Diabetes and the hypoglycemic syndrome

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 Summary


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Predisposing Conditions

Some supportive procedures that may cause ischemia have been associated with NEC. It includes umbilical and venous catheterization and exchange transfusion (2,6). Perinatal factors that cause hypoxia include respiratory distress syndrome, apnea, asphyxia, hypotension, congestive heart failure, patent ductus arteriosus, hypothermia, sepsis, hypoglycemia, and polycythemia. However, some infants with no risk factors develop NEC. Maternal complications associated with fetal distress and shock, such as prolonged rupture of membranes and maternal infection, frequently are observed in these infants (11).

Clinical Manifestations

The symptoms of hypoglycemia usually occur during fasting, especially in the early morning or if a meal is skipped, and during exercise. Some patients must set their alarms at night in order to eat during the night or they will not awaken in the morning owing to profound hypoglycemia. Because some patients have bizarre symptoms with inappropriate behavior or seizures, they are often misdiagnosed and are evaluated by psychiatrists or neurologists. from 1 hour to 34 years, with a mean of 3.8 years.5 The diagnosis of insulinoma was delayed for a variety of reasons, including the infrequency of attacks and the fact that the symptoms could be aborted by the ingestion of food. Delay in diagnosis may result in brain damage, especially in children, or death owing to severe hypoglycemia. The symptoms in patients with insulinoma are attributable to the actions of two hormones insulin and catecholamines. Epinephrine and other cate-cholamines are secreted in response to low blood glucose levels....

Preoperative Management

After the diagnosis of an insulinoma and prior to surgery, it is important to ensure that the patient is protected from hypoglycemic episodes and the resulting damaging effects on the central nervous system. This can be accomplished in most patients by frequent feedings. Diazoxide can also be used preoperatively to decrease the occurrence of hypo-glycemia. One should be aware that diazoxide, the half-life of which is 28 8 hours, has been associated with hypotension on induction of anesthesia.6 Some clinicians recommend discontinuing diazox-ide before surgery to avoid this problem and to be able to monitor blood glucose levels during the operation as an important indicator of the successful removal of the insulinoma.12 We have not had perioperative problems with diazoxide, but it does cause fluid retention and hirsutism. In patients not receiving diazoxide, intravenous glucose infusion is necessary when fasting in preparation for surgery.

Amylin in Type 2 Diabetes Mellitus

In human type 2 diabetes, fasting and stimulated plasma amylin concentrations are generally lower in those treated with insulin (typically exhibiting greater b-cell failure) than in those treated with oral hypoglycemic agents. In patients with insulin-treated type 2 diabetes, fasting concentrations were 1.8 pM (Czyzyk et al., 1996), 2.1 pM (Hartter et al., 1991), and 2.7 pM (van Jaarsveld et al., 1993), and showed only a small increase upon stimulation (Koda et al., 1992), for example, to 2.3 pM (Czyzyk et al., 1996) or 6.1 pM (van Jaarsveld et al., 1993). In comparison, patients treated for type 2 diabetes with oral hypoglycemic agents had fasting plasma amylin concentrations that were somewhat higher (e.g., 4.8 pM, Hartter et al., 1991 5.7 pM, van Jaarsveld et al., 1993 and 3.2 pM, Czyzyk et al., 1996) that became higher upon stimulation (e.g., to 9.4 pM, van Jaarsveld et al., 1993, and 9.8 pM, Czyzyk et al., 1996).

Preprocedure Evaluation

* Metformin (Glucophage, Bristol-Myers Squibb Co.) is a popular oral hypoglycemic. Severe lactic acidosis can occur in patients with compromised renal function on this medication who receive iodinated contrast media. This medication should be stopped in all patients at the time of the procedure and should not be restarted until 48 hours later, after renal function has been assessed. In patients with compromised renal function, metformin should be stopped 48 hours prior to receiving iodinated contrast and the patient placed on another agent until renal function has been reassessed 48 hours after the procedure.

Diabetic autonomic neuropathy

Atic DPN can vary from mild to severe. Cardiac symptoms include fixed tachycardia, orthostatic postprandial hypotension, arrhythmias, and in severe cases, sudden cardiac death. Gastrointestinal symptoms include constipation, nightime diarrhea and gastroparesis with early satiety, nausea and vomiting. Genitourinary symptoms are common in men, with impotence present in nearly all males after 25 years of diabetes. Urinary retention occurs in men and women. Abnormal pupillary responses and abnormal sweating occurs, with anhydrosis of the feet and hands, and gustatory sweating in more severe cases. Abnormal neuroendocrine responses likely contribute to hypoglycemic un-awareness in type 1 patients.

