Materiały źródłowe

• #1 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://www.wjgnet.com/1948-9358/full/v12/i12/2036.htm

  Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. […] In patients with diabetes, it is not easy to determine a specific plasma glucose concentration that is diagnostic of hypoglycemia, because the threshold for the appearance of hypoglycemia symptoms varies among patients. This threshold drops due to recurrent episodes of hypoglycemia and rises in individuals with uncontrolled diabetes. […] The above defense mechanisms are often impaired in patients with diabetes and significant beta-cell failure who lack an initial response to a drop in insulin. This leads to a delay in the secretion of glucose from the liver during hypoglycemia.

• #2 Diabetic hypoglycemia – Wikipedia

  https://en.wikipedia.org/wiki/Diabetic_hypoglycemia

  Diabetic hypoglycemia is a low blood glucose level occurring in a person with diabetes mellitus. It is one of the most common types of hypoglycemia seen in emergency departments and hospitals. […] In general, hypoglycemia occurs when a treatment to lower the elevated blood glucose of diabetes inaccurately matches the body’s physiological need, and therefore causes the glucose to fall to a below-normal level. […] Diabetic hypoglycemia can occur in any person with diabetes who takes any medicine to lower their blood glucose, but severe hypoglycemia occurs most often in people with type 1 diabetes who must take insulin for survival. In type 1 diabetes, iatrogenic hypoglycemia is more appropriately viewed as the result of the interplay of insulin excess and compromised glucose counterregulation rather than as absolute or relative insulin excess alone.

• #3 Diabetes & Hypoglycemia: Behind the Scenes — EMS.Aware

  https://www.emsaware.org/articlesforems/hypoglycemiapatho

  Hypoglycemia is clinically defined as anytime plasma blood glucose falls below 70mg/dL. […] Hypoglycemia is most common with diabetes type 1 patients, but a variety of factors such as alcohol binging, insulin dosing, and pancreatitis can prompt hypoglycemia in an otherwise healthy patient. […] Insulin does not lower blood sugar alone – it is merely a transporter for glucose. […] Clinical manifestations of hypoglycemia are in part because of two factors – central nervous system (CNS) dysfunction and catecholamine surge (fight or flight). […] Hypoglycemia is a state of significant metabolic stress for the body – after all, the body is trying to stay alive, and glucose is necessary for that. […] It is important to note that glucagon can only work when the liver has adequate glycogen stores to utilize.

• #4 Causes of Hypoglycemia | IntechOpen

  https://www.intechopen.com/chapters/82036

  Blood glucose levels may vary during the day, when this variation goes below a specific limit, hypoglycemia occurs. […] Hypoglycemia is usually a result of the complex interaction between hyperinsulinemia and the compromised physiological and behavioral responses attempting to reduce glucose levels. […] In diabetic patients, the complex interaction between hyperinsulinemia and the compromised physiological and behavioral responses to reduced glucose levels can lead to hypoglycemia. […] Diabetes particularly with the use of insulin or sulfonylurea, that is, insulin secretagogue treatment, is the classical cause of hypoglycemia. […] The primary cause of hypoglycemia is a complex interaction between hyperinsulinemia and compromised physiologic and behavioral responses to reducing glucose levels.

• #5 Hypoglycemia in diabetes: pathophysiological mechanisms and diurnal variation – PubMed

  https://pubmed.ncbi.nlm.nih.gov/16876586/

  Iatrogenic hypoglycemia, the limiting factor in the glycemic management of diabetes, causes recurrent morbidity (and sometimes death), precludes maintenance of euglycemia over a lifetime of diabetes and causes a vicious cycle of recurrent hypoglycemia. […] In insulin deficient – T1DM and advanced T2DM – diabetes hypoglycemia is the result of the interplay of therapeutic insulin excess and compromised physiological (defective glucose counterregulation) and behavioral (hypoglycemia unawareness) defenses against falling plasma glucose concentrations. […] The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation (by reducing epinephrine responses in the setting of absent insulin and glucagon responses) and hypoglycemia unawareness (by reducing sympathoadrenal and the resulting neurogenic symptom responses) and thus a vicious cycle of recurrent hypoglycemia.

• #6 Diabetic hypoglycemia – Wikipedia

  https://en.wikipedia.org/wiki/Diabetic_hypoglycemia

  Diabetic hypoglycemia is a low blood glucose level occurring in a person with diabetes mellitus. It is one of the most common types of hypoglycemia seen in emergency departments and hospitals. […] In general, hypoglycemia occurs when a treatment to lower the elevated blood glucose of diabetes inaccurately matches the body’s physiological need, and therefore causes the glucose to fall to a below-normal level. […] Diabetic hypoglycemia can occur in any person with diabetes who takes any medicine to lower their blood glucose, but severe hypoglycemia occurs most often in people with type 1 diabetes who must take insulin for survival. In type 1 diabetes, iatrogenic hypoglycemia is more appropriately viewed as the result of the interplay of insulin excess and compromised glucose counterregulation rather than as absolute or relative insulin excess alone.

• #7 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://www.wjgnet.com/1948-9358/full/v12/i12/2036

  Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. […] The current classification of hypoglycemic episodes in diabetes includes three levels corresponding to the severity of hypoglycemia: Level 1 hypoglycemia: defined as plasma glucose concentration 70 mg/dL but 54 mg/dL. […] A decrease in plasma glucose concentration may lead to two main responses in the body under normal conditions: (1) Increase in endogenous glucose production by glycogenolysis and gluconeogenesis; and (2) Behavioral changes leading to a sensation of hunger and food seeking. […] The above defense mechanisms are often impaired in patients with diabetes and significant beta-cell failure who lack an initial response to a drop in insulin.

• #8 Hypoglycemia – Wikipedia

  https://en.wikipedia.org/wiki/Hypoglycemia

  Glucose is the main source of energy for the brain, and a number of mechanisms are in place to prevent hypoglycemia and protect energy supply to the brain. […] The body can adjust insulin production and release, adjust glucose production by the liver, and adjust glucose use by the body. […] When blood sugar levels fall to the low-normal range, the first line of defense against hypoglycemia is decreasing insulin release by the pancreas. […] This drop in insulin allows the liver to increase glycogenolysis. […] Glycogenolysis is the process of glycogen breakdown that results in the production of glucose. […] Decreased insulin also allows for increased gluconeogenesis in the liver and kidneys. […] Gluconeogenesis is the process of glucose production from non-carbohydrate sources, supplied from muscles and fat.

• #9 Hypoglycemia – Wikipedia

  https://en.wikipedia.org/wiki/Hypoglycemia

  Glucose is the main source of energy for the brain, and a number of mechanisms are in place to prevent hypoglycemia and protect energy supply to the brain. […] The body can adjust insulin production and release, adjust glucose production by the liver, and adjust glucose use by the body. […] When blood sugar levels fall to the low-normal range, the first line of defense against hypoglycemia is decreasing insulin release by the pancreas. […] This drop in insulin allows the liver to increase glycogenolysis. […] Glycogenolysis is the process of glycogen breakdown that results in the production of glucose. […] Decreased insulin also allows for increased gluconeogenesis in the liver and kidneys. […] Gluconeogenesis is the process of glucose production from non-carbohydrate sources, supplied from muscles and fat.

