Materiały źródłowe

• #1 Hypoglycemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK534841/

  Hypoglycemia is often defined by a plasma glucose concentration below 70 mg/dL; however, signs and symptoms may not occur until plasma glucose concentrations drop below 55 mg/dL. […] The body has inherent counter-regulatory mechanisms to prevent hypoglycemic episodes. These counter-regulatory mechanisms include an interplay of hormones and neural signals to regulate endogenous insulin release, increase hepatic glucose output, and alter peripheral glucose utilization. […] A decrease in insulin production as a response to low serum glucose isn’t the body’s first line of defense against hypoglycemia. For endogenous glucose production to take place, particularly hepatic glycogenolysis, low insulin levels are necessary. […] The previously mentioned counter-regulatory mechanisms may occasionally fail to resolve the hypoglycemia. At this point, further counter-regulatory measures are employed, such as growth hormone and cortisol.

• #2 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.

• #3 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.

• #4 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. Previous blood sugar levels can influence an individual’s response to a particular level of blood sugar. However, it is important to note that a patient with repeated hypoglycemia can have almost no symptoms (hypoglycemic unawareness). The threshold at which a patient feels the hypoglycemic symptoms decreases with repeated episodes of hypoglycemia.

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

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10887081/

  Hypoglycemia unawareness describes a condition in which autonomic and neuroglycopenic symptoms of hypoglycemia decrease and hence are hardly perceivable. […] 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.

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

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

  Hypoglycemia unawareness describes a condition in which autonomic and neuroglycopenic symptoms of hypoglycemia decrease and hence are hardly perceivable. […] 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.

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

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10887081/

  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. […] Besides the attenuation of the sympathoadrenal responses, 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.

• #8 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. […] Besides the attenuation of the sympathoadrenal responses, 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.

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

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10887081/

  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. […] Furthermore, there is a paradoxical impairment of glucagon secretion during hypoglycemia in patients with diabetes. […] The concept of hypoglycemia unawareness also includes that recent antecedent hypoglycemic episodes cause a defective counterregulation by reducing epinephrine levels.

• #10 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. […] Furthermore, there is a paradoxical impairment of glucagon secretion during hypoglycemia in patients with diabetes. […] The concept of hypoglycemia unawareness also includes that recent antecedent hypoglycemic episodes cause a defective counterregulation by reducing epinephrine levels.

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

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

  Risk factors for hypoglycemia can be from therapeutic hyperinsulinemia or failure of defense mechanisms from a drop in plasma glucose concentration. […] Impairment in counter-regulatory responses to hypoglycemia: 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. […] The presumed mechanisms of hypoglycemia unawareness are summarized in Figure 2. […] Hypoglycemia causes physical and psychological morbidity in diabetic patients.

• #12 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.

• #13

  https://link.springer.com/article/10.1007/s11892-013-0411-y

  Hypoglycemia is uncommon in the general, nondiabetic population but occurs frequently in persons with diabetes treated with insulin or insulin secretagogues. […] Thus, iatrogenic hypoglycemia explains the majority of cases among persons with type 1 diabetes (T1DM). […] Hypoglycemia is the limiting factor to excellent glycemic control in insulin-treated subjects. […] Recent measurements using continuous glucose monitoring reveal an alarming rate of daytime and nocturnal episodes of hypoglycemia in patients with T1DM. […] Etiological factors underlying hypoglycemia in T1DM include predictable triggers (skipped meals, exercise, insulin over dosage) as well as defective counterregulation, a component of hypoglycemia-associated autonomic failure. […] Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes. Diabetes. 2005;54(12):3592601.

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

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

  Hypoglycemia is defined as a condition where plasma glucose concentration is low, which may expose patients to possible harm. This is common amongst persons who have type 1 diabetes, with an annual incidence of severe hypoglycemia ranging from 3.3% to 13.5%. […] While patients treated with insulin or insulin secretagogues (sulfonylureas and meglitinides) are generally at higher risk, severe hypoglycemia is less common in patients with type 2 diabetes. […] Glucose-lowering medications that do not cause unregulated insulin secretion, such as dipeptidyl peptidase-4 inhibitors, metformin, glucagon-like peptide-1 receptor agonists, thiazolidinediones, and sodium-glucose cotransporter-2 inhibitors are associated with lower risk of hypoglycemia, unless used in combination with insulin or insulin secretagogues.