Pancreas Transplantation

Transplantation of the pancreas as a whole organ is generally performed in uremic patients receiving a kidney transplantation (Robertson et al, 2003), allowing for long term graft function with sustained euglycemia and insulin independence in the vast majority of patients, although the procedure is still associated with perioperative mortality and morbidity (Sutherland et al, 2001 International Pancreas Transplant Registry, 2003). A body of literature supports the beneficial effect of restoring endocrine function by transplanting the pancreas on the performance of the transplanted kidney as well as on the overall survival of both graft and patient (Fioretto et al, 1998 Sutherland et al, 2001 International Pancreas Transplant Registry, 2003). The transplantation can be performed as a simultaneous kidney and pancreas (SKP) procedure using the organs obtained from the same donor. Alternatively, pancreas transplantation can be performed in patients who had already received kidney...

Glucose And Insulin Levels

The ability to measure plasma insulin levels by radioimmunoassay has greatly aided the diagnosis of insulinoma. The diagnosis is made primarily by the recognition of a circulating insulin level that is inappropriately high for the existing level of blood glucose, especially at the time of hypoglycemia. Two types of measurements can be made fasting and following provocative testing. By far, fasting values are the most reliable and less dangerous, but an observed 72-hour fast is most helpful in some patients. Symptoms of hypoglycemia generally occur if the serum glucose levels are below 40 mg mL.

Milana B Boukhman Md Orlo H Clark Md

Insulinomas continue to fascinate physicians because of their interesting and often bizarre clinical manifestations. Because of the unusual clinical presentation the diagnosis is often delayed, usually for over a decade from the time of the first clinical symptoms. However, during the past 15 years, these tumors have been diagnosed earlier, owing to better understanding and awareness of the associated clinical syndromes and to improved diagnostic tests and localization procedures. Although rare, insulinoma is the most common tumor of the endocrine pancreas, occurring in about one person per million population per year. The discovery of insulin by Banting and Best in 1922 ultimately led to the hypothesis by Harris in 1924 that overactivity of islet cells might produce hypoglycemia. This tumor was first described by Wilder and colleagues1 at the Mayo Clinic, who made the diagnosis of endogenous hyperinsulinism in an orthopedic surgeon. Mayo performed an operation on this patient with...

Oralintake Guidelines

Prolonged fasting does not guarantee an empty stomach. In contrast, liquids pass through the stomach quite quickly the halftime of clear liquids is 10 to 20 minutes. There is less content in the stomach of patients 2 hours after consuming small amounts of clear liquids than in the fasting patient.18 The risk of dangerous hypoglycemia should be more of a concern than stomach volume. For that reason, patients should be permitted small quantities of clear liquids up to 2 hours before the procedure, and the old standard of NPO past midnight should be abandoned. These recommendations are especially applicable to infants and children, but they also apply to elderly patients and debilitated patients with diabetes or other metabolic diseases.

Management and Followup 351 Diet

On insulin or oral agents should eat the same amount of food at the same time every day. Patients on insulin may require small snacks between meals and before bedtime to help maintain stable, healthy blood glucose levels and buffer the effect of injected insulin. Care should be taken in the consumption of alcohol and simple sugars. Alcohol intake may cause hypoglycemia, while refined sugars may cause rapid swings in blood glucose levels.

Postoperative Management

After a successful insulinoma resection, transient hyperglycemia in the range of 200 to 400 mg dL for a period of several days to several weeks is the rule and demonstrates a successful outcome. Treatment with small doses of insulin is sometimes necessary to avoid glucosuria and ketoacidosis. Rarely, patients may develop permanent hyperglycemia, especially after a subtotal or near-total pancreatec-tomy. Persistent hypoglycemia, once as high as 10 to 20 of operative cases, can now be expected in only about 5 of patients with benign insulinomas and for some patients with unresectable malignant disease.16 After subtotal or near-total pancreatectomies for nesidioblastosis, children are more prone to developing diabetes mellitus later in life (usually in adolescence) than are the adults who have undergone similar operations.17 Rarely, permanent hyper-glycemia develops after a very limited resection or even enucleation of an insulinoma.

