Journal of the Indian Institute of Science最新文献

Gestational diabetes mellitus (GDM), defined as glucose intolerance that is first recognized during pregnancy beyond 20 weeks of gestation, is rising globally. The prevalence varies widely across populations (1–25%), depending on the population studied. The abnormal glucose homeostasis during pregnancy, GDM is associated with short and long-term metabolic risks, both for the mother and the offspring. The pathophysiological basis of GDM is classically thought to stem from abnormal up-regulation of insulin production relative to the degree of increased insulin resistance intrinsic to pregnancy. Glucose regulation is a complex process involving interactions among multiple endocrine and neurobiological pathways. Studies in non-pregnant humans demonstrate that gliosis (a cellular inflammatory response) in the mediobasal hypothalamus (MBH) is associated with insulin resistance, independent of the level of adiposity. Recent data also suggests that baseline existence of MBH gliosis precedes the onset of glucose dysregulation 1 year later, suggesting that the in addition to the pancreas, brain changes may be a key driver in glucose metabolism. These data provide mechanistic insights into brain pathways which may increase risk for metabolic dysfunction leading to GDM.

The second and third decades of the twenty-first century are marked by a flourishing of space technology which may soon realise human aspirations of a permanent multiplanetary presence. The prevention, control and management of infection with microbial pathogens is likely to play a key role in how successful human space aspirations will become. This review considers the emerging field of medical astro-microbiology. It examines the current evidence regarding the risk of infection during spaceflight via host susceptibility, alterations to the host’s microbiome as well as exposure to other crew members and spacecraft’s microbiomes. It also considers the relevance of the hygiene hypothesis in this regard. It then reviews the current evidence related to infection risk associated with microbial adaptability in spaceflight conditions. There is a particular focus on the International Space Station (ISS), as one of the only two  crewed objects in low Earth orbit. It discusses the effects of spaceflight related stressors on viruses and the infection risks associated with latent viral reactivation and increased viral shedding during spaceflight. It then examines the effects of the same stressors on bacteria, particularly in relation to changes in virulence and drug resistance. It also considers our current understanding of fungal adaptability in spaceflight. The global public health and environmental risks associated with a possible re-introduction to Earth of invasive species are also briefly discussed. Finally, this review examines the largely unknown microbiology and infection implications of celestial body habitation with an emphasis placed on Mars. Overall, this review summarises much of our current understanding of medical astro-microbiology and identifies significant knowledge gaps.

Graphical Abstract

Objectives

This review summarizes the burden and emerging risks of type-2 diabetes and prediabetes in South Asian populations and reviews recent evidence regarding diabetes prevention through lifestyle modifications among South Asians worldwide. We highlight gaps and discrepancies in the current literature, indicate opportunities and consider implications for future research in this area.

Findings

Randomized, controlled trials along with major cohort studies and implementation research have demonstrated lifestyle intervention as an effective, cost-effective, and feasible method for reducing diabetes and prediabetes and their associated risk factors in South Asians, a population at high diabetes risk even of early age onset and with lower body mass index (BMI). However, there is a lack of evidence as to the best methods of diabetes prevention in normal-weight South Asians across age groups as well as individuals with impaired fasting glucose. Future prevention research should also aim to improve community-level education and implementation, ensure individual uptake, and dissemination of proven programs, design culturally tailored programs; and assess long-term outcomes of interventions.

Endocrine pancreas regulates glucose homeostasis and prevents diabetes. Type-1 diabetes is characterized by destruction of the insulin secreting β-cells within the endocrine pancreatic islets, resulting in lower insulin release. People with type-1 diabetes can be transplanted with pancreatic islets obtained from deceased donors which restores the β-cell function. There are around 70 human islet isolation centers around the world which mostly collect endocrine pancreas from deceased donors. They assess the islet yield, functionality, viability, secretory capacity, and purity for transplantation and distribute this to donors. They also distribute a part of the pancreatic tissue for research, so that the cellular mechanisms in the human pancreatic tissue can be understood. This is crucial since human islet tissue has a unique cytoarchitecture compared to murine counterparts and therefore islet research with murine islets does not give complete picture of diabetes in humans. India is poised to take the mantle of the diabetes capital of the world in the near future. Despite this, there are no human islet isolation centers which can facilitate islet transplantation and diabetes research in India. This article highlights the glaring gap in the current infrastructure for diabetes care and provides critical insights into the role and potential of setting up islet tissue banks in the most populous country of the world.

Microorganisms are ubiquitous in nature and form complex community networks to survive in various environments. This community structure depends on numerous factors like nutrient availability, abiotic factors like temperature and pH as well as microbial composition. Categorising accessible biomes according to their habitats would help in understanding the complexity of the environment-specific communities. Owing to the recent improvements in sequencing facilities, researchers have started to explore diverse microbiomes rapidly and attempts have been made to study microbial crosstalk. However, different metagenomics sampling, preprocessing, and annotation methods make it difficult to compare multiple studies and hinder the recycling of data. Huge datasets originating from these experiments demand systematic computational methods to extract biological information beyond microbial compositions. Further exploration of microbial co-occurring patterns across the biomes could help us in designing cross-biome experiments. In this review, we catalogue databases with system-specific microbiomes, discussing publicly available common databases as well as specialised databases for a range of microbiomes. If the new datasets generated in the future could maintain at least biome-specific annotation, then researchers could use those contemporary tools for relevant and bias-free analysis of complex metagenomics data.

