Trabecular bone score in adults with type 1 diabetes: a meta-analysis.

Type 1 diabetes mellitus (T1DM) is associated with a disproportionately high fracture rate despite a minimal decrease in bone mineral density. Though trabecular bone score (TBS), an indirect measure of bone architecture, is lower in adults with T1DM, the modest difference is unlikely to account for the large excess risk and calls for further exploration. INTRODUCTION: Fracture rates in type 1 diabetes mellitus (T1DM) are disproportionately high compared to the modestly low bone mineral density (BMD). Distortion of bone microarchitecture compromises bone quality in T1DM and is indirectly measured by trabecular bone score (TBS). TBS could potentially be used as a screening tool for skeletal assessment; however, there are inconsistencies in the studies evaluating TBS in T1DM. We performed this meta-analysis to address this knowledge gap. METHODS: An electronic literature search was conducted using PubMed, Scopus, and Web of Science resources (all-year time span) to identify studies relating to TBS in T1DM. Cross-sectional and retrospective studies in adults with T1DM were included. TBS and BMD data were extracted for pooled analysis. Fracture risk could not be analyzed as there were insufficient studies reporting it. RESULT: Data from six studies were included (T1DM: n = 378 and controls: n = 286). Pooled analysis showed a significantly lower TBS [standardized mean difference (SMD) = - 0.37, 95% CI - 0.52 to - 0.21; p < 0.00001] in T1DM compared to controls. There was no difference in the lumbar spine BMD (6 studies, SMD - 0.06, 95% CI - 0.22 to 0.09; p = 0.43) and total hip BMD (6 studies, SMD - 0.17, 95% CI - 0.35 to 0.01; p = 0.06) in the case and control groups. CONCLUSIONS: Adults with T1DM have a lower TBS but similar total hip and lumbar spine BMD compared to controls. The risk attributable to the significant but limited difference in TBS falls short of explaining the large excess propensity to fragility fracture in adults with T1DM. Further studies on clarification of the mechanism and whether TBS is suited to screen for fracture risk in adults with T1DM are necessary.

Prandial Insulins: A Person-Centered Choice.

PURPOSE OF REVIEW: Postprandial hyperglycemia, or elevated blood glucose after meals, is associated with the development and progression of various diabetes-related complications. Prandial insulins are designed to replicate the natural insulin release after meals and are highly effective in managing post-meal glucose spikes. Currently, different types of prandial insulins are available such as human regular insulin, rapid-acting analogs, ultra-rapid-acting analogs, and inhaled insulins. Knowledge about diverse landscape of prandial insulin will optimize glycemic management. RECENT FINDINGS: Human regular insulin, identical to insulin produced by the human pancreas, has a slower onset and extended duration, potentially leading to post-meal hyperglycemia and later hypoglycemia. In contrast, rapid-acting analogs, such as lispro, aspart, and glulisine, are new insulin types with amino acid modifications that enhance their subcutaneous absorption, resulting in a faster onset and shorter action duration. Ultra-rapid analogs, like faster aspart and ultra-rapid lispro, offer even shorter onset of action, providing better meal-time flexibility. The Technosphere insulin offers an inhaled route for prandial insulin delivery. The prandial insulins can be incorporated into basal-bolus, basal plus, or prandial-only regimens or delivered through insulin pumps. Human regular insulin, aspart, lispro, and faster aspart are recommended for management of hyperglycemia during pregnancy. Ongoing research is focused on refining prandial insulin replacement and exploring newer delivery methods. The article provides a comprehensive overview of various prandial insulin options and their clinical applications in the management of diabetes.

Long-Term Impact on Offspring (5 to 11 Years of Age) of Metformin Use in Pregnancy in Mothers With Diabetes: A Systematic Review and Meta-Analysis.