Intraoperative Management

Intraoperative monitoring of serum glucose is essential and useful for determining when the insulinoma has been successfully removed. This practice obviates the risk of severe hypoglycemia occurring undetected during manipulation of the tumor and also helps assure the surgeon that all functioning tumor has been removed. Some surgeons use a continuous-flow, enzymatic system, called an artificial beta cell. This system determines and records serum glucose levels at 1-minute intervals. It maintains serum glucose levels in the desired range by infusing serum glucose or insulin as necessary and also records serum glucose values throughout the operation. Serum glucose levels usually increase within 15 to 60 minutes after removal of an insulinoma.13 Intraoperative glucose monitoring can sometimes be misleading as false positives because glucose levels

Management General Supportive Care Table 1094

Metabolic hypoglycemia electrolyte Hypoglycemia secondary to impaired gluconeogenesis, depleted glycogen stores, and elevated circulating insulin levels, is common in FHF and must be treated vigorously. Blood glucose testing should be frequent (eg, every 4 hours) and hypoglycemia treated rapidly, usually with 10 or greater dextrose solution. Electrolyte problems, especially hyokalemia, hypomagnesiumia, and hypophos-phatemia, are common and should be corrected. FHF is a catabolic state and enteral feeding should be commenced early to prevent malnutrition. This may also reduce the likelihood of gastric stress ulceration, but acid inhibition, typically with a proton pump inhibitor, is also used for this purpose. Patients with advanced FHF often require circulatory support with colloid and vasopressors (eg, norepinephrine). Refractory hypotension is usually caused by

Total Subtotal Pancreatectomy

A total pancreatectomy involves removal of the entire gland, the duodenum, distal stomach, distal bile duct, spleen, and the greater omentum (Fig. 3). This procedure was largely abandoned after a high mortality rate was observed both early and late. The metabolic changes that ensue are also challenging to control. As many as 50 of all of the late deaths that occur after total pancreatectomy are a result of iatrogenic hypoglycemia. Moreover, a survival benefit over the Whipple procedure has not been demonstrated for similar stage tumors of the proximal pancreas. Hence, the indication for a total pancreatectomy currently is the finding of carcinoma in the margin of a proximal pan-createctomy in a patient who can tolerate the metabolic demands of a complete resection.

Differential diagnosis Other glycogen storage diseases

Hypoglycemia in children needs to be treated with frequent feeding. A high protein diet may improve weakness in adult forms of GSD. In GSD VII patients should avoid high-carbohydrate meals that exacerbate the out-of-wind phenomenon, and a ketogenic diet may help. Other potential treatments for GSD V are pyridoxine therapy that improves symptoms in some patients and creatine monohydrate that improves anaerobic but not aerobic exercise capability. Adenoviral-mediated delivery of a myophosphorylase cDNA into myoblasts from patients with McArdle's disease restores myophosphorylase to normal levels, and may prove beneficial as a potential future treatment. Enzyme replacement therapy is also being evaluated in GSD II.

The mechanism of GK activation by aUostericsite binders

Regulation of GK activity via the allosteric site facilitates the explanation of the activated kinetic properties of certain GK mutations that have been identified in patients with persistent hyperinsulinemic hypoglycemia of infancy (PHHI). For example, in patients with mutations in one GK allele in which methionine was substituted for valine at residue 455 (V455M), tyrosine for cysteine at residue 214 (Y214C), or valine for alanine at residue 456 (A456V), improved GK activity was exhibited 13 . These residues, which seem to be included in the allosteric site regulatory domain, are important for the activity of GK and also may aid the design of specific GK activators.

Perioperative Management Of Pheochromocytomas

Immediately after resection of a pheochromocy-toma, severe hypotension and cardiovascular collapse can occur, particularly in patients with norepi-nephrine-secreting tumors. This hypotension is largely owing to desensitization of a1-adrenergic receptors, persistence of antihypertensives, and low plasma volume. Preoperative preparation with calcium channel blockers and or alpha-blockade and forced hydration attenuate this effect. Treatment of shock consists of large volumes of intravenous saline or colloid. Intravenous norepinephrine (Levophed) is sometimes required in high doses. Immediately following resection of the pheochro-mocytoma, intravenous 5 dextrose should be infused at a constant rate of about 100 mL hour to prevent hypoglycemia that is otherwise frequently encountered postoperatively.

Acute Fatty Liver of Pregnancy

Upper gastrointestinal hemorrhage (in 30 to 40 of cases) occurs from a variety of causes. Renal dysfunction is generally mild to moderate, but 25 of patients develop severe renal failure and may require dialysis. Coagulopathy (elevated PT), decreased antithrombin III levels, and thrombocytopenia) probably represents both hepatic synthetic dysfunction and peripheral consumption. Frank disseminated intravascular coagulation (DIC) is common (up to 70 ). Pancreatitis develops in up to 30 of patients. Severe hypoglycemia may be seen in 25 to 50 of patients and can occur at any stage in the disease.

