Home Remedies for Hyperglycemia

Blood Sugar Miracle

If you are one of the many people suffering from high blood sugar or diabetes, this is the solution that you have been looking for. This ebook from Duke Anderson can teach you how to reverse the symptoms that you are facing in less than 3 weeks from your OWN home! It doesn't have to be hard to help your blood sugar get to where it needs to be Don't make it any harder! This is the solution that you need to get your blood sugar under control. You don't have to undergo dangerous, expensive surgery, leave scars from needles, or spend huge amounts of money on pharm drugs that end up doing nothing for you. The blood sugar problems that you have are reversible and curable, if you know the methods to use! And you can learn those methods inside this book. This book will mean a lifestyle change for you!

Blood Sugar Miracle Summary

Rating:

4.6 stars out of 11 votes

Contents: Ebook
Author: Duke Anderson
Price: $37.00

My Blood Sugar Miracle Review

Highly Recommended

The writer presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this book are precise.

I give this ebook my highest rating, 10/10 and personally recommend it.

Download Now

Hyperglycemia and the Glycemic Index

In contrast to the numerous processes that protect against blood glucose falling too low, there is only one that protects the body from hyperglycemia the release of insulin into the blood in response to the ingestion of food. Plasma insulin concentration, although neither its rate of increase nor its effectiveness (which depend on intrinsic physiology of the B cells and peripheral insulin sensitivity, respectively), is in large part determined by the increase in arterial blood glucose concentration that follows ingestion of a carbohydrate-containing meal. People who develop type 2 diabetes often have a delayed B cell response to intravenous glucose before showing overt evidence of impaired glucose tolerance in response to a meal. This is because their B cells, although relatively insensitive to hyperglycemia alone, remain sensitive to the hormones GIP and GLP-1, collectively known as incretins and that are released into the circulation from endocrine cells in the intestine in response...

Clinical Significance of Postprandial and Fasting Hyperglycemia in Diabetic and Nondiabetic Populations

As with fasting blood glucose levels, postprandial hyperglycemia in nondiabetic populations is a predictor of insulin resistance and cardiovascular disease (CVD). The combined 20-year mortality data on men from the Whitehall, Paris prospective, and Helsinki policemen studies showed that the highest quintile compared with the lowest for the 2-h postplasma glucose load was associated with a 2.7 increased risk of CVD mortality. The fasting glucose values were less predictive for CVD, with only the top 2.5 conferring a 1.8-fold increased mortality risk. During a 7-year period, elderly women with isolated postprandial hyperglycemia and a 2-h value more than 11.1mmol l and fasting value less than 7.0 mmol l on a 75-g oral glucose tolerance test had an approximately threefold increased risk of heart disease compared with women whose 2-h values were less than 11.1 mmol l.

Hyperglycemia

There are very few reports regarding the development of diabetes or worsening of preexisting diabetes in patients with renal cell carcinoma (Elias 2005 Palgon et al. 1986 Jobe et al. 1993 Callewaert et al. 1999). In one case, the patient was diagnosed with a preexisting insulin-dependent diabetes mellitus that became uncontrollable by insulin therapy. The patient underwent partial nephrectomy because of a histological papillary type and the control of his glycemia improved immediately and insulin need became identical to the premor-bid situation (Callewaert et al. 1999). The other three case reports did not have any history of diabetes melli-tus and the hyperglycemia resolved following nephrec-tomy. The mechanism for this syndrome is unclear and none of these patients had evidence of metastatic disease or family history of diabetes. No specific etiology was found, but the possibility of ectopic glucagon production was considered. Hypothetically, diabetes could develop in patients with...

Endocrine and Electrolyte Emergencies

Diabetic ketoacidosis (DKA) is a syndrome of hyperglycemia, acidosis, dehydration, and electrolyte depletion caused by a relative or absolute deficiency of insulin in the setting of increased stress counter-regulatory hormones. It usually occurs in type I diabetics but may also occur in type II diabetics associated with major concurrent illness, which alters the balance between insulin and counter-regulatory hormones. In either case the end result is uncontrolled catabolism. DKA can be precipitated by any disorder that severely alters the balance between insulin and its counter-regulatory hormones in the diabetic patient. The counter-regulatory hormones include glucagon, epinephrine, growth hormone and cortisol. Of these, glucagon is the most influential, and its levels are elevated four- to five-fold in DKA. These hormones promote gluconeogenesis and lipolysis while inhibiting peripheral glucose utilization. Insulin blocks gluconeogenesis and lipolysis while promoting peripheral...

Pathophysiology of Uncontrolled Diabetes

Pathophysiology Loss Weight

Uncontrolled diabetes mellitus occurs when circulating insulin levels are inadequate to lower elevated blood glucose concentrations. This condition includes a spectrum of metabolic abnormalities that range from the effects of mild insulin deficiency (i.e., hyperglycemia) to the effects of marked and prolonged insulinopenia (i.e., ketoacidosis and fluid and electrolyte depletion). Diabetic ketoacidosis, which is the most severe acute manifestation of insulin deficiency, is almost entirely restricted to patients with type 1 diabetes, or those with severe pancreatic disease of other etiologies. In people without absolute insulin deficiency, although the combination of significant insulin resistance and relatively low levels of insulin can result in significant hyperglycemia, ketone body production sufficient to cause ketosis and metabolic acidosis does not occur. Even low levels of insulin, such as are typically present in type 2 diabetes, suffice to restrain lipolysis and limit the...