OBJECTIVE: Data are scant on the impact of metformin use in gestational diabetes mellitus/diabetes in pregnancy on long-term outcomes in children and mothers beyond 5 years of childbirth. This systematic review and meta-analysis aimed to evaluate the long-term impact of metformin use in pregnancy on children and their mothers. METHODS: Electronic databases were searched for studies evaluating metformin compared with insulin for managing gestational diabetes mellitus/diabetes in pregnancy. The primary outcome was the change in body mass index (BMI) in children at the ages of 5 to 11 years. The secondary outcomes were alterations in other anthropometric measures, obesity, and changes in the levels of lipids and adipocytokines in children and mothers. RESULTS: Children at the age of 9 years born to mothers who were treated with metformin during pregnancy had similar BMI (mean difference [MD], 1.09 kg/m2 [95% confidence interval {CI}, -0.44 to 2.62]; P = .16; I2 = 16%), waist circumference-to-height ratio (MD, 0.13 [95% CI, -0.05 to 0.30]; P = .16; I2 = 94%), dual-energy X-ray absorptiometry (DXA) total fat mass (MD, 0.68 kg [95% CI, -2.39 to 3.79]; P = .66; I2 = 70%), DXA total fat percent (MD, 0.04% [95% CI, -3.44 to 3.51]; P = .98; I2 = 56%), DXA total fat-free mass (MD, 0.81 kg [95% CI, -0.96 to 2.58]; P = .37; I2 = 55%), magnetic resonance imaging visceral adipose tissue volume (MD, 80.97 cm3 [95% CI, -136.47 to 298.41]; P = .47; I2 = 78%), and magnetic resonance spectroscopy liver fat percentage (MD, 0.27% [95% CI, -1.26 to 1.79]; P = .73; I2 = 0%) to those born to mothers who were treated with insulin. Serum adiponectin, leptin, alanine aminotransferase, and ferritin were comparable among groups. In children between the ages of 9 and 11 years, the occurrence of obesity, diabetes, or challenges in motor and social development were comparable between the 2 groups. After 9 years of childbirth, BMI and the risk of developing diabetes were similar between the 2 groups of women. CONCLUSION: Metformin use in pregnancy did not show any adverse effects compared with insulin on long-term outcomes in children and their mothers.

Role of Resmetirom, a Liver-Directed, Thyroid Hormone Receptor Beta-Selective Agonist, in Managing Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Resmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, has recently been approved to treat nonalcoholic steatohepatitis (NASH). This meta-analysis aimed to summarize the efficiency and safety of resmetirom in treating NASH. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) of resmetirom vs placebo in patients with NASH. The primary outcomes were the changes from baseline in hepatic fat content, liver histology, including NASH resolution, and noninvasive markers of hepatic fibrosis. RESULTS: Three randomized controlled trials (n = 2231) met the inclusion criteria. Compared to placebo, resmetirom achieved greater reductions from baseline in hepatic fat content assessed by magnetic resonance imaging proton density fat fraction (for resmetirom 80 mg: MD -27.76% [95%CI: -32.84, -22.69]; for resmetirom 100 mg: MD -36.01% [95%CI: -41.54, -30.48]; P < .00001 for both) and FibroScan controlled attenuation parameter (for resmetirom 80 mg: MD -21.45 dBm [95%CI: -29.37, -13.52]; for resmetirom 100 mg: MD -25.51 dBm [95%CI: -33.53, -17.49]; P < .00001 for both). Resmetirom 80 mg outperformed placebo in NASH resolution and ≥2-point nonalcoholic fatty liver disease activity score reduction. Moreover, resmetirom 80 mg and 100 mg were superior to placebo in cytokeratin-18 (M30) reduction. Greater reductions in liver enzymes, lipids, and reverse triiodothyronine were observed in the resmetirom arms with no impact on triiodothyronine. Nausea and diarrhea were more common with resmetirom than with placebo; other adverse events were comparable. CONCLUSION: Resmetirom improves hepatic fat content, liver enzymes, and fibrosis biomarkers in NASH patients. Resmetirom generally does not affect thyroid function and is well-tolerated.

Hyperprolactinemia Due to Prolactinoma has an Adverse Impact on Bone Health with Predominant Impact on Trabecular Bone: A Systematic Review and Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures. RESULTS: Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 - -0.59); P < 0.0001; I2 = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 - 0.45); P = 0.15; I2 = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 - -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 - -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 - -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 - 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.

Impact of Pheochromocytoma or Paraganglioma on Bone Metabolism: A Systemic Review and Meta-analysis.

INTRODUCTION: Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap. METHODS: Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP). RESULTS: Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery. CONCLUSION: Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.

A gluco-mindful approach to diabetic gastroparesis.

Diabetes gastroparesis is a common manifestation of autonomic neuropathy in persons with long-standing, uncontrolled diabetes. Most discussion about its management revolves around the mitigation of symptoms. Here, we share tips on choosing the right glucose-lowering medication, based upon predominant symptomatology of gastroparesis. We highlight about insulin preparations, and their timing of administration, can be tailored according to need. We also emphasize the need to choose oral glucose lowering drugs with care.

Diabetes Fever.

While diabetes manifests multiple clinical presentations, complications and comorbidities, most modern discourse focuses on the cardiovascular aspects of the syndrome. In this communication, we explore the vast spectrum of fever and diabetes. We highlight the bidirectional interactions between febrile illness and diabetes, as well as drug-drug interactions. These multifaceted connections must be understood by all health care professionals who manage diabetes and/or fever.

