Latest Treatment of Hypoglycemia

Guide To Beating Hypoglycemia

Here's Just A Tiny Glimpse Of The Topics Covered: The 3 main types of hypoglycemia and which type you're most likely suffering from. How snacking on chocolate bars can actually make you Fat and worsen your condition! (If you thought those delicious dark brown bars were great energy- boosters.think again!) The No. 1 question most folks have when it comes to hypoglycemia and hyperglycemia. Why you should insist on a 6-hour Gtt and not a 5-hour one. ( Why it might not be a good idea to consult a doctor to confirm your hypoglycemia. Aside from taking a Gtt, what other methods can you use to determine whether or not you're suffering from this condition? Well, refer Chapter 4, Pgs. 23-26 to take a revealing 67-question test especially designed to find out if you've got the symptoms. An inspiring motivational exercise that will help you effectively banish all of your negative thoughts that prevent you from having peace of mind. 2 good reasons why you should keep a food journal. 3 powerful nutrients that limit the effect of glucose on your blood sugar level. This is vital to a hypoglycemic as it helps slow down the absorption of sugar in the food. The secret impulse that literally forces you to say 'yes' to a candy bar or chocolate whenever you feel the hunger pangs gnawing at you. 2 ingredients that are lethal to a hypoglycemic. 'Hidden sugars' you must know to avoid buying products that can easily worsen your condition. 8 essential rules of food planning that are crucial to your speedy recovery from hypoglycemia. Leave out one of them and it could hurt your chances of recovering. How to create a healthy food plan that's suitable for both vegetarian and non- vegetarian hypoglycemics. Most food plans only focus on non-vegetarians, but this one works great for everybody!

Guide To Beating Hypoglycemia Overview


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TABLE 1253 Clinical Signs of Hypoglycemia

The most common cause of hypoglycemia in non-insulin-dependent children over the age of 1 year is idiopathic ketotic hypoglycemia. It is more a physiologic aberration than a true pathologic syndrome.24 It usually presents in children less than 18 months of age after a period of fasting. Often this is seen on holidays and weekends, when parents sleep late, inadvertently extending the child's usual nighttime fasting period. It is also more common during illnesses preventing normal food intake. These children return to normal after a glucose load and have no suspicious findings in either their history or physical exams. 25 Classically, this problem was thought to arise because these children were small for age, but that idea has been called into question by more recent findings. 24 Currently, alanine, by far the most important amino acid in gluconeogenesis, is thought to play a major role in this disorder. 36 Haymond et al.5 demonstrated lower serum alanine concentrations in these...

TABLE 1254 Treatment of Hypoglycemia

Boluses in neonates should be given with 10 D W. Infants should receive 10 D W whenever possible, although 25 D W is acceptable as well. In older children, 25 D W may be used. 25 D W and especially 50 D W are very hyperosmolar and may cause phlebitis or tissue necrosis, if they extravasate. Even without extravasation, patients commonly complain of pain at the injection site for 1 to 2 weeks. The risk of extravasation is increased when smaller veins, such as those found in infants, are used. In addition to this, hyperosmolar loading in premature neonates is associated with an increased risk of intracranial germinal matrix hemorrhage and subsequent periventricular leukomalacia. The use of 25 D W and 50 D W may also lead to an increased incidence of rebound hypoglycemia due to endogenous insulin release. When time allows, diluting 50 D W or 25 D W to 10 D W with normal saline or half normal saline will decrease the risk of pain, phlebitis, and necrosis at the injection site by decreasing...

Brain Function and Hypoglycemia

The brain malfunction to which hypoglycemia gives rise will be referred to as neuroglycopenia. The brain is often thought of as being incapable of using metabolites other than glucose as a source of energy. This is untrue. It has been known for more than 30 years to be able, under certain circumstances including prolonged fasting, to utilize the 'ketone bodies,' 3-hydroxybutyrate and aceto-acetate. Under these circumstances the need for glucose and its supply through gluconeogenesis is drastically reduced. The survival value of this ability is immense as it permits fat stores rather than structural muscle and other tissue proteins to be utilized for maintenance of vital processes under these stressful conditions. Only when fat stores have become completely exhausted and plasma ketone levels fallen to below normal fasting levels does the brain's demand for glucose rise above the ability of gluco-neogenesis to provide it. Only at this point does hypoglycemia intervene and portend death...

TABLE 1841 Manifestations of Hypoglycemia

In healthy persons, complex regulatory systems maintain a constant level of glucose in the blood. Unfortunately, certain medical conditions may impair the ability of the body to maintain glucose levels, and hypoglycemia results. Chronic ethanol users are at increased risk for hypoglycemia due to diminished glycogen supply and impaired gluconeogenesis. Persons at extremes of age are also potentially at increased risk for hypoglycemia. Young children have a disproportionately higher brain requirement for glucose as well as smaller glycogen reserves. The elderly may have health problems that alter the normal counterregulatory response to hypoglycemia as well as contribute to hypoglycemia (e.g., hepatic or renal disease). Older patients are also more likely to be taking medications that may exacerbate hypoglycemia or blunt the normal response to hypoglycemia (e.g., b-adrenergic antagonists).

Miscellaneous Sources Of Hypoglycemia

The ackee tree is native to Jamaica, where it produces a fruit that is commonly eaten. The unripened fruit contains hypoglycins, a group of toxins that produce vomiting (Jamaican vomiting sickness), central nervous system sedation, and seizures. In addition, hypoglycins inhibit hepatic gluconeogenesis and may contribute to hypoglycemia. Epidemics of hypoglycin-mediated hypoglycemia have occurred only during times of famine, when poor nutrition and the increased eating of unripened fruit are perhaps more commonplace. Ackee is available in the United States in canned form, but only the unripe, fresh fruit is associated with hypoglycemia. The sympathetic nervous system mediates glucose autoregulation partly through the release of epinephrine, which prevents the release of insulin and elevates blood glucose levels. This mechanism explains the role of epinephrine in the counterregulatory response to hypoglycemia. b-adrenergic antagonists interfere with both of these effects, potentially...

TABLE 2095 Pharmacology of Commonly Available Oral Hypoglycemic Agents

Insulin can also be administered as a continuous subcutaneous insulin infusion (CSII), by means of a small pump that delivers insulin subcutaneously into the abdominal wall through a butterfly needle. Insulin is usually infused at a continuous basal rate with preprogrammed boluses just before meals. Both hypoglycemia and ketoacidosis are more frequent in patients with CSII. For emergency department patients with CSII who develop hypoglycemia, marked hyperglycemia, or DKA, it is best to shut off the pump in the emergency department while standard glucose or insulin therapy is administered. A working knowledge of the pharmacology, including time to peak effect and duration of action of the various insulin and oral hypoglycemic preparations, should enable the emergency physician to make adjustments in a patient's usual insulin or oral hypoglycemic regimen, especially if the patient arrives with a home blood glucose diary. It is a good general rule not to change the total number of units...

Cortisol Signals Stress Including Low Blood Glucose

A variety of stressors (anxiety, fear, pain, hemorrhage, infections, low blood glucose, starvation) stimulate release of the corticosteroid hormone cortisol from the adrenal cortex. Cortisol acts on muscle, liver, and adipose tissue to supply the organism with fuel to withstand the stress. Cortisol is a relatively slow-acting hormone that alters metabolism by changing the kinds and amounts of certain enzymes synthesized in its target cell, rather than by regulating the activity of existing enzyme molecules.

TABLE 2021 Potential Etiologies of Hypoglycemia in Adults

Common scenarios in diabetic patients include inadequate food intake, increased physical exertion, incorrect medication dosing, or drug interactions. The characteristics of diabetic patients who are more likely to experience hypoglycemia include male gender, adolescent and very elderly age groups, African American heritage, a past history of hypoglycemia, intensive diabetic medical therapy, insulin use (compared with OHA therapy), polypharmacy (more than five agents), and recent hospitalization.12 and 3 The introduction of metformin, a biguanide, has added another medication to the list of agents encountered in diabetic patients. Metformin improves the end-organ sensitivity to insulin and acts via a number of mechanisms in diabetic patients, including a reduction in hepatic glucose output and enhanced peripheral glucose uptake. Metformin is considered an antihyperglycemia drug rather than a hypoglycemic agent such as the sulfonylureas and insulin. Hypoglycemia is rarely encountered in...

TABLE 2022 Frequency of Presenting Signs and Symptoms in Hypoglycemia

A rapid fall in blood glucose levels or the hypothalamic sensing of neuroglycopenia causes the release of the counterregulatory hormones, primarily the catecholamines epinephrine and norepinephrine. The release of the latter is responsible for the hyperepinephrinemic findings, including anxiety, nervousness, irritability, nausea, vomiting, palpitations, and tremor. Such signs and symptoms were noted in 8 percent of ED patients with hypoglycemia. 4 The rapidity of onset of the hypoglycemic event determines in part the presentation. A gradual onset of hypoglycemia results from a relatively slow decrease in the serum glucose and the development of the neuroglycopenic signs and symptoms. Conversely, a sudden drop in the blood sugar level will produce anxiety, diaphoresis, tremor, and the other hyperepinephrinemic findings. In most cases of hypoglycemia, however, CNS dysfunction predominates with some degree of alteration in the level of awareness, accompanied by diaphoresis and...


