Pathophysiology Of Diabetic Ketoacidosis
Diabetic ketoacidosis is one of the potentially life-threatening acute complications of diabetes mellitus. In the past, diabetic ketoacidosis was considered as the hallmark of Type I diabetes, but current data show that it can be also diagnosed in patients with type II diabetes mellitus. It is often seen among patients who are poorly compliant to insulin administration during an acute illness. It is commonly precipitated by an acute stressful event such as the development of infection leading to overt sepsis, organ infarction such as stroke and heart attack, burns, pregnancy or intake of drugs that affect carbohydrate metabolism such as corticosteroids, anti-hypertensives, loop diuretics, alcohol, cocaine, and ecstasy. The presence of these stressful conditions incite the release of counter-regulatory hormones such as glucagon, catecholamines and growth hormone. These hormones induce the mobilization of energy stores of fat, glycogen and protein. The net effect of which is the production of glucose. As a result of absent or deficient insulin release, diabetic ketoacidosis present with the following metabolic derangements: profound hyperglycemia, hyperketonemiaand metabolic acidosis. The production of ketones outweighs its excretion by the kidneys. This results in further reduction of systemic insulin, elevated concentrations of glucagon, cortisol, growth hormone and catecholamine. In peripheral tissues, such as the liver, lipolysis occurs to free fatty acids, resulting in further production of excess ketones. Thereby, causing ketosis and metabolic acidosis. Symptoms of diabetic ketoacidosis usually develop within 24 hours. Gastrointestinal symptoms such as nausea and vomiting are very prominent. If these symptoms are present in diabetics, investigation for diabetic keto Continue reading >>
Understanding The Presentation Of Diabetic Ketoacidosis
Hypoglycemia, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar nonketotic syndrome (HHNS) must be considered while forming a differential diagnosis when assessing and managing a patient with an altered mental status. This is especially true if the patient has a history of diabetes mellitus (DM). However, be aware that the onset of DKA or HHNS may be the first sign of DM in a patient with no known history. Thus, it is imperative to obtain a blood glucose reading on any patient with an altered mental status, especially if the patient appears to be dehydrated, regardless of a positive or negative history of DM. In addition to the blood glucose reading, the history — particularly onset — and physical assessment findings will contribute to the formulation of a differential diagnosis and the appropriate emergency management of the patient. Pathophysiology of DKA The patient experiencing DKA presents significantly different from one who is hypoglycemic. This is due to the variation in the pathology of the condition. Like hypoglycemia, by understanding the basic pathophysiology of DKA, there is no need to memorize signs and symptoms in order to recognize and differentiate between hypoglycemia and DKA. Unlike hypoglycemia, where the insulin level is in excess and the blood glucose level is extremely low, DKA is associated with a relative or absolute insulin deficiency and a severely elevated blood glucose level, typically greater than 300 mg/dL. Due to the lack of insulin, tissue such as muscle, fat and the liver are unable to take up glucose. Even though the blood has an extremely elevated amount of circulating glucose, the cells are basically starving. Because the blood brain barrier does not require insulin for glucose to diffuse across, the brain cells are rece Continue reading >>
Diabetic Ketoacidosis
OVERVIEW potentially life-threatening complication of diabetes melitus resulting from the consequences of insulin deficiency Diagnostic criteria pH < 7.3 ketosis (ketonemia or ketonuria) HCO3 <15 mmol/L due to high anion gap metabolic acidosis (HAGMA) hyperglycemia (may be mild; euglycemic DKA can occur) PATHOGENESIS increased glucagon, cortisol, catcholamines, GH decreased insulin -> hyperglycaemia -> hyperosmolality + glycosuria -> electrolyte loss -> ketone production from metabolism of TG -> acidosis HISTORY dry, abdominal pain, polyuria, weight loss, coma risk factors: non-compliance, illness, newly diagnosed ROS to rule find out possible precipitant (infection, MI, pneumonia, GI illness) normal insulin regime diabetic control previous