• #10 Hypoglycemia – Wikipedia

  https://en.wikipedia.org/wiki/Hypoglycemia

  Once blood glucose levels fall out of the normal range, additional protective mechanisms work to prevent hypoglycemia. […] The pancreas is signaled to release glucagon, a hormone that increases glucose production by the liver and kidneys, and increases muscle and fat breakdown to supply gluconeogenesis. […] If increased glucagon does not raise blood sugar levels to normal, the adrenal glands release epinephrine. […] Epinephrine works to also increase gluconeogenesis and glycogenolysis, while also decreasing the use of glucose by organs, protecting the brain’s glucose supply. […] After hypoglycemia has been prolonged, cortisol and growth hormone are released to continue gluconeogenesis and glycogenolysis, while also preventing the use of glucose by other organs. […] The effects of cortisol and growth hormone are far less effective than epinephrine. […] In a state of hypoglycemia, the brain also signals a sense of hunger and drives the person to eat, in an attempt to increase glucose.

• #11 Hypoglycemia – Wikipedia

  https://en.wikipedia.org/wiki/Hypoglycemia

  Once blood glucose levels fall out of the normal range, additional protective mechanisms work to prevent hypoglycemia. […] The pancreas is signaled to release glucagon, a hormone that increases glucose production by the liver and kidneys, and increases muscle and fat breakdown to supply gluconeogenesis. […] If increased glucagon does not raise blood sugar levels to normal, the adrenal glands release epinephrine. […] Epinephrine works to also increase gluconeogenesis and glycogenolysis, while also decreasing the use of glucose by organs, protecting the brain’s glucose supply. […] After hypoglycemia has been prolonged, cortisol and growth hormone are released to continue gluconeogenesis and glycogenolysis, while also preventing the use of glucose by other organs. […] The effects of cortisol and growth hormone are far less effective than epinephrine. […] In a state of hypoglycemia, the brain also signals a sense of hunger and drives the person to eat, in an attempt to increase glucose.

• #12 Hypoglycemia – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/hypoglycemia

  Most commonly, symptomatic hypoglycemia is a complication of medication treatment of diabetes mellitus with oral antihyperglycemics (especially sulfonylureas) and insulin. […] Symptomatic hypoglycemia unrelated to treatment of diabetes mellitus is relatively rare, in part because the body has extensive counter-regulatory mechanisms to compensate for low blood glucose levels. Glucagon and epinephrine levels surge in response to acute hypoglycemia and appear to be the first line of defense. Cortisol and growth hormone levels also increase acutely and are important in the recovery from prolonged hypoglycemia. […] Insulinoma is a rare neuroendocrine tumor of insulin-producing beta cells. It typically causes fasting hypoglycemia although postprandial hypoglycemia can also occur. […] Hypoglycemia that occurs after bariatric surgery is a hyperinsulinemic hypoglycemia that develops sometimes years after bariatric (especially roux-en-Y gastric bypass) surgery.

• #13 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8696639/

  Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. […] The above defense mechanisms are often impaired in patients with diabetes and significant beta-cell failure who lack an initial response to a drop in insulin. This leads to a delay in the secretion of glucose from the liver during hypoglycemia. […] It is believed that the impaired sympathoadrenal response is secondary to repeated episodes of hypoglycemia that reduce the autonomic response to other hypoglycemic events. This exposes patients to a vicious cycle of frequent hypoglycemia events and shifts glycemic thresholds for symptoms to lower plasma glucose concentrations close to levels that cause cognitive failure.

• #14 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://www.wjgnet.com/1948-9358/full/v12/i12/2036.htm

  Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. […] In patients with diabetes, it is not easy to determine a specific plasma glucose concentration that is diagnostic of hypoglycemia, because the threshold for the appearance of hypoglycemia symptoms varies among patients. This threshold drops due to recurrent episodes of hypoglycemia and rises in individuals with uncontrolled diabetes. […] The above defense mechanisms are often impaired in patients with diabetes and significant beta-cell failure who lack an initial response to a drop in insulin. This leads to a delay in the secretion of glucose from the liver during hypoglycemia.

• #15 An Overview of Hypoglycemia

  https://www.uspharmacist.com/article/an-overview-of-hypoglycemia

  In T1DM and advanced T2DM, glucose counterregulation is compromised by the impaired secretion of insulin, glucagon, and epinephrine, breaching three physiological defenses against hypoglycemia. […] First, falling plasma glucose concentrations fail to elicit a corresponding decrease in insulin secretion in patients taking insulin or insulin secretagogues. […] Second, hypoglycemia does not trigger glucagon secretion. […] Third, a lower plasma glucose concentration is required to stimulate an epinephrine response. […] Some patients with T1DM or advanced T2DM lose the neurogenic warning symptoms that herald impending hypoglycemia. […] This state, hypoglycemia unawareness, is likely the result of repeated iatrogenic hypoglycemia episodes that lead to impaired epinephrine response and diminished neurogenic symptoms.

• #16 An Overview of Hypoglycemia

  https://www.uspharmacist.com/article/an-overview-of-hypoglycemia

  In T1DM and advanced T2DM, glucose counterregulation is compromised by the impaired secretion of insulin, glucagon, and epinephrine, breaching three physiological defenses against hypoglycemia. […] First, falling plasma glucose concentrations fail to elicit a corresponding decrease in insulin secretion in patients taking insulin or insulin secretagogues. […] Second, hypoglycemia does not trigger glucagon secretion. […] Third, a lower plasma glucose concentration is required to stimulate an epinephrine response. […] Some patients with T1DM or advanced T2DM lose the neurogenic warning symptoms that herald impending hypoglycemia. […] This state, hypoglycemia unawareness, is likely the result of repeated iatrogenic hypoglycemia episodes that lead to impaired epinephrine response and diminished neurogenic symptoms.

• #17 An Overview of Hypoglycemia

  https://www.uspharmacist.com/article/an-overview-of-hypoglycemia

  In T1DM and advanced T2DM, glucose counterregulation is compromised by the impaired secretion of insulin, glucagon, and epinephrine, breaching three physiological defenses against hypoglycemia. […] First, falling plasma glucose concentrations fail to elicit a corresponding decrease in insulin secretion in patients taking insulin or insulin secretagogues. […] Second, hypoglycemia does not trigger glucagon secretion. […] Third, a lower plasma glucose concentration is required to stimulate an epinephrine response. […] Some patients with T1DM or advanced T2DM lose the neurogenic warning symptoms that herald impending hypoglycemia. […] This state, hypoglycemia unawareness, is likely the result of repeated iatrogenic hypoglycemia episodes that lead to impaired epinephrine response and diminished neurogenic symptoms.

• #18 An Overview of Hypoglycemia

  https://www.uspharmacist.com/article/an-overview-of-hypoglycemia

  In T1DM and advanced T2DM, glucose counterregulation is compromised by the impaired secretion of insulin, glucagon, and epinephrine, breaching three physiological defenses against hypoglycemia. […] First, falling plasma glucose concentrations fail to elicit a corresponding decrease in insulin secretion in patients taking insulin or insulin secretagogues. […] Second, hypoglycemia does not trigger glucagon secretion. […] Third, a lower plasma glucose concentration is required to stimulate an epinephrine response. […] Some patients with T1DM or advanced T2DM lose the neurogenic warning symptoms that herald impending hypoglycemia. […] This state, hypoglycemia unawareness, is likely the result of repeated iatrogenic hypoglycemia episodes that lead to impaired epinephrine response and diminished neurogenic symptoms.