Hypoglycemia is a life threatening endocrine emergency that, once recognized, is Hypoglycemia is generally defined as a blood glucose level < 50 mg dl in adults children, and < 30 mg dl in neonates. Glucose homeostasis involves a tightly regulated balance between insulin and its counterregulatory hormones (glucagon, epinephrine, cortisol, growth hormone). An excess of insulin or deficiency of counterregulatory hormones will tip the balance toward hypoglycemia. Hypoglycemia is most often seen as a complication of diabetes therapy but is also seen in nondiabetics, usually as a complication of other disease processes (Table 9A.5). In pediatric patients, hypoglycemia may be seen in the acutely ill or septic child due to lack of oral intake, hypermetabolic state, or secondary to accidental ingestions (alcohol, salicylates, oral hypoglycemics).


No account of dietetic treatment of hypoglycemia would be complete without a brief description of 'nonhypoglycemia', which has been described as a controversial illness and epidemic in the US. Clinically, the illness is indistinguishable from (idio-pathic) reactive hypoglycemia, except that the blood glucose level is never pathologically low during symptomatic episodes. Moreover, although transient 'turns' are often a major feature of the illness, only rarely, if ever, does the patient consider their health, between turns, as normal. The attribution of these patients' illness to hypo-glycemia had its origins in the early 1950s with the appearance, in the US, of a book by Drs Abrahams and Pezet entitled 'Body, Mind and Sugar.' Other American practitioners, notably John Tintera, founder of the Hypoglycemia Foundation Inc., Stephen Gyland, Harry Saltzer and, others, including the medical writer Carlton Fredericks, publicized the concept. This led to 'hypoglycemia' being held, by a large...

Pharmaceutical Equipment

Another area where practice is becoming blurred between BLS and ALS is in the realm of medications. The new basic EMT model curriculum has a module on certain classes of pharmaceuticals to prepare basic EMTs for helping the patient administer his or her medication in a limited fashion. This module includes nitroglycerin for chest pain, inhaled beta-adrenergic agonists for bronchospasm, glucagon for hypoglycemia, and epinephrine preloaded injections for anaphylaxis. The curriculum assumes that the patient already has the medication and the EMT is simply assisting the drugs are not carried on the ambulance. Some states have gone beyond that and allowed limited carrying of medications on BLS ambulances. Drugs carried by ALS services are more extensive, but it must be emphasized that out-of-hospital pharmaceutical interventions are limited to a few that will make a real difference before the patient gets to the hospital. The drugs that can make a real difference when administered by a...

Neuroendocrine Effects of Alcohol

Alcohol activates the sympathetic nervous system, increasing circulating catecholamines from the adrenal medulla. Hypothalamic-pituitary stimulation results in increased circulating cortisol from the adrenal cortex and can, rarely, cause a pseudo-Cushing's syndrome with typical moon-shaped face, truncal obesity, and muscle weakness. Alcoholics with pseudo-Cushing's show many of the biochemical features of Cushing's syndrome, including failure to suppress cortisol with a 48-h low-dose dexamethasone suppression test. However, they may be distinguished by an insulin stress test. In pseudo-Cushing's, the cortisol rises in response to insulin-induced hypoglycemia, but in true Cushing's there is no response to hypoglycemia.

Effects of Alcohol on Liver Function

Central to the effects of ethanol is the liver, in which 60-90 of ethanol metabolism occurs. Ethanol displaces many of the substrates usually metabolized in the liver. Metabolism of ethanol by ADH in the liver generates reducing equivalents. ALDH also generates NADH with conversion of acetaldehyde to acetate. The NADH NAD+ ratio is increased, with a corresponding increase in the lactate pyruvate ratio. If lactic acidosis combines with a 3-hydroxy-butyrate predominant ketoacidosis, the blood pH can fall to 7.1 and hypoglycemia may occur. Severe ketoacidosis and hypoglycemia can cause permanent brain damage. However, in general the prognosis of alcohol-induced acidosis is good. Lactic acid also reduces the renal capacity for urate excretion. Hyperuricemia is exacerbated by alcohol-induced ketosis and acetate-mediated purine generation. Hyperuricemia explains, at least in part, the clinical observation that alcohol misuse can precipitate gout.

Effects of Alcohol Consumption on the Diet

Of alcohol that would be expected after moderate drinking. The metabolism of alcohol by ADH causes a redox change that promotes lipid synthesis in the liver as well as reduced gluconeogenesis and increased lactate production. Thus, even moderate drinking can cause fatty liver with elevated serum triglyceride levels and, in the absence of dietary carbohydrate, may result in low blood glucose levels that impair concentration and even consciousness. The second liver enzyme, CYP2E1, is part of the cytochrome P450 family, and metabolizes alcohol at levels to be expected after heavy drinking. During metabolism of high levels of alcohol, CYP2E1 utilizes adenosine triphosphate (ATP) energy units and thus 'wastes' stored calories, with resultant potential for weight loss. Another form of this enzyme, gastric CYP2E1, exists in the stomach and, as the first of the three alcohol-metabolizing enzymes to encounter alcohol, accounts for about 30 of all alcohol metabolism in men, but only 10 in...

Diabetes And Endocrine Disorders

The main concern for the anesthetist in the perioperative management of diabetic patients is the avoidance of harmful hypoglycemia mild hyper-glycemia is more acceptable. This has been attributed to the difficulties of measuring blood glucose when the reduced level of consciousness preoperatively masks signs and symptoms of hypoglycemia. The immediate perioperative problems facing the diabetic patient are (1) surgical induction of the stress response with catabolic hormone secretion (2) interruption of food intake, which may be prolonged following gastrointestinal procedure (3) altered consciousness, which masks the symptoms of hypoglycemia and necessitates frequent blood glucose estimations and (4) circulatory disturbances associated with anesthesia and surgery, which may alter the absorption of subcutaneous insulin.

Class II Antidysrhythmic Agents b Blockers

B2 receptors are primarily in respiratory, uterine, and vascular smooth muscles as well as in the human liver. b 2 stimulation promotes smooth muscle relaxation and glycogenolysis while b2 blockade is associated with bronchoconstriction and alterations in glucose metabolism, namely hypoglycemia.

Everyday Feeding problems

If children refuse food at mealtimes or show no intention of finishing their meals, they probably do not need the food. This is particularly likely if they have recently had a snack. Small children are readily sated by amounts of food that seem very small to adults. Snacks should be timed closer to previous meals than to following meals - perhaps 2 h before the next meal. Children who eat poorly at one meal often eat much better at the next meal because by then they are hungry. Offering biscuits or confectionery in exchange for an unfinished meal ('because they have not had enough') is neither helpful nor usually necessary. Children learn very quickly that if they do not eat meals they may get foods that are, to them, more enjoyable. Mealtime organization begins to collapse. However, very young children have slight risk of hypo-glycemia if they go for prolonged periods without food so it is advisable to feed them before bed if they have exhibited persistent food refusal earlier in the...

Anoxic Coma A Historical Background

Encephalopathy result secondary to cerebral cortex or brain stem dysfunction. The cerebral cortex is more vulnerable to the effects of hypoglycemia, whereas the brain stem and basal ganglia exhibit less histologic damage during periods of reduced serum glucose. Although periods of hypoglycemia may precipitate or confound anoxic coma, serum glucose must be maintained in a closely controlled range to prevent further neurologic disability. Similar to the detrimental effects of hypoglycemia, periods of hyperglycemia (> 180 mg dl) have been shown to worsen neurologic outcome.

Clinical Evaluation and Management

Bedside stat glucose determinations should be employed to identify hypoglycemia. In such cases, 50 mg of 50 dextrose should be administered. Although administration of one ampule of dextrose is not detrimental in cases ofhyperosmolar coma, identification of hyperglycemic states is important since elevated serum glucose may promote ischemic damage in cases of anoxic coma. Under physiologic conditions, glucose is the brain's only substrate and crosses the blood-brain barrier by facilitated transport. Each minute, the normal brain requires 5.5 mg (31 mmol) of glucose per 100 grams of tissue. However, one of the most significant complications of exogenous insulin therapy is hypoglycemic coma. If there is hypoglycemia, defined in adults as a blood glucose concentration of less than 40 mg dl, loss of cortical function ensues secondary to cerebral cortex and brain stem dysfunction. Neurologic presentation during hypoglycemia can be variable. Some patients will present with focal motor or...