Pathophysiology Of Transplant Rejection

Corticosteroids have a role both in antirejection maintenance and during acute rejection episodes. Corticosteroids inhibit antigen-stimulated I-lymphocyte proliferation and inhibit lymphokine production. A major drawback of the use of steroids is their nonselectivity of immunosuppression, effecting both the cellular and humoral immunity and resulting in significantly increased risk of infection. Other deleterious effects of steroids include osteoporosis, hyperglycemia, hyperkalemia, and growth suppression in children.

Environmental factors

Congential rubella, the first proven viral mediator of IDDM, is associated with an onset of hyperglycemia during the first 5-20 years of life in some 12 of such patients. More recently, enteroviruses, particularly Coxsackie B4, have been proposed as disease pr cipitants. SJL J mice became hyperglycemic after their infection with a Coxsackie virus that had been isolated from the pancreas of a child who died at IDDM onset. Conflicting retrospective analyses of enteroviral serology in children with new-onset IDDM have appeared both before and after this. Acute enteroviral infection during pregnancy, documented by IgM titers, was prospectively associated with a higher risk of IDDM in the offspring before age 3 years. A putative molecular mimic of the Coxsackie P2C protein has been suggested to exist on the P cell autoantigen, glutamic acid decarboxy-lase65 (GAD6S). A superantigen effect was implicated in IDDM pathogenesis after a disproportionate representation of V(3 T lymphocyte clones...

Clinical Features

Isopropanol poisoning should be suspected when the smell of rubbing alcohol is present on the breath, when there is acidosis associated with ketonuria and ketonemia without glycosuria or hyperglycemia, and in the presence of an elevated osmolal gap.7 Acidosis, if present, is mild. The use of alcohol screening panels helps detect unsuspected isopropanolism.

Electrolyte Management

Monitoring and correction of electrolyte imbalances are paramount to the treatment of DKA. Despite the common findings of lowered serum sodium and potassium levels on initial presentation, the body stores of these two electrolytes are depleted even more than is obvious, secondary to the osmotic diuresis and renal excretion of anionic ketoacids. In addition, the hyperglycemia and hyperlipidemia of DKA cause spuriously low serum sodium measurements that do not adequately reflect the degree of sodium deficit. While maintenance sodium levels are 3 meq kg day, children with DKA have a sodium deficit estimated at 6 meq kg. Fluid replacement is best accomplished through two intravenous lines one replacing the fluid deficit as 0.9 NS and a second providing maintenance fluid therapy as 0.45 NS. Decline of the serum sodium level during resuscitation is a potential marker for the development of cerebral edema, and fluid therapy should be adjusted accordingly. Serum sodium levels should be...

Components of Parenteral Nutrition

Difficulties with glucose metabolism are a common problem in preterm infants. This may be due to decreased energy stores, increased gluconeogenesis secondary to stress, decreased insulin secretion, or insulin resistance. When hyperglycemia occurs the glucose infusion rate should be decreased, however the rate should not be decreased below 4-6 mg kg1 min1 (0.022-0.33 mmol kg1 min1) as this is the minimum supply rate necessary to provide adequate energy to the brain. Usually, the infusion of amino acids improves glucose tolerance by decreasing glucose production, stimulating insulin secretion, and enhancing insulin action. The use of continuous insulin infusions to treat hyperglycemia is controversial. If used, the insulin infusion should be initiated at a rate of 0.05 U kg1 h1 and titrated to achieve and maintain a plasma glucose concentration between 80 and 120mgdl1 (4.44-6.66 mmol l1).

Unusual Islet Cell Tumors

VIPomas secrete vasoactive intestinal peptide and cause profuse secretory diarrhea (fasting stool output greater than 1 L day), hypokalemia, and either achlorhydria or hypochlorhydria (watery diarrhea, hypokalemia, and achlorhydria or Verner-Morrison syndrome). Hyperglycemia, hypercalcemia, and cutaneous flushing may be seen. Other, more common causes of diarrhea and malabsorption must be excluded. A diagnosis of VIPoma is established

Dietary Transitions Lifestyle Factors and Diabetes

A dietary change common to all these cases has been the increased consumption of sugar and refined carbohydrates (Popkin, 1998, 2001). Since the key diagnostic feature of diabetes is high blood sugar, often accompanied by sugar in the urine, diabetes is frequently spoken of as sugar diabetes and I've got sugar or I've got high sugar (Carson-Henderson, 2002 Ferzacca, 2000 Lieberman et al., 1999). All carbohydrates cause a rise in blood glucose, and the glycemic index, a measure of the impact of food or a meal on the rise in blood glucose, has a significant but transitory effect on both insulin production and glucose homeostasis (Jenkins et al., 2002 Lieberman, 1993). In general, processed carbohydrate foods have higher glycemic indices than the traditional or unprocessed forms (Jenkins et al., 2002). The modernization of diets has reduced dietary fiber and increased both the fat and refined carbohydrate content of meals (Eaton & Konner, 1985 Trowell & Burkitt, 1981). These...

