Ketoacidosis
GENERAL ketoacidosis is a high anion gap metabolic acidosis due to an excessive blood concentration of ketone bodies (keto-anions). ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) are released into the blood from the liver when hepatic lipid metabolism has changed to a state of increased ketogenesis. a relative or absolute insulin deficiency is present in all cases. CAUSES The three major types of ketosis are: (i) Starvation ketosis (ii) Alcoholic ketoacidosis (iii) Diabetic ketoacidosis STARVATION KETOSIS when hepatic glycogen stores are exhausted (eg after 12-24 hours of total fasting), the liver produces ketones to provide an energy substrate for peripheral tissues. ketoacidosis can appear after an overnight fast but it typically requires 3 to 14 days of starvation to reach maximal severity. typical keto-anion levels are only 1 to 2 mmol/l and this will usually not alter the anion gap. the acidosis even with quite prolonged fasting is only ever of mild to moderate severity with keto-anion levels up to a maximum of 3 to 5 mmol/l and plasma pH down to 7.3. ketone bodies also stimulate some insulin release from the islets. patients are usually not diabetic. ALCOHOLIC KETOSIS Presentation a chronic alcoholic who has a binge, then stops drinking and has little or no oral food intake for a few days (ethanol and fasting) volume depletion is common and this can result in increased levels of counter regulatory hormones (eg glucagon) levels of free fatty acids (FFA) can be high (eg up to 3.5mM) providing plenty of substrate for the altered hepatic lipid metabolism to produce plenty of ketoanions GI symptoms are common (eg nausea, vomiting, abdominal pain, haematemesis, melaena) acidaemia may be severe (eg pH down to 7.0) plasma glucose may be depressed or normal or Continue reading >>
Role Of Beta-hydroxybutyric Acid In Diabetic Ketoacidosis: A Review
Go to: Diabetic ketoacidosis (DKA), a complication of diabetes mellitus, is a severe metabolic disease that often requires intensive treatment. Diagnosis of ketosis associated with DKA can be difficult due to variability in the metabolic state of DKA patients. Recognition of the clinical signs and definitive diagnosis are essential for proper treatment. This article reviews the formation of ketoacids during DKA and the role of β-hydroxybutyric acid in the diagnosis and monitoring of DKA. Go to: Introduction Diabetic ketoacidosis (DKA) is a severe and life threatening metabolic disease caused by an absolute or relative deficiency of insulin in the body (1). A disease of middle-aged dogs and cats, DKA occurs as a complication of diabetes mellitus (1). The clinical presentation can range from ketotic patients that are eating, drinking, and maintaining hydration on their own to the more common ketoacidotic patients that are dehydrated and have other signs such as vomiting, anorexia, and lethargy (1). The intensity of treatment is therefore variable and depends on the severity of clinical signs and the degree of metabolic derangement. Most DKA patients require intensive, in-hospital treatment. Go to: Pathophysiology Decreased insulin production by pancreatic beta cells, decreased activity of insulin receptors at the cellular level, or both, are responsible for the abnormal glucose metabolism and resulting hyperglycemia (1,2). One consequence of this disregulated glucose metabolism is that glucose transport from serum into the cells is inadequate, leading to cellular starvation (1–3). In order to satisfy its cellular energy requirements and maintain cellular integrity, the body utilizes adipose tissue as the main energy source (1,4). This is a protective mechanism designed 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 >>
Euglycemic Diabetic Ketoacidosis: The Clinical Concern Of Sglt2 Inhibitors
Euglycemic diabetic ketoacidosis is a post market warning in patients with type 1 diabetes and type 2 diabetes treated with SGLT-2 inhibitors. We report a case of a 39-year-old obese female with presumed type 2 diabetes for seven years who presented to the emergency department with three days of nausea, vomiting, and abdominal pain. Due to previous total non-adherence with a prescribed insulin regimen, she was recently started on canagliflozin and liraglutide. The diagnosis of euDKA was missed in the initial evaluation as the blood glucose level was only 167 mg/dL. Further work up showed severe metabolic acidosis with an anion gap of 25 and positive ketones in the urine. She was treated successfully with dextrose water 5%/half normal saline and an insulin drip. As part of the work up, she tested positive for glutamic acid decarboxylase autoantibodies. Given the increasing utilization of SGLT-2 inhibitors and the fact that patients can present with near-normal glycemia, the diagnosis can be missed. Vigilance with the use of SGLT-2 inhibitors is necessary to decrease morbidity and potentially mortality particularly in patients with long-standing type 2 diabetes associated with marked β-cell insufficiency, type 1 diabetes mellitus, or latent autoimmune diabetes of adult onset. 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 >>
Diabetic Ketoacidosis