Future Directions for the Treatment of Organic Brain Disease

In terms of preventing or reversing neuronal injury, peptide growth factors are increasingly being investigated as therapeutic regiments. Although currently the most efficacious application of growth factors involves the peripheral nervous system, progress is being made with central nervous system injury during both growth factor application and the generation of neuronal progenitor cells. The mechanisms employed by trophic factors to achieve neuroprotection can be diverse and not well understood. However, peptide growth factors have been shown to prevent neurodegeneration in hippocampal cultures during glutamate toxicity, potassium cyanide administration, hypoglycemia, and NO toxicity. In addition, the neuroprotective effects of peptide growth factors have been intimately linked to the modulation of the signal transduction systems of NO and protein kinase C.

Oral Antidiabetic Agents

The other most popular oral agent is metformin, which does not stimulate insulin secretion and therefore should not cause hypoglycemia by itself. Metformin can cause bloating and diarrhea, but it can also be mildly weight reducing in conjunction with diet. The drugs called thiazolidinediones (TZDs), pio-glitazone and rosiglitazone, improve insulin sensitivity but do not by themselves cause hypoglycemia. TZDs can, however, cause fluid retention and weight gain, so they are sometimes counterproductive in someone trying to lose weight. Finally, a class of drugs called a-glucosidase inhibitors (acarbose and miglitol) inhibit digestion and absorption of carbohydrate. They do not cause hypoglycemia, but they may interfere with the treatment of hypoglycemia by oral carbohydrate.

Endocrine and renal systems

Patients with diabetes mellitus, whether taking oral hypoglycemic therapy or insulin, are commonly found among the surgical population and frequently suffer from its complications, including renal insufficiency, widespread atherosclerosis, coronary artery disease, and hypertension. Tight control of hyperglycemia has been shown to improve surgical outcomes, especially in the neurosurgical, cardiac, and intensive care populations. On the morning of elective surgery, according to current recommendation, half the normal morning dose of long-acting insulin is given subcutaneously along with a 5 percent glucose IV solution as an IV maintenance infusion. Surgical stress, concurrent medications (especially steroids), and complicating infection exacerbate hyperglycemic control. The goal of treatment depends on the care setting, with tighter control being possible in a more critical care unit with more frequent blood glucose monitoring availability. In the immediate perioperative period, when...

Bleeding Complications

The vast majority of postoperative bleeding complications in patients will occur in the first week and will not be seen in the ED. More likely is gastrointestinal bleeding, which should be managed in the usual fashion but may signal graft dysfunction and be accompanied by profound hypoglycemia and progressive coagulopathy. 3 Portal hypertension is reversed by liver transplantation and gastrointestinal (GI) bleeding from varices postoperatively may be indicative of portal vein thrombosis. Another contributing factor that may predispose patients to GI bleeding is high-dose steroids. Cytomegalovirus (CMV), herpes simplex virus (HSV), and candidal infection can also lead to significant bleeding.

Apnea And Home Apnea Monitors

Sepsis, gastroesophageal reflux and aspiration, aspiration with feedings, anemia, and metabolic problems, such as hypoglycemia. Other, more unusual causes include seizures, cardiac dysrhythmias, and posthemorrhagic hydrocephalus. Therapy is directed toward the specific cause.

Clinical Features

Respiration may have been postictal apnea following a seizure. With a seizure, an infant is frequently awake before becoming apneic. Gastroesophageal reflux may lead to apnea and also may occur in awake infants following a feeding. A history of an upper respiratory infection followed by paroxysmal cough with an apneic episode would be suggestive of pertussis. Hypoglycemia may also be associated with apnea, with or without a seizure. The differential diagnosis also includes infection (sepsis or meningitis) and cardiomyopathy. Infantile botulism may be the cause in 5 to 10 percent of SIDS victims.

Therapeutic Implications

Other factors are also important to augment contractility, but are not as amenable to therapy by emergency physicians. Acidosis adversely affects myocardial contractility and may be persistent after hypovolemia has been corrected. Sodium bicarbonate may rapidly improve contractility in such situations. If acidosis is due to respiratory failure, airway control with endotracheal intubation and mechanical ventilation is useful to correct the hypercapnia and decrease the metabolic demand generated by trying to overcome respiratory failure. Temperature control is also important because elevations can cause an increase in oxygen consumption by 400 percent, causing a marginal cardiovascular system to fail. Ideally, a neutral thermal environment should be maintained to avoid such stress. Hypoglycemia frequently occurs during stressful events, and neonates are less able to respond because of decreased glycogen stores and minimal fat necessary for gluconeogenesis. Low serum glucose of less than...

Pathophysiology of Uncontrolled Diabetes

Ketones Glyconeogenesis

In postabsorptive or fasted states, hyperglycemia in uncontrolled diabetes does not resolve and often worsens (Figure 2). Abnormally low insulin concentrations lead to an exaggeration of metabolic responses that normally serve to protect against the development of hypoglycemia during fasting. These

Differential Diagnosis

Acidosis, hypoglycemia, hypocalcemia, anemia, or sepsis. In critically ill premature neonates, a patent ductus arteriosus is the most common cause of congestive heart failure. Among full-term newborns, a hypoplastic left ventricle is the most common cause in the first week of life and coarctation of the aorta is the most common cause in the second week of life. Transposition of the great arteries presents within the first 3 days of life, with either cyanosis or congestive heart failure. 16

Initial Stabilization

Severe degrees of congestive heart failure can present with signs of low cardiac output or cardiogenic shock. Aggressive management is often necessary in secondary derangement, including respiratory insufficiency, acute renal failure, lactic acidosis, disseminated intravascular coagulation, hypoglycemia, and hypocalcemia.

TABLE 1213 Diagnostic Studies in Seizure Patients

In any group of seizure patients, there is a subgroup in which the seizure is a symptom of an underlying disorder and is not due to idiopathic epilepsy. In such cases, correction of the primary problem makes seizure recurrence unlikely. Thus, the primary goal must be to uncover disorders that are readily identifiable and reversible. Symptomatic seizures of hypoglycemia, hypocalcemia, and electrolyte imbalance can be treated immediately. There is little risk of recurrence and no need for anticonvulsant use. Seizures occurring as a result of intracranial infections and craniocerebral trauma may require only immediate or short-term anticonvulsant use. Symptomatic seizures of systemic lupus erythematosus (SLE), sickle cell anemia, leukemia, arteriovenous malformations, and neoplasms may be the heralding

Effects of Status Grand

Late secondary effects include lactic acidosis, elevated CSF pressure, hyperglycemia followed later by hypoglycemia, dysautonomia with hyperthermia, diaphoresis, dehydration, hypertension followed by hypotension, and eventually shock. In addition, excessive muscle activity leads to myolysis, myoglobinuria, and renal failure. Neuropathologic studies indicate nucleovacuolation and ischemic nerve cell damage leading to neuronal dissolution.

Gsd Type Vi Liver Phosphorylase Hers Disease

The enzyme deficient in type VI GSD is liver-specific phosphorylase. It is relatively rare and a benign form of GSD with no heart and skeletal muscle involvement. Most patients with GSD VI disease present with hepatomegaly and growth retardation. Hypoglycemia, hyperlipidemia, and hyperketosis, if present, are usually mild. The hepatomegaly improves and disappears around puberty. Diagnosis rests on enzyme analysis of the liver biopsy. GSD VI is autosomal recessive. Liver phosphorylase gene (PYGL) has been mapped to chromosome 14q21 and has 20 exons. 23 A splice site mutation in intron 13 has been identified in Mennonite population.

Gsd Type Xi Hepatic Glycogenoses With Renal Fanconibickel Syndrome

This rare GSD is caused by defects in the facilitative glucose transporter 2 (GLUT-2), which transports glucose in and out of hepatocytes, pancreatic cells, and the basolateral membranes of intestinal and renal epithelial cells. 30 The disease is characterized by proximal renal tubular dysfunction, impaired glucose and galactose utilization, and accumulation of glycogen in liver and kidney. The affected child presents in the first year of life with failure to thrive, rickets, hepato- and renomegaly, and maybe mild fasting hypoglycemia and hyperlipi-demia. The gene for GLUT 2 has been cloned and is localized to chromosome 3q26.1. It comprises 10 exons and there are about 10 mutations identified. 30

Special Issues Affecting Diagnosis

Most children who present with self-harming thoughts, suicidal threats, or true suicide attempts should have their glucose checked as part of their medical clearance. This is especially true of diabetic children and those with access to a relative's oral hypoglycemic agents. Inpatient monitoring of glucose may be necessary if overdose of an oral hypoglycemic agent is suspected. Most cases, however, will demonstrate hypoglycemia within 6 to 8 h. Management of such overdoses is often complex and is beyond the scope of this chapter. 4. Patients found to have hypoglycemia and non-glucose-reducing substances in their urine should have galactosemia ruled out. The dipstick urine test will be negative for glucose, but the laboratory evaluation for reducing substances will be positive in this case. This disease usually presents during infancy with failure to thrive, vomiting, hepatomegaly, and jaundice.

