Alkaline Phosphatase: The Poor Man's iPTH - An Affordable Approach to Bone Health Assessment.

This review delves into relatively less discussed role of alkaline phosphatase (ALP) as an accessible alternative to intact parathyroid hormone (iPTH) in the context of bone health assessment, particularly focussing on its potential boon for underprivileged individuals with chronic kidney disease (CKD) in South Asia. The financial constraints faced by this demographic often hinder regular monitoring of iPTH levels. ALP emerges as a promising surrogate, offering a cost-effective and practical solution for bone health evaluation in resource-constrained settings.

The KgA1c Paradox: Widening the spectrum.

The term KgA1c paradox is used to describe the unwanted rise in weight that occurs when HbA1c is controlled using conventional therapy. We highlight facets of pathophysiology, prevention, pharmacology, person centred care, and epidemiology, which correspond to the concept of KgA1c paradox. We suggest a novel index, KgA1c product [(BMI) x (HbA1c)], which can be used to evaluate efficacy of drugs, and assess metabolic control in persons with diabetes.

The 6E approach to a healthy life.

The increasing pandemic of metabolic disease has spurred us to focus on promotion of health and prevention of disease. Simple public health messaging is required to inform and motivate the public to follow evidence-based interventions which can help prevent metabolic illnesses and their complications. We present a catchy 6E framework which enjoins individuals to Eat well, Exercise well, Eliminate unhealthy behaviours/habits, Ensure adequate Entertainment, relaxation and sleep, practice Emotional control, and Eschew/avoid extremes. This message can be used at individual, family as well as public health levels, to spread awareness about healthy behaviours and lifestyle.

Expert Consensus on Dipeptidyl Peptidase-4 Inhibitor-Based Therapies in the Modern Era of Type 2 Diabetes Mellitus Management in India.

India has a high prevalence of type 2 diabetes mellitus (T2DM) with unique clinical characteristics compared to other populations. Despite advancements in diabetes therapy, a significant number of patients in India still experience poor glycemic control and complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors continue to be an important component of T2DM treatment due to their favorable efficacy and tolerability profile. Given the current scenario, there is a need to revisit the role of DPP-4 inhibitors in T2DM management in Indian patients. This consensus paper aims to provide guidance on the utilization of DPP-4 inhibitors in T2DM management from an Indian perspective. A consensus group of 100 experts developed recommendations based on an extensive literature review and discussions. The expert group emphasized the importance of timely glycemic control, combination therapy, and targeting the underlying pathophysiology of T2DM. The combinations of DPP-4 inhibitors with metformin and/or sodium-glucose transport protein-2 inhibitors are rationalized in this paper, considering their complementary mechanisms of action. This paper provides valuable insights for clinicians in optimizing the management of T2DM in the Indian population with the use of DPP-4 inhibitors and proposes an algorithm for selecting DPP-4 inhibitor-based therapies.

Quantitative susceptibility mapping in amyotrophic lateral sclerosis: automatic quantification of the magnetic susceptibility in the subcortical nuclei.

Objective: Previous studies have suggested a link between dysregulation of cortical iron levels and neuronal loss in amyotrophic lateral sclerosis (ALS) patients. However, few studies have reported differences in quantitative susceptibility mapping (QSM) values in subcortical nuclei between patients with ALS and healthy controls (HCs). Methods: MRI was performed using a 3 Tesla Prisma scanner (64-channel head coil), including 3D T1-MPRAGE and multi-echo 3D GRE for QSM reconstruction. Automated QSM segmentation was used to measure susceptibility values in the subcortical nuclei, which were compared between the groups. Correlations with clinical scales were analyzed. Group comparisons were performed using independent t-tests, with p < 0.05 considered significant. Correlations were assessed using Pearson's correlation, with p < 0.05 considered significant. Cohen's d was reported to compare the standardized mean difference (SMD) of QSM. Results: Twelve patients with limb-onset ALS (mean age 48.7 years, 75% male) and 13 age-, sex-, and handedness-matched HCs (mean age 44.6 years, 69% male) were included. Compared to HCs, ALS patients demonstrated significantly lower susceptibility in the left caudate nucleus (CN) (SMD = -0.845), right CN (SMD = -0.851), whole CN (SMD = -1.016), and left subthalamic nucleus (STN) (SMD = -1.000). Susceptibility in the left putamen (SMD = -0.857), left thalamus (SMD = -1.081), and whole thalamus (SMD = -0.968) was significantly higher in the patients. The susceptibility of the substantia nigra (SN), CN, and pulvinar was positively correlated with disease duration. Conclusions: QSM detects abnormal iron accumulation patterns in the subcortical gray matter of ALS patients, which correlates with disease characteristics, supporting its potential as a neuroimaging biomarker.