Pharmacological approaches to cerebral protection after cardiac arrest

Immediately after the return of spontaneous circulation cerebral hyperaemia occurs. After 15-30 minutes of reperfusion global cerebral blood flow decreases, which is due, in part to cerebral oedema, with resulting cerebral hypoperfusion. Pharmacological measures to reduce cerebral oedema, including the use of diuretics, may exacerbate the period of hypoperfusion and should be avoided. Corticosteroids increase the risk of infection and gastric haemorrhage, and raise blood glucose concentration but no evidence has been found to support their use.

Physiological Changes

Frey Pancreaticojejunostomy

The diabetes that develops after total pancreatectomy is particularly difficult to manage, however. Patients are exquisitely sensitive to insulin because of enhanced peripheral insulin sensitivity. Hypoglycemic episodes can be frequent, secondary to the lack of glucagon, and the counter-regulation it provides for a fall in blood glucose. Fasting and postprandial hyperglycemia is common because of unsuppressed hepatic glucose production. The paradox of hepatic resistance to insulin, and enhanced peripheral sensitivity to insulin causes difficulty in the management of postoperative diabetes. The duodenum-preserving pancreatic head resections have a lower incident of postoperative diabetes, and may actually result in improved glucose tolerance. This observation sug

Exenatide Antidiabetic [3741

Also moderates peak serum glucagon levels during hyperglycemic periods following meals, but does not interfere with glucagon release in response to hypoglycemia. The dosing regimen for exenatide is 5 or 10 mg twice daily, administered as a subcutaneous injection within an hour before morning and evening meals. Following subcutaneous administration, peak plasma concentrations of exenatide are reached in 2.1 h, and the plasma pharmacokinetic profile is dose proportional. Exenatide has an apparent volume of distribution of 28.3 L, a clearance rate of 9.1 L h, and an apparent in vivo half-life of 2.4 h. Exenatide levels are measurable for up to 10 h after administration. It is primarily excreted unchanged in the urine by glomerular filtration, after which it undergoes proteolytic degradation. The efficacy and safety of exenatide (5 or 10 mg as a twice-daily subcutaneous injection) has been evaluated in three 30-week double-blind, placebo-controlled clinical trials (n 1446). The primary...

Non Chromosomal Syndromes Associations and Sequences

Nevus Flammeus Beckwith

Another example of an infant with the typical macrosomia (birthweight of 3950 g), polycythemia (hematocrit 66 ) and hypoglycemia. Note the macroglossia, nevus flammeus over the glabellar region and the eyelids, and the prominent eyes with relative infraorbital hypoplasia. Figure 3.2. Another example of an infant with the typical macrosomia (birthweight of 3950 g), polycythemia (hematocrit 66 ) and hypoglycemia. Note the macroglossia, nevus flammeus over the glabellar region and the eyelids, and the prominent eyes with relative infraorbital hypoplasia.

Anovulation Is A Characteristic Feature Of Pcos. It Manifests As Menstrual Disturbance 80 Amenorrhoea Oligoamenorrhea

Patient With Hyperandrogenism

Weight gain that is primarily centripetal, especially if associated with extremity wasting, purple striae, easy bruisability, moon facies, and rubor, suggests the presence of Cushing's syndrome, and these patients should be appropriately screened using 24-hour urinary-free cortisol levels or a cortisol level following an overnight dexamethasone suppression test. Other information that should be sought includes the patient's awareness of her body fat distribution, as women with PCOS have a greater prevalence of abdominal obesity (29). Weight gain may also be associated with carbohydrate craving and evidence of postprandial reactive hypoglycemia, particularly in mid-afternoons. For example, Holte and colleagues found that although insulin resistance in obese women with PCOS was reduced by weight loss to similar levels as BMI-matched controls, these patients continued to demonstrate an increased early insulin response to glucose, which could stimulate appetite and persistent weight gain...

Glycogen storage diseases

Type I (GSD I) hypoglycemia, hepatomegaly, kidney enlargement, hyperlipidemia, hyperuri - Infantile form associated with deposition in muscle and liver, with hypoglycemia, recurrent seizures, severe cardiomegaly, and hepatomegaly. - Childhood form associated with hypoglycemia, seizures, growth retardation, weakness, liver dysfunction and hepatomegaly.

Review of Key Concepts

The adrenal medulla secretes mainly epinephrine and norepinephrine, which raise blood glucose levels and help the body adapt to physical activity and stress. 6. The adrenal cortex secretes aldosterone, which promotes Na+ retention and K+ excretion cortisol and corticosterone, which raise blood glucose and fatty acids levels and aid in stress adaptation and tissue repair and androgens and estrogens, which contribute to reproductive development and physiology.