Chapter References

Pershad J, Monroe K, Atchison J Childhood hypoglycemia in an urban emergency department Epidemiology and a diagnostic approach to the problem. Pediatr Emerg Care 14 268, 1998. 3. Pagliara AS, Karl IE, Haymond M, et al Hypoglycemia in infancy and childhood Part I. J Ped 82 365, 1973. 4. Crigler JF Intermittent hypoglycemia of children. Postgrad Med 51 210,1972. 5. Haymond MW, Pagliara AS Ketotic hypoglycemia. Clin Endocrinol Metab 12 447, 1983. 6. Pagliara AS, Karl IE, Haymond M, et al Hypoglycemia in infancy and childhood. Part II. J Ped 82 558, 1973. 7. Lebowitz MR, Blumenthal SA The molar ratio of insulin to C-peptide An aid to the diagnosis of hypoglycemia due to surreptitious (or inadvertent) insulin administration. Arch Intern Med 153 650, 1993. 8. Sheehy TW Case report Factitious hypoglycemia in diabetic patients. Am J Med Sci 304 298, 1992. 10. Pontiroli AE, Calderara A, Pajetta E, et al Intranasal glucagon as a remedy for hypoglycemia Studies in healthy patients and type I...

What are the challenges in attributing causation

It is sometimes difficult to decide what constitutes a true adverse drug effect. As an extreme example, a patient in a diabetes trial of glycemic control was involved in a car accident that caused the death of the other driver. Is it possible that the accident could have been caused by the study subject suffering a hypoglycemic attack Should this fatality be classified as an adverse effect and the consequence of tight control of blood sugar

Characteristics And Epidemiology Of Dementia

Most diagnostic criteria for the dementia syndrome stipulate that two or more cognitive functions must be sufficiently impaired so as to interfere with social and or occupational functioning and that there must not be clouding of consciousness. Clouding of consciousness, particularly in the context of a sudden onset of confusion, disorientation, hallucinations, disturbance in attention, or marked behavior change, is typically indicative of delirium (also termed acute confusional state). Delirium may be caused by an acute or chronic systemic illness (e.g., bacterial infection, hypoglycemia), adverse effects of medication, or serious neurological event requiring immediate medical attention. Untreated, these illnesses may result in death or irreversible impairment.

Glucose Galactose Malabsorption

Intestinal transport of glucose and galactose. It is characterized by the neonatal onset of severe, watery, acidic diarrhea. The diarrhea is profuse and contains sugar. In children given lactose, fecal sugar mainly consists of glucose and galactose with only small amounts of lactose, since lactase activity is usually adequate. Hyperosmotic dehydration and metabolic acidosis are the rule. Related gastrointestinal signs and symptoms include increase of abdominal gas, distension, and vomiting. Intermittent or permanent glycosuria after fasting or after a glucose load is frequent. Thus the combination of reducing sugar in the stool and slight glycosuria despite low blood glucose levels is highly suggestive of glucose-galactose malabsorption.

The Effects of Feeding on Blood Glucose Glucose

Ordinarily, the rates of change of glucose inflow from the gut into the glucose pool and the outflow of glucose into the tissues are so well aligned that arterial blood glucose levels rarely fall below fasting levels after a meal, and then only temporarily. Venous blood glucose levels do so more often. The somewhat unnatural conditions resulting from ingestion of large amounts of a glucose solution on an empty stomach may produce a 'reactive hypogly-cemia' due to persistence of insulin action after plasma insulin has fallen to basal levels and all of the glucose has been absorbed from the gut. Such a reactive hypoglycemia may be, but rarely is, sufficiently severe to produce (neuroglycopenic) symptoms even in perfectly healthy individuals.

Status Epilepticus

May occur in a person with chronic epilepsy (the most frequent cause being noncompliance) or in a person with an acute systemic or brain disease (such as hypoglycemia or stroke). The classification of SE follows the international classification of epileptic seizures. In clinical praxis, often only two major types are distinguished convulsive and nonconvulsive status epilepticus. SE, particularly convulsive SE, is a life-threatening condition that requires emergency treatment. Prolonged seizure activity causes systemic complications and brain damage.

Interpretation of Growth Curves

More recent growth curves have been developed from serial ultrasound measurements of fetal growth in normal pregnancies, providing continuous rather than cross-sectional growth patterns. The growth of a preterm infant is better correlated with serially determined fetal growth rates than with cross-sectional neonatal growth curves. Serial ultrasound measurements of fetal growth also more accurately determine how environmental factors can inhibit (for example, maternal undernutrition globally, or hypoglycemia specifically) or enhance (for example, maternal overnutrition globally or hyperglycemia specifically) growth.

Endocrine Pancreas Insulin

Glucagon is a product of the a cells whose primary function is, in a general sense, to counter the effects of insulin by increasing glucose levels. Like insulin, it is synthesized in an inactive form, proglucagon, that requires cleavage to glucagon prior to release. The principal stimulator of glucagon secretion is hypoglycemia, whereas the prime inhibitor is insulin.

Dietary Interventions

Tolerance tests, had patterns of blood glucose levels similar to the pattern seen in adults with functional reactive hypoglycemia. Similar results have also been found in aggressive criminal offenders. A subsequent study showed that the patterns that Langseth and Dowd found can be normal variations in childhood, but the Langseth and Dowd study was followed by two correlational studies that suggested an association between sugar intake and hyperactivity. The hyperactive children who consumed more sugar displayed more hyperactive and aggressive behavior.

Initial Interventions

Patients may be unresponsive or have an altered mental status for many reasons. Four possible diagnoses (hypoxia, opioid intoxication, hypoglycemia, and Wernicke encephalopathy) may be easily overlooked, but are readily treated by the administration of specific antidotes. Within the first few minutes after the patient's arrival, the administration of empiric antidotes supplemental oxygen, 1.0 to 2.0 mg intravenous naloxone in adults and 0.01 mg kg in children, 50 mL 50 dextrose in water (50 D W) for adults and 1 gm kg glucose as 10 or 25 D W for children, and 100 mg thiamine in adults should be considered after taking into account the medical history, vital signs, and laboratory data immediately available. These treatments are simple, inexpensive, and generally without undue risk of an adverse reaction when used appropriately. Thamine is generally not administered for unexplained unresponsiveness in children. However, 1 g kg of glucose is often administered when serum glucose cannot...

TABLE 92 Neonatal Resuscitation Drug Chart

DEXTROSE To provide metabolic substrate and expansion of plasma volume, 10 percent dextrose in water (D10W) at 100 (mL kg) day or 6 to 8 (mg kg) min should be infused. If the Dextrostix is less than 45 mg dL, 5 mL kg of 10 or 15 glucose solution should be infused 25 dextrose infusions should be avoided because of the risk of rebound hypoglycemia.

The Blood Glucose Concentration

Failure to appreciate the differences between arterial and venous blood glucose is a major cause of the confusion that has surrounded the recognition and diagnosis of hypoglycemia and been responsible for nonhypoglycaemia becoming a common diagnosis amongst those whom Singer and coworkers refer to as, the folk sector. In the fasting subject the concentration of glucose in arterial and venous blood is virtually identical but may differ by as much as 2.5 mmol following ingestion of a carbohydrate-rich meal. Because it is arterial blood glucose that determines glucose supply to the brain, regulates the secretion of insulin and other hormones, and is itself homeostatically controlled, it is necessary to define hypoglycemia in terms of glucose in arterial (or more realistically free flowing capillary) than in venous blood.

The Role of the Liver in Glucose Homeostasis

Figure 1 Schematic representation of homeostatic control of blood glucose level and mechanism of hypoglycemia. Hypoglycemia results whenever inflow of glucose from the gut and or liver fails to meet the outflow of glucose from the glucose pool, which consists of glucose dissolved in the extracellular water only. Imbalance arises from (1) excessive outflow into the tissues due to insulin (or very rarely IGF-II) overproduction or activity or (2) in the fasting state, an inability of the liver to liberate or produce glucose at a rate sufficient to meet the non-insulin-dependent, and obligatory, requirements of the brain and red blood cells for glucose. Figure 1 Schematic representation of homeostatic control of blood glucose level and mechanism of hypoglycemia. Hypoglycemia results whenever inflow of glucose from the gut and or liver fails to meet the outflow of glucose from the glucose pool, which consists of glucose dissolved in the extracellular water only. Imbalance arises from (1)...

The Postprandial Syndrome

Symptoms wax and wane during middle life but often remit completely for years or may never recur. They are not progressive and never cause severe neurological dysfunction such as coma, psychosis, or dementia. Hypoglycemia cannot be demonstrated during spontaneous symptomatic episodes in most people with the postprandial syndrome and some other explanation should be sought for them.