Psychological First Aid.

In this communication, we discuss the concept of psychological first aid, as relevant to diabetes management. Psychological first aid, in the diabetes care context, is defined as "the empathic support, counselling and education to improve coping skills, and optimize selfcare of persons living with diabetes, so that psychological well-being can be optimized." Various models can help provide structured psychological first aid. We feel that each and every health care provider should be able to provide effective first aid, including psychological first aid.

Oneirotherapy in Overweight and Obesity.

Oneirotherapy is a form of psychotherapy that is based on visual imagery and symbolism. In this communication. We discuss the role of oneirotherapy, or using vivid imagery, as adjuvant therapy in obesity care. Oneirotherapy can be used to promote acceptance of, and adherence to, prescribed therapy. It may also help improve quality of life and enhance self-esteem. However, oneirotherapy alone, without following a healthy lifestyle and or taking antiobesity medication, will help manage weight only in one's dreams.

Endocrine Entropy.

This communication defines and describes the novel concept of endocrine entropy. The authors share insights regarding the various facets of entropy in endocrine epidemiology, physiology, clinical presentation and management. The discussion opens up a new way of approaching endocrinology. Recent advances in artificial intelligence, assessment and addressal of entropy may become integral part of endocrine diagnostics and therapeutics.

Endocrine Entropy.

This communication defines and describes the novel concept of endocrine entropy. The authors share insights regarding the various facets of entropy in endocrine epidemiology, physiology, clinical presentation and management. The discussion opens up a new way of approaching endocrinology. Recent advances in artificial intelligence, assessment and addressal of entropy may become integral part of endocrine diagnostics and therapeutics.

Volume loss in the left anterior-superior subunit of the hypothalamus in amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Amyotrophic lateral sclerosis (ALS) causes motor neuron loss and progressive paralysis. While traditionally viewed as motor neuron disease (MND), ALS also affects non-motor regions, such as the hypothalamus. This study aimed to quantify the hypothalamic subregion volumes in patients with ALS versus healthy controls (HCs) and examine their associations with demographic and clinical features. METHODS: Forty-eight participants (24 ALS patients and 24 HCs) underwent structural MRI. A deep convolutional neural network was used for the automated segmentation of the hypothalamic subunits, including the anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tuberal (supTub), inferior tuberal (infTub), and posterior (posHyp). The neural network was validated using FreeSurfer v7.4.1, with individual head size variations normalized using total intracranial volume (TIV) normalization. Statistical analyses were performed for comparisons using independent sample t-tests. Correlations were calculated using Pearson's and Spearman's tests (p < 0.05). The standard mean difference (SMD) was used to compare the mean differences between parametric variables. RESULTS: The volume of the left a-sHyp hypothalamic subunit was significantly lower in ALS patients than in HCs (p = 0.023, SMD = -0.681). No significant correlation was found between the volume of the hypothalamic subunits, body mass index (BMI), and ALSFRS-R in patients with ALS. However, right a-sHyp (r = 0.420, p = 0.041) was correlated with disease duration, whereas right supTub (r = -0.471, p = 0.020) and left postHyp (r = -0.406, p = 0.049) were negatively correlated with age. There was no significant difference in the volume of hypothalamic subunits between males and females, and no significant difference was found between patients with revised ALS Functional Rating Scale (ALSFRS-R) scores ≤41 and >41 and those with a disease duration of 9 months or less. DISCUSSION AND CONCLUSION: The main finding suggests atrophy of the left a-sHyp hypothalamic subunit in patients with ALS, which is supported by previous research as an extra-motor neuroimaging finding for ALS.