• #19 Hypoglycemia in diabetes: pathophysiological mechanisms and diurnal variation – PubMed

  https://pubmed.ncbi.nlm.nih.gov/16876586/

  Loss of the glucagon response, a key feature of defective glucose counterregulation, is plausibly attributed to insulin deficiency, specifically loss of the decrement in intraislet insulin that normally signals glucagon secretion as glucose levels fall. […] Reduced neurogenic symptoms, a key feature of hypoglycemia unawareness, are largely the result of reduced sympathetic neural responses to falling glucose levels. […] The mechanism(s) by which hypoglycemia shifts the glycemic thresholds for sympathoadrenal activation to lower plasma glucose concentrations, the key feature of both components of HAAF, is not known. […] It does not appear to be the result of the release of a systemic mediator such as cortisol or epinephrine during antecedent hypoglycemia or of increased blood-to-brain glucose transport.

• #20 Mechanisms of Hypoglycemia Counterregulation

  https://www.medscape.org/viewarticle/438362

  The Diabetes Control and Complications Trial (DCCT) convincingly established the benefits of tight glucose control in the avoidance of long-term diabetic complications. […] However, a pitfall of the aggressive management of diabetes using intensive insulin regimens is an increased frequency of hypoglycemia. […] At the 62nd Scientific Sessions of the American Diabetes Association, several symposia were dedicated to the discussion of issues related to the pathogenesis and treatment of impaired hypoglycemia counterregulation in diabetes. […] In patients with type 1 diabetes of long duration ( 5 years), epinephrine constitutes the main defense against hypoglycemia, because the pancreatic alpha cell glucagon secretory response to hypoglycemia is irreversibly lost. […] However, clinical studies have shown that the epinephrine response is also impaired in type 1 patients undergoing intensive insulin treatment.

• #21 Hypoglycemia in diabetes: pathophysiological mechanisms and diurnal variation – PubMed

  https://pubmed.ncbi.nlm.nih.gov/16876586/

  Iatrogenic hypoglycemia, the limiting factor in the glycemic management of diabetes, causes recurrent morbidity (and sometimes death), precludes maintenance of euglycemia over a lifetime of diabetes and causes a vicious cycle of recurrent hypoglycemia. […] In insulin deficient – T1DM and advanced T2DM – diabetes hypoglycemia is the result of the interplay of therapeutic insulin excess and compromised physiological (defective glucose counterregulation) and behavioral (hypoglycemia unawareness) defenses against falling plasma glucose concentrations. […] The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation (by reducing epinephrine responses in the setting of absent insulin and glucagon responses) and hypoglycemia unawareness (by reducing sympathoadrenal and the resulting neurogenic symptom responses) and thus a vicious cycle of recurrent hypoglycemia.

• #22 Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications

  https://www.mdpi.com/2227-9059/12/2/391

  Hypoglycemia is a particular problem in people with diabetes while it can also occur in other clinical circumstances. […] The pathophysiological mechanisms are manifold, but mainly concern altered brain glucose sensing, cerebral adaptations, and an impaired hormonal counterregulation with an attenuated release of glucagon, epinephrine, growth hormone, and other hormones, as well as impaired autonomous and neuroglycopenic symptoms. […] The impaired hormonal counterregulatory response to recurrent hypoglycemia can lead to a vicious cycle of frequent and poorly recognized hypoglycemic episodes. […] There is a shift in glycemic threshold to trigger hormonal counterregulation, resulting in hypoglycemia-associated autonomic failure and leading to the clinical syndrome of hypoglycemia unawareness.

• #23 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8696639/

  Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. […] The above defense mechanisms are often impaired in patients with diabetes and significant beta-cell failure who lack an initial response to a drop in insulin. This leads to a delay in the secretion of glucose from the liver during hypoglycemia. […] It is believed that the impaired sympathoadrenal response is secondary to repeated episodes of hypoglycemia that reduce the autonomic response to other hypoglycemic events. This exposes patients to a vicious cycle of frequent hypoglycemia events and shifts glycemic thresholds for symptoms to lower plasma glucose concentrations close to levels that cause cognitive failure.

• #24 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://www.wjgnet.com/1948-9358/full/v12/i12/2036.htm

  It is believed that the impaired sympathoadrenal response is secondary to repeated episodes of hypoglycemia that reduce the autonomic response to other hypoglycemic events. This exposes patients to a vicious cycle of frequent hypoglycemia events and shifts glycemic thresholds for symptoms to lower plasma glucose concentrations close to levels that cause cognitive failure. […] Hypoglycemia causes physical and psychological morbidity in diabetic patients. Symptomatic hypoglycemia constitutes a concern and a distraction. […] Hypoglycemia in diabetes is associated with increased morbidity and constitutes a barrier to glycemic control. Much effort must be invested in hypoglycemia prevention, including patient education, appropriate dietary and exercise regimens, adjustment of the treatment regimen, and implementation of glucose monitoring systems as appropriate.

• #25 Hypoglycemia in diabetes: pathophysiological mechanisms and diurnal variation – PubMed

  https://pubmed.ncbi.nlm.nih.gov/16876586/

  Loss of the glucagon response, a key feature of defective glucose counterregulation, is plausibly attributed to insulin deficiency, specifically loss of the decrement in intraislet insulin that normally signals glucagon secretion as glucose levels fall. […] Reduced neurogenic symptoms, a key feature of hypoglycemia unawareness, are largely the result of reduced sympathetic neural responses to falling glucose levels. […] The mechanism(s) by which hypoglycemia shifts the glycemic thresholds for sympathoadrenal activation to lower plasma glucose concentrations, the key feature of both components of HAAF, is not known. […] It does not appear to be the result of the release of a systemic mediator such as cortisol or epinephrine during antecedent hypoglycemia or of increased blood-to-brain glucose transport.

• #26 Hypoglycemia and the Central Nervous System | [current-page:pager]touchENDOCRINOLOGY

  https://touchendocrinology.com/diabetes/journal-articles/hypoglycemia-and-the-central-nervous-system/

  Hypoglycemia is not limited to patients with type 1 diabetes, but frequently occurs in patients with type 2 diabetes as well. As the ratelimiting step for insulin therapy in diabetes, hypoglycemia precludes the maintenance of long-term euglycemia and the long-term benefits associated with tight glucose control. […] Recognizing the impact of hypoglycemia and the development of novel therapies aimed at reducing iatrogenic hypoglycemia are all vital to improve blood sugar management and improve the lives of people with diabetes. […] The exact mechanisms for the shift in the glycemic threshold are not fully understood, but clinical and basic science research has begun to discover critical adaptations within the CNS that contribute to HAAF. Several possibilities have been investigated, including increased brain glucose transport, enhanced glucose metabolism, glycogen supercompensation, and altered neuronal activity. […] Although some studies have shown that glucose transport to the brain may be increased after prolonged hypoglycemia, studies investigating individuals with HAAF and patients with type 1 diabetes found no change in global bloodbrain glucose transport after antecedent hypoglycemia.