Miscellaneous Effects

Other side effects from phenytoin include gingival hyperplasia, hirsutism, hypocalcemia, megaloblastic anemia responsive to folate administration, lymphoma, and hemorrhagic disease of the newborn responsive to vitamin K (T.a.ble., 1Z2.-.4). Gingival hyperplasia is so common, its absence should suggest poor compliance. Another clinically significant effect in some is hyperglycemia, felt to be secondary to inhibition of insulin release. This can lead to diabetic ketoacidosis or nonketotic hyperosmolar coma in diabetics. The teratogenic fetal hydantoin syndrome is well described, so oral phenytoin therapy in a pregnant patient should never be initiated or continued by an emergency physician without consultation and close follow-up from an attending neurologist and obstetrician.

Glucagon Counters Low Blood Glucose

Liver State

FIGURE 23-26 The well-fed state the lipogenic liver. Immediately after a calorie-rich meal, glucose, fatty acids, and amino acids enter the liver. Insulin released in response to the high blood glucose concentration stimulates glucose uptake by the tissues. Some glucose is exported to the brain for its energetic needs, and some to fat and muscle tissue. In the liver, excess glucose is oxidized to acetyl-CoA, which is used to synthesize fatty acids for export as triacylglycerols in FIGURE 23-26 The well-fed state the lipogenic liver. Immediately after a calorie-rich meal, glucose, fatty acids, and amino acids enter the liver. Insulin released in response to the high blood glucose concentration stimulates glucose uptake by the tissues. Some glucose is exported to the brain for its energetic needs, and some to fat and muscle tissue. In the liver, excess glucose is oxidized to acetyl-CoA, which is used to synthesize fatty acids for export as triacylglycerols in

Hyperosmolar Hyperglycemic Nonketotic Syndrome

The disease process discussed in this chapter is frequently referred to as nonketotic hyperosmolar coma to characterize the syndrome of severe hyperglycemia, hyperosmolarity, and a relative lack of ketonemia in patients with poorly controlled or undiagnosed type 2 diabetes mellitus. The literature is replete with a score of other acronyms for this syndrome. The nomenclature used by the American Diabetes Association, hyperosmolar nonketotic state (HNS) and hyperosmolar hyperglycemic nonketotic syndrome (HHNS) are both commonly used and more appropriate. This chapter uses the HHNS designation. Placing emphasis on the presence or lack of coma, is likely to underestimate the severity of disease, and thus coma should be excluded from the nomenclature. In fact, although patients may present with a host of symptoms referable to the central nervous system, less than ten percent actually present with coma.1 What is more typical, is a broad range of clinical presentations that correlate with...

Diagnosis of Underlying Causes

New-onset diabetes should be a diagnosis of exclusion as a cause of acute hyperglycemia. In the presence of a previously established diagnosis of diabetes, poor compliance may be a factor, particularly among youth but, again, it should be reserved as an etiology of exclusion for the adult presentation. A thorough history documentation and physical examination should guide the evaluation and, based on history or clinical findings, might include electrocardiogram and determination of the levels of cardiac enzymes, such as CK-MB and troponin I or T, to rule out ischemic heart disease or myocardial infarction complete neurologic exam and computed axial tomography (CAT) of the head to exclude cerebral vascular accident chest radiograph to assess for pneumonia and urinalysis to rule out infection or rhabdomyolysis. Cellular and skin abscess should be sought. In sexually active females, the pelvis should be examined to rule out cervicitis or pelvic inflammatory disease as an occult...

Mechanism of Hypokalemia Induced Glucose Intolerance

The precise molecular mechanism of hypokalemia-induced glucose intolerance is not completely understood however, the bulk of clinical and experimental evidence indicates that glucose-mediated beta cell insulin release plays a major role. Studies in normal volunteers have shown that thiazide-induced potassium deficiency sufficient to produce sustained hypokalemia is associated with decreased glucose utilization and subnormal plasma insulin response to hyperglycemia of 125 mg dl (hyperglycemic glucose clamp). However, glucose uptake is normal under these circumstances, indicating that tissue resistance is not the major cause of impaired glucose uptake. Furthermore, the plasma insulin response to hyperglycemia (an estimate of beta cell sensitivity) is directly related to the degree of body potassium deficit. Moreover, the impairment in plasma insulin response to hyperglycemia can be completely prevented by coadministration of potassium with thiazides in an amount sufficient to prevent...

The Pancreas Secretes Insulin or Glucagon in Response to Changes in Blood Glucose

Healthy Pancreas And Insulin

Triggers the release of insulin by exocytosis. Stimuli from the parasympathetic and sympathetic nervous systems also stimulate and inhibit insulin release, respectively. A simple feedback loop limits hormone release insulin lowers blood glucose by stimulating glucose uptake by the tissues the reduced blood glucose is detected by the 3 cell as a diminished flux through the hexokinase reaction this slows or stops the release of insulin. This feedback regulation holds blood glucose concentration nearly constant despite large fluctuations in dietary intake.