First-trimester fasting plasma glucose as a predictor of subsequent gestational diabetes mellitus and adverse fetomaternal outcomes: A systematic review and meta-analysis.

BACKGROUND: The implication of intermediately elevated fasting plasma glucose (FPG) in the first trimester of pregnancy is uncertain. PURPOSE: The primary outcome of the meta-analysis was to analyze if intermediately elevated first-trimester FPG could predict development of GDM at 24-28 weeks. The secondary outcomes were to determine if the commonly used FPG cut-offs 5.1 mmol/L (92 mg/dL), 5.6 mmol/L (100 mg/dL), and 6.1 mmol/L (110 mg/dL) correlated with adverse pregnancy events. DATA SOURCES: Databases were searched for articles published from 2010 onwards for studies examining the relationship between first-trimester FPG and adverse fetomaternal outcomes. STUDY SELECTION: A total of sixteen studies involving 115,899 pregnancies satisfied the inclusion criteria. DATA EXTRACTION AND DATA SYNTHESIS: Women who developed GDM had a significantly higher first-trimester FPG than those who did not [MD 0.29 mmoL/l (5 mg/dL); 95 % CI: 0.21-0.38; P < 0.00001]. First-trimester FPG ≥5.1 mmol/L (92 mg/dL) predicted the development of GDM at 24-28 weeks [RR 3.93 (95 % CI: 2.67-5.77); P < 0.0000], pre-eclampsia [RR 1.55 (95%CI:1.14-2.12); P = 0.006], gestational hypertension [RR1.47 (95%CI:1.20-1.79); P = 0.0001], large-for-gestational-age (LGA) [RR 1.32 (95%CI:1.13-1.54); P = 0.0004], and macrosomia [RR1.29 (95%CI:1.15-1.44); P < 0.001]. However, at the above threshold, the rates of preterm delivery, lower-segment cesarean section (LSCS), small-for gestational age (SGA), and neonatal hypoglycemia were not significantly higher. First-trimester FPG ≥5.6 mmol/L (100 mg/dL) correlated with occurrence of macrosomia [RR1.47 (95 % CI:1.22-1.79); P < 0.0001], LGA [RR 1.43 (95%CI:1.24-1.65); P < 0.00001], and preterm delivery [RR1.51 (95%CI:1.15-1.98); P = 0.003], but not SGA and LSCS. LIMITATIONS: Only one study reported outcomes at first-trimester FPG of 6.1 mmol/L (110 mg/dL), and hence was not analyzed. CONCLUSION: The risk of development of GDM at 24-28 weeks increased linearly with higher first-trimester FPG. First trimester FPG cut-offs of 5.1 mmol/L (92 mg/dL) and 5.6 mmol/L (100 mg/dL) predicted several adverse pregnancy outcomes.

