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.

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.

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.

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.

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.

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.

South Asian Endocrinology: Challenges and Concerns, Collaboration and Consolidation.

The practice of endocrinology in South Asia poses many challenges but simultaneously offers unique opportunities. The population in this region is predisposed to diabetes and cardiovascular disease at a much lower body mass index compared to Caucasians. Dietary deficiencies, higher prevalence of infection and distinct environmental and genetic factors further complicate the presentation of endocrine disorders. Over the past few decades, important breakthroughs have been made to confront these challenges. Collaboration among the endocrine fraternity of the South Asian countries will help to consolidate these gains and pave the way forward for a healthier region.

PURsuit of Endocrinology (PURE): A National Survey among First-Year Endocrinology Residents Across India.

Background: Endocrinology has been a popular choice of super-specialisation in India in recent years. The PURsuit of Endocrinology (PURE) survey aims to determine the factors that facilitated the selection of endocrinology as the area of super-specialisation among first-year residents across India. Methods: We conducted an electronic questionnaire-based survey among first-year residents across India. The questionnaire evaluated the respondents' demographics, feeder speciality, challenges during preparation, factors influencing endocrinology as a career preference, unappealing aspects of the subject and future career plans. Results: A total of 81 (43 males and 38 females) responses were recorded. The mean age was 31.3 ± 3.3 years, with 63% married. Internal medicine was the feeder speciality in 92.5% of cases. Work-life balance was the critical consideration for pursuing endocrinology in 91.4%, followed by professional satisfaction (64.2%) and the scope of having a solo practice (43.2%). Interestingly, there was less emphasis on monetary satisfaction (12.3%). Almost half of the respondents intended to practice in a government academic institution (46.9%) or in an independent set-up (45.7%). Conclusions: The PURE survey suggests that work-life balance and professional satisfaction are the key driving factors behind the choice of endocrinology. An increasing interest among the residents to join as faculty in academic institutions, apart from having self-owned private clinics, is a welcome finding.

Cardiac Autonomic Neuropathy in Prediabetes: A Case-Control Study.

Introduction: Early detection and diagnosis of diabetic autonomic neuropathy, especially cardiac autonomic neuropathy (CAN), have gained attention recently because of their elevated cardiovascular mortality risk. Although the connection between type 2 diabetes mellitus and autonomic neuropathy is well established, evidence is emerging that the association might predate the stage of prediabetes. Objective: The present study was undertaken to compare the prevalence of CAN in prediabetes versus that in normoglycemic controls. Materials and Methods: The study population was selected by purposive sampling from individuals attending a tertiary care hospital from January 2018 to June 2019. Fifty individuals with prediabetes diagnosed by the American Diabetes Association's glycated haemoglobin criteria and 50 age- and gender-matched healthy controls were recruited. CAN was assessed by standard cardiovascular reflex tests, as described by Ewing and Clarke. Changes in R-R with deep breathing, Valsalva manoeuver, and changes in blood pressure (BP) in response to standing and sustained handgrip were evaluated. Three-time domains [standard deviation of normal-to-normal intervals (SDNN), root mean square of successive RR intervals (rMSSD) and percentage of successive normal to normal R-R (NN) intervals that differ by more than 50 ms (pNN50)] and four frequency domain indices [very low-frequency band (VLF), low-frequency band (LF), high-frequency band (HF), LF/HF ratio) of heart rate variability (HRV)] were examined. Results: The mean heart rate was 71.37 ± 7.94 and 65.59 ± 8.73 beats/min in patients with prediabetes and controls, respectively (P < 0.05). All three-time-domain indices of HRV were significantly lower in persons with prediabetes compared to controls. The peak frequency of LF, peak power of LF, normalised unit of LF, and LF/HF ratio was significantly lower in subjects with prediabetes than in controls. There was no difference in the traditional cardiovascular autonomic reflex testing. Conclusion: Our study demonstrates the presence of subclinical autonomic dysfunction in persons with prediabetes. Early detection of CAN in prediabetes can have future implications for cardiovascular risk reduction.