• #27 Hypoglycemia and the Central Nervous System | [current-page:pager]touchENDOCRINOLOGY

  https://touchendocrinology.com/diabetes/journal-articles/hypoglycemia-and-the-central-nervous-system/

  Hypoglycemia is not limited to patients with type 1 diabetes, but frequently occurs in patients with type 2 diabetes as well. As the ratelimiting step for insulin therapy in diabetes, hypoglycemia precludes the maintenance of long-term euglycemia and the long-term benefits associated with tight glucose control. […] Recognizing the impact of hypoglycemia and the development of novel therapies aimed at reducing iatrogenic hypoglycemia are all vital to improve blood sugar management and improve the lives of people with diabetes. […] The exact mechanisms for the shift in the glycemic threshold are not fully understood, but clinical and basic science research has begun to discover critical adaptations within the CNS that contribute to HAAF. Several possibilities have been investigated, including increased brain glucose transport, enhanced glucose metabolism, glycogen supercompensation, and altered neuronal activity. […] Although some studies have shown that glucose transport to the brain may be increased after prolonged hypoglycemia, studies investigating individuals with HAAF and patients with type 1 diabetes found no change in global bloodbrain glucose transport after antecedent hypoglycemia.

• #28 Hypoglycemia and the Central Nervous System | [current-page:pager]touchENDOCRINOLOGY

  https://touchendocrinology.com/diabetes/journal-articles/hypoglycemia-and-the-central-nervous-system/

  Enhanced glucose metabolism is another potential mechanism. With more efficient glucose metabolism, the brain could maintain energy levels despite lower blood-glucose concentrations. […] Increased glucokinase activity has been hypothesized to play a major role. […] Increased glycogen content following hypoglycemia (termed glycogen supercompensation) may also contribute to HAAF. […] Both animal and human studies have shown glycogen levels to increase above basal levels following hypoglycemia. […] Alterations on potassium channel (KATP) activity and on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) have been implicated in the pathogenesis of HAAF. […] Taken together, many mechanisms may contribute to HAAF.

• #29 Hypoglycemia and the Central Nervous System | [current-page:pager]touchENDOCRINOLOGY

  https://touchendocrinology.com/diabetes/journal-articles/hypoglycemia-and-the-central-nervous-system/

  Enhanced glucose metabolism is another potential mechanism. With more efficient glucose metabolism, the brain could maintain energy levels despite lower blood-glucose concentrations. […] Increased glucokinase activity has been hypothesized to play a major role. […] Increased glycogen content following hypoglycemia (termed glycogen supercompensation) may also contribute to HAAF. […] Both animal and human studies have shown glycogen levels to increase above basal levels following hypoglycemia. […] Alterations on potassium channel (KATP) activity and on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) have been implicated in the pathogenesis of HAAF. […] Taken together, many mechanisms may contribute to HAAF.

• #30 Hypoglycemia and the Central Nervous System | [current-page:pager]touchENDOCRINOLOGY

  https://touchendocrinology.com/diabetes/journal-articles/hypoglycemia-and-the-central-nervous-system/

  Enhanced glucose metabolism is another potential mechanism. With more efficient glucose metabolism, the brain could maintain energy levels despite lower blood-glucose concentrations. […] Increased glucokinase activity has been hypothesized to play a major role. […] Increased glycogen content following hypoglycemia (termed glycogen supercompensation) may also contribute to HAAF. […] Both animal and human studies have shown glycogen levels to increase above basal levels following hypoglycemia. […] Alterations on potassium channel (KATP) activity and on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) have been implicated in the pathogenesis of HAAF. […] Taken together, many mechanisms may contribute to HAAF.

• #31 Mechanisms of Hypoglycemia Counterregulation

  https://www.medscape.org/viewarticle/438362

  This „double whammy” (lack of glucagon and epinephrine response) places intensively treated type 1 diabetes patients at significant risk for recurrent hypoglycemia. […] In addition, frequent antecedent hypoglycemia reduces the counterregulatory responses to future hypoglycemia by 50% — creating a vicious cycle of iatrogenic hypoglycemia-associated autonomic failure, where hypoglycemia induces further hypoglycemia. […] Another series of studies was based on the observation that glucocorticoids blunt stress responses in animals, raising the question of whether cortisol is associated with hypoglycemia-associated autonomic failure. […] These studies suggest that cortisol (stress) is a major determinant of hypoglycemia-associated autonomic failure. […] Thus, antecedent exercise is also a causative factor in hypoglycemia-associated autonomic failure.

• #32 Targeting the VMN to Understand Hypoglycemia Pathogenesis | American Diabetes Association

  https://professional.diabetes.org/rdb/targeting-vmn-understand-hypoglycemia-pathogenesis

  While the goal of diabetes treatment is normoglycemia, most therapeutics (especially insulin and insulin secretagogues) carry with them a significant risk of potentially life-threatening hypoglycemia; this risk increases with the intensity of therapy. […] From information gathered in previous studies, we defined a novel subset of neurons within the ventromedial hypothalamus (VMN) that, when silenced, lowers baseline blood glucose, decreased the CRR to both insulin-induced hypoglycemia and glucoprivation, and eliminates hypoglycemia associated autonomic failure (HAAF)-like responses. […] We will further evaluate the role of these cells in the CRR to understand the mechanisms, define the site and mechanisms responsible for HAAF, and understand the role of these cells in diabetes. […] By understanding the mechanisms underlying the CRR, and the failure of the CRR in HAAF, we will identify potential targets for interventions to prevent or mitigate HAAF.

• #33 Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications

  https://www.mdpi.com/2227-9059/12/2/391

  It is suggested that hypoglycemia unawareness syndrome is mainly induced by recent antecedent hypoglycemic episodes causing defective glucose counterregulation. […] The absence of symptoms of hypoglycemia reflects the attenuation of the sympathoadrenal response. […] Hypoglycemia unawareness syndrome is commonly observed in individuals with recurrent hypoglycemic episodes disrupting the normal release of counterregulatory hormones, such as glucagon, growth hormone (GH), and epinephrine. […] The blunted hormonal response leads to impaired glucose counterregulation and reduced awareness of hypoglycemia. […] Recurrent hypoglycemic episodes can trigger adaptive responses within the central nervous system. […] Over time, the brain adapts to the lower glucose levels, resetting the threshold for glucose sensing to lower values.

• #34 Diabetes & Hypoglycemia: Behind the Scenes — EMS.Aware

  https://www.emsaware.org/articlesforems/hypoglycemiapatho

  As insulin is released in an attempt to facilitate the transfer of glucose into the cells and thus continue normal metabolism, it prompts a shift in the balance of electrolytes from the extracellular to the intracellular space. […] The brain needs two things – glucose and oxygen – to function properly. […] During times of hypoglycemia, both the afferent and efferent nerves slowly become dysfunctional. […] As the brain continues to be starved of glucose and blood plasma glucose levels drop, CNS dysfunction will worsen accordingly. […] Patients experiencing hypoglycemia can be assessed using the Whipples triad. […] Hypoglycemia episodes in patients experiencing sepsis are prone to higher mortality rates. […] Alcohol has a negative effect on glycogenolysis, glycolysis (the breakdown of glucose), gluconeogenesis (the creation of glycogen), and metabolism overall. […] Glucagon only works on the patients own pre-existing glycogen stores and will thus produce no response if these stores are depleted.