Inhibition of Glucagon Secretion

Amylin Secrtion

This chapter describes a physiological and profound effect of amylin to inhibit meal-related glucagon secretion. Glucagon is processed from a large precursor, proglucagon, in a tissue-specific manner in pancreatic a-cells. In addition to amino acid nutrient stimuli, glucagon is also secreted in response to stressful stimuli, such as hypoglycemia and hypovolemia. Glucagon primarily acts on liver to initiate glycogenolysis and gluconeogenesis, resulting in a rapid increase in endogenous production of glucose. With longer stimulation, glucagon action at the liver results in a glucose-sparing activation of free fatty acid oxidation and production of ketones. During hypoglycemia, glucagon secretion is clearly a protective feedback, defending the organism against damaging effects of low glucose in brain and nerves (neuroglycopenia). Amino acid-stimulated glucagon secretion during meals has a different purpose amino acids stimulate insulin secretion, which mobilizes amino acid transporters...

Do Mutations Cause Crime

Testicular Atrophy Picture

Fense has been dormant during the last two decades. However, there has been no shortage of creative tactics by defense counsel, especially those involved in murder trials. In the last 20 years, low blood sugar levels, high blood sugar levels, premenstrual syndrome, and posttraumatic stress syndrome have all been offered almost always unsuccessfully as a basis for an insanity plea.

Effects on Digestive Secretions

Amylin Secrtion

Amylin Inhibition of Gastric Acid Secretion During Hypoglycemia Insulin stimulation of gastric acid secretion (Isenberg et al., 1969) appears to be secondary to its hypoglycemic effect. For example, increases in plasma glucose concentration inhibit gastric acid secretion (Lam et al., 1993 Moore, 1980), including that stimulated by insulin (Stacher et al., 1976). Increases in glucose also inhibit amino acid-stimulated acid secretion (Lam et al., 1995). Studies using microinjection of D-glucose into different brain regions indicate that glucose-induced inhibition of gastric acid secretion appears to be localized to structures around the nucleus tractus solitarius (Sakaguchi and Sato, 1987). Amylin inhibition of gastric acid secretion was not associated with (explained by) changes in plasma glucose concentration (Gedulin et al., 1997b). Several amylinergic effects, for example, inhibition of gastric emptying (Gedulin and Young, 1998 Gedulin et al., 1997c) and inhibition of glucagon...

Pancreatic Islet Cell Transplantation

The main indication for allogeneic islet transplantation is T1DM (Brendel et al, 2001 Hering and Ricordi, 1999). Transplantation of islets of Langerhans can be performed in uremic patients as either SIK or IAK procedure, since chronic immunosuppression therapy is already implemented to sustain the function of the kidney graft. More recently, ITA has been introduced for the treatment of selected patients with brittle T1DM associated with hypoglycemic unawareness (absence of autonomic symptoms at glycemic levels < 54 mg dL), severe metabolic lability (mean amplitude of glucose excursions > 11.1 mmol L or 200 mg dL), progressive secondary diabetes complications, and failure of intensive insulin therapy despite strict compliance (Robertson et al, 2003 Shapiro et al, 2000 Shapiro and Ricordi, 2004). In these patients the risk associated with metabolic lability and hypoglycemic unawareness (often life threatening) justifies that related to the transplantation procedure and chronic...

Telestroke In Clinical Practice Networks of Care

University of Maryland investigators reported 23 telemedicine consultations and 27 telephone consultations preceding transfer among patients with suspected acute stroke.36 Of the 23 telemedicine consultations, 2 were aborted because of technical difficulties, but 5 of the 21 patients receiving successful TeleStroke consultation received IV rt-PA. No patient experienced complications. Diagnoses included sub-arachnoid hemorrhage, intracerebral hemorrhage, seizure, hypoglycemia, and transient ischemic attack as well as acute ischemic stroke (both anterior and posterior circulations).

Preoperative Treatment Of Patients With Pheochromocytomas

Beta-adrenergic blockade may be considered for P-adrenergic symptoms such as flushing or tachycardia once there is adequate alpha-blockade. It is important to institute alpha-blockade first because blocking vasodilating P-adrenergic receptors without also blocking vasoconstricting ai-adrenergic receptors can lead to hypertensive crisis if serum norepinephrine levels are high. Even labetalol, a mixed a p-blocker, has been reported to cause an unexpected exacerbation of hypertension. Propranolol 10 to 40 mg orally four times daily is occasionally required. Propranolol crosses the placenta and can cause intrauterine growth retardation. Newborns of mothers taking propra-nolol at delivery exhibit bradycardia, respiratory depression, and hypoglycemia.