DKA’s/admissions previous ICU admissions EXAMINATION volume assessment signs of cause e.g. (infection) GCS work of breathing INVESTIGATIONS ABG electrolytes osmolality urinalysis: ketones pregnancy test standard investigations to rule out cause: FBC, ECG, CXR MANAGEMENT Goals (1) establish precipitant and treat (2) assess severity of metabolic derangement (3) cautious fluid resuscitation with replacement of body H2O (4) provision of insulin (5) replacement of electrolytes Resuscitate intubation for airway protection if required O2 as required IV access fluid boluses (20mL/kg boluses of NS/HMN) urinary catheter Acid-base and Electrolyte abnormalities will have a severe metabolic acidosis with probable incomplete respiratory compensation K+ may be normal but patient will have a whole body K+ deficiency -> needs to be replaced once < 5mmol/L -> use KH2PO4 Na+ may be deranged acidaemia rarely requires HCO3- therapy and will respond to other treatments Specific therapy start insulin infusion (avoid bolus) 0.1u/kg/hr aim to lower glucose Continue reading >>
Diabetic Ketoacidosis (dka)
Diabetic ketoacidosis is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with significant fluid and electrolyte loss. DKA occurs mostly in type 1 diabetes mellitus (DM). It causes nausea, vomiting, and abdominal pain and can progress to cerebral edema, coma, and death. DKA is diagnosed by detection of hyperketonemia and anion gap metabolic acidosis in the presence of hyperglycemia. Treatment involves volume expansion, insulin replacement, and prevention of hypokalemia. Diabetic ketoacidosis (DKA) is most common among patients with type 1 diabetes mellitus and develops when insulin levels are insufficient to meet the body’s basic metabolic requirements. DKA is the first manifestation of type 1 DM in a minority of patients. Insulin deficiency can be absolute (eg, during lapses in the administration of exogenous insulin) or relative (eg, when usual insulin doses do not meet metabolic needs during physiologic stress). Common physiologic stresses that can trigger DKA include Some drugs implicated in causing DKA include DKA is less common in type 2 diabetes mellitus, but it may occur in situations of unusual physiologic stress. Ketosis-prone type 2 diabetes is a variant of type 2 diabetes, which is sometimes seen in obese individuals, often of African (including African-American or Afro-Caribbean) origin. People with ketosis-prone diabetes (also referred to as Flatbush diabetes) can have significant impairment of beta cell function with hyperglycemia, and are therefore more likely to develop DKA in the setting of significant hyperglycemia. SGLT-2 inhibitors have been implicated in causing DKA in both type 1 and type 2 DM. Continue reading >>
Infections In Patients With Diabetes Mellitus: A Review Of Pathogenesis
Go to: Diabetes mellitus (DM) is a clinical syndrome associated with deficiency of insulin secretion or action. It is considered one of the largest emerging threats to health in the 21st century. It is estimated that there will be 380 million persons with DM in 2025.[1] Besides the classical complications of the disease, DM has been associated with reduced response of T cells, neutrophil function, and disorders of humoral immunity.[2–4] Consequently, DM increases the susceptibility to infections, both the most common ones as well as those that almost always affect only people with DM (e.g. rhinocerebral mucormycosis).[4] Such infections, in addition to the repercussions associated with its infectivity, may trigger DM complications such as hypoglycemia and ketoacidosis. This article aims to critically review the current knowledge on the mechanisms associated with the greater susceptibility of DM for developing infectious diseases and to describe the main infectious diseases associated with this metabolic disorder. Continue reading >>
Diabetic Ketoacidosis: Evaluation And Treatment