• #35 Hypoglycemia (Low Blood Sugar): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/11647-hypoglycemia-low-blood-sugar

  Hypoglycemia happens when the level of sugar (glucose) in your blood drops below the range thats healthy for you. Its also called low blood sugar or low blood glucose. Hypoglycemia is common in people with diabetes, especially Type 1 diabetes. […] Low blood sugar often happens due to excess insulin whether your body naturally makes too much or you inject too much synthetic insulin. Other hormonal and metabolic issues can also lead to low blood sugar. […] Hypoglycemia happens when your blood sugar drops below a healthy range. Several factors can contribute to this for people with diabetes. Hypoglycemia can develop if things like food, exercise and diabetes medications are out of balance. […] Common situations that can lead to hypoglycemia for people with diabetes include: Taking too much insulin, the wrong insulin or injecting it into your muscle instead of in your fat tissue.

• #36 Low blood sugar (hypoglycaemia)

  https://www.nhs.uk/conditions/low-blood-sugar-hypoglycaemia/

  Diabetes causes high blood sugar (hyperglycaemia). Diabetes medicines treat your condition by lowering your blood sugar, but they can sometimes make it go too low. […] This is common if you take insulin. It can also happen with some other diabetes medicines, such as gliclazide and glimepiride. […] You’re more likely to get low blood sugar if you: take too much insulin; have problems with the way you inject insulin, such as injecting in the same place too often; miss or delay meals, or do not eat enough carbohydrate; do a lot of exercise without eating more carbohydrate or reducing your insulin dose; drink a lot of alcohol, particularly without eating. […] Sometimes it’s not clear why it happens.

• #37 Mechanisms of Hypoglycemia Counterregulation

  https://www.medscape.org/viewarticle/438362

  The Diabetes Control and Complications Trial (DCCT) convincingly established the benefits of tight glucose control in the avoidance of long-term diabetic complications. […] However, a pitfall of the aggressive management of diabetes using intensive insulin regimens is an increased frequency of hypoglycemia. […] At the 62nd Scientific Sessions of the American Diabetes Association, several symposia were dedicated to the discussion of issues related to the pathogenesis and treatment of impaired hypoglycemia counterregulation in diabetes. […] In patients with type 1 diabetes of long duration ( 5 years), epinephrine constitutes the main defense against hypoglycemia, because the pancreatic alpha cell glucagon secretory response to hypoglycemia is irreversibly lost. […] However, clinical studies have shown that the epinephrine response is also impaired in type 1 patients undergoing intensive insulin treatment.

• #38 Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications

  https://www.mdpi.com/2227-9059/12/2/391

  Hormonal dysregulation has been identified as a significant factor contributing to the development of hypoglycemia unawareness syndrome. […] In individuals with T1D or prolonged type 2 diabetes (T2D), unregulated insulin release from subcutaneous depots or the sustained effects of sulfonylureas can result in elevated systemic insulin levels during hypoglycemia. […] The relative insulin excess increases glucose uptake and suppresses glucose production in the liver, despite the development of hypoglycemia. […] The concept of hypoglycemia unawareness also includes that recent antecedent hypoglycemic episodes cause a defective counterregulation by reducing epinephrine levels. […] Physiologically, in response to hypoglycemia, plasma levels of epinephrine increase. […] After recent antecedent hypoglycemia, epinephrine levels are significantly reduced.

• #39 Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications

  https://www.mdpi.com/2227-9059/12/2/391

  Hormonal dysregulation has been identified as a significant factor contributing to the development of hypoglycemia unawareness syndrome. […] In individuals with T1D or prolonged type 2 diabetes (T2D), unregulated insulin release from subcutaneous depots or the sustained effects of sulfonylureas can result in elevated systemic insulin levels during hypoglycemia. […] The relative insulin excess increases glucose uptake and suppresses glucose production in the liver, despite the development of hypoglycemia. […] The concept of hypoglycemia unawareness also includes that recent antecedent hypoglycemic episodes cause a defective counterregulation by reducing epinephrine levels. […] Physiologically, in response to hypoglycemia, plasma levels of epinephrine increase. […] After recent antecedent hypoglycemia, epinephrine levels are significantly reduced.

• #40 Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications

  https://www.mdpi.com/2227-9059/12/2/391

  Hormonal dysregulation has been identified as a significant factor contributing to the development of hypoglycemia unawareness syndrome. […] In individuals with T1D or prolonged type 2 diabetes (T2D), unregulated insulin release from subcutaneous depots or the sustained effects of sulfonylureas can result in elevated systemic insulin levels during hypoglycemia. […] The relative insulin excess increases glucose uptake and suppresses glucose production in the liver, despite the development of hypoglycemia. […] The concept of hypoglycemia unawareness also includes that recent antecedent hypoglycemic episodes cause a defective counterregulation by reducing epinephrine levels. […] Physiologically, in response to hypoglycemia, plasma levels of epinephrine increase. […] After recent antecedent hypoglycemia, epinephrine levels are significantly reduced.

• #41 Causes of Hypoglycemia | IntechOpen

  https://www.intechopen.com/chapters/82036

  Both absolute and relative insulin excess is a major cause of hypoglycemia. […] Absolute insulin excess occurs due to excessive insulin doses, wrong time of injection, wrong insulin type, and decreased insulin clearance as in renal failure and ill-timed. […] The relative insulin excess occurs due to decreased exogenous glucose delivery, increased insulin sensitivity, and decreased endogenous glucose production. […] Gastroparesis, that is, delayed gastric emptying, is common autonomic neuropathy in patients with long-standing diabetes. […] Neuropathy is also associated with hypoglycemia, particularly hypoglycemia-associated autonomic failure (HAAF). […] The hormonal deficiency was found to be associated with hypoglycemia. […] Hypoglycemia developing secondary to an underlying illness is associated with increased nutritional body demand due to increased metabolic response in critically ill patients.

• #42 Diabetic Hypoglycemia | Calgary Guide

  https://calgaryguide.ucalgary.ca/diabetic-hypoglycemia/diabetic-hypoglycemia-clinical-findings/

  With many hypoglycemic events over time: Brain feels no need to ? glucose, so it ? autonomic epinephrine secretion! […] This is the normal sequence of hormone responses to ?ing plasma glucose levels. But this normal hormonal response will be blunted over time if there is 1) continued hypoglycemia dampening the sympathetic nervous system, and 2) long-standing diabetic neuropathy! […] Lack of glucagon effect reinforces hypoglycemia.

• #43 Causes of Hypoglycemia | IntechOpen

  https://www.intechopen.com/chapters/82036

  Hypoglycemia can also occur in acute renal failure and end-stage renal disease (ESR), this is due to reduced renal insulinase-mediated insulin clearance. […] The fear of hypoglycemia is common in patients with diabetes. […] In diabetic patients with depression, hypoglycemia can occur frequently as a result of poor adherence to medications, diet, physical activity, smoking cessation, poor self-care, and blood glucose monitoring. […] Cognitive dysfunction and dementia may increase the risk of hypoglycemia, especially in elderly patients.