Endocrine Fever.

Fever is usually thought to be of an infectious or inflammatory etiology. In this brief communication, we explore the multifaceted connections between fever and endocrine dysfunction. Impaired resistance to infection often leads to fever in conditions like diabetes and Cushing's syndrome. Additionally, several endocrine disorders, including hyperthyroidism, subacute thyroiditis, carcinoid syndrome, and pheochromocytoma, can manifest as fever. Furthermore, fever can be an adverse effect of various endocrine treatments, such as bisphosphonates and antithyroid drugs. We refer to these scenarios as 'endocrine fever.' Increased awareness of these clinical associations can aid in prompt diagnosis and management of these conditions.

Role and Significance of Dietary Protein in the Management of Type 2 Diabetes and Its Complications in India: An Expert Opinion.

BACKGROUND: Obesity, prediabetes, and type 2 diabetes mellitus (T2DM) pose a triple burden in India. Almost two-thirds of people with diabetes (PWD) in India are found to have suboptimal glycemic, blood pressure, and lipid control. Medical nutrition therapy (MNT) in diabetes has emphasized on the amount and type of carbohydrates for years. However, protein, an important macronutrient in diabetes management, needs to be focused upon, especially in India, where the consumption is found to be lower than the recommendations provided by most guidelines. AIM: An expert committee attempted to review the role of dietary protein in the management of T2DM, arrive at a consensus on the significance of increasing dietary protein for various benefits, and offer practical guidance on ways to improve protein intake among Indians. METHODOLOGY: A total of 10 endocrinologists and diabetologists, one nephrologist, and three registered dietitians representing four zones of India formed the expert committee. An in-depth review of literature in the Indian context was carried out, and the draft document was shared with the expert committee, and their views were incorporated into the same. The expert committee then assembled virtually to deliberate on various aspects of the role of protein in T2DM management. The experts from various specialties gave their valuable inputs and suggestions from their extensive personal clinical experience and research work, which helped to reach a consensus on the role and significance of protein in the management of T2DM and its complications in India. RESULTS: There is abundant evidence that MNT is essential for the prevention and management of T2DM and its complications. Experts agreed that increasing protein intake offers myriad health benefits, namely reducing glycemic variability, improving glycemic control, increasing insulin sensitivity, improvement in lipid profile and immunity, and helping in weight management and preservation of muscle mass in PWD. The expert committee suggested aiming for an increase in protein intake by at least 5-10% of the current intake in lieu of carbohydrates in PWD. Experts also highlighted the need for more data quantifying the unmet protein needs in the Indian PWD, especially among vegetarians. Randomized controlled trials to study the effect of protein in diabetes complications such as cardiovascular disease (CVD) and diabetic kidney disease (DKD) and comorbid conditions such as sarcopenia among the Indian population are also warranted. CONCLUSION: Increasing protein quantity and quality in the diets of Indian PWD could significantly contribute to positive health outcomes. Increased protein intake, preferably through dietary sources to meet the requirements and, when required using diabetes-specific protein supplements (DSPS), is recommended in the prevention and control of T2DM.

NANOCRINOLOGY.

We conceptualize and define nanocrinology as the science that studies the nanometric and subnanometric precision that operates in diagnostic and therapeutic endocrinology. It includes advanced generation assays, which can detect low concentrations of hormones, and modern drug delivery systems that allow more efficient delivery of endocrinotropic agents. Nanocrinology is a rapidly growing field of endocrinology, and we call for greater research and adoption of this science.

Insulin hesitancy: A language-based model.

Psychological insulin resistance is a well known entity. This communication proposes the term 'insulin hesitancy' to describe the hesitation that a person living with diabetes experiences, when advised to take insulin. It approaches hesitancy through a triage model, based upon the language used by the patient. By identifying the predominant adverb, "will not", "shall not", or "cannot" in the patient's speech, the diabetes care professional can assess the degree of insulin hesitancy, and tailor his or her conversation towards overcoming it.

The endocrinology of the urinary bladder.

The urinary bladder primarily functions as a reservoir for urine. Apparently, it serves only a mechanical and passive role in the urinary tract, but closer scrutiny reveals that it has several meaningful endocrine interactions. This vital organ has an intricate plexus of neurons that release neurohormones concerned with the functioning of the bladder. Endocrine disorders, most notably diabetes, can cause a broad spectrum of bladder dysfunction. The current review explores the bladder as a source of neurotransmitters, a target for organ damage due to uncontrolled endocrinopathy, a beneficiary of hormonal therapy, and a tool to improve endocrine health.