Dietary Management

Because of their short duration and modest severity, acute spontaneous neuroglycopenic episodes require no specific treatment beyond ingestion of a rapidly assimilable form of carbohydrate (e.g., a lump of sugar), exactly as for iatrogenic hypoglycemia. Figure 2 Investigation of reactive hypoglycemia. Steps in the diagnosis of reactive hypoglycemia of unknown etiology. Figure 2 Investigation of reactive hypoglycemia. Steps in the diagnosis of reactive hypoglycemia of unknown etiology. There is no evidence that this ever produces rebound hypoglycemia and should it do so the grounds for making a diagnosis of essential reactive hypoglyce-mia should be reviewed. Dietary prevention of reactive hypoglycemia, whether of the 'idiopathic', alimentary variety, or secondary to some other disease, is based on the premise that it is caused by imbalance between the timing and amount of insulin secreted in response to the ingestion of a meal and disposal of the glucose derived from it. Evidence for...

Hepatic and Renal Failure

Considering the importance of the liver and kidney in the maintenance of blood glucose levels hypogly-cemia is remarkably rare in both liver and kidney disease. In liver disease hypoglycemia is virtually confined to patients with acute toxic hepatic necrosis, whether due to overwhelming viral infection or specific hepatotoxins such as poisonous mushrooms, unripe akee fruit, and paracetamol in excess. Its appearance always portends an extremely poor prognosis. The association of hypoglycemia with primary cancer of the liver is comparatively common and due to overexpression and secretion of aberrant, or big IGF-II, and is not, as was once supposed, due to nonspecific destruction of hepatic tissue. Hypoglycemia is very rarely due to hepatic secondaries except from IGF-II secreting tumors. Kidney failure is one of the commoner causes of hypoglycemia in nondiabetic hospital inpatients and does not carry as grave a prognostic significance as in patients with liver disease. It generally...

Inborn Errors of Metabolism

Hypoglycemia is a manifestation of many inborn errors of metabolism (see Table 1) especially in children but also occasionally in adults. It is particularly important in some varieties of liver glycogen storage diseases, especially types I and III, and in disorders of fatty acid metabolism in which it is often the presenting symptom. Type I liver glycogen storage disease is due to a defect in glucose-6-phosphatase activity and produces a severe form of fasting hypoglycemia. Fortunately, this responds to dietary therapy in the form of continuous feeding with slowly absorbed starch solution through a nasal or gastrostomy tube, especially during the night when the body normally has to resort to glycogenolysis to maintain the supply of glucose to the brain. Hypoglycemia in untreated type I patients produces hypoinsulinemia and high to very high plasma ketone levels. Children with abnormalities of fatty acid metabolism, on the other hand, are characterized by hypoglycemia, hypoinsulinemia,...

Disorders of Fatty Acid Oxidation

Disorders of fatty-acid oxidation have been recognized only since the early 1980s, but as a group they represent the most common inborn errors of metabolism. Fat provides a significant source of energy in the form of glucose and ketone bodies during times of metabolic stress (such as febrile illness) or during prolonged fasting. Free fatty acids, released from the adipose tissue, are transported into the mitochondria via the carnitine shuttle system, where they undergo fi-oxidation (Figure 4), the progressive cleavage from an 18-carbon very long-chain fatty acid to the two-carbon aceto-acetyl CoA, the substrate for glucose (via the TCA (Tricarboxylic acid) cycle) and ketones. A deficiency of any of the enzymes in this pathway can cause symptoms of hypoketotic hypoglycemia and hepatic encephalo-pathy, with hyperammonemia (due to secondary inhibition of the urea cycle) and sudden death. Many cases of what would previously have been diagnosed as Reye syndrome are now known to be due to...

Glycogen Storage Disorders

Degradation lead to hypoglycemia and or liver disease because of excessive accumulation of glycogen. Muscle glycogen is an important substrate for energy production for normal muscle function, so disorders are usually indicated by cramping with exercise. Glycogen storage disease (GSD) type I (GSD I) (Figure 6), the most common disorder, is due to a deficiency of glucose-1-phosphatase in the liver, kidney, and intestinal mucosa. Symptoms typically occur in infancy when the frequency of feeding decreases. Profound hypoglycemia can occur progressive hepatomegaly and liver dysfunction are due to storage of glycogen. Other metabolic derangements include lactic acidaemia, which is due to increased pyruvate production increased fatty-acid synthesis causes hypertriglyceridemia and hypercholesterolemia (causing xanthomas) hyperuricemia (causing gout and renal calculi) is due to decreased renal excretion (lactate is preferentially excreted) and increased uric-acid production owing to phosphate...

Clinical Applications And Implications For Drug Delivery

Be transported with high affinity by both MCTs and the sodium-dependent multivitamin transporter (SMVT) in Caco-2 cells.73 The hypoglycemic agent nateglinide has also been demonstrated to be transported in part by MCTs, but other significant transport mechanisms exist.74 The ineffectiveness of the anticancer drug 6-mercaptopurine (6-MP) in the central nervous system of patients with acute lymphoblastic leukemia has been attributed to a high rate of 6-MP efflux across the BBB by MCTs.75

Antiviral and Common HIV Medications

Antimicrobial agents used against opportunistic infections are numerous and a comprehensive review is beyond the scope of this chapter however, several agents warrant mention. TMP-SMX to treat and prevent Pneumocystis carinii pneumonia (PCP) has a 40 to 60 percent incidence of cutaneous reactions in HIV-positive patients. Parenteral pentamidine also used against PCP may result in nephrotoxicity, hepatic toxicity, hypoglycemia secondary to pancreatic necrosis, hypotension, and ventricular tachycardia at therapeutic doses.19 Dapsone, a second-line agent for PCP and toxoplasmosis, may have significant adverse effects at therapeutic doses and in overdose its use may result in headache, nausea, rash, neuropathy, and seizures. The two most important adverse effects of dapsone use are methemoglobinemia and hemolysis. Hemolysis is most common with patients who have G6PD deficiency.20

Specific Nutritional Issues

Hypoalbuminemia and coagulopathy from decreased synthesis of coagulation factors. In end stage liver disease, hypoglycemia can result from decreased hepatic gluconeogenesis from amino acids. Decreased activity of the urea cycle enzymes results in hyperammonemia and hepatic encephalopathy, the ultimate expression of which can be cerebral edema.

AGlucosidase Inhibitors

Acarbose acts to decrease postprandial glucose concentrations by decreasing gastrointestinal absorption of carbohydrates. Acarbose inhibits the brush-border enzyme a-glucosidase, thereby preventing the metabolism of polysaccharides into smaller units for absorption. By itself, acarbose does not cause hypoglycemia. To date, experience with acarbose overdose is limited. However, flatulence, bloating, and malabsorption can complicate use of this medication and should be expected in overdose.

Ketones And The Ketogenic Diet

The KD is certainly a radical departure from a typical dietary regimen it must not be regarded as a fad diet but rather as a strictly controlled medical therapy. The diet is begun in the hospital. Children are ordinarily fasted for 24-36 h, followed by gradual increments in ketogenic foods over the next 3 d. This protocol allows ketosis to develop gradually, initiated by the fast and later maintained by the diet. Precautions against hypoglycemia and other acute medical complications are taken. Once a child is stable on the KD, the goal is to maintain the diet for 2 yr. The child's medical and nutritional status is monitored closely. Because the KD is a chronic therapy, justified concerns may be raised about the effects of this unusual dietary regimen on growth, metabolism, arterial atherogenesis, and renal function (Freeman et al., 1994 Couch et al., 1999). In most cases, acute side effects can be managed, although there is a 5-8 incidence of renal stones (Herzberg et al., 1990) and...

TABLE 1541 Drugs Contraindicated with MAOIs

Drug interactions involving MAOIs can be grouped into three categories pharmacodynamic, pharmacokinetic, and idiosyncratic. The most common pharmacodynamic reaction involves indirect-acting sympathomimetics. They have the potential to produce a hyperadrenergic condition similar to the tyramine reaction (see above) and can be found in over-the-counter preparations, drugs of abuse, and some prescription products. Pharmacokinetic drug interactions have been noted with MAOIs because they are metabolized through the cytochrome oxidase enzyme system and thus can inhibit the metabolism of other drugs. The potentiation of opiate and sedative-hypnotic drugs is an example of this type of enzyme inhibition. Tranylcypromine and phenelzine have been shown to increase insulin release and predispose to hypoglycemia, especially in patients taking oral sulfonylureas agents. Insulin dosage may also warrant reduction. Serotonin syndrome is a rare, potentially life-threatening idiosyncratic reaction. It...

Pyruvate Kinase Is Allosterically Inhibited by ATP

At least three isozymes of pyruvate kinase are found in vertebrates, differing in their tissue distribution and their response to modulators. High concentrations of ATP, acetyl-CoA, and long-chain fatty acids (signs of abundant energy supply) allosterically inhibit all isozymes of pyruvate kinase (Fig. 15-19). The liver isozyme (L form), but not the muscle isozyme (M form), is subject to further regulation by phosphorylation. When low blood glucose causes glucagon release, cAMP-dependent protein kinase phosphorylates the L isozyme of pyruvate kinase, inactivating it. This slows the use of glucose as a fuel in liver, sparing it for export to the brain and other organs. In muscle, the effect of increased cAMP is quite different. In response to epinephrine, cAMP activates glycogen breakdown and glycolysis and provides the fuel needed for the fight-or-flight response.