Biophysiological Factors

Presenting problems may be related to neurological or biochemical factors. Such factors may place boundaries on how much change is possible. Malnutrition, hypoglycemia, and allergic reactions have been associated with hyperactivity, learning disabilities, and mental retardation. Biochemical abnormalities are found in some children with serious behavior disturbances such as those labeled autistic. However, this only establishes that abnormalities in biochemistry are present, not that they cause a certain disorder (e.g., cause certain behaviors). Biochemical changes may be a result of stress related to social conditions such as limited opportunities due to discrimination. Drugs, whether prescribed or not, may influence how clients appear and behave. Certain kinds of illness are associated with particular kinds of psychological changes.

Medical Treatment Of Insulinomas Diet

Acute episodes of hypoglycemia are reversed with carbohydrate. Patients frequently learn this practice for themselves before the diagnosis is made and snack frequently. This often results in weight gain. More severe attacks, including coma, require intravenous glucose administration. Many patients with hyperinsulinism find that they do better on a highprotein diet, as do patients with reactive hypo-glycemia. This has added appeal in that the total carbohydrate and fat intake can be decreased, as well as total daily calories. The most commonly used and effective drug for the management of hyperinsulinism with hypoglycemia is diazoxide. It is currently primarily used for its diabetogenic action in the treatment of hyperinsulinism. The dose of diazoxide ranges from 300 to 800 mg daily in patients with hyperinsulinism. Diazoxide inhibits insulin secretion by a direct action on beta cells and also by stimulating epinephrine release, which itself further inhibits insulin release....

Fasting Test and Insulinto Glucose Ratio

The most useful diagnostic test is the demonstration of fasting hypoglycemia in the face of inappropriately high levels of insulin in the serum. The patient is fasted, and blood samples are obtained every 6 hours or when symptoms develop for blood glucose and insulin measurements. The fast is continued until hypoglycemia or symptoms appear, or for a maximum of 72 hours. One-third of insulinoma patients become hypoglycemic within 12 hours of fasting, 80 within 24 hours, 90 within 48 hours, and 98 within 72 hours. Although insulin levels are not always elevated in patients with insulinoma (normal serum insulin levels are less than 30 mU mL), Ketotic hypoglycemia of infancy Severe malnutrition, muscle wasting Late pregnancy 1. Diagnosis of islet cell tumors by C-peptide suppression test. During this test, commercial insulin is infused into patients to induce hypoglycemia. As expected, with values of serum glucose of 40 mg per 100 mL or less, normal individuals suppress their endogenous...

Myopathies associated with endocrinemetabolic disorders and carcinoma

Paraneoplatic Endocrinal

Diabetes is not associated with a generalized myopathy, however muscle necrosis or inflammation may occur in diabetic amyotrophy. In Flier's syndrome, there is muscle pain, cramps, fatigue, acanthosis nigricans and progressing enlargement of the hands and feet, and impaired glucose tolerance. Hypoglycemia may be associated with muscle atrophy as part of a motor neuron type syndrome. It does not produce primary myopathy.

Implementation Of An Acute Stroke Team And Acute Stroke Protocols

The overwhelming prerogative, in thrombolysis for acute ischemic stroke, is the need for rapid, yet complete, evaluation of potential therapeutic candidates within the 3-hour treatment window. Time is the acute stroke clinician's worst enemy.33 The acute stroke protocol should begin at the first of point of contact with the healthcare system the call to an ambulance dispatcher. Stroke symptoms should be recognized and given high priority for dispatch. Emergency medical technicians (EMTs) should be trained to identify potential thrombolysis candidates in the field by recognizing signs of stroke,73,74 and several simple scales have been created for this purpose.75-78 Prenotification by the EMTs, before hospital arrival, allows time for notification of the acute stroke team and preparation of the CT scanner before patient arrival, and has been associated with fewer in-hospital delays in treatment.79,80 The initial evaluation, after arrival in the emergency department, should include a...

Defects of fatty acid metabolism

In children CT is associated with cardiomyopathy and myopathy, and in infants CT with recurrent acute episodes of hypoglycemic encephalopathy with hypoke-tonemia. There are 3 forms 1) Isolated skeletal muscle involvement, rhabdomyolysis, VACD and myoglobinuria worse than in CPT2 and triggered by fasting or exercise 2) A severe and often fatal childhood form with hypertrophic cardiomyopathy, recurrent episodes of hypoketotic hypoglycemia. 3) A milder childhood form with recurrent episodes of hypoketotic hypoglycemia.