Efficacy and safety of albiglutide, a once-weekly glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: No meta-analysis has holistically analyzed and summarized the therapeutic efficacy and safety of albiglutide in type 2 diabetes (T2D). This meta-analysis addresses this knowledge gap. METHODS: Randomized controlled trials involving patients with T2D receiving albiglutide in the intervention arm and either a placebo or an active comparator in the control arm were searched through electronic databases. The primary outcome was the change from baseline (CFB) in glycated hemoglobin (HbA1c); secondary outcomes included CFB in fasting plasma glucose, body weight, and adverse events (AE). RESULTS: From 443 initially screened articles, data from 12 randomized controlled trials involving 6423 subjects were analyzed. Albiglutide, at both doses, outperformed placebo in terms of HbA1c reductions (for albiglutide 30 mg: mean differences -1.04%, 95% confidence interval [CI] [-1.37--0.72], P < .00001, I2 = 89%; and for albiglutide 50 mg: mean differences -1.10%, 95% CI [-1.45--0.75], P < .00001, I2 = 90%). Higher proportions of subjects achieved HbA1c < 7% in the albiglutide arm than in placebo (for albiglutide 30 mg: odds ratio 6.26, 95% CI [2.50-15.70], P < .0001, I2 = 82%; and for albiglutide 50 mg: odds ratio 5.57, 95% CI [2.25-13.80], P = .0002, I2 = 84%). Albiglutide had glycemic efficacy comparable to other glucose-lowering drugs. CFB in body weight was similar with albiglutide and placebo. AE profile, including gastrointestinal AE, was identical with albiglutide and placebo, except for higher drug-related AE and injection-site reaction with albiglutide. CONCLUSION: Albiglutide provides reassuring data on good glycemic efficacy, tolerability, and safety over an extended period of clinical use in patients with T2D. Albiglutide 30 mg has comparable efficacy and safety profiles to albiglutide 50 mg.

Insulin Access Enhancement in India: Expert Views on Integrating Interchangeable Biosimilar Insulin Glargine.

Achieving and maintaining optimal glycemic targets is the fundamental goal of the management of diabetes. However, failure of oral antidiabetic drugs (OADs) to sustain the targeted glycemic levels in individuals with progressing disease often requires initiation of insulin therapy. This article consolidates the expert opinions of 377 doctors who participated in 34 advisory board meetings held digitally (n=23) and in person (n=11) across India. The present report underscores the need for readily available alternatives, such as biosimilar insulins, in the Indian healthcare market to make insulin accessible to every patient with diabetes. The introduction of biosimilar insulins in the Indian healthcare market is the key to making insulin accessible to every patient with diabetes. Biosimilars are biologic products that closely resemble reference/originator biologics and demonstrate no clinically meaningful differences in safety and effectiveness. The concept of interchangeability serves as a pivotal differentiator for biosimilars, underlining their reliability and safety, and plays a significant role in their broader acceptance and integration into healthcare systems. The 'interchangeability' designation by the United States Food and Drug Administration (USFDA) elevates the biosimilar concept, promoting faster and broader adoption of insulin biosimilars, especially benefiting patients prone to non-adherence to insulin therapy. Healthcare providers are encouraged to consider the option of initiating or transitioning to biosimilar insulin glargine to address the insulin accessibility challenges.

Global Warming and Endocrinology: The Hyderabad Declaration of the South Asian Federation of Endocrine Societies.

Global warming and endocrine disorders are intertwined issues posing significant challenges. Greenhouse gases emanating from human activities drive global warming, leading to temperature rise and altered weather patterns. South Asia has experienced a noticeable temperature surge over the past century. The sizable population residing in the region heightens the susceptibility to the impact of global warming. In addition to affecting agriculture, water resources, and livelihood, environmental changes interfere with endocrine functioning. Resulting lifestyle changes increase the risk of metabolic and endocrine disorders. Individuals with diabetes face heightened vulnerability to extreme weather due to impaired thermoregulation. A high ambient temperature predisposes to heat-related illnesses, infertility, and nephropathy. Additionally, essential endocrine drugs and medical devices are susceptible to temperature fluctuations. The South Asian Federation of Endocrine Societies (SAFES) calls for collaboration among stakeholders to combat climate change and promote healthy living. Comprehensive approaches, including the establishment of sustainable food systems, promotion of physical activity, and raising awareness about environmental impacts, are imperative. SAFES recommends strategies such as prioritizing plant-based diets, reducing meat consumption, optimizing medical device usage, and enhancing accessibility to endocrine care. Raising awareness and educating caregivers and people living with diabetes on necessary precautions during extreme weather conditions are paramount. The heat sensitivity of insulin, blood glucose monitoring devices, and insulin pumps necessitates proper storage and consideration of environmental conditions for optimal efficacy. The inter-connectedness of global warming and endocrine disorders underscores the necessity of international collaboration guided by national endocrine societies. SAFES urges all stakeholders to actively implement sustainable practices to improve endocrine health in the face of climate change.