• #15 Alcohol and hypoglycemia: Link, signs, and treatment

  https://www.medicalnewstoday.com/articles/alcohol-and-hypoglycemia

  Doctors associate alcohol consumption with a higher risk of hypoglycemia or low blood sugar. […] The liver is responsible for keeping blood sugar within the typical limits. […] When someone consumes alcohol, the liver may then neglect blood sugar level maintenance in favor of breaking down alcohol. The person may then experience hypoglycemia. […] Alcohol may make hypoglycemia more likely. The mechanism behind this effect involves the liver. […] However, problems arise if the liver must choose between balancing blood sugar and detoxification because it cannot perform these actions simultaneously. If the organ has to choose between maintaining blood sugar or detoxifying alcohol, the liver metabolizes alcohol. If it cannot fulfill its role in maintaining blood sugar levels at the time, a person may experience hypoglycemia.

• #16 Diabetic hypoglycemia – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/diabetic-hypoglycemia/symptoms-causes/syc-20371525

  Diabetic hypoglycemia occurs when someone with diabetes doesn’t have enough sugar (glucose) in his or her blood. Glucose is the main source of fuel for the body and brain, so you can’t function well if you don’t have enough. […] Most of the body’s glucose comes from food. The hormone insulin lowers blood sugar (glucose) levels when blood sugar is too high. If you have type 1 or type 2 diabetes and need insulin to control your blood sugar, taking more insulin than you need can cause your blood sugar level to drop too low and result in hypoglycemia. […] Your blood sugar can also drop too low if, after taking your diabetes medication, you eat less than usual, or if you exercise more than you typically do, which uses extra glucose. Maintaining the balance between insulin, food and activity isn’t always easy. But your health care provider, certified diabetes care and education specialist, and registered dietitian can work with you to try to prevent low blood sugar levels.

• #17 Hypoglycemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hypoglycemia/symptoms-causes/syc-20373685

  If you have diabetes, you might not make insulin (type 1 diabetes) or you might be less responsive to it (type 2 diabetes). As a result, glucose builds up in the bloodstream and can reach dangerously high levels. To correct this problem, you might take insulin or other medications to lower blood sugar levels. […] But too much insulin or other diabetes medications may cause your blood sugar level to drop too much, causing hypoglycemia. Hypoglycemia can also occur if you eat less than usual after taking your regular dose of diabetes medication, or if you exercise more than you typically do. […] Hypoglycemia in people without diabetes is much less common. Causes can include: […] Insulin overproduction. A rare tumor of the pancreas (insulinoma) can cause you to produce too much insulin, resulting in hypoglycemia. Other tumors also can result in too much production of insulin-like substances. Unusual cells of the pancreas that produce insulin can result in excessive insulin release, causing hypoglycemia.

• #18 Hypoglycemia – Harvard Health

  https://www.health.harvard.edu/a_to_z/hypoglycemia-a-to-z

  Hypoglycemia triggers the release of body hormones, such as epinephrine (adrenaline) and norepinephrine (noradrenaline), which serve to raise the low sugar level. […] Hypoglycemia occurs because of too high a dose of insulin or one of the sulfonylureas (glyburide, glipizide and others), or a change in diet or exercise without adjusting glucose-lowering medications. […] Hypoglycemia can occur, although rarely, in people who do not have diabetes. When it does occur outside of diabetes, hypoglycemia can be caused by a variety of medical problems. […] A pancreatic tumor, called an insulinoma, that abnormally secretes insulin. […] If an insulinoma is suspected, the doctor may order a supervised 48-hour fast. During that period, blood levels of glucose and insulin will be measured when symptoms occur. A blood glucose level of less than 60 milligrams per deciliter at the time of symptoms and with a measurable level of insulin strongly suggests the person has an insulinoma. […] An insulinoma is treated with surgery to remove the tumor. Hypoglycemia caused by problems with the adrenal or pituitary glands is treated by replacing the missing hormones with medication.