Nonketotic Hyperosmolar Syndrome

Nonketotic hyperosmolar syndrome (NKHS) consists of hyperglycemia, hyperosmolarity, severe dehydration and altered mental status without significant ketosis or acidosis. As with DKA, the underlying mechanism of NKHS is a relative insulin deficiency in the setting of elevated stress counterregulatory hormones. In contrast to DKA, insulin levels are sufficient to prevent significant ketoacidosis. The result is severe hyper-glycemia, osmotic diuresis, profound dehydration, and electrolyte depletion. Diuretic medication (exacerbates fluid losses and thiazides promote hyperglycemia)

Hormones and Glucose Homeostasis

Insulin is the only major hormone capable of lowering blood glucose levels (Table 1). It does so by inhibiting glycogen breakdown in the liver and inhibiting gluconeogenesis and by encouraging glucose uptake by peripheral tissues. It achieves this mainly by activating the glucose transporter protein, GLUT-4, an action that is enhanced by exercise and hyperglycemia. Consequently, insulin lowers The release of insulin from the B cells of the pancreatic islets depends on the concentration of glucose in the blood perfusing them. At blood glucose levels less than approximately 3.5-4.0 mmoll-1, insulin secretion is minimal (constitutive). This means that as the arterial blood glucose declines toward its basal level in the postabsorptive state, plasma insulin levels also decline. However, they never decline low enough in the nondiabetic subject to permit uncontrolled liberation of glucose by the liver or fatty acids by adipocytes. This does, of course, happen when the B cells are destroyed,...

Prevention and Treatment of Diuretic Induced Hypokalemia

The first approach to preventing diuretic-induced hypokalemia is to use the lowest dose possible (Table 1). With regard to thiazide diuretics, the majority of the blood pressure lowering effect is seen at doses of 12.5-25 mg day. At higher doses, further blood pressure lowering is minimal, but rather, metabolic side-effects such as hypokalemia, hyperglycemia, and hypercholesterolemia become more prevalent.

Nutrient Requirements Ruminants

Little glucose is available for absorption from the digestive tract of ruminants. However, glucose is required by nervous tissue, muscle, adipose, mammary gland, and gravid uterus. Glucose requirements of ruminants are met through gluconeogenesis, primarily from proprionate, amino acids (e.g., alanine, glutamine, aspartate, glutamate), glycerol, and lactate. In spite of the lower blood glucose concentrations and extra metabolic steps required to provide glucose, requirements of ruminants appear to be similar to nonruminants.

Latino and Hispanic Traditional Medicine

Health beliefs show great heterogeneity within and between ethnic groups. The traditional system is based on a hot-cold dichotomy of foods, physiological states, illnesses, and medications (Weller et al., 1999). Diabetes is classified as a hot ailment. Health is restored or maintained by a balance of hot and cold elements. Traditional healthcare practitioners such as curanderos are consulted for treatment of diabetes and its complications. Herbs and medicinal preparations may be purchased from botanics. Many herbs are thought to have a beneficial effect on diabetes. Nopal or prickly pear cactus lowers blood glucose (Broadhurst, 1997). Papaya is also thought to cure diabetes. Prayer is an important component of healing activities. The majority of Latinos are Catholic (Hunt, Arar, & Akana, 2000 Hunt, Valenzuela, & Pugh, 1998 Weller et al., 1999).

Pancreatic Stem Cells

Pancreas Duct Cell Marker

The most comprehensive effort in this direction was carried out by Finegood et al., who studied b-cell dynamics throughout the lifespan of the rat. Their results imply a significant contribution of progenitor cells to the b-cell mass in the first weeks after birth and then a shift to tissue maintenance by slow replication of b-cells. In addition, significant b-cell neogenesis was deduced in a similar study of chronic hyperglycemia in rats. These kinetic studies suggest that adult pancreatic progenitors exist. However, they do not help determine the molecular and anatomical origins of these cells.

Conclusion Of Critical Medical Anthropology

Type 2 diabetes is rapidly becoming a worldwide epidemic as populations adopt modernized or Westernized lifestyles. Evolutionary evidence for the selective advantage of diabetes thrifty genotypes and phenotypes predisposes humans to the deleterious and diabetogenic effects of contemporary culture. Recent dietary changes are characterized by an abundance of calorically dense, sugary and fatty foods with low fiber content. In addition, labor-saving, energy-efficient daily activity patterns reduce caloric needs and energy expenditure. The result is a high prevalence of obesity, insulin resistance, hyperglycemia, and other physiological abnormalities comprising Syndrome X.

Box 112 Biochemistry In Medicine

When ingestion of a carbohydrate-rich meal causes blood glucose to exceed the usual concentration between meals (about 5 mM), excess glucose is taken up by the myocytes of cardiac and skeletal muscle (which store it as glycogen) and by adipocytes (which convert it to triacylglycerols). Glucose uptake into myocytes and adipocytes is mediated by the glucose transporter GLUT4. Between meals, some GLUT4 is present in the plasma membrane, but most is sequestered in the membranes of small intracellular vesicles (Fig. 1). Insulin released from the pancreas in response to high blood glucose triggers the movement of these intra-cellular vesicles to the plasma membrane, where they fuse, thus exposing GLUT4 molecules on the outer surface of the cell (see Fig. 12-8). With more GLUT4 molecules in action, the rate of glucose uptake increases 15-fold or more. When blood glucose levels return to normal, insulin release slows and most GLUT4 molecules are removed from the plasma membrane and stored in...

Fibrocalculous Pancreatic Diabetes

Given the underlying problem of malnutrition they benefit from high calorie intake, especially the protein content. There is a need for further investigation into the roles of nutritional, environmental, and genetic factors to establish the etiopathogenesis of this illness.

