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Frontiers in Endocrinology 2022A large number of inborn errors of metabolism present with hypoglycemia. Impairment of glucose homeostasis may arise from different biochemical pathways involving... (Review)
Review
A large number of inborn errors of metabolism present with hypoglycemia. Impairment of glucose homeostasis may arise from different biochemical pathways involving insulin secretion, fatty acid oxidation, ketone bodies formation and degradation, glycogen metabolism, fructose and galactose metabolism, branched chain aminoacids and tyrosine metabolism, mitochondrial function and glycosylation proteins mechanisms. Historically, genetic analysis consisted of highly detailed molecular testing of nominated single genes. However, more recently, the genetic heterogeneity of these conditions imposed to perform extensive molecular testing within a useful timeframe new generation sequencing technology. Indeed, the establishment of a rapid diagnosis drives specific nutritional and medical therapies. The biochemical and clinical phenotypes are critical to guide the molecular analysis toward those clusters of genes involved in specific pathways, and address data interpretation regarding the finding of possible disease-causing variants at first reported as variants of uncertain significance in known genes or the discovery of new disease genes. Also, the trio's analysis allows genetic counseling for recurrence risk in further pregnancies. Besides, this approach is allowing to expand the phenotypic characterization of a disease when pathogenic variants give raise to unexpected clinical pictures. Multidisciplinary input and collaboration are increasingly key for addressing the analysis and interpreting the significance of the genetic results, allowing rapidly their translation from bench to bedside.
Topics: Female; Genetic Testing; Humans; Hypoglycemia; Molecular Diagnostic Techniques; Phenotype; Pregnancy
PubMed: 35422763
DOI: 10.3389/fendo.2022.826167 -
Clinical Cardiology Aug 2014Hypoglycemia in people with diabetes mellitus (DM) has been potentially linked to cardiovascular morbidity and mortality. Pathophysiologically, hypoglycemia triggers... (Review)
Review
Hypoglycemia in people with diabetes mellitus (DM) has been potentially linked to cardiovascular morbidity and mortality. Pathophysiologically, hypoglycemia triggers activation of the sympathoadrenal system, leading to an increase in counter-regulatory hormones and, consequently, increased myocardial workload and oxygen demand. Additionally, hypoglycemia triggers proinflammatory and hematologic changes that provide the substrate for possible myocardial ischemia in the already-diseased diabetic cardiovascular system. Hypoglycemia creates electrophysiologic alterations causing P-R-interval shortening, ST-segment depression, T-wave flattening, reduction of T-wave area, and QTc-interval prolongation. Patients who experience hypoglycemia are at an increased risk of silent ischemia as well as QTc prolongation and consequent arrhythmias. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed an increase in all-cause mortality with intensive glycemic control, whereas the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study and Veteran's Affairs Diabetes Trial (VADT) showed no benefit with aggressive glycemic control. Women, elderly patients, and those with renal insufficiency are more vulnerable to hypoglycemic events. In fact, hypoglycemia is the most common metabolic complication experienced by older patients with DM in the United States. The concurrent use of medications like β-blockers warrants caution in DM because they can mask warning signs of hypoglycemia. Here we aim to elucidate the pathophysiology, review the electrocardiographic changes, analyze the current clinical literature, and consider the safety considerations of hypoglycemia as it relates to the cardiovascular system. In conclusion, in the current era of DM and its vascular ramifications, hypoglycemia from a cardiologist's perspective deserves due attention.