• #19 Hypoglycemia in Children: Major Endocrine-Metabolic Causes and Novel Therapeutic Perspectives

  https://www.mdpi.com/2072-6643/15/16/3544

  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. […] Glucose is the main energy substrate for the brain. Since the intracerebral transport of glucose depends on its plasma concentration and the brain can store only limited reserves of glycogen, glucose homeostasis is finely regulated by insulin and counter-regulatory hormones: glucagon, epinephrine, cortisol and growth hormone (GH). […] After carbohydrate intake, plasma glucose levels increase and pancreatic beta-cells secrete insulin, which stimulates glucose uptake by peripheral tissues.

• #20 Hypoglycemia in Children: Major Endocrine-Metabolic Causes and Novel Therapeutic Perspectives

  https://www.mdpi.com/2072-6643/15/16/3544

  During fasting, insulin secretion is suppressed, while serum concentrations of counter-regulatory hormones increase. […] If blood glucose falls below 65 mg/dL, cortisol and GH secretion increases, activating proteolysis, lipolysis and gluconeogenesis. […] Infants and younger children have a relatively greater brain volume relative to body mass. They therefore exhibit a glucose utilization rate per kg of body weight 2–3 times higher than that of adults. […] The main causes of hypoglycemia can be classified into endocrine or metabolic etiology. […] Hyperinsulinism is a medical condition characterized by inappropriately high insulin secretion compared to plasma glucose concentration, leading to a continuous stimulation of hepatic glycogen synthesis and glucose uptake by skeletal muscles and adipose tissue.

• #21 Hypoglycemia in Children: Major Endocrine-Metabolic Causes and Novel Therapeutic Perspectives

  https://www.mdpi.com/2072-6643/15/16/3544

  Congenital hyperinsulinism (CH) is the most common cause of persistent hypoglycemia in infants and children. […] CH is associated with several mutations including channelopathies, due to subunit mutations of beta-cell ATP-sensitive potassium channels (K-ATP channels), and metabolopathies, due to activating mutations of the enzymes glucokinase and glutamate dehydrogenase. […] Once the laboratory diagnosis of CH on a critical sample has been established, a genetic test should be performed and ABCC8/ KCNJ11 mutations must be investigated first. […] Treatment includes an emergency approach that aims to quickly restore normal blood glucose values, based on the administration of intravenous glucose solution or intravenous glucagon administration, and a long-term therapy that aims to prevent brain damage and promote normal development and growth of the child.

• #22 Hypoglycemia in Children: Major Endocrine-Metabolic Causes and Novel Therapeutic Perspectives

  https://www.mdpi.com/2072-6643/15/16/3544

  The main drug used for medical therapy is diazoxide. […] Hyperinsulinism may occur also in the setting of specific syndromes, such as Beckwith–Wiedemann syndrome (BWS). […] Counter-regulatory hormone deficiencies may be isolated or part of panhypopituitarism. […] Cortisol deficiency leads to decreased proteolysis, lipolysis and gluconeogenesis, resulting in an incapacity to raise glucose levels. […] Gluconeogenesis (GNG) is a metabolic process characterized by the conversion of substrates such as lactate, pyruvate, alanine and glycerol into glucose, in order to maintain normal blood glucose levels during fasting. […] Mitochondrial fatty-acid-oxidation (mFAO) disorders are due to genetic defects of enzymes involved in their transport and beta oxidation inside of the mitochondria, resulting in a lack of substrates for ketogenesis. […] Hypoglycemia represents a common metabolic-endocrine emergency that might cause permanent neurological consequences, if not treated promptly.