MEN Type I Syndrome

Hyperinsulinemic Hypoglycemia in Infants and Children In infants and children with hypoglycemia owing to organic hyperinsulinism, the pathology patterns are distinctly different from the pathology patterns seen in adults. Because of the different pathology, the localization techniques that are successful for adults are often not effective in infants and children. In addition, different patterns of pathology in the pediatric population necessitate a different surgical approach. Despite the active debate in the medical community about the best method or combination of methods for treating infants with hyperinsulinism, there is no general agreement regarding the best management. Many authorities favor near-total (95 ) pancreatec-tomy as a procedure of choice when treating infants with persistent hypoglycemia.42 Unfortunately, even after 95 pancreatectomy, about one-third of the infants remain hypoglycemic, although they may be easier to manage. In addition, over 70 develop diabetes...


Less than 10 of patients with MEN type I have an insulinoma, and less than 10 of patients with insulinomas have MEN type I.20,21 The median age of onset is in the third decade. There is a 1 to 1 male-to-female ratio. In MEN type I, approximately 80 are associated with multifocal islet disease.22 Although the insulin-producing tumor may be one of several islet cell tumors in the patient, the tumor that is making the insulin is usually solitary and relatively large, on the order of 2 to 4 cm. Patients usually present with symptoms of neuroglycopenia during fasting hypoglycemia (< 40 mg dL). The diagnosis is made by documenting hypoglycemia in association with inappropriately increased plasma levels of insulin and C peptide during a prolonged fast. Other causes of hypoglycemia include medications (insulin, sul-fonylureas), liver dysfunction, renal failure, wasting, and growth hormone (GH) deficiency. Once a diagnosis is made, preparations for surgical approach by preoperative...


Search for and correct factors which may mimic (eg, hypoglycemia) or exacerbate (eg, hypokalemia, infection, and gastrointestinal bleeding) encephalopathy. Light restraints are preferable to sedatives for patients with mild intermittent agitation. If necessary, a short-acting sedative such as propofol (5 to 10 g kg min) should be used for severe agitation when the violent patient puts himself or the nursing staff at risk of injury. Lactulose has traditionally not been used in the treatment of FHF and can result in significant fluid losses and colonic gaseous distention, and the latter may complicate subsequent transplant. However, there has been recent renewed interest in use of lactulose, in part because high serum ammonia levels correlate with a risk of neurological complications including herniation. Patients with advanced hepatic encephalopathy (stage III

Liver Disease

Nutritional deficiencies are common in liver disease. There is an alteration in the normal serum amino acid concentrations with a rise in aromatic amino acids (tyrosine, phenylalanine, and methionine) and a fall in branched-chain amino acids (valine, leucine, and isoleucine). The aromatic amino acids are normally removed by the liver. It is postulated that the rise in aromatic amino acids precipitates hepatic encephalopathy, as these amino acids act as false neurotransmitters. In addition, branched-chain amino acids are preferentially used by patients in liver failure because they do not require the liver for metabolism. However, studies have failed to demonstrate an improved outcome in patients with liver failure who are fed a branched-chain amino acid fortified diet or enteral solution (Als-Nielsen, 2003). There is a tendency to limit protein intake in patients with cirrhosis to prevent encephalopathy. However, these patients have an increased protein demand. Further limiting their...


Centrations, indicating that ARNT is crucial in the response to hypoxia and hypoglycemia. Furthermore, embryonic failure caused by defective angiogenesis was noted in Arnt- - embryos when tested in vivo, an result similar to that observed in mice bearing defective VEGF genes. These studies suggest that ARNT and HIF-1a may be key tran-scriptional regulators of downstream genes controlling angiogenesis in response to hypoxia or changes in nutrient concentration.


Management of the refeeding syndrome is prophylactic and includes the following (1) gradual titration of caloric intake during refeeding and low sodium intake to minimize edema, (2) continuous slow IV infusion of glucose and frequent finger sticks to manage hypoglycemia, and (3) repletion of phosphate and magnesium. Oral refeed-ing on a behavioral unit is the preferable setting for weight restoration however, if despite these measures the patient develops symptomatic bradycardia or a widened QT interval, or seizures, more aggressive management, up to and including intensive care, may be required.


The refeeding syndrome is characterized by fluid and electrolyte shifts (especially hypokalemia, hypophosphatemia, and hypomagnesemia), hypoglycemia, low levels of thiamine, and potentially serious consequences, including severe edema, congestive heart failure, transaminitis, cardiac arrhythmias, Wernicke's encephalopathy, seizures, delirium, and death. This syndrome is encountered most frequently in patients of very low body weight (eg, < 60 of ideal body weight) who are being aggressively re-fed, and has been described in victims of famine and prisoners of war, as well as in underweight patients with eating disorders. NG and IV feeding are associated with higher risk of such complications than oral refeeding (Crook et al, 2001 Faintuch et al,2001).

