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Molecular Neurobiology Dec 2018Diabetes is a metabolic disease afflicting millions of people worldwide. A substantial fraction of world's total healthcare expenditure is spent on treating diabetes.... (Review)
Review
Diabetes is a metabolic disease afflicting millions of people worldwide. A substantial fraction of world's total healthcare expenditure is spent on treating diabetes. Hypoglycemia is a serious consequence of anti-diabetic drug therapy, because it induces metabolic alterations in the brain. Metabolic alterations are one of the central mechanisms mediating hypoglycemia-related functional changes in the brain. Acute, chronic, and/or recurrent hypoglycemia modulate multiple metabolic pathways, and exposure to hypoglycemia increases consumption of alternate respiratory substrates such as ketone bodies, glycogen, and monocarboxylates in the brain. The aim of this review is to discuss hypoglycemia-induced metabolic alterations in the brain in glucose counterregulation, uptake, utilization and metabolism, cellular respiration, amino acid and lipid metabolism, and the significance of other sources of energy. The present review summarizes information on hypoglycemia-induced metabolic changes in the brain of diabetic and non-diabetic subjects and the manner in which they may affect brain function.
Topics: Animals; Brain; Diabetes Mellitus; Energy Metabolism; Humans; Hypoglycemia; Recurrence; Signal Transduction
PubMed: 29637442
DOI: 10.1007/s12035-018-1044-6 -
Current Atherosclerosis Reports Sep 2013Severe hypoglycemia in patients with diabetes is associated with increased risk of adverse cardiovascular events and death. Recent large randomized clinical trials in... (Review)
Review
Severe hypoglycemia in patients with diabetes is associated with increased risk of adverse cardiovascular events and death. Recent large randomized clinical trials in individuals with type 2 diabetes have shown that intensive glycemic control may result in increased mortality, and hypoglycemia has been investigated as a possible cause. Acute hypoglycemia is a proarrhythmic, proinflammatory, and prothrombotic state, and several mechanisms have been proposed to explain how hypoglycemia might increase cardiovascular morbidity and mortality. However, data from large clinical trials do not provide strong evidence to establish hypoglycemia as a cause of increased mortality. Severe hypoglycemia is also a marker of frailty and a predictor of adverse outcomes in patients with diabetes. Individualized therapy should be the goal in patients with diabetes to avoid severe hypoglycemia and any related adverse outcomes.
Topics: Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Risk Factors
PubMed: 23881546
DOI: 10.1007/s11883-013-0351-7 -
Journal of Diabetes Science and... Jan 2012The practice of glycemic control with intravenous insulin in critically ill patients has brought clinical focus on understanding the effects of hypoglycemia, especially... (Review)
Review
BACKGROUND
The practice of glycemic control with intravenous insulin in critically ill patients has brought clinical focus on understanding the effects of hypoglycemia, especially in children. Very little is published on the impact of hypoglycemia in this population. We aimed to review the existing literature on hypoglycemia in critically ill neonates and children.
METHODS
We performed a systematic review of the literature up to August 2011 using PubMed, Ovid MEDLINE and ISI Web of Science using the search terms "hypoglycemia or hypoglyc*" and "critical care or intensive care or critical illness". Articles were limited to "all child (0-18 years old)" and "English".
RESULTS
A total of 513 articles were identified and 132 were included for review. Hypoglycemia is a significant concern among pediatric and neonatal intensivists. Its definition is complicated by the use of a biochemical measure (i.e., blood glucose) for a pathophysiologic problem (i.e., neuroglycopenia). Based on associated outcomes, we suggest defining hypoglycemia as <40-45 mg/dl in neonates and <60-65 mg/dl in children. Below the suggested threshold values, hypoglycemia is associated with worse neurological outcomes, increased intensive care unit stay, and increased mortality. Disruptions in carbohydrate metabolism increase the risk of hypoglycemia incritically ill children. Prevention of hypoglycemia, especially in the setting of intravenous insulin use, will be best accomplished by the combination of accurate measuring techniques, frequent or continuous glucose monitoring, and computerized insulin titration protocols.