General Approach to Treatment of Ischemic Stroke

Upon entry of patients with ischemic stroke into the emergency medical service (EMS) or emergency department setting, priority should be given to airway management and oxygenation. Patients should be placed on oxygen, the head of the bed slightly elevated, and a monitor and intravenous line established. Unless there is hypotension, fluids should be administered judiciously to prevent cerebral edema. Volume depletion in patients with ischemic stroke deserves prompt treatment, because it may contribute to decreased cerebral blood flow in the ischemic region. Avoidance of dextrose-containing solutions is warranted except in those with proven hypoglycemia. Hyperglycemia has been associated with an increase in infarct volume and poor long-term outcome. 67 Patients with fever should have antipyretics promptly administered. Experimental studies suggest that hyperthermia increases CNS metabolic demands, whereas hypothermia has demonstrated neuroprotective effects.

Definition and epidemiology of diabetes and impaired glucose tolerance

The diagnosis of DM applies to a heterogeneous group of disorders that are all characterized by high levels of glucose in the blood.8 This hyperglycemia is due either to absent or minimal insulin secretion from insulin-producing (3 cells of the pancreas, or to insufficient insulin secretion to overcome a variable degree of insulin resistance that is present in a large proportion of the general population. As insulin is the primary hormone that prevents hyperglycemia, both by inhibiting hepatic glucose production and facilitating glucose clearance by muscle, insufficient insulin quickly results in an elevated glucose level. The clinical classification of diabetes and the associated characteristics and suspected causes of each type are listed in Table 15.1.

Hepatic Glucose Metabolism

During infection, the liver increases glucose production to defend against hypoglycemia. In fact, the increase in hepatic glucose production is the major reason why patients with infection have an elevated blood glucose concentration. For example, patients with active malaria can have an increase in fasting glucose concentration due to an increase in gluconeo-genesis and overall glucose production. Approximately 75 of cancer patients, like patients with infection, also have an elevated rate of glucose production. Cancer patients also have a mild form of injury approximately 75 have an elevated rate of hepatic glucose production. In 18 studies, hepatic glucose production for normals ranges between 1.6 and 3.0mg kg min, with an average of 2.1 mg kg min. Glucose production for cancer patients without weight loss ranges from 1.7 to 5.1 mg kg min, with a mean of 2.75 mg kg min. This is a 30 increase in the fasting rate of hepatic glucose production. For cancer patients with weight loss,...

Essentiality and Metabolic Functions of Chromium

Symptoms of a patient on total parenteral nutrition (TPN) were reversed by supplemental Cr. Diabetic symptoms, including elevated blood glucose, weight loss, impaired nerve conduction, brain disorders, and abnormal respiratory quotient, that were refractory to exogenous insulin were reversed following increased intake of the essential nutrient Cr. Upon daily addition of supplemental Cr to the patient's TPN solution for 2 weeks, diabetic symptoms were alleviated and exogenous insulin requirement declined from 45 units per day to zero. These findings have been repeated and documented in the scientific literature on several occasions. The hallmark sign of marginal Cr deficiency is impaired glucose tolerance. The effects of Cr on people with high, low, and normal glucose tolerance as well as diabetes are illustrated in Figure 1. Chromium leads to a decrease in blood glucose in people with elevated blood sugar and an increase in those with low blood sugar due to its role in normalizing...

Carbohydrate Metabolism and Gluconeogenesis in the Cancer Bearing Organism

Resting Metabolic Rate Cancer

One of the earliest metabolic abnormalities described in cancer patients was that of glucose intolerance (Rohdenberg et al., 1919). Glucose intolerance is evidenced by increased concentrations and delayed clearance of blood glucose following oral or intravenous glucose administration (Holroyde and Reichard, 1981). Such an effect may be due, at least in part, to tissue insensitivity to insulin as well as a defective response of P cells of the pancreas to insulin secretion following hyperglycemia. Despite this fact, in experimental systems, insulin may actually modify or even reverse the cachexia of neoplasia (Moley et al., 1985 Beck and Tisdale, 1989a).

Nutrients in the soil in the absence of permanently cultivated fields hotcold health systems See humoral medicine human

The phrase hunter-gatherers minimizes sometimes heavy dependence on fishing. Also referred to as foragers. hydropathy. The treatment of diseases with the copious and frequent use of pure water. hypotheses. Predictions, which may be derived from theories, about how variables are related. hypercholesterolemia. One of the genetic forms of coronary heart disease that manifests in the 4th or 5th decade of life. Genetically deficient low-density lipoprotein (LDL) protein receptors (LDLRs) in the liver cause LDL cholesterol to accumulate in the blood, resulting in high blood cholesterol, atherosclerosis and heart disease. hyperglycemia. Too high a level of glucose in the blood.

Delays in Secretory Activation

A number of pathological conditions may delay secretory activation in women, including cesarean section, diabetes, obesity, and stress during parturition. The role of cesarean section is controversial, but if there is one it is likely to have only a modest effect. However, poorly controlled diabetes, stress from delivery, or obesity are associated with significant decreases in early milk production. Because each of these conditions is related to higher blood glucose, hyperglycemia may be an underlying factor in the delay in lactation. However, once it is established, diabetics do not have a problem in maintaining lactation. Thus, compensatory factors may override initiation defects to ensure infant nutrition in these disorders.