• #44 Causes of Hypoglycemia | IntechOpen

  https://www.intechopen.com/chapters/82036

  Hypoglycemia can also occur in acute renal failure and end-stage renal disease (ESR), this is due to reduced renal insulinase-mediated insulin clearance. […] The fear of hypoglycemia is common in patients with diabetes. […] In diabetic patients with depression, hypoglycemia can occur frequently as a result of poor adherence to medications, diet, physical activity, smoking cessation, poor self-care, and blood glucose monitoring. […] Cognitive dysfunction and dementia may increase the risk of hypoglycemia, especially in elderly patients.

• #45 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://www.wjgnet.com/1948-9358/full/v12/i12/2036.htm

  It is believed that the impaired sympathoadrenal response is secondary to repeated episodes of hypoglycemia that reduce the autonomic response to other hypoglycemic events. This exposes patients to a vicious cycle of frequent hypoglycemia events and shifts glycemic thresholds for symptoms to lower plasma glucose concentrations close to levels that cause cognitive failure. […] Hypoglycemia causes physical and psychological morbidity in diabetic patients. Symptomatic hypoglycemia constitutes a concern and a distraction. […] Hypoglycemia in diabetes is associated with increased morbidity and constitutes a barrier to glycemic control. Much effort must be invested in hypoglycemia prevention, including patient education, appropriate dietary and exercise regimens, adjustment of the treatment regimen, and implementation of glucose monitoring systems as appropriate.

• #46 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8696639/

  The presumed mechanisms of hypoglycemia unawareness are summarized in Figure 2. […] Hypoglycemia causes physical and psychological morbidity in diabetic patients. […] In systematic follow-up of patients over 18 years from the DCCT/EDIC, no significant reduction in long-term cognitive function was demonstrated in patients with type 1 diabetes. […] Concern about hypoglycemia is a barrier to diabetes treatment and control, while patients experiencing recurrent episodes of hypoglycemia are also at risk of depression and anxiety. […] In a meta-analysis of more than 900000 patients, a 2-fold increase in the risk of cardiovascular morbidity was observed amongst patients with type 2 diabetes and severe hypoglycemia. […] Hypoglycemia in diabetes is associated with increased morbidity and constitutes a barrier to glycemic control. Much effort must be invested in hypoglycemia prevention, including patient education, appropriate dietary and exercise regimens, adjustment of the treatment regimen, and implementation of glucose monitoring systems as appropriate.

• #47 Hypoglycemia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/122122-overview

  Hypoglycemic symptoms are related to sympathetic activation and brain dysfunction secondary to decreased levels of glucose. Stimulation of the sympathoadrenal nervous system leads to sweating, palpitations, tremulousness, anxiety, and hunger. […] Reduction in cerebral glucose availability (ie, neuroglycopenia) can manifest as confusion, difficulty with concentration, irritability, hallucinations, focal impairments (eg, hemiplegia), and, eventually, coma and death. […] The adrenergic symptoms often precede the neuroglycopenic symptoms and, thus, provide an early warning system for the patient. […] Studies have shown that the primary stimulus for the release of catecholamines is the absolute level of plasma glucose; the rate of decrease of glucose is less important. […] However, it is important to note that a patient with repeated hypoglycemia can have almost no symptoms (hypoglycemic unawareness).

• #48 Hypoglycemia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/122122-overview

  Hypoglycemic symptoms are related to sympathetic activation and brain dysfunction secondary to decreased levels of glucose. Stimulation of the sympathoadrenal nervous system leads to sweating, palpitations, tremulousness, anxiety, and hunger. […] Reduction in cerebral glucose availability (ie, neuroglycopenia) can manifest as confusion, difficulty with concentration, irritability, hallucinations, focal impairments (eg, hemiplegia), and, eventually, coma and death. […] The adrenergic symptoms often precede the neuroglycopenic symptoms and, thus, provide an early warning system for the patient. […] Studies have shown that the primary stimulus for the release of catecholamines is the absolute level of plasma glucose; the rate of decrease of glucose is less important. […] However, it is important to note that a patient with repeated hypoglycemia can have almost no symptoms (hypoglycemic unawareness).

• #49 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8696639/

  The presumed mechanisms of hypoglycemia unawareness are summarized in Figure 2. […] Hypoglycemia causes physical and psychological morbidity in diabetic patients. […] In systematic follow-up of patients over 18 years from the DCCT/EDIC, no significant reduction in long-term cognitive function was demonstrated in patients with type 1 diabetes. […] Concern about hypoglycemia is a barrier to diabetes treatment and control, while patients experiencing recurrent episodes of hypoglycemia are also at risk of depression and anxiety. […] In a meta-analysis of more than 900000 patients, a 2-fold increase in the risk of cardiovascular morbidity was observed amongst patients with type 2 diabetes and severe hypoglycemia. […] Hypoglycemia in diabetes is associated with increased morbidity and constitutes a barrier to glycemic control. Much effort must be invested in hypoglycemia prevention, including patient education, appropriate dietary and exercise regimens, adjustment of the treatment regimen, and implementation of glucose monitoring systems as appropriate.

• #50 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://www.wjgnet.com/1948-9358/full/v12/i12/2036.htm

  It is believed that the impaired sympathoadrenal response is secondary to repeated episodes of hypoglycemia that reduce the autonomic response to other hypoglycemic events. This exposes patients to a vicious cycle of frequent hypoglycemia events and shifts glycemic thresholds for symptoms to lower plasma glucose concentrations close to levels that cause cognitive failure. […] Hypoglycemia causes physical and psychological morbidity in diabetic patients. Symptomatic hypoglycemia constitutes a concern and a distraction. […] Hypoglycemia in diabetes is associated with increased morbidity and constitutes a barrier to glycemic control. Much effort must be invested in hypoglycemia prevention, including patient education, appropriate dietary and exercise regimens, adjustment of the treatment regimen, and implementation of glucose monitoring systems as appropriate.

• #51 Hypoglycemia in diabetes: pathophysiological mechanisms and diurnal variation – PubMed

  https://pubmed.ncbi.nlm.nih.gov/16876586/

  Iatrogenic hypoglycemia, the limiting factor in the glycemic management of diabetes, causes recurrent morbidity (and sometimes death), precludes maintenance of euglycemia over a lifetime of diabetes and causes a vicious cycle of recurrent hypoglycemia. […] In insulin deficient – T1DM and advanced T2DM – diabetes hypoglycemia is the result of the interplay of therapeutic insulin excess and compromised physiological (defective glucose counterregulation) and behavioral (hypoglycemia unawareness) defenses against falling plasma glucose concentrations. […] The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation (by reducing epinephrine responses in the setting of absent insulin and glucagon responses) and hypoglycemia unawareness (by reducing sympathoadrenal and the resulting neurogenic symptom responses) and thus a vicious cycle of recurrent hypoglycemia.

• #52 Diabetic hypoglycemia – Wikipedia

  https://en.wikipedia.org/wiki/Diabetic_hypoglycemia

  For people with insulin-requiring diabetes, hypoglycemia is one of the recurrent hazards of treatment. It limits the achievability of normal glucoses with current treatment methods. Hypoglycemia is a true medical emergency, which requires prompt recognition and treatment to prevent organ and brain damage. […] In patients with type 1 diabetes mellitus, as plasma glucose levels fall, insulin levels do not decrease they are simply a passive reflection of the absorption of exogenous insulin. Also, glucagon levels do not increase. Therefore, the first and second defenses against hypoglycemia are already lost in established type 1 diabetes mellitus. […] The problem is compounded since, in the absence of an appropriate epinephrine response, the usual responses of glycogenolysis and gluconeogenesis may also be lost or blunted. […] Since repeated hypoglycemia is common in people with diabetes who strive to keep their glucose levels near normal, the incidence of hypoglycemic unawareness becomes more prevalent in patients who follow 'intensive treatment’ protocols.