Topics: Arrhythmias, Cardiac; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus; Heart Conduction System; Heart Rate; Humans; Hypoglycemia; Hypoglycemic Agents; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors
PubMed: 24895268
DOI: 10.1002/clc.22288 -
Polskie Archiwum Medycyny Wewnetrznej Oct 2016Hypoglycemia is the major barrier for optimal glycemic control in patients on maintenance insulin therapy. It is widely known that good glycemic control leads to... (Review)
Review
Hypoglycemia is the major barrier for optimal glycemic control in patients on maintenance insulin therapy. It is widely known that good glycemic control leads to prevention of or delay in the development of microvascular complications, and can reduce macrovascular events. It is thought that hypoglycemia may predispose patients to cognitive deterioration and may negatively affect the cardiovascular system. Hypoglycemia per se can contribute to a blunted counterregulatory response and disabling hypoglycemia, while hypoglycemia avoidance restores normal response to low blood glucose levels. There are some new approaches to reducing the incidence of hypoglycemia occurrence, including education programs, insulin regimens, the type of insulin used, as well as new technologies for insulin delivery and blood glucose measurement. However, none of these approaches have been able to eliminate the incidence of hypoglycemia completely. The current paper summarizes the physiology and major aspects of hypoglycemia‑related health consequences and possible ways to avoid hypoglycemia.
Topics: Cardiovascular Diseases; Cognition Disorders; Diabetes Complications; Diabetes Mellitus; Humans; Hypoglycemia; Insulin
PubMed: 27906880
DOI: 10.20452/pamw.3586 -
Current Diabetes Reports Aug 2016Hypoglycemia is a frequent occurrence in children and adolescents with type 1 diabetes. A variety of efforts have been made to standardize the definition of hypoglycemia... (Review)
Review
Hypoglycemia is a frequent occurrence in children and adolescents with type 1 diabetes. A variety of efforts have been made to standardize the definition of hypoglycemia and to define one of its most significant psychosocial consequences-fear of hypoglycemia (FOH). In addition to documenting the experience of FOH in children and adolescents type 1 diabetes and their parents, studies have investigated the relations between FOH and glycemic control and diabetes technology use. This review provides a summary of the recent FOH literature as it applies to pediatric type 1 diabetes.
Topics: Adolescent; Behavior; Child; Diabetes Mellitus, Type 1; Fear; Female; Humans; Hypoglycemia; Male; Parents; Risk Factors
PubMed: 27370530
DOI: 10.1007/s11892-016-0762-2 -
BMJ Open Diabetes Research & Care Jul 2022The number of patients with diabetes is increasing among older adults in the USA, and it is expected to reach 26.7 million by 2050. In parallel, the percentage of older... (Review)
Review
The number of patients with diabetes is increasing among older adults in the USA, and it is expected to reach 26.7 million by 2050. In parallel, the percentage of older patients with diabetes in long-term care facilities (LTCFs) will also rise. Currently, the majority of LTCF residents are older adults and one-third of them have diabetes. Management of diabetes in LTCF is challenging due to multiple comorbidities and altered nutrition. Few randomized clinical trials have been conducted to determine optimal treatment for diabetes management in older adults in LTCF. The geriatric populations are at risk of hypoglycemia since the majority are treated with insulin and have different levels of functionality and nutritional needs. Effective approaches to avoid hypoglycemia should be implemented in these settings to improve outcome and reduce the economic burden. Newer medication classes might carry less risk of developing hypoglycemia along with the appropriate use of technology, such as the use of continuous glucose monitoring. Practical clinical guidelines for diabetes management including recommendations for prevention and treatment of hypoglycemia are needed to appropriately implement resources in the transition of care plans in this vulnerable population.
Topics: Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus; Humans; Hypoglycemia; Long-Term Care
PubMed: 35858714
DOI: 10.1136/bmjdrc-2021-002705 -
The Journal of Pediatrics Jun 2022To evaluate, using video documentation, the sensitivity, specificity, and interobserver reliability of visualizable signs of neonatal hypoglycemia at different glucose... (Clinical Trial)
Clinical Trial
OBJECTIVES
To evaluate, using video documentation, the sensitivity, specificity, and interobserver reliability of visualizable signs of neonatal hypoglycemia at different glucose concentrations in neonates.
STUDY DESIGN
In a prospective cohort study of 145 neonates with and without risk factors for hypoglycemia, 430 videos were recorded before blood glucose measurements and analyzed by 10 blinded investigators of different professions. The primary outcome measures were sensitivity and specificity for clinical detection of hypoglycemia.