CONCLUSION
Studies on hypoglycemia in critically ill children have focused on spontaneous hypoglycemia. With the current practice of maintaining blood glucose within a narrow range with intravenous insulin, the risk factors and outcomes associated with insulin-induced hypoglycemia should be rigorously studied to prevent hypoglycemia and potentially improve outcomes of critically ill children.
Topics: Adolescent; Child; Child, Preschool; Critical Illness; Humans; Hypoglycemia; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Prognosis; Risk Factors
PubMed: 22401322
DOI: 10.1177/193229681200600107 -
Seminars in Perinatology Apr 2000After a brief history of the development of neonatal hypoglycemia, this review emphasizes the current approach to the anticipation, diagnosis, and management of the... (Review)
Review
After a brief history of the development of neonatal hypoglycemia, this review emphasizes the current approach to the anticipation, diagnosis, and management of the neonate with a low plasma glucose concentration. Current techniques for studying the neurophysiological and endocrine-metabolic effects of significant hypoglycemia provide new approaches for establishing relevant definitions of significant hypoglycemia, its prognosis, and pathogenesis. The inadequacy of glucose oxidase strips for screening, the definition of high-risk infants, new definitions for low plasma glucose concentrations, and their treatment are presented as well as the ability of the neonate to respond to significantly low glucose values. New data concerning the hereditary aspects of hyperinsulinemia (Glaser, this issue), hereditary defects in branched-chain amino acid, 3-methylglutaconic aciduria and mitochondrial betaoxidation, and degradation of fatty acids (Ozand, this issue), the role of glucose transporters (Vannucci and Vannucci, this issue), and the newer computed tomography and magnetic resonance imaging techniques (Kinnala, this issue) to study neonatal hypoglycemia are reviewed elsewhere in this issue.
Topics: Blood Glucose; Follow-Up Studies; Humans; Hypoglycemia; Infant, Newborn; Prognosis; Recurrence
PubMed: 10805169
DOI: 10.1053/sp.2000.6364 -
Current Opinion in Clinical Nutrition... Jul 2019The Roux-en-Y gastric bypass surgery (RYGB) improves glucose control in majority of patients with type 2 diabetes. However, a minority group of individuals develop a... (Review)
Review
PURPOSE OF REVIEW
The Roux-en-Y gastric bypass surgery (RYGB) improves glucose control in majority of patients with type 2 diabetes. However, a minority group of individuals develop a life-threatening complication of hyperinsulinemic hypoglycemia. The goal of this review is to identify underlying mechanisms by which RYGB cause hypoglycemia and describe pathogenesis-driven strategies to diagnose and treat this condition.
RECENT FINDINGS
Gastric bypass leads to higher and earlier peak levels of glucose and lower nadir glucose after eating along with larger insulin and glucagon-like peptide 1 (GLP-1) secretion, resetting the balance between glucose appearance and clearance after this procedure. These weight-loss independent glycemic effects of RYGB have been attributed to changes in ingested glucose appearance as a result of rapid nutrient emptying from stomach pouch to the intestine and increased glucose clearance as a result of prandial hyperinsulinemia. The exaggerated effect of RYGB on postmeal glucose metabolism is a syndrome of postprandial hyperinsulinemic hypoglycemia manifesting in a group of individuals several years after this surgery. Affected patients have larger systemic appearance of ingested glucose and greater postmeal secretion of insulin and GLP-1 compared to those with history of RYGB without symptomatic hypoglycemia. Current evidence supporting a multifactorial model of glucose dysregulation among patients with hypoglycemia will be highlighted in this review.
SUMMARY
Hypoglycemia after RYGB is a life-threatening condition and likely represents the extreme glycemic phenotype of this procedure. Diagnosis is challenging and treatment options are limited.