Diabetic ketoacidosis is characterized by a serum glucose level greater than 250 mg per dL, a pH less than 7.3, a serum bicarbonate level less than 18 mEq per L, an elevated serum ketone level, and dehydration. Insulin deficiency is the main precipitating factor. Diabetic ketoacidosis can occur in persons of all ages, with 14 percent of cases occurring in persons older than 70 years, 23 percent in persons 51 to 70 years of age, 27 percent in persons 30 to 50 years of age, and 36 percent in persons younger than 30 years. The case fatality rate is 1 to 5 percent. About one-third of all cases are in persons without a history of diabetes mellitus. Common symptoms include polyuria with polydipsia (98 percent), weight loss (81 percent), fatigue (62 percent), dyspnea (57 percent), vomiting (46 percent), preceding febrile illness (40 percent), abdominal pain (32 percent), and polyphagia (23 percent). Measurement of A1C, blood urea nitrogen, creatinine, serum glucose, electrolytes, pH, and serum ketones; complete blood count; urinalysis; electrocardiography; and calculation of anion gap and osmolar gap can differentiate diabetic ketoacidosis from hyperosmolar hyperglycemic state, gastroenteritis, starvation ketosis, and other metabolic syndromes, and can assist in diagnosing comorbid conditions. Appropriate treatment includes administering intravenous fluids and insulin, and monitoring glucose and electrolyte levels. Cerebral edema is a rare but severe complication that occurs predominantly in children. Physicians should recognize the signs of diabetic ketoacidosis for prompt diagnosis, and identify early symptoms to prevent it. Patient education should include information on how to adjust insulin during times of illness and how to monitor glucose and ketone levels, as well as i Continue reading >>
Diabetic Ketoacidosis And Hypersmolar Non-ketotic Coma
Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are the most serious acute metabolic complications of diabetes. Recent data indicate there are more than 144,000 hospital admissions per year for DKA in the United States and the number of cases show an upward trend, with a 30% increase in the annual number of cases between 1995 and 2009. Treatment of DKA utilizes a large number of resources with an annual medical expense of $2.4 billion. The rate of hospital admissions for HHS is lower than for DKA, accounting for less than 1% of all diabetes-related admissions. Although DKA and HHS are often discussed as separate entities, they represent points along a spectrum of hyperglycemic emergencies due to poorly controlled diabetes. Both DKA and HHS are characterized by insulinopenia and severe hyperglycemia. Clinically, they differ only by the degree of dehydration and the severity of metabolic acidosis. DKA has long been considered a key clinical feature of type 1 diabetes (T1D), but in contrast to popular belief, DKA is more common in patients with type 2 diabetes (T2D). T2D now accounts for up to one half of all newly diagnosed diabetes in children ages 10-21 years. In the U.S., the SEARCH for Diabetes in Youth Study found that 29.4% of participants under 20 years of age with T1D presented with DKA, compared with 9.7% of youth with T2D. In community-based studies more than 40% of patients with DKA are older than 40 and more than 20% are older than 55. Patients with T2D may develop DKA under stressful conditions such as trauma, surgery or infections. In addition, in recent years an increasing number of unprovoked ketoacidosis cases without precipitating cause have been reported in children, adolescents and adult subjects with T2D. HHS occurs most commonl Continue reading >>
Diabetic Ketoacidosis (dka)
Tweet Diabetic ketoacidosis (DKA) is a dangerous complication faced by people with diabetes which happens when the body starts running out of insulin. DKA is most commonly associated with type 1 diabetes, however, people with type 2 diabetes that produce very little of their own insulin may also be affected. Ketoacidosis is a serious short term complication which can result in coma or even death if it is not treated quickly. Read about Diabetes and Ketones What is diabetic ketoacidosis? DKA occurs when the body has insufficient insulin to allow enough glucose to enter cells, and so the body switches to burning fatty acids and producing acidic ketone bodies. A high level of ketone bodies in the blood can cause particularly severe illness. Symptoms of DKA Diabetic ketoacidosis may itself be the symptom of undiagnosed type 1 diabetes. Typical symptoms of diabetic ketoacidosis include: Vomiting Dehydration An unusual smell on the breath –sometimes compared to the smell of pear drops Deep laboured breathing (called kussmaul breathing) or hyperventilation Rapid heartbeat Confusion and disorientation Symptoms of diabetic ketoacidosis usually evolve over a 24 hour period if blood glucose levels become and remain too high (hyperglycemia). Causes and risk factors for diabetic ketoacidosis As noted above, DKA is caused by the body having too little insulin to allow cells to take in glucose for energy. This may happen for a number of reasons including: Having blood glucose levels consistently over 15 mmol/l Missing insulin injections If a fault has developed in your insulin pen or insulin pump As a result of illness or infections High or prolonged levels of stress Excessive alcohol consumption DKA may also occur prior to a diagnosis of type 1 diabetes. Ketoacidosis can occasional Continue reading >>