• #53 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8696639/

  The presumed mechanisms of hypoglycemia unawareness are summarized in Figure 2. […] Hypoglycemia causes physical and psychological morbidity in diabetic patients. […] In systematic follow-up of patients over 18 years from the DCCT/EDIC, no significant reduction in long-term cognitive function was demonstrated in patients with type 1 diabetes. […] Concern about hypoglycemia is a barrier to diabetes treatment and control, while patients experiencing recurrent episodes of hypoglycemia are also at risk of depression and anxiety. […] In a meta-analysis of more than 900000 patients, a 2-fold increase in the risk of cardiovascular morbidity was observed amongst patients with type 2 diabetes and severe hypoglycemia. […] Hypoglycemia in diabetes is associated with increased morbidity and constitutes a barrier to glycemic control. Much effort must be invested in hypoglycemia prevention, including patient education, appropriate dietary and exercise regimens, adjustment of the treatment regimen, and implementation of glucose monitoring systems as appropriate.

• #54 Hypoglycemia in Patients With Type 1 Diabetes

  https://www.uspharmacist.com/article/hypoglycemia-in-patients-with-type-1-diabetes

  Although there is an unclear relationship between A1C and hypoglycemia in patients with diabetes, studies have shown that severe hypoglycemia is associated with increasing A1C levels and the development of long-term complications, such as cardiovascular diseases, retinopathy, nephropathy, neuropathy, ischemia, and dementia.

• #55 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8696639/

  The presumed mechanisms of hypoglycemia unawareness are summarized in Figure 2. […] Hypoglycemia causes physical and psychological morbidity in diabetic patients. […] In systematic follow-up of patients over 18 years from the DCCT/EDIC, no significant reduction in long-term cognitive function was demonstrated in patients with type 1 diabetes. […] Concern about hypoglycemia is a barrier to diabetes treatment and control, while patients experiencing recurrent episodes of hypoglycemia are also at risk of depression and anxiety. […] In a meta-analysis of more than 900000 patients, a 2-fold increase in the risk of cardiovascular morbidity was observed amongst patients with type 2 diabetes and severe hypoglycemia. […] Hypoglycemia in diabetes is associated with increased morbidity and constitutes a barrier to glycemic control. Much effort must be invested in hypoglycemia prevention, including patient education, appropriate dietary and exercise regimens, adjustment of the treatment regimen, and implementation of glucose monitoring systems as appropriate.

• #56 Low blood sugar: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000386.htm

  The goal of treatment is to correct your low blood sugar level. It is also important to try and identify the reason why the blood sugar was low to prevent another low blood sugar episode from happening. […] If low blood sugar is caused by an insulinoma, surgery to remove the tumor will be recommended. […] Severe low blood sugar is a medical emergency. It can cause seizures and brain damage. Severe low blood sugar that causes you to become unconscious is called hypoglycemic or insulin shock. […] Even one episode of severe low blood sugar may make it less likely for you to have symptoms that allow you to recognize another episode of low blood sugar.

• #57 Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

  https://www.wjgnet.com/1948-9358/full/v12/i12/2036.htm

  It is believed that the impaired sympathoadrenal response is secondary to repeated episodes of hypoglycemia that reduce the autonomic response to other hypoglycemic events. This exposes patients to a vicious cycle of frequent hypoglycemia events and shifts glycemic thresholds for symptoms to lower plasma glucose concentrations close to levels that cause cognitive failure. […] Hypoglycemia causes physical and psychological morbidity in diabetic patients. Symptomatic hypoglycemia constitutes a concern and a distraction. […] Hypoglycemia in diabetes is associated with increased morbidity and constitutes a barrier to glycemic control. Much effort must be invested in hypoglycemia prevention, including patient education, appropriate dietary and exercise regimens, adjustment of the treatment regimen, and implementation of glucose monitoring systems as appropriate.

• #58 Hypoglycemia in diabetes: pathophysiological mechanisms and diurnal variation – PubMed

  https://pubmed.ncbi.nlm.nih.gov/16876586/

  Iatrogenic hypoglycemia, the limiting factor in the glycemic management of diabetes, causes recurrent morbidity (and sometimes death), precludes maintenance of euglycemia over a lifetime of diabetes and causes a vicious cycle of recurrent hypoglycemia. […] In insulin deficient – T1DM and advanced T2DM – diabetes hypoglycemia is the result of the interplay of therapeutic insulin excess and compromised physiological (defective glucose counterregulation) and behavioral (hypoglycemia unawareness) defenses against falling plasma glucose concentrations. […] The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation (by reducing epinephrine responses in the setting of absent insulin and glucagon responses) and hypoglycemia unawareness (by reducing sympathoadrenal and the resulting neurogenic symptom responses) and thus a vicious cycle of recurrent hypoglycemia.

• #59

  https://link.springer.com/article/10.1186/2251-6581-11-17

  Hypoglycemia is one of the most important complications of diabetes treatment. […] Episodes hypoglycemia may lead to impairment of counter-regulatory system, with the potential of development of hypoglycemia unawareness. […] Hypoglycemia typically arises when abnormalities in the mechanisms involved in glucose homeostasis is existed. In patients with type 1 diabetes secretion of both counter-regulatory hormones of insulin and glucagon is severely interrupted. […] The combination of glucagon absence and the attenuated epinephrine response causes the clinical syndrome of defective glucose counter-regulation, a syndrome that has been shown to increase the risk of severe hypoglycemia by 25-fold or even higher during strict treatment compared to when a normal epinephrine responses is presented.

• #60 Hypoglycemia in diabetes: pathophysiological mechanisms and diurnal variation – PubMed

  https://pubmed.ncbi.nlm.nih.gov/16876586/

  Iatrogenic hypoglycemia, the limiting factor in the glycemic management of diabetes, causes recurrent morbidity (and sometimes death), precludes maintenance of euglycemia over a lifetime of diabetes and causes a vicious cycle of recurrent hypoglycemia. […] In insulin deficient – T1DM and advanced T2DM – diabetes hypoglycemia is the result of the interplay of therapeutic insulin excess and compromised physiological (defective glucose counterregulation) and behavioral (hypoglycemia unawareness) defenses against falling plasma glucose concentrations. […] The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation (by reducing epinephrine responses in the setting of absent insulin and glucagon responses) and hypoglycemia unawareness (by reducing sympathoadrenal and the resulting neurogenic symptom responses) and thus a vicious cycle of recurrent hypoglycemia.