Ventricular fibrillation and pulseless ventricular tachycardia

Pulseless electrical activity is uncommon in children. It usually occurs secondary to hypoxemia, hypovolemia, hypothermia, hypoglycemia, hyperkalemia, cardiac tamponade, tension pneumothorax, severe acidosis or drug overdose. Successful resuscitation depends on treatment of the underlying etiology. VI.Serum glucose concentration should be determined in all children undergoing resuscitation. Glucose replacement is provided with 25 dextrose in water, 2 to 4 mL kg (0.5 to 1 g kg) IV over 20 to 30 minutes for hypoglycemia. In neonates, 10 dextrose in water, 5 to 10 mL kg (0.5 to 1 g kg), is recommended.

Transport Van Seatbelt Issue

Other passenger said he was fumbling with his seatbelt and fell while straining to look out the front window. The other passenger said the boy's wheelchair spun around during the accident and then he fell to the ground. A third passenger indicated the boy was acting funny just before the accident and kept saying his belt was too tight, then he got weirder afterwards. The boy was taken to the hospital and found to have an impacted fracture of his left femur (Fig. 12), as well as low blood sugar. The boy's mother was very upset and decided to sue the van company, because she claimed her son's wheelchair was not properly restrained and that during the accident his chair spun violently and his left thigh slammed into the post, causing the fracture.

Complications And Mortality

Major complications related to therapy of DKA include hypoglycemia, hypokalemia, hypophosphatemia, ARDS, and cerebral edema. The goal of therapy is to produce a gradual return to normal metabolic balance. Rapid shifts of water, electrolytes and other solutes can be avoided by using isotonic saline as the initial intravenous fluid, using continuous intravenous low-dose insulin, replacing potassium early, and avoiding bicarbonate. Above all, a basic understanding of the pathophysiology of DKA, constant monitoring of the patient, and attention to detail are essential to prevent complications of therapy.

TABLE 2041 Common Symptoms and Signs in Alcoholic Ketoacidosis

There are no specific physical findings associated solely with AKA. The most common findings are tachycardia, tachypnea, and diffuse, mild to moderate abdominal tenderness. Volume depletion resulting from anorexia, diaphoresis, and vomiting causes the frequently seen tachycardia and hypotension. Most patients are awake at presentation. Mental status changes in patients with ketoacidosis should alert clinicians to other potential causes, such as toxic ingestion, hypoglycemia, alcohol-withdrawal seizures, postictal state, or unrecognized head injury.

TABLE 2075 Clinical Presentation of Myxedema Coma

Laboratory evaluation of patients with suspected myxedema coma may reveal anemia hyponatremia hypoglycemia elevated transaminases, creatine phosphokinase, and lactate dehydrogenase levels hypercholesterolemia and arterial blood-gas abnormalities (decreased P o2 and increased Pco2). The electrocardiogram may demonstrate sinus bradycardia, prolongation of the QT interval, and low voltage with flattening or inversion of T waves. A chest radiograph may demonstrate an enlarged cardiac contour caused by a pericardial effusion. 910

Cardiovascular Complications

Most standard emergency department treatments for hypertension and cardiac disease can be utilized in diabetics with appropriate precautions. Moderate to severely elevated glucose levels should be decreased by utilizing small intravenous doses of regular insulin, but the glucose level should not be tightly controlled the patient is undergoing a stressful event and the added stress and consequences of hypoglycemia should be avoided. There is a risk for intraocular bleed from thrombolytic administration to a diabetic with proliferative retinopathy. Even though the risk of intraocular bleed is low, proliferative retinopathy is an absolute contraindication to thrombolytic therapy. The challenge to the emergency physician is expedient evaluation for proliferative retinopathy while simultaneously evaluating the need for thrombolytics.

Additional Characteristics Of Capecitabine

Mouse colon 26 causes progressive weight loss and physiological changes associated with cachexia when it grows to a certain size (1-2 g). Capecitabine and 5'-DFUR could reverse this progressive weight loss and improve hypoglycemia, hyperglucocorticism, and hepatic malfunctions, as well as inhibit tumor growth. This mechanism of action has not yet been clarified (38). In contrast, cyclophosphamide, nimustine, and 2'-deoxy-5-fluorouridine (FUdR) were only minimally effective in reversing the weight loss. 5-FU, tegafur, cisplatin, doxorubicin, and mitomycin C were not active in this regard. Reversal of the weight loss was observed within 3 d following the administration of 5'-DFUR to cachectic mice with large tumor burdens even at doses that failed to inhibit tumor growth. The results suggest that 5'-DFUR reverses cachexia independently of its antiproliferative activity. In an additional cachexia model, mice bearing MAC-16 carcinoma, both capecitabine and 5'-DFUR reversed weight loss and...

Adrenal Insufficiency And Shock

Laboratory clues to the possible concomitant presence of adrenal insufficiency may be mild hypoglycemia, hyponatremia, hyperkalemia, and eosinophilia. Azotemia is, however, nonspecific and is often present in dehydration from any cause. In suspected cases, a serum cortisol should be drawn prior to steroid treatment.

Mental Status Examination

Reversible causes of altered mental status such as hypoglycemia, narcotic overdose, hypoxia, or hypercarbia should be quickly investigated and treated. If a structural etiology of altered mental status is indicated by history or associated neurologic findings, a noncontrast head CT or possibly other neuroimaging study is needed emergently.

Other polyendocrine autoimmunity syndromes

Rarely, diabetes mellitus results from a decreased biological response to a normal amount of insulin. In type A insulin resistance, the problem lies in the insulin receptor, which is quantitatively or qualitatively abnormal, but in the type B syndrome autoantibodies to the insulin receptor produce diabetes mellitus. In vitro, using short-term culture experiments, these antibodies mimic the action of insulin, which may account for the occurrence of hypoglycemia in some patients. More typically, however, there is massive insulin resistance, so that even 15 000 units of insulin per day may not lower blood glucose, and prolonged in vitro experiments reveal the antagonistic properties of the antibodies. About one-third of these patients have other autoimmune diseases, including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, primary biliary cirrhosis,

Mechanisms Involved in Ectopic Hormone Production by Nonendocrine Neoplasms

Overexpression of insulin-like growth factor-II (IGF-II) in mesenchymal and adrenal neoplasms may be related to the loss of imprinting of the gene, as discussed in Chapter 15 (Gicquel et al., 1995). The high level of IGF-II may induce hypoglycemia by inhibiting the output of glucose from the liver (cf. Fradkin et al., 1989). However, these mechanisms may not comprise the majority of alterations leading to the elaboration of hormone-like substances by nonendocrine neoplasms. It is tempting to speculate that in a number of instances the aberrant hormone production may be the result of evolving karyotypic instability with its associated gene amplification and gene translocations.

PMS and Dietary Factors

Several mechanisms proposed for the development of PMS symptoms have been claimed to be promoted by magnesium deficiency. Low magnesium status may also be responsible not only for exacerbating gonadal hormone imbalance in women, but may promote an increase in the aldosterone-to-oestrogen ratio. Enhanced aldosterone levels promote potassium and magnesium excretion and sodium retention, thus inducing fluid retention as found in PMS-H. In addition, deficient levels of magnesium decrease blood glucose control in two ways by decreasing the ability of the liver to metabolize glucose and by increasing insulin secretion in response to glucose. Hence, changes in appetite and craving, both common PMS symptoms, may be closely linked to magnesium deficiency through loosening of blood glucose control. A low blood glucose supply to the brain may cause craving as a signal for increased energy intake. Even the decreased brain dopamine levels postulated to be responsible for anxiety and irritability...

Fatty Liver in Ruminants

In dairy cows, fatty liver is present in early lactation in conjunction with hypoglycemia and negative energy balance. However, evaluation of liver biopsies from cows around calving showed that liver triglyceride content peaked around calving. By day 1 postpartum, approximately half of the cows had more than 15 liver triglyceride. The association of fatty liver with ketosis may be due to impaired gluconeogenic capacity in the liver in conjunction with fatty infiltration. 6 In fatty liver, TAG synthesis in the liver increases and transport of fat in lipoprotein out of the liver decreases. In general, the ability of ruminants to secrete VLDL is lower

Case presentation 2

A 73-year-old woman with diabetes mellitus and community-acquired pneumonia was admitted to hospital and treated with a third generation cephalosporin, intravenous fluids, insulin, and supplemental oxygen. She gradually improved, with defervescence of her fever by day 5 and improvement in her cough and dyspnea. On day 8 she developed watery offensive diarrhea with severe abdominal cramping. She was anorexic and hypoglycemic. Her temperature increased to 38-5 C, her heart rate increased to 135 beats per minute, she became hypotensive, and on her peripheral blood smear she had 22-4 x 109 WBC L with 15 bands. Given her worsening clinical picture, she was transferred to the intensive care unit.