The diabetic lung.

The coronavirus disease 2019 (COVID-19) pandemic drew our attention to the interplay between pulmonary health and diabetes. The impact of poorly controlled diabetes in worsening COVID-19 outcome is well-recognized. This article explores the broad spectrum of associations between the lung and diabetes. The lung can be the target of organ damage in diabetes, be the origin of a disease process affecting glycaemic status, and also contribute to metabolic complications. Diabetes can be a part of several pulmonary syndromes. Medications used for diabetes can adversely affect the lungs and vice versa. On the other hand, certain glucose-lowering drugs have the potential to improve respiratory function. The close link between diabetes and lung disease calls for a combined approach to managing these conditions.

Primary thyroid lymphoma: Case series of patients from a developing country.

This communication describes the screening and diagnostic tools that can be used to identify obstructive sleep apnoea (OSA). It highlights the need to screen for OSA in all persons with metabolic syndrome and uses the term 'somnometabolic syndrome' to emphasise this. Somnometabolic syndrome can be easily screened at the primary care level, and should be an integral part of diabetes care.

Glucagon-Like Peptide 1 Receptor Agonists (GLP1RA) and Sodium-glucose co-transporter-2 inhibitors (SGLT2i): Making a pragmatic choice in diabetes management.

The availability of newer glucose-lowering drugs has created opportunities for comprehensive diabetes care. Two classes of drugs, GLP1RA (glucagon-like peptide 1 receptor agonists), and SGLT2i (sodium glucose cotransporter 2 inhibitors) have demonstrated their efficacy in glucose control as well as cardiovascular risk reduction. While both can be used together, there is an ongoing debate regarding their relative advantages and limitations. We present a clinical perspective to compare and control these two classes of drugs, and promote rational prescription in diabetes praxis.

Prediabetes: A pragmatic triage for preventive pharmacotherapy.

Prediabetes is a commonly encountered condition that bears a significant risk of progression to diabetes. While lifestyle modification remains the treatment of choice, drug therapy is emerging as a therapeutic option to prevent its progression to diabetes and associated complications. This paper proposes a comprehensive triage system to identify persons with prediabetes who may benefit from preventive pharmacotherapy.

Diabetes and severe COVID-19 infection: Connecting the dots.

Diabetes is a significant risk factor for coronavirus disease 2019 (COVID-19) severity, poor prognosis, and mortality. Uncontrolled hyperglycaemia is associated with impaired innate and adaptive immunity predisposing to severe infection. In addition, there are other mechanisms linked to diabetes such as the upregulation of angiotensin-converting enzyme-2 receptor that might aid in viral entry and spread. The chronic low-grade inflammation and endothelial dysfunction might provide the backdrop to the development of cytokine storm and thromboembolic complications. Understanding the pathophysiology behind severe COVID-19 in diabetes will help to optimise management.

Metabolic optimization in diabetes: A hierarchial model.

Diabetes care involves a rational understanding of the complex clinical and pharmacological interactions. If we have clarity of thought in our goals and aims, it becomes much easier to plan treatment strategies. The hierarchal model of metabolic modulation and optimization represents an effort to achieve simplicity and straightforwardness in deciding aims of diabetes care, planning approaches, and choosing the right arsenal for intervention. This model lists the targets of therapy as symptomatic, glucometabolic, vasculometabolic, barometabolic and viscerometabolic optimization.

Pulmocrinology: Interplay of pulmonary and endocrine diseases.

The interplay between pulmonary and endocrine systems modify and influence the pathogenesis and manifestation of several disease processes. Endocrine dysfunctions predispose to numerous pulmonary disorders, including various respiratory infections. On the other hand, pulmonary conditions like chronic obstructive pulmonary disease and obstructive sleep apnoea can produce critical metabolic and endocrine derangements. Varied manifestations such as primary adrenal insufficiency, hypophysitis and hypercalcaemia can result from chronic granulomatous conditions like tuberculosis and sarcoidosis. Various endocrine consequences of coronavirus disease 2019 are also getting apparent during the pandemic. Tumours of the lung can secrete different hormones that give rise to several endocrine paraneoplastic syndromes. This review focuses on the clinically relevant interaction between these two diverse but interrelated systems. We suggest the portmanteau term "pulmocrinology" to delineate the multifaceted relationship evident in pathophysiology, clinical features and therapeutics of various pulmonary and endocrine disorders.