Efficacy and Safety of Novel Thiazolidinedione Rivoglitazone in Type-2 Diabetes a Meta-Analysis.

No meta-analysis has analyzed the safety and efficacy of rivoglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge gap. Electronic databases were searched for RCTs involving T2DM patients receiving rivoglitazone in the intervention arm, and placebo/active comparator in the control arm. The primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids, and adverse events. From initially screened 24 articles, data from 3 RCTs (3591 patients) that fulfilled all criteria was analzsed. HbA1c was significantly lower with standard-dose (1 mg/d) [MD-0.86% (95%CI:-1.11--0.61); P < 0.01; I2 = 87%] and high-dose (1.5-2 mg/d) [MD-0.97%(95%CI:-1.03--0.90); P < 0.01; I2 = 19%] rivoglitazone compared to placebo. When compared to pioglitazone (30-45 mg/d), HbA1c lowering was comparable with standard-dose [MD 0.05%(95%CI:-0.01 - 0.11); P = 0.08; I2 = 11%], but superior with high-dose [MD -0.11%(95%CI:-0.18- -0.04); P < 0.01; I2 = 0%] rivoglitazone. Triglycerides were significantly lower with standard-dose [MD-17.95 mg/dl (95%CI:-34.23--1.66); P = 0.03; I2 = 0%] and high-dose [MD-40.41 mg/dl (95%CI:-72.90- -7.93);P = 0.01;I2 = 71%] rivoglitazone compared to placebo. Adiponectin significantly improved with standard-dose [MD 7.94 ng/ml (95%CI: 5.48-10.39); P < 0.01;I2 = 98%] and high-dose [MD 13.82 ng/ml (95%CI: 8.16-19.48); P < 0.01; I2 = 100%] rivoglitazone compared to placebo. hsCRP was significantly lower with standard-dose [MD -1.00 mg/L (95% CI: -1.20 - -0.80); P < 0.01; I2 = 6%] and high-dose [MD -1.50 mg/L (95%CI:-1.59- -1.40); P < 0.01; I2 = 0%] rivoglitazone compared to placebo. Treatment-emergent adverse events with standard-dose [Risk ratio (RR) 1.16 (95%CI: 0.84 -1.60); P = 0.38; I2 = 0%] and high-dose [RR1.34 (95%CI: 0.99-1.83); P = 0.06; I2 = 0%] rivoglitazone was comparable to placebo. Severe adverse events with standard-dose [RR1.88 (95%CI: 0.69-5.12);P = 0.22;I2 = 0%] and high-dose [RR 1.27 (95% CI: 0.45 - 3.59); P = 0.68; I2 = 0%] rivoglitazone was comparable to placebo. This meta-analysis highlights the good glycaemic efficacy and safety of both standard and high-dose rivoglitazone, and appears to be better than lobeglitazone in T2DM.

Metformin in COVID-19: Is There a Role Beyond Glycemic Control?

Context: The coronavirus disease 2019 (COVID-19) pandemic is still a cause of worldwide health concern. Diabetes and its associated comorbidities are risk factors for mortality and morbidity in COVID-19. Selecting the right antidiabetic drug to achieve optimal glycemic control might mitigate some of the negative impacts of diabetes. Metformin continues to be the most widely administered antidiabetic agent. There is evidence of its beneficial outcome in COVID-19 independent of its glucose-lowering effect. Evidence Acquisition: A thorough literature search was conducted in PubMed, Google Scholar, Scopus, and Web of Science to identify studies investigating metformin in COVID-19. Results: Several overlapping mechanisms have been proposed to explain its antiviral properties. It could bring about conformational changes in the angiotensin-converting enzyme-2 receptor and decrease viral entry. The effects on the mammalian target of the rapamycin pathway and cellular pH have been proposed to reduce viral protein synthesis and replication. The immunomodulatory effects of metformin might counter the detrimental effects of hyperinflammation associated with COVID-19. Conclusions: These findings call for broader metformin usage to manage hyperglycemia in COVID-19.