Relevance Of The Autonomic Innervation Of The Pancreatic Islet

Autonomic nerves entering the pancreas after atropi-nization. This results in the inhibition of insulin secretion and stimulation of glucagon secretion. This activation is of marked importance during various forms of stresses or physical exercise, when hyperglycemia is achieved by the sympathetically induced inhibition of insulin secretion and stimulation of glucagon secretion. Therefore, the hyperglycemia and increased glucose turnover associated with these conditions are executed to a large degree by the islet sympathetic nerves.

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...

Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a common complication among children with IDDM, accounting for 14 to 31 percent of all diabetes-related hospital admissions. 67 It is the single most common cause of death in diabetic patients under 24 years of age.7 DKA is considered to be present when there is hyperglycemia (i.e., blood glucose level > 250 mg dL), ketonemia (i.e., ketones > 1 2 dilution of serum), and metabolic acidosis (i.e., pH < 7.2 and plasma bicarbonate 15 meq L)5 accompanied by glucosuria and ketonuria. The majority of patients are also moderately to severely dehydrated. Precipitating factors for the initial presentation or for DKA include stress such as trauma, infection, vomiting, and psychological disturbances.5 growth hormone, epinephrine, and norepinephrine), which antagonize insulin. 2 These hormonal abnormalities result in increased glucose production (promoting glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis) and decreased utilization. With progressive...

Nonhuman Primate Models For Metabolic Diseases And Drug Discovery

Nonhuman primate models for metabolic diseases have been utilized successfully to provide more informative mechanism studies and predictive efficacy studies for cholesterol-lowering and antidiabetic drugs. Barbara Hansen et al. have established a colony of obese rhesus monkeys at the Obesity and Diabetes Research Center. These monkeys first develop fasting hyperinsulinemia, hyperglycemia, and insulin resistance and then eventually become diabetic with retinopathy and nephropathy upon aging, displaying many characteristics similar to that of the human condition (Ortmeyer et al., 2000). When these monkeys were treated with the antidiabetic drug TZD, the compromised glycogen synthase activity in diabetic muscle was restored close to the normal level, contributing to improved insulin sensitivity and indicating that these animals respond to antidiabetic drugs in a similar way to humans.

TABLE 1254 Treatment of Hypoglycemia

Hyperinsulinemic patients may also be given diazoxide to inhibit insulin release and activity. 6 More recent literature has suggested that octreotide may be a better choice it is not associated with the rare hypotensive effects of diazoxide. Octreotide dosing for this potential indication is controversial and not yet established. Diazoxide is given intravenously at 3 to 5 mg kg for neonates and 1 to 3 mg kg for children every 8 h. Diazoxide should be given over at least 30 min to prevent severe hypotension. In children who are able to eat, feedings every 3 to 4 h will often suffice as well. If given only simple carbohydrates, these children will develop postprandial hyperglycemia with subsequent rebound hypoglycemia secondary to stimulation of insulin secretion. Therefore, their diet should consist of complex carbohydrates, proteins, and fats as well. Feedings of raw cornstarch at night usually maintain safe glucose levels for a number of hours and are not typically associated with...

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.

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.

Gestational Diabetes Mellitus

This disorder, which is defined as hyperglycemia first detected during pregnancy, occurs in 2-5 of pregnant women. Often, one cannot determine whether glucose intolerance antedated the pregnancy or whether hyperglycemia was provoked by the hormonal milieu associated with pregnancy. Hyperglycemia remits postpartum in 90 of women with gestational diabetes, but these women are at increased risk for subsequent development of diabetes, which is usually type 2. Although most cases of this form of diabetes are detected by blood glucose screening performed as a routine procedure early in the third trimester, the current recommendation is that universal screening is probably unwarranted. A woman younger than age 25 years, of normal body weight, without a family history of diabetes or a personal history of poor pregnancy outcome, and from an ethnic group with low rates of diabetes is at sufficiently low risk of gestational diabetes that glucose testing can be omitted. In contrast, women with...

Control of Blood Glucose Level

A first and very basic goal of diabetes care is to eliminate the symptoms of hyperglycemia. Treatment is inadequate if the person remains polyuric, thirsty, or continues to lose weight from hypergly-cemia. To cause symptoms, however, hyperglycemia usually must average more than 11 mM (200mg dl). Since blood glucose in the 7-11 mM (125-200 mg dl) range is distinctly abnormal and does cause long-term diabetic complications, freedom from symptoms is only the beginning of adequate therapy.

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

Complications Of Immunosuppressive Agents

Therapeutic immunosuppression is accompanied by a number of side effects and complications. Common and most life-threatening are the variety of infections that occur with the suppression of cell-mediated immunity. The agents of immunosuppression also have a number of nonspecific toxicities that complicate their use. Combined toxicities can produce or worsen preexisting renal insufficiency, hypertension, and hyperglycemia. Hypertension is perhaps the best example of combined toxicity. Cyclosporine and FK506 inhibit T-cell proliferation. Nephrotoxicity is a common and usually reversible side effect manifest by elevated serum creatinine levels, hypertension, hyperkalemia, hyperuricemia, and gout. Patients are sensitive to dehydration.12 Other side effects include headache, hirsutism, gingival hyperplasia, hyperglycemia, hypomagnesemia, hypercholesterolemia, hypertriglyceridemia, hepatotoxicity, and hemolytic uremic syndrome. Unlike those of other immunosuppressive agents, blood levels of...