Diabetes Mellitus

Although patients with diabetes mellitus have a substantially increased surgical mortality rate than non-diabetic patients 105 , these complications are more likely to be a consequence of the end-organ disease such as cardiovascular disease, renal disease, and altered wound healing 106-108 . While evidence suggests that tight control of blood sugar in insulin-dependent diabetics slows the progression of end-organ disease 109 , tight control is associated with additional risks such as hypoglycemia and even death 110 . The goal of perioperative management of stable type I or type II diabetic patients is primarilyto avoid hypoglycemia. Although patients are generally NPO after midnight prior to surgery, a glass of clear juice may be taken upto2h prior to surgery to avoid hypoglycemia. Patients with type I diabetes should not administer in sulin and patients with type II diabetes should not take the oral hypoglycemia agents on the morning of surgery. Diabetic patients should be scheduled...


The vital role of GK in glucose homeostasis has been established for some time. Developments over the last decade, including the discovery of the regulatory function of GKRP, identification of maturity-onset diabetes of the young (MODY-2-), permanent neonatal diabetes (PNDM-) and (Persistent Hyperinsulinemic Hypoglycemia of Infancy) PHHI-related GK mutations, and the identification of novel GKAs and their co-crystal structures with GK, have radically improved our knowledge of GK structure and function. The structural categories of GKAs revealed thus far can be categorized as either carbon nitrogen-centered, aromatic ring-centered activators, or a few special cases that do not fit into either category. These categories of GKAs seem to make comparable polar and non-polar interactions at the allosteric binding site, in spite of their considerable differences in structure. More significantly, in various animal models of T2D, GKAs have exhibited beneficial effects on glucose homeostasis,...


Historically, strict blood glucose control in diabetics was only shown to reduce or delay the onset of microvascular disease such as retinopathy and neuropathy (Figures 8.21, 8.22 and 8.23)29. The UK Prospective Diabetes Study (UKPDS) compared conventional glucose control (fasting glucose < 15 mmol L) with an intensive strategy (< 6 mmol L) in over 4000 patients. Early data demonstrated the relationship between glycosylated hemoglobin (HbAlc) and microvascular events, and also hinted at a relationship with acute myocardial infarction rates (Figures 8.24-8.26)30. However, more recently the Diabetes Control and Complications Trial Epidemiology of Diabetes Interventions and Complications (DCCT EDIC) Study compared conventional treatment (preventing symptoms of hypoglycemia or hyperglycemia) with intensive glucose control (glucose 3.9-6.7mmol L and HbAlc < 6.05 )32. They demonstrated that, in 1400 patients over 17 years of follow-up (but a mean treatment period of 6.5 years), type 1...

Clinical Studies

Recognizing that type 1 diabetes was characterized not only by insulin deficiency, but also by amylin deficiency, Cooper (Cooper, 1991) predicted that certain features of the disease could be related thereto, and he proposed amylin insulin co-replacement therapy. Although the early physiological rationale was flawed, the idea that glucose control could be improved over that attainable with insulin alone without invoking the ravages of worsening insulin-induced hypoglycemia was vindicated. The proposal spawned a first-in-class drug development program that ultimately led to marketing approval by the U.S. Food and Drug Administration of the amylinomimetic pramlintide acetate in March 2005. The prescribers' package insert (Amylin Pharmaceuticals Inc., 2005), which includes a synopsis of safety and efficacy of pramlintide, is included as Appendix 1. The principal risk of pramlintide co-therapy was an increased probability of insulin-induced hypoglycemia, especially at the initiation of...


The patient exhibits signs and symptoms of hypoglycemia during fasting. or glucagon may be useful to establish the presence of an insulinoma.8 Adjunctive tests to confirm the diagnosis of insulinoma include an assay for elevated levels of proinsulin and C peptide. Proinsulin is the precursor of insulin.9,10 Proteolytic cleavage of this protein results in production of C peptide. The differential diagnosis should include other causes of hypoglycemia such as postprandial hypoglycemia, alimentary hyperinsulinism, adrenal insufficiency, hepatitis or cirrhosis, and sulfonylurea overuse (Table 15-1). The presence of circulating insulin-binding antibodies should alert the clinician that the patient is surreptitiously taking insulin.11 Table 15-1. CAUSES OF HYPOGLYCEMIA Adapted from Cryer PE. Hypoglycemia. In Braunwald E, Fauci AS, Kosper DL, et al, editors. Harrison's principles of internal medicine. 15th ed. New York McGraw-Hill 2001. p. 2138. treat their symptoms by eating frequent small...