Verapamil improves One-Year C-Peptide Levels in Recent Onset Type-1 Diabetes: A Meta-Analysis.

Meta-analysis studying the role of verapamil in improving C-peptide in people with recent-onset type-1 diabetes (T1DM) has not been conducted to date. We undertook this meta-analysis to address this knowledge gap. Electronic databases were systematically reviewed for RCTs having individuals with T1DM receiving verapamil in the treatment arm and placebo in the control arm over the standard of care. The primary outcome was to evaluate changes in the C-peptide area under the curve (AUC) at a one-year follow-up. Secondary outcomes were to assess alterations in C-peptide AUC, glycated hemoglobin (HbA1c), blood pressure, heart rate, and side effects at different time intervals over a one-year follow-up. From the initially screened 27 articles, data from two RCTs (112 patients) satisfied the inclusion criteria and were analyzed. Compared to placebo, C-peptide AUC in individuals receiving verapamil was not different at three months [MD 0.17 nmol/L (95%CI: -0.05-0.38); P = 0.13; I2 = 86%] but significantly higher at 1-year [MD 0.27 nmol/L (95%CI: 0.19-0.35); P < 0.01; I2 = 12%]. The verapamil arm showed similar changes in HbA1C at three months [MD 0.23% (95%CI: -0.43-0.90); P = 0.49; I2 = 88%] and 1-year [MD 0.18% (95% CI: -0.74 - 1.10); P = 0.70; I2 = 89%] compared to placebo. Occurrence of treatment-emergent adverse events [Risk ratio (RR) 1.90 (95%CI: 0.52-6.91); P = 0.33; I2 = 63%], serious adverse events [RR 1.40 (95%CI: 0.50-3.93); P = 0.53], constipation [RR4.11 (95%CI: 0.93-18.13); P = 0.06; I2 = 0%], headache [RR0.48 (95%CI: 0.16-1.43); P = 0.19; I2 = 0%], severe hypoglycemia [RR 0.87 (95%CI: 0.06 - 13.51); P = 0.92] were comparable across groups. Verapamil was well tolerated, and its use over one year was associated with significant improvements in C-peptide AUC though the HbA1c remained unchanged.

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.

The AACE 2022 Guideline: An Academic Appraisal.

The American Association of Clinical Endocrinology (AACE) 2022 guideline provides comprehensive and evidence-based guidance on contemporary diabetes management. The statement reiterates the importance of person-centred, team-based care for optimum outcomes. The recent strides to prevent cardiovascular and renal complications have been aptly incorporated. The recommendations on virtual care, continuous glucose monitors, cancer screening, infertility and mental health are relevant. However, focused discussions on non-alcoholic fatty liver disease and geriatric diabetes care could have been helpful. Outlining targets for prediabetes care is a notable addition and is likely to be the most effective strategy in addressing the rising burden of diabetes.

Expression of programmed death ligand-1 (PD-L1) and tumor infiltrating lymphocytes (TILs) in breast carcinoma and their clinical significance.

Background and Aim: Carcinoma of the breast is the second most common cause of cancer death in women. Expression of programmed death ligand-1 (PD-L1) in cancer cells plays an important role in tailored therapy. This can be evaluated by immunohistochemistry using a monoclonal PD-L1 antibody in formalin-fixed and paraffin-embedded (FFPE) specimens. Our aim was to evaluate the expression of PD-L1 and tumor infiltrating lymphocytes (TILs) in invasive carcinoma of breast and their clinicopathological correlation. Materials and Methods: Immunohistochemical staining for PD-L1 and TILs was done in paraffin-embedded tissues of histologically diagnosed 50 cases of breast carcinoma. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) 22 software. Results: Out of these 50 cases, PD-L1 and TIL expression were seen in 16 (32%) cases and 18 (36%) cases, respectively. PD-L1 positivity was seen in 33.33% cases of grade 1 breast carcinoma, 13.79% of cases of grade 2 breast carcinoma, and in 75% case of grade 3 breast carcinoma. TILs showed positivity in 6.9% cases of grade 1 breast carcinoma, 13.79% of cases of grade 2 breast carcinoma, and in 100% cases of grade 3 breast carcinoma. Proportion of patients having PD-L1 expression was higher in grade 3 carcinoma than in grade 1 or 2. The differences were statistically significant (Chi-square value = 13.417, degree of freedom = 1, P < 0.05). The Chi-square value for TILs was 28.07, degree of freedom was 1, and P value was <0.05, which was statistically significant. Conclusion: Both PD-L1 and TILs showed maximum positivity in grade 3 breast carcinoma.