Diabetes mellitus is the name given to a group of conditions whose common hallmark is a raised blood glucose concentration (hyperglycemia) due to an absolute or relative deficiency of the pancreatic hormone insulin. In the UK there are 1.4 million registered diabetic patients, approximately 3 % of the population. In addition, an estimated 1 million remain undiagnosed. It is a growing health problem: In 1998, the World Health Organization (WHO) predicted a doubling of the worldwide prevalence of diabetes from 150 million to 300 million by 2025. For a very tiny minority, diabetes is a secondary feature of primary endocrine disease such as acromegaly (growth hormone excess) or Cushing’s syndrome (excess corticosteroid), and for these patients successful treatment of the primary disease cures diabetes. Most diabetic patients, however, are classified as suffering either type 1 or type 2 diabetes. Type 1 diabetes Type 1 diabetes, which accounts for around 15 % of the total diabetic population, is an autoimmune disease of the pancreas in which the insulin-producing β-cells of the pancreas are selectively destroyed, resulting in an absolute insulin deficiency. The condition arises in genetically susceptible individuals exposed to undefined environmental insult(s) (possibly viral infection) early in life. It usually becomes clinically evident and therefore diagnosed during late childhood, with peak incidence between 11 and 13 years of age, although the autoimmune-mediated β-cell destruction begins many years earlier. There is currently no cure and type 1 diabetics have an absolute life-long requirement for daily insulin injections to survive. Type 2 diabetes This is the most common form of diabetes: around 85 % of the diabetic population has type 2 diabetes. The primary prob Continue reading >>
Advanced Diabetic Ketoacidosis
Diabetic ketoacidosis (DKA) is a dangerous condition characterized by a severe rise in blood sugar or hyperglycemia, depleted bodily fluids, shock, and in some cases unconsciousness. Coma and even death may occur if DKA is left untreated or if it becomes more severe due to excessive vomiting. Symptoms of DKA In the early stages of DKA, the affected individual appears flushed and breathes rapidly and deeply. This is called hyperventilation. As the condition progresses, the skin may turn pale, cool and clammy, dehydration may begin to set in and the heart rate may become rapid and breathing shallow. Nausea, vomiting and severe abdominal cramps. Blurred vision Fruity or pungent smelling breath due to the presence of acetone and ketones in the breath. Pathophysiology Although DKA can occur in patients with type 2 diabetes, it mainly develops in people with type 1 diabetes who need to take insulin for their condition. If individuals do not receive insulin, they will develop DKA. If there is a shortage of insulin, the body fails to use glucose in the blood for energy and instead fats are broken down in the liver. When these fats are broken down, acidic compounds called ketones are produced as a by-product. These ketones build up in the body and eventually cause ketoacidosis. Aside from missed or inadequate doses of insulin, another common cause of DKA is infection or illness as this can raise the level of hormones that counteract the effects of insulin. In addition, the dehydration caused by major injury or surgery can raise levels of these hormones. Diagnosis and treatment Blood tests are performed to check the sugar levels and blood pH, which is classified as acidic if it is below the usual 7.3. Unlike non-ketotic hyperosmolar coma, in DKA the blood and urine levels of keto Continue reading >>
Ask The Diabetes Team
Question: From Cleveland, Ohio, USA: My son's pump malfunctioned last night in the middle of the night and we don't know exactly how long he was not receiving his insulin. He woke up with a "high" glucose and an episode of vomiting. Being on vacation, we did not have ketostix, but the smell of his breath gave evidence to his high ketones. We immediately bolused him via injection and changed his site. We continued frequent blood sugar checks and started pushing fluids. The vomiting continued for two more episodes and his blood sugar finally started coming down so he stopped vomiting and was able to keep fluids down. We were with extended family, who, of course, had questions. One of the questions was,"Why do high blood sugars and ketones cause vomiting?" I realized that even after dealing with my son's illness for eight years and working as an ICU nurse and treating DKA in patients, I don't know the pathophysiology of this process! My guess is it has something to do with the metabolic changes and the changeover to an acid state in the blood. I really don't know and I can't find the answer anywhere on the net. I appreciate any information and please be as technical as you'd like. Answer: First of all, a big thumbs-up to you for managing this degree of probable DKA in a levelheaded and successful way. But....a big thumbs down for traveling without ketone strips (blood - if you have the correct meter - or urine) or back-up insulin (other than fast acting insulin). I preach that if you have a pump, then there should be some insulin glargine (or other long-acting insulin) available in case of pump malfunction/misbehavior. I presume you travel with your emergency glucagon kit? All these things should be together. Your question, somewhat surprisingly to me, is not uncommon. Why Continue reading >>
Diabetic Ketoacidosis