Insulin Resistance Introduction

Thiazide diuretics remain the cornerstone of antihypertensive therapy and have been shown to reduce morbidity and mortality in hypertensive populations throughout the world. However, their use has been associated with a high incidence of endocrine disturbances including glucose intolerance. Glucose intolerance induced by thiazide diuretics was first reported in the late 1950s. Since then a variety of thiazides as well as loop diuretics have been reported to cause mild glucose intolerance, overt hyperglycemia, and rarely nonketotic hyperosmolar states. More recently, the clinical importance of insulin resistance in relation to cardiovascular morbidity has been identified. It is now known that insulin resistance is a risk factor for cardiovascular disease, including myocardial infarction. The fact that many untreated lean and obese hypertensives exhibit underlying tissue resistance to insulin indicates that this may be a predisposing factor to glucose intolerance and development of...

Placental Insufficiency and Fetal Growth

Pregnancies in which these abnormalities are observed are also associated with fetal hypoxia and reduced concentrations of glucose and amino acids in the fetal circulation and reduced activity of the system A amino acid transporter within the placenta. However, in vitro studies have shown that the hypoglycemia observed in some IUGR fetuses is not caused by a decreased glucose transport capacity within the placenta (expression and activity of GLUT1) and IUGR fetuses are actually hypertriglyceridemic compared to their appropriately grown counterparts. The fetal blood concentrations of the trace elements are also either normal or elevated in IUGR. Thus, while it is possible that the placenta from IUGR fetuses may limit the supply of amino acids there is no evidence that placental delivery is the first limiting factor in the supply of glucose, lipids, or trace elements. IUGR is a complicated syndrome in which almost all aspects of placental and fetal metabolism are...

Relevance Of The Autonomic Innervation Of The Pancreatic Islet

Another important function of the parasympathetic nerves is to stimulate glucagon secretion during hypoglycemia, which provides a mechanism for the recovery of circulating glucose. The protection against hypoglycemia is also achieved by other mechanisms, for example, the secretion of adrenaline and cortisol from the adrenals as well as direct stimulation of the release of glucose from the liver, but the primary involvement of glucagon in this respect has been established. The glucagon response to hypoglycemia is due to direct stimulation of glucagon secretion by the low glucose level and by the reduced intraislet concentration of insulin, and several studies have shown that the autonomic nerves also contribute to a major degree. Thus, ganglionic blockade is associated with more than 75 inhibition of the glucagon response to hypoglycemia in conjunction with lowered responses of markers for parasympathetic activation, as demonstrated both in humans and in experimental animals. In...

Laboratory Evaluation

The selection of particular laboratory tests emerges from diagnostic needs suggested by the history and by the findings of mental status examination and physical examination. Fluid and electrolyte disorders are common in elderly patients. Hypoglycemia can precipitate aggressive or agitated behavior, and an elevated white blood cell count may signify infection in patients with acute changes in mental status. Tests that can be helpful when a patient presents with agitation are listed in Table 281-3.

Secondary Causes of Headache

DRUG-RELATED AND TOXIC OR METABOLIC HEADACHES Various drugs, such as nitrates, MAOIs, or chronically used analgesics, may cause headache. Such metabolic conditions as hypoxia, hypercapnia, and hypoglycemia and such toxins as monosodium glutamate and carbon monoxide may cause headache as well. Withdrawal from alcohol may also result in headache. Such headaches can be identified either in the history or through appropriate laboratory testing. 4

Gestational Diabetes Mellitus

Poorly controlled gestational diabetes is associated with an increase in the incidence of preeclampsia, polyhydramnios, fetal macrosomia, birth trauma, operative delivery, and neonatal hypoglycemia. There is an increased incidence of hyperbilirubinemia, hypocalcemia, and erythremia. Later development of diabetes mellitus in the mother is also more frequent. The prevalence of gestational diabetes is higher in black, Hispanic, Native American, and Asian women than white women. The prevalence of gestational diabetes is 1.4 to 14 percent.

Calcitonin Gene Related Polypeptide CGRP

CGRP nerves are also localized to the pancreas, where they are scattered throughout the parenchyma with particular density along small blood vessels and within the islets. Exogenous administration of the peptide under various experimental conditions leads to the inhibition of insulin secretion and stimulation of glucagon secretion. The physiological relevance of the CGRP nerves has been studied in animals treated with capsaicin, which destroys C-fibers and is followed by marked reduction of the CGRP nerves in the pancreatic islets. In capsaicin-treated mice, the glucagon response to neuroglycopenia induced by the glucose analog, 2-deoxyglucose (2-DG) is inhibited and the glucose recovery from insulin-induced hypoglycemia is impaired, suggesting a stimulatory role of the sensory fibers on glucagon secretion. Furthermore, insulin secretion is augmented after capsaicin, suggesting a tonic inhibitory influence of the sensory nerves on the b cells. These studies therefore suggest a...

Disorders of Protein Metabolism Amino Acid Disorders

Symptoms typically occur in the newborn period, except in the case of arginase deficiency, but milder late-onset variants have been well described. Symptoms include lethargy, poor feeding, vomiting, tachypnea, and progressive encephalopathy. Routine biochemical testing shows respiratory alkalosis and hyperammonemia. The liver transaminases are usually elevated. Hypoglycemia is not typical.

Intensive Care Procedures 351

The causes for anxiety in the intensive care unit can be secondary to an inability to communicate due to continuous noise (alarms, personnel, and equipment), continuous ambiguous lighting, excessive stimulation (inadequate analgesia, frequent measurements of vital signs, repositioning, lack of mobility, room temperature, sleep deprivation, and the underlying disease that led to ICU admission. Causes for agitation include extreme anxiety, delirium, adverse drug effects, and pain. If agitation is present, it is important to identify and treat any underlying physiological disturbances hyp-oxemia, hypoglycemia, hypotension, pain, withdrawal from alcohol, and other drug effects. Special attention should be paid to the treatment of agitation, because it can pose a serious threat to patients by contributing to ventilator dyssynchrony, increase in oxygen consumption, or inadvertent removal of devices and catheters (Jacobi et al. 2002).

Differential Diagnosis Of Seizures

In newborns, the problems partly reflect the intrauterine experience. Jitteriness or hyperexcitability appears as high-amplitude tremulousness easily brought out by passive movement of the extremities or jarring of the crib. Drug-withdrawn infants are irritable and tremulous and may have diaphoresis, vomiting, and diarrhea. In addition, seizures may occur. Sepsis, hypoglycemia, and hypocalcemia may produce nonepileptic paroxysmal activity in addition to seizures. Hyperekplexia, or startle disease, mimics tonic and clonic seizures. Near-miss sudden infant death syndrome (SIDS) remains a multifactorial condition in which seizures are part of the differential diagnosis and might be considered part of the cause.

Initiation and Stimulation of Eating Mechanisms Underpinning Hunger

Integrated with other critical hypothalamic energy regulatory systems. The system consists of two peptides, termed orexin-A and orexin-B, along with two orexin receptors, orexin-1 (OX1) and orexin-2 (OX2). The strongest and most reliable effect on food intake is produced by orexin-A. The endogenous orexin system responds to insulin-induced hypoglycemia and food restriction. Moreover, leptin reduces orexin-A concentration in the hypothalamus, and partially blocks orexin-A induced changes in feeding behavior.

Modulation Of Alertness

Foods, such as warm milk, turkey, or bananas, facilitate sleep. Turkey and bananas have a known direct physiological effect They are good dietary sources of tryptophan, which is a precursor chemical for serotonin. Milk also contains tryptophan, but the quantities are lower The value of milk, particularly, warm milk, could well have more to do with stimulus-induced expectations (the warm milk might be a conditioned stimulus, associated with a bedtime routine). Nevertheless, although a banana at bedtime might improve sleep quality (which might perhaps impact alertness the following day), it is not obvious that a banana at breakfast would make a person less alert. Indeed, there is evidence that it might improve alertness. Dietary supplements of tryptophan are reported to be useful to reduce the symptoms of depression, including psychomotor retardation. Glucose is an important substance for neural functioning. Because there are no stores of glucose in the brain, availability in the blood...

Gastroschisis and Omphalocele

Omphaloceles are found in one out of 6000 to 10,000 births, while gastroschisis occurs twice as frequently in the newborn population. Omphaloceles have a higher (37 percent) incidence of associated anomalies, including chromosomal abnormalities. Three specific syndromes are associated with omphalocele the upper midline pentalogy of Cantrell, Haller, and Ravitch (sternal, ventral, diaphragmatic, pericardial, and cardiac defects) the lower midline syndrome (vesicointestinal fissure) and the Beckwith-Wiedemann syndrome (macroglossia, visceromegaly, and hypoglycemia).