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,

Descent rules See rules of descent

A group of metabolic diseases characterized by high blood sugar or hyperglycemia. A form of diabetes with onset in childhood is often called Type 1 diabetes genetic factors play a major role and insulin deficiency is almost total. Type 2 or adult-onset diabetes is related to obesity. dialect. A variety of a language spoken in a particular area or by a particular social group. diarrheal. Disease characterized by a high number and frequent bowel movements with watery stool. disability. From a relativist perspective, impairment-disability is a mapping of what a particular culture or subculture perceives as anomalous physical or behavioral differences. A more etic definition from the World Health Organization defines disabilities as any restriction or lack resulting from an impairment of ability to perform an activity in the manner or within the range considered normal for a human being. disease. A biomedically measurable lesion or anatomical or physiological...

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...

Effects of growth hormone and insulinlike growth factor 1 deficiency on ageing and longevity

Abstract Present knowledge on the effects of growth hormone (GH) insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGF1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In...

Glucose levels and the risk for cardiovascular disease in nondiabetic patients

Many prospective studies have consistently showed that the relationship between glucose levels and the subsequent risk of cardiovascular disease extends well below the diabetic threshold. For example, after 10 years of follow up in the Whitehall study of 18050 non-diabetic male civil servants, there was up to a twofold increase in coronary heart disease and stroke mortality in subjects whose 2 hour postload capillary glucose value was greater than 5-4 mmol l compared to those with lower glucose levels. This increase was independent of age, smoking, blood pressure, cholesterol, and occupation.26,27 The relationship of non-diabetic-range hyperglycemia and cardiovascular disease was also clearly noted after 14 years in the Rancho Bernardo study.28 In this prospective study of 3458 non-diabetic men and women aged 40-70 with a fasting plasma glucose < 7-8 mmol l, the age-adjusted ischemic heart disease mortality rates approximately doubled in men as the fasting glucose rose from 5 to 7...

Case presentation 3

A 74-year-old retired schoolteacher presents with an infection in his left forefoot. He gives a history of type 2 diabetes mellitus of 8 years' duration, which has required insulin for control of blood sugar for the last 4 years. He is a non(never)-smoker, with a daily alcohol intake of 4-5 units. His family doctor reports that his blood sugar control has deteriorated over the last year, and that he had an episode a week previously that may have been a transient ischemic attack.

Diabetes Educational and Community Based Interventions

A public health campaign of educating tribal members on low-fat diets, cigarette smoking, and exercise was developed by a Mohawk community (Hood, Kelly, Martinez, Shuman, & Secer-Walker, 1987). An important and successful school and community-based project was initiated among the Zuni Indians of New Mexico (Cole et al., 2001 Teufel & Ritenbaugh, 1998). The Zuni Diabetes Prevention Program eliminated soft drinks and snack foods from school vending machines, provided good-tasting water, promoted a school-based wellness and exercise program, and developed supportive social networks. These interventions resulted in increased activity, decreased soft drink consumption, and a decrease in the incidence of hyperglycemia.

Toxic Epidermal Necrolysis

Prolabial blistering and erosive lesions are disfiguring and often impair adequate oral intake, contributing to hypovolemia. Ocular complications include purulent conjunctivitis, painful erosions, and potential blindness. Anogenital lesions are common. Additional mucous membrane involvement includes the gastrointestinal, urinary, and respiratory tracts. The two major complications and leading causes of death in TEN are infection and hypovolemia with electrolyte disorders. A broad range of pathogens is usually found, with staphylococcal and pseudomonal species predominating. The mortality rate has been reported as being between 25 and 30 percent. These clinical variables are associated with poor prognosis advanced age extensive disease idiopathic nature multiple medication use steroid therapy azotemia hyperglycemia leukopenia and thrombocytopenia.7 The differential diagnosis of TEN includes staphylococcal scalded skin syndrome (SSSS) EM, toxic shock syndrome (staphylococcal and...

Diabetes Complications

The most frequent complications of long-term diabetes occur because of abnormalities in the blood vessels and nerves caused by chronic hyperglycemia. Diabetes is the leading cause of blindness, kidney failure, and amputations of the lower limb. There are also abnormalities that occur in the immune, cardiovascular, and digestive systems as well as periodontal disease, sexual dysfunction, and complications of pregnancy (ADA, 2002a Harris, 1995). Diabetes also is associated with psychological and social dysfunction. Because type 2 diabetes often does not have an acute onset, it may go undiagnosed for a number of years until a consequence of the disease is treated and the underlying diabetes is diagnosed (ADA, 2002a Centers for Disease Control, 2001).

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...

Traumatic Brain Injury

Systemic Causes Once an injury has occured, the greatest benefit for patients can be provided by preventing the systemic causes of secondary injury. These include correcting hypoxemia, hypotension, anemia, hyperglycemia, and hyperthermia, and evacuation of intracranial masses. Hypotension (SBP < 90) and hypoxemia (Po2 < 60) have been associated with a doubling of TBI mortality.8 Anemia (hematocrit < 30 percent) also leads to increased mortality due to decreased oxygen-carrying capacity. Patients with acute subdural hematomas have a 30 percent mortality rate if operated on within four hours compared to a 90 percent mortality rate after four hours.9

Clinical Significance

The incidence of insulin resistance without overt hyperglycemia is unknown, but overt hyperglycemia occurs in about 15 of patients treated with thiazide diuretics. The incidence of hyperglycemia caused by loop diuretics is lower because these agents tend to cause less potassium wastage than thiazides. Glucose concentrations are mildly elevated (120-150 mg dl) in most cases however, severe hyperglycemia with glycosuria can be precipitated even by mild to moderate (25-50 mg day) doses of thiazides.