Print Overview Diabetic ketoacidosis is a serious complication of diabetes that occurs when your body produces high levels of blood acids called ketones. The condition develops when your body can't produce enough insulin. Insulin normally plays a key role in helping sugar (glucose) — a major source of energy for your muscles and other tissues — enter your cells. Without enough insulin, your body begins to break down fat as fuel. This process produces a buildup of acids in the bloodstream called ketones, eventually leading to diabetic ketoacidosis if untreated. If you have diabetes or you're at risk of diabetes, learn the warning signs of diabetic ketoacidosis — and know when to seek emergency care. Symptoms Diabetic ketoacidosis signs and symptoms often develop quickly, sometimes within 24 hours. For some, these signs and symptoms may be the first indication of having diabetes. You may notice: Excessive thirst Frequent urination Nausea and vomiting Abdominal pain Weakness or fatigue Shortness of breath Fruity-scented breath Confusion More-specific signs of diabetic ketoacidosis — which can be detected through home blood and urine testing kits — include: High blood sugar level (hyperglycemia) High ketone levels in your urine When to see a doctor If you feel ill or stressed or you've had a recent illness or injury, check your blood sugar level often. You might also try an over-the-counter urine ketones testing kit. Contact your doctor immediately if: You're vomiting and unable to tolerate food or liquid Your blood sugar level is higher than your target range and doesn't respond to home treatment Your urine ketone level is moderate or high Seek emergency care if: Your blood sugar level is consistently higher than 300 milligrams per deciliter (mg/dL), or 16.7 mill Continue reading >>
Diabetic Ketoacidosis In Pregnancy
Diabetic ketoacidosis is a serious metabolic complication of diabetes with high mortality if undetected. Its occurrence in pregnancy compromises both the fetus and the mother profoundly. Although predictably more common in patients with type 1 diabetes, it has been recognised in those with type 2 diabetes as well as gestational diabetes, especially with the use of corticosteroids for fetal lung maturity and β2-agonists for tocolysis.1–3 Diabetic ketoacidosis usually occurs in the second and third trimesters because of increased insulin resistance, and is also seen in newly presenting type 1 diabetes patients. With increasing practice of antepartum diabetes screening and the availability of early and frequent prenatal care/surveillance, the incidence and outcomes of diabetic ketoacidosis in pregnancy have vastly improved. However, it still remains a major clinical problem in pregnancy since it tends to occur at lower blood glucose levels and more rapidly than in non-pregnant patients often causing delay in the diagnosis. The purpose of this article is to illustrate a typical patient who may present with diabetic ketoacidosis in pregnancy and review the literature on this relatively uncommon condition and provide an insight into the pathophysiology and management. MAGNITUDE OF THE PROBLEM In non-pregnant patients with type 1 diabetes, the incidence of diabetic ketoacidosis is about 1–5 episodes per 100 per year with mortality averaging 5%–10%.4 The incidence rates of diabetic ketoacidosis in pregnancy and the corresponding fetal mortality rates from different retrospective studies5–8 are summarised in the table 1. As is evident from the table, both the incidence and rates of fetal loss in pregnancies have fallen in recent times compared with those before. In 1963 Continue reading >>
Diabetic Ketoacidosis
Patient professional reference Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use. You may find the Pre-diabetes (Impaired Glucose Tolerance) article more useful, or one of our other health articles. See also the separate Childhood Ketoacidosis article. Diabetic ketoacidosis (DKA) is a medical emergency with a significant morbidity and mortality. It should be diagnosed promptly and managed intensively. DKA is characterised by hyperglycaemia, acidosis and ketonaemia:[1] Ketonaemia (3 mmol/L and over), or significant ketonuria (more than 2+ on standard urine sticks). Blood glucose over 11 mmol/L or known diabetes mellitus (the degree of hyperglycaemia is not a reliable indicator of DKA and the blood glucose may rarely be normal or only slightly elevated in DKA). Bicarbonate below 15 mmol/L and/or venous pH less than 7.3. However, hyperglycaemia may not always be present and low blood ketone levels (<3 mmol/L) do not always exclude DKA.[2] Epidemiology DKA is normally seen in people with type 1 diabetes. Data from the UK National Diabetes Audit show a crude one-year incidence of 3.6% among people with type 1 diabetes. In the UK nearly 4% of people with type 1 diabetes experience DKA each year. About 6% of cases of DKA occur in adults newly presenting with type 1 diabetes. About 8% of episodes occur in hospital patients who did not primarily present with DKA.[2] However, DKA may also occur in people with type 2 diabetes, although people with type 2 diabetes are much more likely to have a hyperosmolar hyperglycaemic state. Ketosis-prone type 2 diabetes tends to be more common in older, overweight, non-white people with type 2 diabetes, and DKA may be their Continue reading >>
Acute Complications Of Diabetes - Diabetic Ketoacidosis