Discharge Planning for People with Inpatient Hyperglycaemia: A Review on Pharmacological Management.

Inadequate glycaemic control post-discharge is the root cause of readmission in people with diabetes mellitus (DM) and is often linked to improper discharge planning (DP). A structured DP plays a crucial role in ensuring continuing home care and avoiding readmissions. DP should help patients in self-care and provide appropriate guidance to maintain optimal glycaemic control. There is a scarcity of reports and recommendations on the proper DP for people with DM on insulin therapy. The present review provides important consideration based on experts' opinions from the National Insulin and Incretin summit (NIIS), focusing on the effective treatment strategies at the time of discharge, especially for insulin therapy. A review of literature from PubMed and Embase was conducted. The consensus was derived, and recommendations were made on effective DP for patients with DM. Recommendations were drawn at the NIIS for post-discharge treatment for medical and surgical cases, stress-induced hyperglycaemia, elderly, pregnant women, and coronavirus disease 2019 (COVID-19) cases. The committee also recommended a comprehensive checklist to assist the physicians during discharge.

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.

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.

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis.

BACKGROUND AND AIMS: No meta-analysis has analysed the safety and efficacy of lobeglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for RCTs involving type-2 diabetes patients receiving lobeglitazone in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids and adverse events. RESULTS: From initially screened 65 articles, data from 4 RCTs (828 patients) which fulfilled all criteria was analysed. Over 24 weeks, when compared to sitagliptin 100 mg/d and half maximal pioglitazone dose (15 mg/d), lobeglitazone 0.5 mg/day had comparable impact on HbA1c [MD 0.03% (95%CI: 0.11-0.17); P = 0.65; I2 = 0%], fasting glucose [MD 1.47 mg/dl (95%CI: 4.66-7.60); P = 0.64; I2 = 0%], triglycerides [MD-9.96 mg/dl (95%CI: 43.55-23.62); P = 0.56; I2 = 81%], LDL-cholesterol [MD0.74 mg/dl (95%CI: 4.60-6.09); P = 0.79; I2 = 0%] and HDL-cholesterol [MD1.55 mg/dl (95%CI: 3.72-6.82); P = 0.56]. Occurrence of treatment-emergent adverse events (AEs) [RR 1.07 (95% CI:0.78-1.47); P = 0.67; I2 = 0%] and severe AEs [RR 1.05(95%CI: 0.42-2.65); P = 0.91; I2 = 0%] were similar. Edema and weight gain were significantly higher with lobeglitazone compared to controls [RR 2.58 (95%CI: 1.08-6.17); P = 0.03; I2 = 0%]. Lobeglitazone 0.5 mg/d compared to half-maximal pioglitazone (15 mg/d), had similar edema and weight gain [RR 1.65 95% CI: 0.78-1.47)]. BMD percent changes at neck of femur was comparable in both groups [MD 0.07% (95%CI: 0.19-0.33); P = 0.60; I2 = 91%]. Low dose lobeglitazone (0.25 mg/d) was inferior to high dose lobeglitazone (0.5 mg/d) with regards to glycaemic efficacy with advantage of lower weight gain and edema. CONCLUSION: The current evidence makes lobeglitazone unlikely to replace pioglitazone as the preferred thiazolidinedione in T2DM.