Over the past decade there have been many advances in diabetes technologies, such as continuous glucose monitors (CGMs), insulin-delivery devices, and hybrid closed loop systems. Now most CGMs (Medtronic-Guardian, Dexcom-G6, and Abbott-Libre-2) have MARD values of < 10%, in contrast to two decades ago when the MARD used to be > 20%. In addition, the majority of the new CGMs do not require calibrations, and the latest CGMs last for 10–14 days. An implantable 6-months CGM by Eversense-3 is now approved in the USA and Europe. Recently, the FDA approved Libre 3 which provides real-time glucose values every minute. Even though it is approved as an iCGM it is not interoperable with automatic-insulin-delivery (AID) systems. The newer CGMs that are likely to be launched in the next few months in the USA include the 10–11 days Dexcom G7 (60% smaller than the existing G6), and the 7-days Medtronic Guardian 4. Most of the newer CGM have several features like automatic initialization, easy insertion, predictive alarms, and alerts. It has also been noticed that an arm insertion site might have better accuracy than abdomen or other sites, like the buttock for kids. Lag time between YSI and different sensors have been reported differently, sometimes it is down to 2–3 min; however, in many instances, it is still 15–20 min, especially when the rate of change of glucose is > 2 mg/min. We believe that in the next decade there will be a significant increase in the number of people who use CGM for their day-to-day diabetes care.

Indian people are at high risk for type 2 diabetes (T2DM) even at younger ages and lower body weights. Already 74 million people in India have the disease, and the proportion of those with T2DM is increasing across all strata of society. Unique aspects, related to lower insulin secretion or function, and higher hepatic fat deposition, accompanied by the rise in overweight (related to lifestyle changes) may all be responsible for this unrelenting epidemic of T2DM. Yet, research to understand the causes, pathophysiology, phenotypes, prevention, treatment, and healthcare delivery of T2DM in India seriously lags behind. There are major opportunities for scientific discovery and technological innovation, which if tapped can generate solutions for T2DM relevant to the country’s context and make leading contributions to global science. We analyze the situation of T2DM in India, and present a four-pillar (etiology, precision medicine, implementation research, and health policy) strategic research framework to tackle the challenge. We offer key research questions for each pillar, and identify infrastructure needs. India offers a fertile environment for shifting the paradigm from imprecise late-stage diabetes treatment toward early-stage precision prevention and care. Investing in and leveraging academic and technological infrastructures, across the disciplines of science, engineering, and medicine, can accelerate progress toward a diabetes-free nation.

Diabetes and related metabolic non-communicable diseases (NCDs), such as hypertension and obesity, are no longer only a problem in affluent industrialized countries; prevalence rates are rapidly rising in developing nations like India as well. Given that diabetes is becoming increasingly prevalent in India on account of rapid urbanization and economic development, reliable epidemiological data are essential for estimating the effects and determinants of diabetes and facilitating the development of prevention and control methods. Though several regional studies exist, the marked heterogeneity between states and regions of India limits the generalizability of their results. The national Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study was designed and conducted to provide accurate and comprehensive state- and national-level data on the prevalence of diabetes and other metabolic NCDs in India. The ICMR-INDIAB study was conducted in all 30 states/union territories of India between 2008 and 2020. The study reports on the prevalence of various cardiometabolic disease risk factors such as diabetes, prediabetes, obesity, hypertension and dyslipidemia, assessment of knowledge of diabetes in the general population and those with known diabetes, achievement of diabetes treatment targets and the role of migration, diet and physical inactivity on diabetes. This study, the largest nationally representative population-based study conducted in India, thereby helps to estimate the burden of diabetes and other metabolic NCDs in a representative sample of adults living in both urban and rural India.

Diabetic foot ulcers are one of the common secondary complications associated with diabetes and are characterized by delayed or absence of healing. Of the several factors contributing to poor healing, chronic low-grade inflammation significantly worsens wound healing resulting in adverse outcomes. As the innate immune system plays a vital role in wound healing, a closer look at their alterations may provide insights into developing novel treatment strategies to promote healing. In this review, we discuss the role of the innate immune system in driving chronic inflammation both at the wound site and at the systemic level, resulting in poor healing outcomes. Specifically, we highlight the findings from preclinical and clinical studies that describe the dysregulations of the innate system at the cellular and molecular level and how they contribute to low-grade chronic inflammation in wounds. Our review of the literature shows that preexisting low-grade inflammation, which is associated with altered myeloid cell phenotype and function, is key to impaired wound healing responses in individuals with diabetes. Hence, we suggest that modulating circulating myeloid cell function and low-grade chronic inflammation could be a helpful strategy in promoting diabetic foot ulcer healing.

Type 1 diabetes is a complex, chronic disease in which the insulin-producing beta cells in the pancreas are sufficiently altered or impaired to result in requirement of exogenous insulin for survival. The development of type 1 diabetes is thought to be an autoimmune process, in which an environmental (unknown) trigger initiates a T cell-mediated immune response in genetically susceptible individuals. The presence of islet autoantibodies in the blood are signs of type 1 diabetes development, and risk of progressing to clinical type 1 diabetes is correlated with the presence of multiple islet autoantibodies. Currently, a “staging” model of type 1 diabetes proposes discrete components consisting of normal blood glucose but at least two islet autoantibodies (Stage 1), abnormal blood glucose with at least two islet autoantibodies (Stage 2), and clinical diagnosis (Stage 3). While these stages may, in fact, not be discrete and vary by individual, the format suggests important applications of precision medicine to diagnosis, prevention, prognosis, treatment and monitoring. In this paper, applications of precision medicine in type 1 diabetes are discussed, with both opportunities and barriers to global implementation highlighted. Several groups have implemented components of precision medicine, yet the integration of the necessary steps to achieve both short- and long-term solutions will need to involve researchers, patients, families, and healthcare providers to fully impact and reduce the burden of type 1 diabetes.