- [Voiceover] Oftentimes we think of diabetes mellitus as a chronic disease that causes serious complications over a long period of time if it's not treated properly. However, the acute complications of diabetes mellitus are often the most serious, and can be potentially even life threatening. Let's discuss one of the acute complications of diabetes, known as diabetic ketoacidosis, or DKA for short, which can occur in individuals with type 1 diabetes. Now recall that type 1 diabetes is an autoimmune disorder. And as such, there's an autoimmune destruction of the beta cells in the pancreas, which prevents the pancreas from producing and secreting insulin. Therefore, there is an absolute insulin deficiency in type 1 diabetes. But what exactly does this mean for the body? To get a better understanding, let's think about insulin requirements as a balancing act with energy needs. Now the goal here is to keep the balance in balance. As the energy requirements of the body go up, insulin is needed to take the glucose out of the blood and store it throughout the body. Normally in individuals without type 1 diabetes, the pancreas is able to produce enough insulin to keep up with any amount of energy requirement. But how does this change is someone has type 1 diabetes? Well since their pancreas cannot produces as much insulin, they have an absolute insulin deficiency. Now for day-to-day activities, this may not actually cause any problems, because the small amount of insulin that is produced is able to compensate and keep the balance in balance. However, over time, as type 1 diabetes worsens, and less insulin is able to be produced, then the balance becomes slightly unequal. And this results in the sub-acute or mild symptoms of type 1 diabetes such as fatigue, because the body isn Continue reading >>
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 >>
Diabetes: Mechanism, Pathophysiology And Management-a Review
Anees A Siddiqui1*, Shadab A Siddiqui2, Suhail Ahmad, Seemi Siddiqui3, Iftikhar Ahsan1, Kapendra Sahu1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi (INDIA)-110062. School of Pharmacy, KIET, Ghaziabad U.P. SGC college of Pharmacy, Baghpat(UP) Corresponding Author:Anees A Siddiqui E-mail: [email protected] Received: 20 February 2011 Accepted: 02 May 2011 Citation: Anees A Siddiqui, Shadab A Siddiqui, Suhail Ahmad, Seemi Siddiqui, Iftikhar Ahsan, Kapendra Sahu “Diabetes: Mechanism, Pathophysiology and Management-A Review” Int. J. Drug Dev. & Res., April-June 2013, 5(2): 1-23. Copyright: © 2013 IJDDR, Anees A Siddiqui et al. This is an open access paper distributed under the copyright agreement with Serials Publication, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Related article at Pubmed, Scholar Google Visit for more related articles at International Journal of Drug Development and Research The prevalence of diabetes is rapidly rising all over the globe at an alarming rate. Over the last three decades, the status of diabetes has been changed, earlier it was considered as a mild disorder of the elderly people. Now it becomes a major cause of morbidity and mortality affecting the youth and middle aged people. According to the Diabetes Atlas 2006 published by the International Diabetes Federation, the number of people with diabetes in India currently around 40.9 million is expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken. The main force of the epidemic of diabetes is the rapid epidemiological transition associated with changes in dietary patterns and decreased physical activity a Continue reading >>
How Does Diabetic Ketoacidosis Cause Vomiting?
DKA can occur in people who are newly diagnosed with type 1 diabetes and have had ketones building up in their blood prior to the start of treatment. It can also occur in people already diagnosed with type 1 diabetes that have missed an insulin dose, have an infection, or have suffered a traumatic event or injury. With type 1 diabetes, the pancreas is unable to make the hormone insulin, which the body’s cells need in order to take in glucose from the blood. In the case of type 2 diabetes, the pancreas is unable to make sufficient amounts of insulin in order to take in glucose from the blood. Glucose, a simple sugar we get from the foods we eat, is necessary for making the energy our cells need to function. People with diabetes can’t get glucose into their cells, so their bodies look for alternative energy sources. Meanwhile, glucose builds up in the bloodstream, and by the time DKA occurs, blood glucose levels are often greater than 22 mmol/L (400 mg/dL) while insulin levels are very low. Since glucose isn’t available for cells to use, fat from fat cells is broken down for energy instead, releasing ketones. Ketones accumulate in the blood, causing it to become more acidic. As a result, many of the enzymes that control the body’s metabolic processes aren’t able to function as well. A higher level of ketones also affects levels of sugar and electrolytes in the body. As ketones accumulate in the blood, more ketones will be passed in the urine, taking sodium and potassium salts out with them. Over time, levels of sodium and potassium salts in the body become depleted, which can cause nausea and vomiting. The result is a vicious cycle. The most important prevention strategies are to monitor blood glucose levels routinely, keep blood glucose levels controlled (e.g., Continue reading >>