Hyperosmolar Hyperglycemic State
Acute hyperglycemia, or high blood glucose, may be either the initial presentation of diabetes mellitus or a complication during the course of a known disease. Inadequate insulin replacement (e.g., noncompliance with treatment) or increased insulin demand (e.g., during times of acute illness, surgery, or stress) may lead to acute hyperglycemia. There are two distinct forms: diabetic ketoacidosis (DKA), typically seen in type 1 diabetes, and hyperosmolar hyperglycemic state (HHS), occurring primarily in type 2 diabetes. In type 1 diabetes, no insulin is available to suppress fat breakdown, and the ketones resulting from subsequent ketogenesis manifest as DKA. This is in contrast to type 2 diabetes, in which patients can still secrete small amounts of insulin to suppress DKA, instead resulting in a hyperglycemic state predominated simply by glucose. The clinical presentation of both DKA and HHS is one of polyuria, polydipsia, nausea and vomiting, volume depletion (e.g., dry oral mucosa, decreased skin turgor), and eventually mental status changes and coma. In patients with altered mental status, fingerstick glucose should always be checked in order to exclude serum glucose abnormalities. Several clinical findings pertaining only to DKA include a fruity odor to the breath, hyperventilation, and abdominal pain. HHS patients, in contrast to those with DKA, will present with more extreme volume depletion. The treatment of both DKA and HHS is primarily IV electrolyte and fluid replacement. Insulin for hyperglycemia may be given with caution and under vigilant monitoring of serum glucose. Other treatment options depend on the severity of symptoms and include bicarbonate and potassium replacement. Osmotic diuresis and hypovolemia Hypovolemia resulting from DKA can lead to acute Continue reading >>
Diabetic Ketoacidosis And Hyperglycaemic Hyperosmolar State
The hallmark of diabetes is a raised plasma glucose resulting from an absolute or relative lack of insulin action. Untreated, this can lead to two distinct yet overlapping life-threatening emergencies. Near-complete lack of insulin will result in diabetic ketoacidosis, which is therefore more characteristic of type 1 diabetes, whereas partial insulin deficiency will suppress hepatic ketogenesis but not hepatic glucose output, resulting in hyperglycaemia and dehydration, and culminating in the hyperglycaemic hyperosmolar state. Hyperglycaemia is characteristic of diabetic ketoacidosis, particularly in the previously undiagnosed, but it is the acidosis and the associated electrolyte disorders that make this a life-threatening condition. Hyperglycaemia is the dominant feature of the hyperglycaemic hyperosmolar state, causing severe polyuria and fluid loss and leading to cellular dehydration. Progression from uncontrolled diabetes to a metabolic emergency may result from unrecognised diabetes, sometimes aggravated by glucose containing drinks, or metabolic stress due to infection or intercurrent illness and associated with increased levels of counter-regulatory hormones. Since diabetic ketoacidosis and the hyperglycaemic hyperosmolar state have a similar underlying pathophysiology the principles of treatment are similar (but not identical), and the conditions may be considered two extremes of a spectrum of disease, with individual patients often showing aspects of both. Pathogenesis of DKA and HHS Insulin is a powerful anabolic hormone which helps nutrients to enter the cells, where these nutrients can be used either as fuel or as building blocks for cell growth and expansion. The complementary action of insulin is to antagonise the breakdown of fuel stores. Thus, the relea Continue reading >>
Understanding And Treating Diabetic Ketoacidosis