• #61

  https://link.springer.com/article/10.1186/2251-6581-11-17

  Hypoglycemia is one of the most important complications of diabetes treatment. […] Episodes hypoglycemia may lead to impairment of counter-regulatory system, with the potential of development of hypoglycemia unawareness. […] Hypoglycemia typically arises when abnormalities in the mechanisms involved in glucose homeostasis is existed. In patients with type 1 diabetes secretion of both counter-regulatory hormones of insulin and glucagon is severely interrupted. […] The combination of glucagon absence and the attenuated epinephrine response causes the clinical syndrome of defective glucose counter-regulation, a syndrome that has been shown to increase the risk of severe hypoglycemia by 25-fold or even higher during strict treatment compared to when a normal epinephrine responses is presented.

• #62

  https://link.springer.com/article/10.1186/2251-6581-11-17

  Hypoglycemia-associated autonomic failure (HAAF) in type 1 diabetes apparently results from recent antecedent hypoglycemia that caused by both defective counter-regulatory response and hypoglycemia unawareness. […] The mechanisms of defect in glucose counter-regulation in type 2 diabetes are the same as type 1 diabetes which includes both defect in hypoglycemia counter-regulation mechanism and deficiency of sense of hypoglycemia.

• #63 Mechanisms of Hypoglycemia Counterregulation

  https://www.medscape.org/viewarticle/438362

  The vicious cycle of prior hypoglycemia begetting hypoglycemic unawareness implies that strategies to prevent hypoglycemia may be beneficial in restoring the hormonal, neuronal, and cognitive impairments of deficient counterregulation. […] These studies suggest that hypoglycemic unawareness can be resolved and glucose counterregulation can be achieved by preventing the occurrence of hypoglycemia. […] Long-standing type 1 diabetes is associated with an impairment in the hormonal counterregulatory response to a hypoglycemic challenge. […] Cortisol and stress may blunt the counterregulatory response and contribute to hypoglycemia-associated autonomic failure in type 1 diabetes. […] Exercise may impede the counterregulatory response and contribute to hypoglycemia-associated autonomic failure in type 1 diabetes.

• #64 Hypoglycemia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hypoglycemia_pathophysiology

  The pathophysiology of hypoglycemia depends on the failure of physiological defense mechanisms and hormones such as insulin, glucagon, and epinephrine to correct hypoglycemia. Most of these defense mechanisms are hormones that control glycogenolysis and gluconeogenesis. […] The pathophysiology of hypoglycemia mainly relies on the failure of physiological defense mechanisms and hormones such as insulin, glucagon and epinephrine to correct hypoglycemia. Most of these hormones control glycogenolysis and gluconeogenesis, including: […] The most important and the first mechanism to counter-regulate hypoglycemia is the ability to suppress insulin release. This happens early when blood glucose level is between 80-85 mmHg. This can not occur in patients with absolute beta-cell failure, type 1 diabetes mellitus, and long-standing type 2 diabetes. High insulin levels inhibit hepatic glycogenolysis causing more hypoglycemia.

• #65 Hypoglycemia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hypoglycemia_pathophysiology

  The pathophysiology of hypoglycemia depends on the failure of physiological defense mechanisms and hormones such as insulin, glucagon, and epinephrine to correct hypoglycemia. Most of these defense mechanisms are hormones that control glycogenolysis and gluconeogenesis. […] The pathophysiology of hypoglycemia mainly relies on the failure of physiological defense mechanisms and hormones such as insulin, glucagon and epinephrine to correct hypoglycemia. Most of these hormones control glycogenolysis and gluconeogenesis, including: […] The most important and the first mechanism to counter-regulate hypoglycemia is the ability to suppress insulin release. This happens early when blood glucose level is between 80-85 mmHg. This can not occur in patients with absolute beta-cell failure, type 1 diabetes mellitus, and long-standing type 2 diabetes. High insulin levels inhibit hepatic glycogenolysis causing more hypoglycemia.

• #66 Hypoglycemia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hypoglycemia_pathophysiology

  Hypoglycemia stimulates secretion of glucagon. This happens when blood glucose level falls between 65-70 mmHg. Failure to secrete glucagon may be the result of beta-cell failure and high insulin level that inhibits glucagon secretion. […] Epinephrine response to hypoglycemia becomes suppressed in many patients. This happens when blood glucose level falls between 65-70 mmHg. A suppressed epinephrine response causes defective glucose counter-regulation and hypoglycemia unawareness occurs. This may be due to shifting the glycemic threshold for the sympathoadrenal response to a lower plasma glucose concentration. […] The progression to hypoglycemia is actually because of decreased glucose synthesis rather than increased use due to the direct effect of insulin on the liver. […] The net result is continued glucose utilization by skeletal muscle and inhibition of glucose release, glycogenolysis, and gluconeogenesis in the liver.

• #67 Hypoglycemia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hypoglycemia_pathophysiology

  Hypoglycemia stimulates secretion of glucagon. This happens when blood glucose level falls between 65-70 mmHg. Failure to secrete glucagon may be the result of beta-cell failure and high insulin level that inhibits glucagon secretion. […] Epinephrine response to hypoglycemia becomes suppressed in many patients. This happens when blood glucose level falls between 65-70 mmHg. A suppressed epinephrine response causes defective glucose counter-regulation and hypoglycemia unawareness occurs. This may be due to shifting the glycemic threshold for the sympathoadrenal response to a lower plasma glucose concentration. […] The progression to hypoglycemia is actually because of decreased glucose synthesis rather than increased use due to the direct effect of insulin on the liver. […] The net result is continued glucose utilization by skeletal muscle and inhibition of glucose release, glycogenolysis, and gluconeogenesis in the liver.

• #68 Hypoglycemia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hypoglycemia_pathophysiology

  Hypoglycemia stimulates secretion of glucagon. This happens when blood glucose level falls between 65-70 mmHg. Failure to secrete glucagon may be the result of beta-cell failure and high insulin level that inhibits glucagon secretion. […] Epinephrine response to hypoglycemia becomes suppressed in many patients. This happens when blood glucose level falls between 65-70 mmHg. A suppressed epinephrine response causes defective glucose counter-regulation and hypoglycemia unawareness occurs. This may be due to shifting the glycemic threshold for the sympathoadrenal response to a lower plasma glucose concentration. […] The progression to hypoglycemia is actually because of decreased glucose synthesis rather than increased use due to the direct effect of insulin on the liver. […] The net result is continued glucose utilization by skeletal muscle and inhibition of glucose release, glycogenolysis, and gluconeogenesis in the liver.

• #69 Hypoglycemia in patient with type 2 diabetes treated with insulin: it can happen | BMJ Open Diabetes Research & Care

  https://drc.bmj.com/content/8/1/e001194

  In people without diabetes, hypoglycemia is rare since endogenous insulin secretion is inhibited as glucose levels fall below normal. Individuals with diabetes, treated with insulin, sulfonylureas or other insulin secretagogues, are at increased hypoglycemic risk because glucose levels will continue to fall until either insulin boluses or the effect of oral medication are cleared. […] With increased duration of diabetes, in both T1D and advanced T2D, progressive loss of cells prevents paracrine cross-talk between the and cells leading to impaired glucagon release during hypoglycemia. This increases vulnerability to hypoglycemia. Thus, duration of T1D and, in T2D, the duration of insulin treatment are important predictors of hypoglycemic risk. […] In summary, these pathophysiological changes, which both diminish symptomatic responses as well as reduce the ability of the body to resist the glucose-lowering effect of insulin, explain why individuals with T1D or long-standing T2D both are vulnerable to hypoglycemia during treatment.

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