Diabetic ketoacidosis causes

NIDDM is a much more common disease than IDDM, accounting for about 85—90% of all cases of diabetes meUitus. Whereas NIDDM may be present at any age, the incidence increases dramatically with advanced age over 10% of the population reaching 70 years of age has NIDDM. Patients with NIDDM do not require insulin treatment to maintain life or prevent the spontaneous occurrence of diabetic ketoacidosis. Therefore, NIDDM is frequendy asymptomatic and unrecognized, and diagnosis requires screening for elevations in blood or urinary sugar. Most forms of NIDDM are associated with a family history of the disease, and NIDDM is commonly associated with and exacerbated by obesity. The causes of NIDDM are not well understood and there may be many molecular defects which lead to NIDDM. 

Insulin is necessary for controlling type 1 diabetes mellitus that is caused by a marked decrease in the amount of insulin produced by die pancreas. Insulin is also used to control the more severe and complicated forms of type 2 diabetes mellitus. However, many patients can control type 2 diabetes with diet and exercise alone or with diet, exercise, and an oral antidiabetic drug (see section Oral Antidiabetic Dmgp ). Insulin may also be used in the treatment of severe diabetic ketoacidosis (DKA) or diabetic coma. Insulin is also used in combination with glucose to treat hypokalemia by producing a shift of potassium from die blood and into die cells. 

Diabetic ketoacidosis A reversible but life-threatening short-term complication primarily seen in patients with type 1 diabetes caused by the relative or absolute lack of insulin that results in marked ketosis and acidosis. 

Hyperosmolar hyperglycemic state A potentially fatal short-term complication most commonly seen in older patients with type 2 diabetes caused by an insufficiency of insulin action that leads to alterations of osmolality and hyperglycemia, but without the ketosis and acidosis seen in diabetic ketoacidosis. 

The following factors have been suggested as alternatives to consider when presented with a potential case of exposure to carbon monoxide diabetic ketoacidosis, hypothyroidism and myxedema coma, labyrinthitis, and lactic acidosis toxic exposures resulting in methemoglobinemia ingestion of alcohols or narcotics and diseases that cause gastroenteritis, encephalitis, meningitis, and acute respiratory distress syndrome. 

For persons with type 1 diabetes, insulin replacement therapy is necessary to sustain life. Pharmacologic insulin is administered by injection into the subcutaneous tissue using a manual injection device or an insulin pump that continuously infuses insulin under the skin. Interruption of the insulin replacement therapy can be life-threatening and can result in diabetic ketoacidosis or death. Diabetic ketoacidosis is caused by insufficient or absent insulin and results from excess release of fatty acids and subsequent formation of toxic levels of ketoacids. 

However, short-acting, regular soluble insulin is the only type that should be administered intravenously because the dilution causes the hexameric insulin to immediately dissociate into monomers. It is particularly useful for intravenous therapy in the management of diabetic ketoacidosis and when the insulin requirement is changing rapidly, such as after surgery or during acute infections. 

Normally, the sum of the cations exceeds the sum of the anions by no more than 12-16 mEq/L (or 8-12 mEq/L if the formula used for estimating the anion gap omits the potassium level). A larger-than expected anion gap is caused by the presence of unmeasured anions (lactate, etc) accompanying metabolic acidosis. This may occur with numerous conditions, such as diabetic ketoacidosis, renal failure, or shock-induced lactic acidosis. Drugs that may induce an elevated anion gap metabolic acidosis (Table 58-1) include aspirin, metformin, methanol, ethylene glycol, isoniazid, and iron. 

Ition of the ketone bodies may be as high as 5000 mg/24 hr, and the blood concentration may reach 90 mg/dl (versus less than 3 mg/dL in normal individuals). A frequent symptom of diabetic ketoacidosis is a fruity odor on the breath which result from increased production of acetone. An elevation of the ketone body concentration in the blood results in acidemia. [Note The carboxyl group of a ketone body has a pKa about 4. Therefore, each ketone body loses a proton (H+) as it circulates in the blood, which lowers the pH of the body. Also, excretion of glucose and ketone bodies in the urine results in dehydration of the body. Therefore, the increased number of H+, circulating in a decreased volume of plasma, can cause severe acidosis (ketoacidosis)]. Ketoacidosis may also be seen in cases of fasting (see p. 327). 