Temporal and spatial progression of microstructural cerebral degeneration in ALS: A multicentre longitudinal diffusion tensor imaging study.

OBJECTIVE: The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA) along the CST as a longitudinal marker of disease progression in ALS. METHODS: The study cohort consisted of 114 patients with ALS and 110 healthy controls from the second prospective, longitudinal, multicentre study of the Canadian ALS Neuroimaging Consortium (CALSNIC-2). DTI and clinical data from a harmonized protocol across 7 centres were collected. Thirty-nine ALS patients and 61 controls completed baseline and two follow-up visits and were included for longitudinal analyses. Whole brain-based spatial statistics and hypothesis-guided tract-of-interest analyses were performed for cross-sectional and longitudinal analyses. RESULTS: FA was reduced at baseline and longitudinally in the CST, mid-corpus callosum (CC), frontal lobe, and other ALS-related tracts, with alterations most evident in the CST and mid-CC. CST and pontine FA correlated with functional impairment (ALSFRS-R), upper motor neuron function, and clinical disease progression rate. Reduction in FA was largely located in the upper CST; however, the longitudinal decline was greatest in the lower CST. Effect sizes were dependent on region, resulting in study group sizes between 17 and 31 per group over a 9-month interval. Cross-sectional effect sizes were maximal in the upper CST; whereas, longitudinal effect sizes were maximal in mid-callosal tracts. CONCLUSIONS: Progressive microstructural alterations in ALS are most prominent in the CST and CC. DTI can provide a biomarker of cerebral degeneration in ALS, with longitudinal changes in white matter demonstrable over a reasonable observation period, with a feasible number of participants, and within a multicentre framework.

Assessment of Hydration Status Using Conventional Method and Salivary Osmolarity as a Point-of-care Tool.

Dehydration is a well-known problem worldwide, and its assessment can be challenging due to confusing physical signs. The most effective way to assess hydration status is through the costly stable isotope methodology, but this approach has practical limitations. More commonly accepted and utilized indicators of hydration status are hematological and urinary parameters. However, hematological markers require invasive methods, and urinary markers have varying degrees of success in tracking hydration changes. While alterations in body weight can serve as a means of promptly evaluating hydration status, various factors such as food consumption, fluid intake, fecal losses, and urine production can impact these changes. Researchers have turned their attention to saliva as a potential marker and point-of-care (POC) testing to address the limitations of existing biomarkers. Saliva is appealing due to its easy collection process and similarities to extracellular fluid in terms of water and ion concentrations. Recent studies have shown that saliva flow rate, osmolarity/osmolality, and total protein concentration can effectively monitor changes in body mass during acute dehydration. Misdiagnosing dehydration can have severe clinical consequences, leading to morbidity and even mortality. This narrative review focuses on recognizing the significance of hydration assessment, monitoring, and the potential of salivary osmolarity (SOSM) as an assessment tool. Healthcare professionals can improve their practices and interventions to optimize hydration and promote overall wellness using such tools.

Diabetes Mellitus and Fluid Imbalance: The Need for Adequate Hydration.

The effect of hydration in modulating metabolic disease risk is a comparatively recent concept. Diabetic patients are at increased risk of dehydration due to osmotic diuresis. Undiagnosed or undertreated hyperglycemia may lead to electrolyte imbalance and elevated renal burden of glucose excretion, which may alter fluid reabsorption in the kidney. Also, the presence of one or more contributory factors, such as inadequate fluid intake, strenuous exercise, high temperatures, alcohol consumption, diarrhea, acute illnesses, fever, nausea, and vomiting, may put diabetic patients at increased risk of dehydration and electrolyte imbalance. Certain antidiabetic agents used by diabetic patients may cause fluid retention/deficits and/or electrolyte abnormalities in a few patients. Thus, drinking ample amounts of water and fluids with appropriate electrolyte composition is important to prevent dehydration. Successful management of dehydration in patients with diabetes is an unmet need and can best be accomplished by maintaining adequate hydration status.