Diabetic ketoacidosis (DKA) is a serious metabolic disorder that can occur in animals with diabetes mellitus (DM).1,2 Veterinary technicians play an integral role in managing and treating patients with this life-threatening condition. In addition to recognizing the clinical signs of this disorder and evaluating the patient's response to therapy, technicians should understand how this disorder occurs. DM is caused by a relative or absolute lack of insulin production by the pancreatic b-cells or by inactivity or loss of insulin receptors, which are usually found on membranes of skeletal muscle, fat, and liver cells.1,3 In dogs and cats, DM is classified as either insulin-dependent (the body is unable to produce sufficient insulin) or non-insulin-dependent (the body produces insulin, but the tissues in the body are resistant to the insulin).4 Most dogs and cats that develop DKA have an insulin deficiency. Insulin has many functions, including the enhancement of glucose uptake by the cells for energy.1 Without insulin, the cells cannot access glucose, thereby causing them to undergo starvation.2 The unused glucose remains in the circulation, resulting in hyperglycemia. To provide cells with an alternative energy source, the body breaks down adipocytes, releasing free fatty acids (FFAs) into the bloodstream. The liver subsequently converts FFAs to triglycerides and ketone bodies. These ketone bodies (i.e., acetone, acetoacetic acid, b-hydroxybutyric acid) can be used as energy by the tissues when there is a lack of glucose or nutritional intake.1,2 The breakdown of fat, combined with the body's inability to use glucose, causes many pets with diabetes to present with weight loss, despite having a ravenous appetite. If diabetes is undiagnosed or uncontrolled, a series of metab Continue reading >>
Diabetic Ketoacidosis
Abbas E. Kitabchi, PhD., MD., FACP, FACE Professor of Medicine & Molecular Sciences and Maston K. Callison Professor in the Division of Endocrinology, Diabetes & Metabolism UT Health Science Center, 920 Madison Ave., 300A, Memphis, TN 38163 Aidar R. Gosmanov, M.D., Ph.D., D.M.Sc. Assistant Professor of Medicine, Division of Endocrinology, Diabetes & Metabolism, The University of Tennessee Health Science Center, 920 Madison Avenue, Suite 300A, Memphis, TN 38163 Clinical Recognition Omission of insulin and infection are the two most common precipitants of DKA. Non-compliance may account for up to 44% of DKA presentations; while infection is less frequently observed in DKA patients. Acute medical illnesses involving the cardiovascular system (myocardial infarction, stroke, acute thrombosis) and gastrointestinal tract (bleeding, pancreatitis), diseases of endocrine axis (acromegaly, Cushing`s syndrome, hyperthyroidism) and impaired thermo-regulation or recent surgical procedures can contribute to the development of DKA by causing dehydration, increase in insulin counter-regulatory hormones, and worsening of peripheral insulin resistance. Medications such as diuretics, beta-blockers, corticosteroids, second-generation anti-psychotics, and/or anti-convulsants may affect carbohydrate metabolism and volume status and, therefore, could precipitateDKA. Other factors: psychological problems, eating disorders, insulin pump malfunction, and drug abuse. It is now recognized that new onset T2DM can manifest with DKA. These patients are obese, mostly African Americans or Hispanics and have undiagnosed hyperglycemia, impaired insulin secretion, and insulin action. A recent report suggests that cocaine abuse is an independent risk factor associated with DKA recurrence. Pathophysiology In Continue reading >>
Diabetic Ketoacidosis
Etiology In DKA, there is a reduction in the net effective concentration of circulating insulin along with an elevation of counter-regulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). These alterations lead to extreme manifestations of metabolic derangements that can occur in diabetes. The two most common precipitating events are inadequate insulin therapy or infection. Underlying medical conditions such as MI or stroke that provoke the release of counter-regulatory hormones are also likely to result in DKA in patients with diabetes. Drugs that affect carbohydrate metabolism, such as corticosteroids, thiazides, sympathomimetic agents (e.g., dobutamine and terbutaline), and second-generation antipsychotic agents, may participate in the development of DKA. [1] [9] The use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors has also been implicated in the development of DKA in patients with both type 1 and type 2 diabetes. [10] [11] [12] Pathophysiology Reduced insulin concentration or action, along with increased insulin counter-regulatory