Neuroglycopenic Syndromes

Considered further here) can be recognized. They are not mutually exclusive, nor do they depend upon the ultimate cause of the hypoglycemia. This syndrome is more insidious and may go completely unrecognized unless or until the patient loses consciousness. Often, however, there is loss of spontaneous activity, impairment of cognitive function and the onset of somnolence that is more discernible to the bystander than to the patient and which, when it occurs de novo in an insulin-treated diabetic, is often referred to as 'hypoglycemia unawareness.' Acute can proceed to subacute neuroglycopenia and both can progress to stupor or coma unless relieved by food or injection of glucagon. Even when this is not done, however, full recovery, under the influence of endogenous counter-regulatory mechanisms, is almost invariable and is the reason why treatment with insulin is so safe despite the potential dangers of hypoglycemia. ensuing months or years if the cause of the hypo-glycemia is remedied.

Insulinoma Clinical Features

Patients with insulinoma develop profound hypoglycemia during fasting or after exercise. The clinical picture includes the signs and symptoms of neu-roglycopenia (anxiety, tremor, confusion, and obtundation) and the sympathetic response to hypoglycemia (hunger, sweating, and tachycardia). These bizarre complaints initially may be attributed to malingering or a psychosomatic etiology unless the association with fasting is recognized. Many patients eat excessively to avoid symptoms, causing significant weight gain. Whipple triad refers to the clinical criteria for the diagnosis of insulinoma (a) hypoglycemic symptoms during fasting, (b) blood glucose levels less than 50 mg dL, and (c) relief of symptoms after administration of glucose. Factitious hypoglycemia (excess exogenous insulin administration) and postprandial reactive hypoglycemia must be excluded. A supervised, in-hospital 72-h fast is required to diagnose insulinoma. Patients are observed for hypoglycemic episodes and have 6-h...

Adrenogenital Syndrome

Patients can present with vomiting, lethargy, and failure to thrive. Profound volume deficit can lead to shock. Glucocorticoid deficiency can result in hypoglycemia, and mineralocorticoid deficiency causes hyponatremia and hyperkalemia. Metabolic acidosis may be present. Initial resuscitation is with 0.9 NS until adequate perfusion is reestablished. Hypoglycemia is treated with intravenous glucose. In infants, 25 dextrose in a dose of 2 to 4 mL kg is usually adequate. In older children and adolescents, 50 dextrose in a dose of 1 to 2 mL kg is appropriate. Neonates are best treated with 10 dextrose at 1 to 2 mL kg, to avoid rapid shifts in osmolarity. Treatment also consists of initiating glucocorticoid therapy with cortisol at a dose of 50 mg m 2 dose intravenously every 6 h. Mineralocorticoid therapy is not necessary during the acute adrenal crisis.

Pharmacological Management of Undernutrition

Gynecomastia and hypoglycemia were noted furthermore, the increase in muscle bulk failed to produce a parallel increase in muscle strength. Inadequate data regarding the safety and efficacy of growth hormone administration precludes routine clinical use. Similarly, the role of insulin-like growth factor (IGF-I) in the management of undernutrition is questionable. Although the data suggest that exo-genously administered IGF-I may enhance nitrogen retention, gluconeogenesis, and maintenance of normal gastrointestinal function, evidence-based outcome studies are lacking.

Peripheral Endocrine Organs

Of peripheral sources of protein hormones, the pancreas, the source of insulin and glucagon, has received the most emphasis. Deficiency of insulin action, due to lack of or response to insulin, results in diabetes. Insulin is produced by pancreatic islets of Langerhans. Cells within the islets also secrete glucagon, SRIH, pancreatic polypeptide, and amylin. Cellular uptake of glucose and amino acids is stimulated by insulin. Insulin and glucagon act in concert in the liver to maintain energetic and glucose ho-meostasis. Increased blood concentrations of insulin result in reduced blood concentrations of glucose. Low blood glucose induces secretion of pancreatic glucagon, which activates hepatic gluconeogenesis.

Procedures For Msms Screening

The clinical severity of target diseases, except for PKU and homocystinuria (HCU), is quite heterogeneous. 7,8 Patients with severe forms of the diseases present clinical crises with metabolic acidosis, hyperammonemia, and or hypoglycemia in the newborn period and may not survive in spite of intensive care. Liver transplantations have been tried for patients with severe forms of organic acidemias and urea cycle disorders. Patients with milder forms may experience intermittent and sometimes life-threatening crises because of catabolic conditions with or without progressive brain dysfunction. Other symptoms of fatty acid oxidation disorders are muscle weakness and pain with high CK values. Some patients with mild forms of the diseases may not show any symptoms without medical intervention.

Rosmarinic Acid And Medicinal Applications

RA (Fig. 1) is an important caffeoyl ester (phenolic depside) with proven medicinal properties and well-characterized physiological functions. RA is found in substantial quantities in several species in the family Lamiaceae with medicinal uses. Salvia lavandulifolia is used as choleretic, antiseptic, astringent, and hypoglycemic drug in southern Europe and contains high quantities of rosmarinic acid (19). RA-containing Ocimum sanctum (holy basil) is widely used to reduce fevers and against gastrointestinal disease in India. In Mexico, high RA-containing Hyptis verticillata is widely used by Mixtec Indians against gastrointestinal disorders and skin infections (11). In Indonesia and several other parts of the southeast Asia, RA-containing Orthosiphon aristatus is known for its diuretic properties and is also used against bacterial infections and inflammations of the urinary system (14). Salvia cavaleriei, a high RA-containing species, is used in China for treatment of dysentery, boils,...

Chemicals Increasing Arousal

Another manipulation produces complex physiological effects and elicits changes in feelings that may be due to autonomic arousal. In this technique, called the hypoglycemic clamp, blood glucose is experimentally lowered by a continuous injection of insulin into the veins of normal volunteers. The resulting hypoglycemic state produces increases both in autonomic arousal and in unpleasant emotional feelings belonging to Thayer's (1996) tense arousal factor (Gold, MacLeod, Frier, & Deary, 1995 Hepburn, Deary, Munoz, & Frier, 1995 McCrimmon, Frier, & Deary, 1999). Since the effects of the hypoglycemic state are complex, the mood effects may well be produced by some other mechanism than self-perception. Nonetheless, in the absence of an articulated alternative, we may take these effects as some support for Schachter's model.

TABLE 2833 Physiologic Changes Associated with Eating Disorders

Periods of starvation result in hypoglycemia, which is a poor prognostic indicator. Hypoglycemia is often associated with hypothermia, coma, and infections, and may be fatal. Starvation leads to low insulin levels that are insensitive to both glucose and amino acid infusion. Gastric distention and reduced gastric emptying produce enhanced satiation and prolonged intermeal intervals. Food has been demonstrated to remain in the stomachs of anorexics for up to 24 h.

Ischaemic encephalopathy

Glucose is the major energy source for neurons. Low blood glucose concentrations can have a profound effect on CNS function, especially cerebral function. The clinical signs shown by cats with hypoglycaemia depend not only on the absolute serum glucose concentration, but also on the rate of change. Compensatory mechanisms are in place for any chronic cause of hypoglycaemia (e.g. insulinoma). The most common cause of hypoglycaemia is insulin overdosage in a diabetic cat, manifesting with stupor, depression, seizures and coma. Insulin-secreting islet cell tumours are very uncommon in cats and hypoglycaemia associated with other neoplasms, such as hepatoma, is uncommon. Affected cats are frequently normal between episodes. Young kittens with anorexia from systemic disease or other causes can become hypogly-caemic rapidly, and become stuporous and comatose. The demonstration of a low blood glucose concentration (< 2mmol l) with signs of cerebral dysfunction is supportive of...

Carbohydrate and Lipid Metabolism Are Integrated by Hormonal and Allosteric Mechanisms

Liver, either glucagon (indicating low blood glucose) or epinephrine (signaling the need to fight or flee) has the effect of maximizing the output of glucose into the bloodstream. In muscle, epinephrine increases glycogen breakdown and glycolysis, which together provide fuel to produce the ATP needed for muscle contraction.

Role of Fas FasL in immune privilege and immune escape

Under normal conditions, transplantation of major histocompatibility complex (MHC)-mismatched tissues results in their rejection by a strong T cell response specific for alloantigens. There are, however, certain 'immune privileged' tissues, such as Sertoli cells in testis and corneal and retinal pigment epithelium in the eye, that are not rejected upon transplantation into an MHC-disparate host. Recent studies have demonstrated that these tissues avoid rejection because they constitutively express FasL. Thus, Sertoli cells from a normal mouse are not rejected upon transplantation into an MHC-mis-matched host, whereas testis grafts from gld gld mice (that have nonfunctional FasL) are immunologically rejected. It is thought that as the T cells that recognize the transplanted tissue become activated, they increase expression of Fas and become susceptible to Fas-mediated apoptosis and are killed by FasL expressed by the transplanted tissue. This raises the possibility that engineering...