• #23 Postprandial hypoglycaemia in adults: pathogenesis, diagnosis and management – Sulaiman – Journal of Laboratory and Precision Medicine

  https://jlpm.amegroups.org/article/view/6042/html

  Postprandial hypoglycaemia (PPH) develops due to the dysregulated insulin release from pancreatic -cells in the presence of low blood glucose levels. […] PPH develops when insulin secretion fails to suppress, in response to falling blood glucose concentrations and normal counter-regulatory response of glucagon and epinephrine is blunted. Excessive insulin suppresses glycogenolysis, gluconeogenesis. Therefore, hypoglycaemia results from reduced glucose production rather than its increased utilisation. […] Its aetiology is unknown. There is no previous history of gastrointestinal tract surgery. […] PPH is a well-known late complication of upper gastrointestinal surgery. […] Following surgery, rapid transition of food to small intestine causes early and higher glycaemic peak and increased GLP-1 secretion, triggering larger insulin synthesis, leading to a rapid drop in blood glucose, with a nadir in 90 to 180 minutes after meals.

• #24 Postprandial hypoglycaemia in adults: pathogenesis, diagnosis and management – Sulaiman – Journal of Laboratory and Precision Medicine

  https://jlpm.amegroups.org/article/view/6042/html

  A blunted glucagon response to insulin-induced hypoglycaemia is well documented in patients post-RYGB compared to the same patients before surgery. […] It is unclear why individual patients who develop hypoglycaemia show much enhanced pancreatic -cell stimulation and exaggerated GLP-1 response, compared to those who do not develop hypoglycaemia after surgery. […] Diagnosis of endogenous hyperinsulinemia is confirmed when in the presence of plasma glucose of 3.0 mmol/L, there is detectable plasma insulin with high C-peptide, proinsulin of 5.0 pmol/L, suppressed plasma free fatty acid and -OHB. […] Surgical resection of insulinoma is the preferred treatment. Nevertheless, surgery is the last option to treat other causes of severe endogenous hyperinsulinism, refractory to dietary modification and medical therapy.

• #25 Alcoholism and Its Relation to Hypoglycemia – An Overview

  https://pubs.sciepub.com/ajms/2/3/2/

  Alcoholism is the enhanced consumption of ethanol (120ml/day) and hypoglycemia is a condition where there is decreased blood glucose levels (50mg/dl or 2.8mmol/L). […] Enhanced ethanol oxidation raises NADH levels which inhibit key or regulatory enzymes of gluconeogenesis thus blocks release of glucose from liver leading to hypoglycemia. […] Alcoholic hypoglycemia occurs as a result of prolonged fasting and excess alcohol intake, when the hepatic glycogen store becomes depleted and alcohol inhibits gluconeogenesis. […] Alcoholic hypoglycemia is due to inhibition of gluconeogenesis by ethanol and alcoholic ketosis is due to accumulation of beta hydroxy butyrate by increased concentrations of NADH. Thus alcoholic hypoglycemia and alcoholic ketosis are the sequential events occurring one after another in alcoholism and liver can replenish its function on supply of glucose and the most salient feature of liver is that changes in liver can be seen only after chronic alcoholism associated which is also with malnutrition. Further research is required to know the mechanism in liver that helps to maintain the reduced hepatic redox state during alcoholism longer than expected.

• #26 Scientists explain how alcohol causes hypoglycemia (too low blood sugar)

  https://www.medicalnewstoday.com/releases/93141

  Scientists at the leading Swedish medical university Karolinska Institutet have now disclosed the mystery how alcohol may cause exaggerated insulin secretion resulting in severe hypoglycemia (too low blood sugar). […] This mechanism, which is described in the latest number of Endocrinology, explains how alcohol ingestion may harm the human brain by decreasing the blood glucose concentration to inappropriately low levels. […] Hypoglycemia induced by alcohol ingestion is a well known clinical problem in diabetic patients. […] However, the mechanisms underlying this phenomenon have largely remained elusive. […] „We have now found that alcohol exerts substantial influences on pancreatic microcirculation by evoking a massive redistribution of pancreatic blood flow from the exocrine into the endocrine (insulin-producing) part via mechanisms mediated by the messenger molecule nitric oxide and the vagus nerve, augmenting late phase insulin secretion, and thereby evoking hypoglycemia” says lead investigator ke Sjholm.