hormones, leads to the hyperglycemia, volume depletion, and electrolyte imbalance that underlie the pathophysiology of DKA. Hormonal alterations in DKA lead to increased gluconeogenesis, hepatic and renal glucose production, and impaired glucose utilization in peripheral tissues, which result in hyperglycemia and hyperosmolarity. Insulin deficiency leads to release of free fatty acids from adipose tissue (lipolysis), hepatic fatty acid oxidation, and formation of ketone bodies (beta-hydroxybutyrate and acetoacetate), which result in ketonemia and acidosis. Studies have demonstrated the elevation of proinflammatory cytokines and inflammatory biomarkers (e.g., CRP), markers of oxidative stress, lipid peroxidatio Continue reading >>
Diabetic Ketoacidosis In Type 1 And Type 2 Diabetes Mellitusclinical And Biochemical Differences
Background Diabetic ketoacidosis (DKA), once thought to typify type 1 diabetes mellitus, has been reported to affect individuals with type 2 diabetes mellitus. An analysis and overview of the different clinical and biochemical characteristics of DKA that might be predicted between patients with type 1 and type 2 diabetes is needed. Methods We reviewed 176 admissions of patients with moderate-to-severe DKA. Patients were classified as having type 1 or type 2 diabetes based on treatment history and/or autoantibody status. Groups were compared for differences in symptoms, precipitants, vital statistics, biochemical profiles at presentation, and response to therapy. Results Of 138 patients admitted for moderate-to-severe DKA, 30 had type 2 diabetes. A greater proportion of the type 2 diabetes group was Latino American or African American (P<.001). Thirty-five admissions (19.9%) were for newly diagnosed diabetes. A total of 85% of all admissions involved discontinuation of medication use, 69.2% in the type 2 group. Infections were present in 21.6% of the type 1 and 48.4% of the type 2 diabetes admissions. A total of 21% of patients with type 1 diabetes and 70% with type 2 diabetes had a body mass index greater than 27. Although the type 1 diabetes group was more acidotic (arterial pH, 7.21 ± 0.12 vs 7.27 ± 0.08; P<.001), type 2 diabetes patients required longer treatment periods (36.0 ± 11.6 vs 28.9 ± 8.9 hours, P = .01) to achieve ketone-free urine. Complications from therapy were uncommon. Conclusions A significant proportion of DKA occurs in patients with type 2 diabetes. The time-tested therapy for DKA of intravenous insulin with concomitant glucose as the plasma level decreases, sufficient fluid and electrolyte replacement, and attention to associated problems remai Continue reading >>
Diabetic Ketoacidosis And Patho
pathophysiology ketogenesis due to insulin deficiency leads to increased serum levels of ketones anad ketonuria acetoacetate, beta-hydroxybutyrate; ketone bodies produced by the liver, organic acids that cause metabolic acidosis respiration partially compensates; reduces pCO2, when pH < 7.2, deep rapid respirations (Kussmaul breathing) acetone; minor product of ketogenesis, can smell fruity on breath of ketoacidosis patients elevated anion gap Methanol intoxication Uremic acidosis Diabetic ketoacidosis Paraldehyde ingestions Intoxicants (salicyclate, ethylene glycol, nipride, epinephrine, norepinephrine) Lactic acidosis (drug induced; didanosine, iron, isoniazid, metformin, zidovudine) Ethanol ketoacidosis Severe renal failure starvation Blood glucose regulation (6) 1. When blood glucose levels rise above a set point, 2. the pancreas secretes insulin into the blood. 3. Insulin stimulates liver and muscle cells to make glycogen, dropping blood glucose levels. 4. When glucose levels drop below a set point, 5. the pancreas secretes glucagon into the blood. 6. Glucagon promotes the breakdown of glycogen and the release of glucose into the blood. (The pancreas signals distant cells to regulate levels in the blood = endocrine function.) Insulin and Glucagon (Regulation) (10) 1. High blood glucose 2. Beta cells 3. Insulin 4. Glucose enters cell 5. Blood glucose lowered 6. Low blood glucose 7. Alpha cells 8. Glucagon 9. Liver releases glucose from glycogen 10. Blood glucose raised What is the manifestations (symptoms) of Type 1? (10) 1. Extreme thirst 2. Frequent urination 3. Drowsiness, lethargy 4. Sugar in urine 5. Sudden vision change 6. Increased appetite 7. Sudden weight loss 8. Fruity, sweet, or wine like odor on breath 9. Heavy, laboured breathing 10. Stupor, unconscious Continue reading >>