Topics: Blood Glucose; Gastric Bypass; Humans; Hypoglycemia; Insulin; Insulin-Secreting Cells; Obesity, Morbid; Postoperative Complications; Postprandial Period
PubMed: 31082828
DOI: 10.1097/MCO.0000000000000574 -
Endocrinology and Metabolism Clinics of... Mar 2013For people with diabetes, hypoglycemia remains the limiting factor in achieving glycemic control. This article reviews recent advances in how the brain senses and... (Review)
Review
For people with diabetes, hypoglycemia remains the limiting factor in achieving glycemic control. This article reviews recent advances in how the brain senses and responds to hypoglycemia. Novel mechanisms by which individuals with insulin-treated diabetes develop hypoglycemia unawareness and impaired counterregulatory responses are outlined. Prevention strategies for reducing the incidence of hypoglycemia are discussed.
Topics: Animals; Awareness; Central Nervous System; Diabetes Mellitus; Glucagon; Health Knowledge, Attitudes, Practice; Humans; Hypoglycemia
PubMed: 23391237
DOI: 10.1016/j.ecl.2012.11.005 -
Endocrine Nov 2023Continuous Glucose Monitoring (CGM) is a key tool for insulin-treated people with diabetes (PwD). CGM devices include both real-time CGM (rtCGM) and intermittently... (Review)
Review
PURPOSE
Continuous Glucose Monitoring (CGM) is a key tool for insulin-treated people with diabetes (PwD). CGM devices include both real-time CGM (rtCGM) and intermittently scanned CGM (isCGM), which are associated with an improvement of glucose control and less hypoglycemia in clinical trials of people with type 1 and type 2 diabetes.
METHODS
This is an expert position to update a previous algorithm on the most suitable choice of CGM for insulin-treated PwD in light of the recent evidence and clinical practice.
RESULTS
We identified six different clinical scenarios, including type 1 diabetes, type 2 diabetes, pregnancy on intensive insulin therapy, regular physical exercise, new onset of diabetes, and frailty. The use of rtCGM or isCGM is suggested, on the basis of the predominant clinical issue, as suboptimal glucose control or disabling hypoglycemia, regardless of baseline HbA or individualized HbA target.
CONCLUSION
The present algorithm may help to select the best CGM device based on patients' clinical characteristics, needs and clinical context, offering a further opportunity of a "tailored" therapy for people with insulin-treated diabetes.
Topics: Humans; Insulin; Blood Glucose; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Blood Glucose Self-Monitoring; Hypoglycemia
PubMed: 37676398
DOI: 10.1007/s12020-023-03473-w -
Diabetes Technology & Therapeutics May 2023Automated insulin delivery (AID) may benefit individuals with long-standing type 1 diabetes where frequent exposure to hypoglycemia impairs counterregulatory responses....
Automated insulin delivery (AID) may benefit individuals with long-standing type 1 diabetes where frequent exposure to hypoglycemia impairs counterregulatory responses. This study assessed the effect of 18 months AID on hypoglycemia avoidance and glucose counterregulatory responses to insulin-induced hypoglycemia in long-standing type 1 diabetes complicated by impaired awareness of hypoglycemia. Ten participants mean ± standard deviation age 49 ± 16 and diabetes duration 34 ± 16 years were initiated on AID. Continuous glucose monitoring was paired with actigraphy to assess awake- and sleep-associated hypoglycemia exposure every 3 months. Hyperinsulinemic hypoglycemic clamp experiments were performed at baseline, 6, and 18 months postintervention. Hypoglycemia exposure was reduced by 3 months, especially during sleep, with effects sustained through 18 months ( ≤ 0.001) together with reduced glucose variability ( < 0.01). Hypoglycemia awareness and severity scores improved ( < 0.01) with severe hypoglycemia events reduced from median (interquartile range) 3 (3-10) at baseline to 0 (0-1) events/person·year postintervention ( = 0.005). During the hypoglycemic clamp experiments, no change was seen in the endogenous glucose production (EGP) response, however, peripheral glucose utilization during hypoglycemia was reduced following intervention [pre: 4.6 ± 0.4, 6 months: 3.8 ± 0.5, 18 months: 3.4 ± 0.3 mg/(kg·min), < 0.05]. There were increases over time in pancreatic polypeptide (Pre:62 ± 29, 6 months:127 ± 44, 18 months:176 ± 58 pmol/L, < 0.01), epinephrine (Pre: 199 ± 53, 6 months: 332 ± 91, 18 months: 386 ± 95 pg/mL, = 0.001), and autonomic symptom (Pre: 6 ± 2, 6 months: 6 ± 2, 18 months: 10 ± 2, < 0.05) responses. AID led to a sustained reduction of hypoglycemia exposure. EGP in response to insulin-induced hypoglycemia remained defective, however, partial recovery of glucose counterregulation was evidenced by a reduction in peripheral glucose utilization likely mediated by increased epinephrine secretion and, together with improved autonomic symptoms, may contribute to the observed clinical reduction in hypoglycemia.