• #27 Scientists explain how alcohol causes hypoglycemia (too low blood sugar)

  https://www.medicalnewstoday.com/releases/93141

  According to Professor Sjholm the discovery is very important. This novel mechanism may in part underlie the well known hypoglycemic properties of alcohol in diabetic patients or in alcoholics with hepatic failure. […] Alcohol intake might provoke sustained hypoglycemia in type 2 diabetes patients being treated with hypoglycemic sulfonylureas, such as glibenclamide, because many of these drugs have a long biological half-life. […] Furthermore, many alcoholics are malnourished and/or have liver cirrhosis and might therefore be unable to mount a gluconeogenetic response to hypoglycemia, Professor Sjholm says.

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

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

  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. […] Clinical and epidemiological studies based on tens of thousands of patients with type 1 and type 2 diabetes from a variety of health services in different world regions showed a 1.5- to 6-fold increase in the risk of cardiovascular events and mortality among patients who experienced severe hypoglycemia. […] Hypoglycemia in diabetes is associated with increased morbidity and constitutes a barrier to glycemic control.

• #29 Mechanisms of hypoglycemia unawareness and implications in diabetic patients

  https://www.wjgnet.com/1948-9358/full/v6/i7/912.htm

  The youngest patients are most vulnerable to the adverse consequences of hypoglycemia. […] In patients with T2DM and coronary artery disease, severe hypoglycemia was associated with ischemic electrocardiogram changes and chest pain. […] Patients in the older age-groups are especially vulnerable to HU. […] Pregnancy is associated with a high risk of severe hypoglycemia in diabetic subjects. […] Hypoglycemia and HU are associated with significant reductions in quality of life measures in both T1DM and T2DM patients. […] The psychological consequences of HU include subsequent fear to hypoglycemia, and secondary poor treatment compliance, increased anxiety and decreased levels of satisfaction and happiness. […] The economic consequences of severe hypoglycemia events and HU in patients with diabetes are higher than that of a mild episode. […] Prevention of HU is an important part of modern day intensive diabetes therapy. […] The treatment options for the management of HU are listed in Table 1. […] HU is a complex, difficult-to-study phenomenon that carries with it great risk to patients.

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

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

  Targeting the VMN to 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.

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

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

  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. […] My project will investigate the role of the brain in hypoglycemia. […] We are particularly interested in understanding how these brain systems change following repeated hypoglycemia and contribute to hypoglycemia associated autonomic failure. […] Currently, we do not have a strong grasp on the mechanisms responsible for hypoglycemia associated autonomic failure that exacerbates the risk of diabetic shock and seizures in type 1 and advanced type 2 diabetic patients. […] My project will attempt to reveal the brain systems that no longer function properly in patients with hypoglycemia associated autonomic failure.

• #32 The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis | Acta Pharmacologica Sinica

  https://www.nature.com/articles/s41401-019-0345-2

  Mitochondria serve as sensors of energy regulation and glucose levels, which are impaired by diabetes progression. Catalpol is an iridoid glycoside that exerts a hypoglycemic effect by improving mitochondrial function, but the underlying mechanism has not been fully elucidated. […] After oral administration of catalpol (200mgkg1d1) for 8 weeks, db/db mice exhibited a decreased fasting blood glucose level and restored mitochondrial function in skeletal muscle. […] Thus, catalpol improves skeletal muscle mitochondrial function by activating AMPK-mediated mitochondrial biogenesis. […] A strong association of insulin resistance and T2DM development with mitochondrial dysfunction is evident, and mitochondrial dysfunction causes insulin resistance. […] Mitochondrial biogenesis is dynamically regulated; new mitochondria are constantly produced to maintain the appropriate number of morphologically normal active organelles to meet the constantly changing bioenergetic needs of the cell via oxidative metabolism.

