 111486 (2024).

Type 1 diabetes is often underrepresented and poorly characterized in many low and middle-income countries (LMICs). However, several of these regions report disease patterns that significantly differ from the classical form of Type 1 diabetes encountered in industrialized countries. These differences include a later age of onset, varying modes of clinical presentation, and differences in markers of islet autoimmunity. Notably, the presentation of the disease shows considerable heterogeneity.

The extent to which these variations are explained by genetic factors or by the impact of poor socio-economic conditions in modifying the disease phenotype remains unclear. However, these differences highlight the urgent need for comprehensive studies in these resource-limited settings to better understand the condition and to establish adequate diabetes services in these often economically disadvantaged communities. Addressing these challenges is crucial to improving outcomes for individuals with Type 1 diabetes in LMICs.

Background and Aims:
Simultaneous Pancreas Kidney Transplant (SPKT) offers a dual benefit, replacing both pancreas and kidney function in patients with end-stage renal disease (ESRD) and diabetes mellitus (DM). This procedure can eliminate the need for dialysis and insulin therapy in these patients. Our study aimed to review the outcomes of SPKT at a tertiary care center in India.

Materials and Methods:
This retrospective study included data of patients who underwent SPKT from January 2014 to July 2024. Two groups were formed based on the period of surgery: Group A (2014-2019) and Group B (2020-2024). We analyzed various outcomes including graft survival, complications, and long-term results.

Results:
A total of 46 patients underwent SPKT during the study period. The median age of recipients was 28 years, with 8 patients having type 1 diabetes and 1 having type 2 diabetes. The median serum creatinine in recipients was 3.3 mg/dL. Out of 19 patients in Group A, 9 needed relaparotomy, and 4 had graft pancreatectomy due to complications. In Group B, 7 needed relaparotomy, and 4 had graft failure. At one year, graft survival was 100% for kidneys and 78% for pancreas in Group A, while in Group B, it was 100% for kidneys and 85% for pancreas.

Overall, 5 deaths occurred within 3 months post-SPKT, including one due to COVID-19. However, all patients were independent of dialysis and insulin therapy by the end of one year.

Conclusion:
SPKT offers favorable graft and patient survival outcomes, and is an effective treatment for type 1 diabetes with ESRD. While early complications were observed, timely intervention helped improve graft survival and patient outcomes over time, with fewer complications in recent years.

DYOD-SL is a multicenter cloud-based prospective database launched in 2020 to estimate disease burden, streamline resource allocation/distribution, develop care strategies, and create a platform for research in Young Onset Diabetes (YOD) in Sri Lanka. Nationwide data from patients with disease onset on or before the age of 25 years are included in the database.

In this lecture, I will discuss data from 3157 patients who have been entered in the database. Among them, 1769 (56%) patients were classified as Type 1 Diabetes (T1D), 1089 (34.5%) as Type 2 Diabetes (T2D), and the rest (9.5%) had other types of diabetes. T1D was more common (81.2%) in those with BMI 23.

The mean HbA1C in the cohort was 10.02% in 2021 and gradually declined annually: 9.3% in 2022, 8.9% in 2023, and 8.7% in 2024.

Prevalence of complications included nephropathy (8.1%), retinopathy (6.6%), neuropathy (4.1%), moderate-high-risk diabetic foot disease (1.9%), and macrovascular complications (0.5%). Hypertension and dyslipidemia were observed in 2.7% and 14%, respectively. Among patients over 18 years, overweight and obesity were present in 22.2% and 10.4%, respectively.