Topics: Humans; Adult; Middle Aged; Aged; Glucose; Diabetes Mellitus, Type 1; Insulin; Blood Glucose; Blood Glucose Self-Monitoring; Hypoglycemia; Hypoglycemic Agents; Insulin, Regular, Human; Diabetes Complications; Epinephrine
PubMed: 36763336
DOI: 10.1089/dia.2022.0506 -
Journal of Diabetes Investigation Apr 2021Alcohol consumption has been reported to cause hypoglycemia. However, the mechanism involved has not been unequivocally established. This study comprised healthy...
AIMS/INTRODUCTION
Alcohol consumption has been reported to cause hypoglycemia. However, the mechanism involved has not been unequivocally established. This study comprised healthy volunteers. We carried out a prospective trial to compare the effects of glucose and alcohol consumption, alone or in combination, on glucose and lipid metabolism.
MATERIALS AND METHODS
A 75-g oral glucose tolerance test (OGTT), a combined 75-g glucose plus 20-g alcohol tolerance test (OGATT) and a 20-g alcohol tolerance test (OATT) were carried out in the participants. Plasma glucose, insulin, triglyceride and ethanol concentrations during each test were compared.
RESULTS
We studied 10 participants. Their plasma glucose concentrations 15 and 30 min after the intake of 75 g of glucose were significantly higher during the OGATT than the OGTT. Hypoglycemia occurred in five participants after the OGATT, which was significantly more frequently than after the OGTT (P = 0.046). Hypoglycemia did not occur after the OATT, and the ethanol concentration was significantly lower after the OGATT than the OATT. The changes in triglyceride concentration from 30 min after the consumption of 75 g of glucose were significantly greater during the OGATT than the OGTT. The plasma insulin concentrations peaked after 60 min during both the OGTT and OGATT, and were significantly higher during the OGATT (P = 0.047). There were no differences between the two interventions in the Matsuda or disposition indexes.
CONCLUSIONS
Hypoglycemia occurred more frequently after the simultaneous consumption of alcohol plus glucose than after the consumption of glucose alone, suggesting that alcohol in the combination of glucose induces reactive hypoglycemia.
Topics: Adult; Alcohol Drinking; Blood Glucose; Central Nervous System Depressants; Ethanol; Female; Glucose; Glucose Tolerance Test; Healthy Volunteers; Humans; Hypoglycemia; Insulin; Male; Prospective Studies
PubMed: 33448697
DOI: 10.1111/jdi.13375 -
Nutrients Aug 2023Hypoglycemia is due to defects in the metabolic systems involved in the transition from the fed to the fasting state or in the hormone control of these systems. In... (Review)
Review
Hypoglycemia is due to defects in the metabolic systems involved in the transition from the fed to the fasting state or in the hormone control of these systems. In children, hypoglycemia is considered a metabolic-endocrine emergency, because it may lead to brain injury, permanent neurological sequelae and, in rare cases, death. Symptoms are nonspecific, particularly in infants and young children. Diagnosis is based on laboratory investigations during a hypoglycemic event, but it may also require biochemical tests between episodes, dynamic endocrine tests and molecular genetics. This narrative review presents the age-related definitions of hypoglycemia, its pathophysiology and main causes, and discusses the current diagnostic and modern therapeutic approaches.
Topics: Infant; Humans; Child; Child, Preschool; Hypoglycemia; Hypoglycemic Agents; Brain Injuries; Causality; Disease Progression
PubMed: 37630734
DOI: 10.3390/nu15163544