• #33 Multiple beta cell-independent mechanisms drive hypoglycemia in Timothy syndrome | Nature Communications

  https://www.nature.com/articles/s41467-024-52885-3

  The canonical G406R mutation that increases Ca2+ influx through the CACNA1C-encoded CaV1.2 Ca2+ channel underlies the multisystem disorder Timothy syndrome (TS), characterized by life-threatening arrhythmias. Severe episodic hypoglycemia is among the poorly characterized non-cardiac TS pathologies. […] While hypothesized from increased Ca2+ influx in pancreatic beta cells and consequent hyperinsulinism, this hypoglycemia mechanism is undemonstrated because of limited clinical data and lack of animal models. […] Unexpectedly, these mice do not show hyperactive beta cells or hyperinsulinism in the setting of normal intrinsic beta cell function, suggesting dysregulated glucose homeostasis. […] Patient data confirm the absence of hyperinsulinism. […] We discover multiple alternative contributors, including perturbed counterregulatory hormone responses with defects in glucagon secretion and abnormal hypothalamic control of glucose homeostasis.

• #34 Multiple beta cell-independent mechanisms drive hypoglycemia in Timothy syndrome | Nature Communications

  https://www.nature.com/articles/s41467-024-52885-3

  The leading hypothesis, although without supporting evidence, for hypoglycemia in individuals with TS is that increased Ca2+ influx through the mutant CaV1.2 channels in insulin-secreting pancreatic beta cells leads to inappropriately high insulin secretion. […] Whether CACNA1C variants contribute to hyperinsulinism, however, has not been definitively demonstrated. […] We therefore generated a Cacna1cG406R knockin mutation in exon 8 by CRISPR/Cas9. […] Unexpectedly, we find that hyperinsulinism does not underlie the hypoglycemia in TS2 mice. […] Together, our data demonstrate that the proposed hyperinsulinism driven by expression of the mutant CaV1.2TS channel in pancreatic beta cells is not the etiology for the severe episodic hypoglycemia suffered by patients with TS. […] Several independent lines of evidence bolster this conclusion. First, we show that serum insulin levels are reduced, not elevated, in the TS2 mice.

• #35 Hypoglycemia: Clinical Signs, Treatment, Prognosis

  https://www.cliniciansbrief.com/article/hypoglycemia-0

  Hypoglycemia is a manifestation of a pathologic process not a diagnosis. It is always secondary to a disorder that disrupts or overwhelms one or more of the homeostatic mechanisms responsible for maintenance of normoglycemia. […] Hypoglycemia occurs when the rate of glucose removal exceeds the rate of its addition to blood. Endogenous or exogenous substances that mimic or potentiate insulin action or enhance or accelerate glucose metabolism increase glucose removal, whereas failure of endogenous glucose production decreases the rate of glucose addition to blood. Disruptions of the pathways responsible for glucose addition or removal may overwhelm homeostatic mechanisms and produce clinical hypoglycemia. […] Clinical disorders produce hypoglycemia through one or more pathophysiologic mechanisms. Clinical hypoglycemia can be broadly divided into several categories: hyperinsulinemic hypoglycemia, hypoinsulinemic hypoglycemia, and miscellaneous disorders.

• #36 Hypoglycemia: Clinical Signs, Treatment, Prognosis

  https://www.cliniciansbrief.com/article/hypoglycemia-0

  Hyperinsulinemic hypoglycemia is the most common mechanism of hypoglycemia in dogs and cats, with relative or absolute insulin excess being a common feature. […] Insulinoma, a neuroendocrine tumor of the pancreas, is the most common disorder associated with hyperinsulinemic hypoglycemia due to excess production of endogenous insulin. […] Hypoinsulinemic hypoglycemia describes hypoglycemia that develops independent of insulin; in associated conditions, blood insulin is appropriately low with hypoglycemia. Non-insulin-mediated hypoglycemia may develop via one of several mechanisms. Several tumor types produce humoral insulin-like substances that promote hypoglycemia. Hypoinsulinemic hypoglycemia can also occur with disorders that increase use of glucose by body tissues or those associated with failure of hepatic glucose production.

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