Connecting the Dots: Hydration, Micronutrients, and Immunity.

Dehydration, often unnoticed, can occur in adults due to heat-related illnesses, viral infections, and upper respiratory tract infections, leading to deficits in fluids, electrolytes, and energy (FEE), even without diarrhea. This fluid deficit, in turn, impairs immunity at cellular and molecular levels. Physiologically, the immune system rapidly reacts to threats by adjusting its structural permeability, allowing water and small solutes to be passed, facilitated by proteins like aquaporins (AQPs). These AQPs are also essential for immune cell communication and adjustments of the cytoskeleton for functions like chemotaxis and phagocytosis. Apart from hydration, maintaining an optimal intake of essential micronutrients, including vitamins C and E, copper, zinc, and selenium, is also critical for supporting immune function and acting as antioxidants. Transient alterations in immune function caused by acute stressors or nondiarrheal conditions heighten vulnerability to coexisting illnesses, particularly cold and upper respiratory tract infections, while also elevating the likelihood of recurrent health issues. Supplementing fluids with known FEE content according to quality standards and enhanced taste is recommended during acute illness and until complete recovery. Thus, dehydration, caused by various acute conditions, can impair immunity and delay recovery. Prioritizing hydration and nutrition in healthcare and general settings is imperative, even when diarrhea is absent.

The Acute Coronary Syndrome Risk in Medically Managed Subjects with Type 2 Diabetes Mellitus - Is the ASCVD Risk Score Failing Here?

Objectives: Type 2 Diabetics have elevated risk for acute coronary syndrome (ACS). The current management algorithm focuses on atherosclerotic cardiovascular (ASCVD) risk score to stratify this risk. However, in medically managed subjects, this algorithm may not be accurate. This study compares the ASCVD risk score in an Indian population with T2DM under medical supervision and the actual incidence of ACS. It also compared the ASCVD risk scores in cases with T2DM who developed ACS to controls and tried to estimate whether the ASCVD risk score is different in the two subsets, evaluating the utility of the ASCVD risk score in predicting ACS. Methodology: This is an electronic medical record (EMR) based case-control study. Only records of subjects with T2DM where details of age, sex, body mass index, blood pressure, duration of diabetes, family history of ACS, lipid profile, renal and liver function tests were included. The incidence of ACS was calculated in the selected records, and the records of subjects with ACS were compared with age and sex-matched subjects without ACS. Data are summarized as median and interquartile range (IQR). Wilcoxon rank-sum test was used for checking differences in continuous variables and Pearson's Chi-squared test for categorical data. Univariate and multivariate logistic regression analyses were used to check the effect of ASCVD scores and other variables on the occurrence of ACS.Statistical data analyses were performed using JASP, version 0.16.4 (JASP Team [2022]) for MS Windows. Results: Of the 1226 EMRs included in the analysis, 207 had ACS. The actual incidence of ACS was 16.85% in 6 years, higher than the mean predicted 10-year incidence of 14.56 percent (p <0.05). The cases were age and sex-matched with controls and the ASCVD incidence was estimated in the two groups. The mean ASCVD score in the cases was 14.565 ± 8.709 (Min: 1.5, Max: 38.3) and controls 13.114 ± 8.247 (Min: 1.4, Max: 45). The chance of development of ACS increases with elevated systolic blood pressure (per mmHg rise OR: 1.04, 95% CI: 1.03, 1.06; p <0.001), positive family history (OR: 5.70, 95% CI: 3.41, 9.77; p <0.001), statin use (OR: 2.26, 95% CI: 1.46, 3.52; p <0.001), and longer duration of diabetes (for every year increase OR: 1.19, 95% CI: 1.13, 1.25; p <0.001). Conclusion: The ASCVD risk score underestimates the ACS risk in subjects with T2DM under medical supervision and may not differ in those who developed and did not develop ACS. We also conclude that factors like a negative family history (30% less risk), longer duration of diabetes, and higher SBP are relevant in those who developed ACS.