The glucagon/insulin ratio can rise under certain pathological conditions (i.e., insulin-dependent diabetes). A small percentage of diabetics develop ketoacidosis, a condition that results from the overproduction and underuhlization of ketone bodies. Increased concentrations of p hydmxybutyrate and acetoacetate, which are acids, can cause a drop in the pH of the blood. This acidification, known as acidosis, can impair the ablLity of the heart to contract and result in a loss of consciousness and coma, which, in rare cases, may be fatal. Diabetic ketoacidosis may manifest as abdominal pain, nausea, and vomiting. A subject may hyperventilate (breathe quickly and deeply) to correct acidosis, as described under Sodium, Potassium, and Water in Chapter 10. It is the responsibility of the clinician, when confronted with a subject whose breath smells of acetone or who is hyperventilating, to facilitate prompt treatment. 

D. Decreased insulin levels cause fatty acid synthesis to decrease and glucagon levels to increase. Adipose triacylglycerols are degraded. Fatty acids are converted to ketone bodies in liver a ketoacidosis can occur. There is increased decarboxylation of acetoacetate to form acetone, which causes the odor associated with diabetic ketoacidosis. 

Secondary gout is a result of hyperuricemia attributable to several identifiable causes. Renal retention of uric acid may occur in acute or chronic kidney disease of any type or as a consequence of administration of drugs diuretics, in particular, are implicated in the latter instance. Organic acidemia caused by increased acetoacetic acid in diabetic ketoacidosis or by lactic acidosis may interfere with tubular secretion of urate. Increased nucleic acid turnover and a consequent increase in catabolism of purines may be encountered in rapid proliferation of tumor cells and in massive destruction of tumor cells on therapy with certain chemotherapeutic agents. 

The transfer of intracellular K" into ECF invariably occurs in acidosis as H shifts intraceHularly and shifts outward to maintain electrical neutrality. As a general rule, K concentrations are expected to rise 0.2 to 0.7 mmol/L for every 0.1 unit drop in pH. When the underlying cause of the acidosis is treated, normokalemia will rapidly be restored. Extracellular redistribution of may also occur in (1) dehydration, (2) shock with tissue hypoxia, (3) insulin deficiency (e.g., diabetic ketoacidosis), (4) massive intravascular or extracorporeal hemolysis, (5) severe burns, (6) tumor lysis syndrome, and (7) violent muscular activity, such as that occurring in status epilepticus. Finally, important iatrogenic causes of redistribution hyperkalemia include digoxin toxicity and P adrenergic blockade, especially in patients with diabetes or on dialysis. ... 

Alcohol taken in excess tends to prevent gluconeogenesis from lactate in the liver, because oxidation of ethanol to acetaldehyde competes for the NAD" that is necessary for the conversion of lactate to pyruvate. Severe acidosis, such as diabetic ketoacidosis, may suppress lactate conversion and cause a shift in the lactate-pyruvate equilibrium with the accumulation of H. This shift may, in part, be responsible for the lactic acidosis seen in diabetics. 

Treatment is by correction of the cause of the acidosis (e.g., insulin administration in diabetic ketoacidosis) and neutralization of the acid with NaHCOs, sodium lactate, or TRIS [tris(hydroxymethyl)aminomethane] buffer. Problems that may occur following alkali replacement therapy include development of respiratory alkalosis, particularly if the low CO2 tension persists, and further decline in the pH of CSF, which may decrease consciousness. The alkaline overshoot results from resumption of oxidation of organic anions (e.g., lactate, acetoacetate) with resultant production of bicarbonate from CO2. Severe acidosis should be corrected slowly over several hours. Potassium replacement therapy frequently is needed because of the shift of intracellular K" " to extracellular fluid and loss of K+ in the urine. 

Arterial blood gases and serum electrolytes should be measured regularly in patients with CKD. These patients should also have a complete medical history and review of medications to determine if there are other potential causes of acid-base disturbances (e.g., diabetic ketoacidosis, ingestion of toxins, or GI disorders). The anion gap, indicating the differences in unmeasured anions and cations, should also be calculated (see Chap. 51). An elevated anion gap (>17 mEq/L) is often present in those with CKD due to the accumulation of organic anions, phosphates, and sulfates. 

Acid-base disorders such as lactic acidosis and diabetic ketoacidosis can release endogenous intracellular phosphorus and cause... 

D-Fructose is the sweetest natural sugar. Its use as a natural sweetener is, therefore, increasing rapidly. It is absorbed slowly from the intestine, and thus does not cause abrupt changes in the serum levels of carbohydrates. It has little, if any, effect on insulin secretion. Thus, it exerts beneficial effects as a component of diets for mild and well-balanced diabetes, but should be taken within caloric restriction,445 as obesity impairs D-glucose tolerance and increases the insulin resistance of peripheral tissue.446 Use of D-fructose in the direct treatment of diabetic ketoacidosis does not offer advantages over routine, fluid therapy, and may even be dangerous on the basis that rapid infusion of large amounts of D-fructose may cause lactate acidosis. 

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