Ketosis, prevention

It would seem that normally the oxidation of ketone bodies would proceed largely to completion in the liver by the ketolytic mechanism. Whenever the supply of carbohydrates here is sufficiently reduced, appreciable amounts of ketones then escape oxidation and pass into the blood. When the concentration of ketones becomes sufficiently elevated, a ketonuria occurs and also some ketones will be utilized by the tissues. Such a theory would largely limit the ketolysis mechanism to the liver. It would explain the specificity of the sugars in preventing ketonuria and the discrepancy between the amount of D-glucose required to prevent ketosis and the caloric value of the fat spared. It is further supported by the demonstration that the liver is capable of exhibiting ketolysis. 

Patients with type I diabetes may have islet cell antibodies and human leukocyte antigens (HLA). They are dependent on insulin to prevent ketosis and hence have insulinopenia. Affected individuals consist mostly of children and young adults. 

Some of the side effects of valproate administration to young children to control seizures (ketosis and liver damage) are associated with sequestration of CoA as valproyl CoA, which is poorly metabolized, and the administration of pantothenate supplements (generally together with carnitine Section 14.1) prevents depletion of CoA and reduces the risk of liver damage (Thurston and Hauhart, 1992). In the same way, pantothenate supplements protect mice against neural tube defects caused by valproate (Sato et al., 1995). 

In therapeutics, agents affecting volume and compo.sition of body Iluids include various clas.ses of parenteral producLs. Ideally, il would be desirable lo have available parenleral fluids that provide adequate calories and important proteins and lipids lo mimic, as closely as possible, an appropriate diet. Unfortunately, this is not the case. Usually, sufficient earbohydnite is. idminisiered intravenously to prevent ketosis, and in some cases, il is necessary lo give further. sources of carbohydrate by vein lo reduce protein wa.sie. Sources of... 

Approximately 5% to 10% of aU cases of diabetes mellitus are in this category. Patients usually have abrupt onset of symptoms (e.g., polyuria, polydipsia, and rapid weight loss). Patients have insulinopenia (a deficiency of insulin) caused by loss of pancreatic islet (3-ceUs and are dependent on insulin to sustain life and prevent ketosis. Most patients have antibodies that identify an autoimmune process (see later discussion) some patients have no evidence of autoimmunity and are classified as type 1 idiopathic. The peak incidence is in childliood and adolescence. Approximately 75% acquire the disease before age 30 years, but the onset in the remainder may occur at any age. Age at presentation is not a criterion for classification. 

Insulin is the principal drug used to prevent ketosis and sustain life in the treatment of patients with type I (insulin-dependent) diabetes mellitus. Delivery of proteins such as insulin is a challenge because of the molecular size and the sensitivity of the molecule to the loss of its biological activity through minor alterations in the three-dimensional structure. The normal mode of delivery of insulin to patients at the present time is through intramuscular, subcutaneous, or intravenous injections. These delivery methods are not ideal because of (1) the need for training of the patient or the caretaker in the basic steps of injection, (2) the fear of needles by patients, and (3) the feeling of pain and possible fibrotic formation at the injection site. These inconveniences could lead to noncompliance. A variety of approaches for insulin delivery have been... 

HONK coma occurs mostly in elderly, non-insulin dependent diabetics, and develops relatively slowly over days or weeks. The level of insulin is sufficient to prevent ketosis but does not prevent hyperglycacmia and osmotic diuresis. Precipitating factors include severe illness, dehydration, glucocorticoids, diuretics, parenteral nutrition, dialysis and surgery. Extremely high blood glucose levels (above 35 mmol/l. and usually above 50 mmol/l) accompany severe dehydration resulting in impaired consciousness. 

Conditions that result in increased production of metabolic acids include lactic acidosis and diabetic ketoacidosis. Lactic acidosis occurs with anaerobic metaboUsm in the presence of severe hypoxemia (i.e., Pao < 36 mm Hg). Any condition that prevents adequate oxygenation resulting in hypoxemia, such as respiratory failure or lung cancer, as well as any condition causing a decrease in perfusion to body tissues, such as heart failure or shock of any form, will result in anaerobic metabolism and lactic acid buildup. In diabetic ketoacidosis, the lack of insulin to move glucose into the cells results in a form of starvation and the production and accumulation of ketoacids (i.e., ketosis) owing to the use of lipids for fuel. 

In pure carbohydrate-induced hyperlipemia, restriction of carbohydrate compatible with acceptability of the diet and prevention of ketosis is recommended. Thus 50—70% of calories may be given as fat with a carbohydrate content below 25%. If a significant amount of the fat comes from unsaturated sources, it may be cleared from plasma faster than saturated fats (Engelberg 1964) and hypercholesterolemia may be further reduced. Such a regimen should also be optimal in the combination of essential hypercholesterolemia and hyperhpemia. 

The prevention of ketosis by similating the tricarboxylic acid cycle and thereby bringing about oxidation of the ketone bodies. Fatty acids and ketogenic amino acids are precursors of ketone bodies. The antiketogenic factors are precursors of glucose these include the carbohydrates, glucogenic amino acids, and the glycerol portion of fat. 

Ketosis— The most common causes of this condition— which is characterized by an excess of ketones in the blood— are (1) diabetes (2) diets high in fat and protein, but low in carbohydrate (3) fevers and (4) starvation. A mild ketosis in normally healthy people is usually not dangerous, unless it occurs regularly over a long period of time, flien, it may lead to such problems as (1) excessive urinary loss of sodium and water (2) acidosis which provokes the loss of calcium from bone, and potassium from muscle and (3) the accumulation of uric acid (a waste product of protein metabolism) in the blood, and sometimes in the soft tissues where it causes damage and pain (the latter disorder is commonly called gout). Uric acid buildup is usually treated with alkalizers to prevent the formation of kidney stones. However, the alkalizers may cause other alterations in mineral metabolism. 

---