RESULTS
The overall sensitivity to detect low blood glucose (<55 mg/dL [<3.1 mmol/L]) based on signs was 30%, and the specificity was 82%. Significantly more investigators suspected hypoglycemia while viewing videos of infants with blood glucose levels of 46-54 mg/dL (2.6-3.0 mmol/L) and 30-45 mg/dL (1.7-2.5 mmol/L) compared with ≥55 mg/dL (≥3.1 mmol/L) (29 ± 3% and 31 ± 4% vs 18 ± 1%; P = .001; P = .007). After 48 hours of life, significantly more investigators suspected hypoglycemia in videos of infants with blood glucose levels of ≤45 mg/dL (≤2.5 mmol/L) compared with blood glucose levels of >45 mg/dL (>2.5 mmol/L) (28.9 ± 8.1% vs 10.9 ± 1.8%; P = .007). For blood glucose levels 30-45 mg/dL (1.7-2.5 mmol/L), sensitivity varied widely between investigators, ranging from 5% to 62%. Three hypoglycemic episodes <30 mg/dL (<1.7 mmol/L) were only partially recognized.
CONCLUSIONS
Clinical observation of signs is neither sensitive nor specific to detect neonatal hypoglycemia, and there are large interobserver differences. Thus, guidelines on neonatal hypoglycemia should reconsider whether distinguishing between asymptomatic and symptomatic hypoglycemia provides useful information for the management of neonatal hypoglycemia, because it may pose a risk for systematic under-recognition and undertreatment, leading to an increased risk for neurodevelopmental impairment.
TRIAL REGISTRATION
German Clinical Trials Register: DRKS00021500 www.drks.de/drks_web/setLocale_EN.do.
Topics: Blood Glucose; Humans; Hypoglycemia; Infant; Infant, Newborn; Infant, Newborn, Diseases; Prospective Studies; Reproducibility of Results
PubMed: 35240137
DOI: 10.1016/j.jpeds.2022.02.045 -
Frontiers in Endocrinology 2020Severe hypoglycemia is defined as a condition with serious cognitive dysfunction, such as a convulsion and coma, requiring external help from other persons. This... (Review)
Review
Severe hypoglycemia is defined as a condition with serious cognitive dysfunction, such as a convulsion and coma, requiring external help from other persons. This condition is still lethal and is reported to be the cause of death in 4-10% in children and adolescents with type 1 diabetes. The incidence of severe hypoglycemia in the pediatric population was previously reported as high as more than 50-100 patient-years; however, there was a decline in the frequency of severe hypoglycemia during the past decades, and relationship with glycemic control became weaker than previously reported. A lot of studies have shown the neurological sequelae with severe hypoglycemia as cognitive dysfunction and abnormalities in brain structure. This serious condition also provides negative psychosocial outcomes and undesirable compensatory behaviors. Various possible factors, such as younger age, recurrent hypoglycemia, nocturnal hypoglycemia, and impaired awareness of hypoglycemia, are possible risk factors for developing severe hypoglycemia. A low HbA level is not a predictable value for severe hypoglycemia. Prevention of severe hypoglycemia remains one of the most critical issues in the management of pediatric patients with type 1 diabetes. Advanced technologies, such as continuous glucose monitoring (CGM), intermittently scanned CGM, and sensor-augmented pump therapy with low-glucose suspend system, potentially minimize the occurrence of severe hypoglycemia without worsening overall glycemic control. Hybrid closed-loop system must be the most promising tool for achieving optimal glycemic control with preventing the occurrence of severe hypoglycemia in pediatric patients with type 1 diabetes.
Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Prevalence
PubMed: 33042005
DOI: 10.3389/fendo.2020.00609 -
Transactions of the American Clinical... 2014It is well established that diabetes can lead to multiple microvascular and macrovascular complications. Several large scale randomized multicenter studies have shown... (Review)
Review
It is well established that diabetes can lead to multiple microvascular and macrovascular complications. Several large scale randomized multicenter studies have shown that intensifying glucose control decreases microvascular and, to a certain extent, macrovascular complications of diabetes. However, intensifying glucose control in both type 1 and type 2 diabetes increases the risk of developing hypoglycemia, one of the most feared complications of people with the disease. The mechanisms responsible for intensive therapy causing increased hypoglycemia in patients with diabetes have been extensively investigated. It is now known that a single episode of hypoglycemia can blunt the body's normal counterregulatory defenses against subsequent hypoglycemia or exercise. Similarly, a single bout of exercise can also blunt counterregulatory responses against subsequent hypoglycemia. Both neuroendocrine and autonomic nervous system responses are reduced by prior hypoglycemia and/or exercise. Work from several laboratories has identified multiple physiologic mechanisms involved in the pathogenesis of this hypoglycemia and exercise-associated counterregulatory failure. By continuing to study these mechanisms, some promising approaches to amplify counterregulatory responses to hypoglycemia are being discovered.
Topics: Animals; Autonomic Nervous System; Autonomic Nervous System Diseases; Blood Glucose; Cardiovascular Diseases; Exercise; Humans; Hypoglycemia; Hypoglycemic Agents; Prognosis; Risk Factors
PubMed: 25125745
DOI: No ID Found -
Current Diabetes Reports Sep 2019New more stable formulations of glucagon have recently become available, and these provide an opportunity to expand the clinical roles of this hormone in the prevention... (Review)
Review
PURPOSE OF REVIEW
New more stable formulations of glucagon have recently become available, and these provide an opportunity to expand the clinical roles of this hormone in the prevention and management of insulin-induced hypoglycemia. This is applicable in type 1 diabetes, hyperinsulinism, and alimentary hypoglycemia. The aim of this review is to describe these new formulations of glucagon and to provide an overview of current and future therapeutic opportunities that these may provide.
RECENT FINDINGS
Four main categories of glucagon formulation have been studied: intranasal glucagon, biochaperone glucagon, dasiglucagon, and non-aqueous soluble glucagon. All four have demonstrated similar glycemic responses to standard glucagon formulations when administered during hypoglycemia. In addition, potential roles of these formulations in the management of congenital hyperinsulinism, alimentary hypoglycemia, and exercise-induced hypoglycemia in type 1 diabetes have been described. As our experience with newer glucagon preparations increases, the role of glucagon is likely to expand beyond the emergency use that this medication has been limited to in the past. The innovations described in this review likely represent early examples of a pending large repertoire of indications for stable glucagon.
Topics: Blood Glucose; Diabetes Mellitus, Type 1; Exercise; Glucagon; Homeostasis; Hormones; Humans; Hypoglycemia
PubMed: 31493043
DOI: 10.1007/s11892-019-1216-4 -
Primary Care Diabetes Apr 2014Hypoglycemia continues to be a significant problem for patients with diabetes. The incidence remains high but patients may also be under-reporting hypoglycemic events... (Review)
Review
Hypoglycemia continues to be a significant problem for patients with diabetes. The incidence remains high but patients may also be under-reporting hypoglycemic events for various reasons, including hypoglycemia unawareness and deliberate non-reporting. This restricts the ability of healthcare professionals to manage treatment effectively. The aim of this article is to focus specifically on the issues associated with hypoglycemia unawareness and undisclosed hypoglycemia. The article provides general practice teams with an overview of these problems and, through patient narratives, suggests ways to mitigate them.
Topics: Awareness; Biomarkers; Blood Glucose; Diabetes Mellitus; Health Knowledge, Attitudes, Practice; Humans; Hypoglycemia; Hypoglycemic Agents; Patient Education as Topic; Risk Factors; Treatment Outcome
PubMed: 24100231
DOI: 10.1016/j.pcd.2013.09.002