Volume Depletion and Increased Catecholamines

Volume depletion may reduce both renal blood flow and glomerular filtration rate, thereby reducing the filtered load of glucose and promoting hyperglycemia. In addition, it has been postulated that reduction in blood pressure and flow to muscle, the primary site of insulin-mediated glucose uptake, may be attributed to volume depletion. Thus volume depletion could reduce tissue sensitivity to insulin indirectly by limiting delivery to muscle bed. Increased plasma catecholamine levels accompanying volume depletion may increase glycogenolysis, thereby increasing glucose input. However, most patients with diuretic-induced glucose intolerance have mild hyperglycemia and are not markedly volume depleted. Moreover, if dietary sodium intake is increased during diuretic therapy, volume depletion and increased catecholamine levels can be prevented. Thus, these catecholamines probably play a minor role in producing hyperglycemia except in patients with severe volume depletion. Therefore, other...

Other Abnormalities of Glucose Tolerance

Stress hyperglycemia This denotes an individual who is frankly hyperglycemic (> 7.8mmol l) under conditions of intercurrent illness or during treatment with medications that provoke diabetes. Such people may revert to normal glucose tolerance following removal of the stress. Although not an official category of diabetes, such abnormal glucose values in hospitalized patients cannot be ignored since there is strong evidence that treatment to normoglycemia significantly lowers mortality, at least for patients with acute myocardial infarction or with critical illness in an intensive care unit. Precipitants of stress hyperglycemia are listed in Table 4.

Etiology Pathogenesis

The importance of genetic factors is indicated by the observation that only about a third of diabetic patients develop nephropathy and that this is independent of the severity or control of hyperglycemia (2). Some but not all of the genes that have been implicated in affecting the susceptibility for or progression of diabetic nephropathy are promoter of RAGE (advanced glycation end-product receptor), histocompatibility antigen DR3 4, angiotensin-converting enzyme, angiotensinogen, bradykinin receptor, aldose reductase, transforming growth factor-P, and apolipopro-tein E (12). Experimental data indicate that many different cell types in all structural compartments of the kidney are stimulated by hyperglycemia and other stimuli (e.g., advanced glycation end products and reactive oxygen species) to produce cytokines, growth factors (e.g., transforming growth factor-P, platelet-derived growth factor-P) and other humoral mediators that cause increased extracellular matrix production...

Endocrine and Metabolic Mechanisms

Another important target of prenatal events is the liver, where glucocorticoids regulate several metabolic processes, including hepatic enzymes regulating carbohydrate and fat metabolism. Rats exposed to DEX in the last trimester of pregnancy show increased phosphoenolpyru-vate carboxykinase (PEPCK) gene transcription and increased activity of this rate-limiting enzyme of gluconeogenesis in the liver.9 These animals have adult hyperglycemia and increased hepatic glucocorticoid receptor expression. Similarly, structural changes in the liver and altered expression patterns of gluconeogenic enzymes and glucose handling have been reported after a maternal low protein diet.56 Neuroendocrine regulatory systems are also vulnerable to disturbances in early life which can lead to permanent structural changes, including reduced cerebral vascularity57 and dysfunction of central nervous system regulation. Maternal low protein nutrition results in structural changes in the mediobasal hypothalamic...

Health Risks due to Overweight Obesity

Increasing body fatness is accompanied by profound changes in physiological function. These changes are, to a certain extent, dependent on the regional distribution of adipose tissue. Generalized obesity results in alterations in total blood volume and cardiac function while the distribution of fat around the thoracic cage and abdomen restricts respiratory excursion and alters respiratory function. The intra-abdominal visceral deposition of adipose tissue, which characterizes upper body obesity, is a major contributor to the development of hypertension, elevated plasma insulin concentrations and insulin resistance, hyperglycemia, and hyperlipidemia. The alterations in metabolic and physiological function that follow an increase in adipose tissue mass are predictable when considered in the context of normal homeostasis.

Perioperative Support in Severe Malnutrition

Increased morbidity and mortality risks are associated with malnourished surgical patients. The Veteran's Affairs Parenteral Nutrition Cooperative Trial evaluated the benefits of preoperative PN in patients with varying degrees of malnutrition. Significant benefit was demonstrated only among those patients who were severely malnourished (albumin < 3.0g dl). Interestingly, an increased rate of infectious complications was observed in mildly and moderately malnourished patients receiving PN compared to the control group. If enteral access is available and feeds are tolerated, preoperative en-teral nutrition support has been found to be equally effective when utilized for 7-14 days or longer in malnourished surgical patients. Early studies that suggested increased adverse outcomes with paren-teral compared to enteral support were often based on management techniques that are no longer consistent with standard of practice, which included the overfeeding of macronutrients, rapid infusion...

Lipid Soluble Thiamin Derivatives

In recent years, several lipid-soluble derivatives of thiamin have been introduced, of which the best known is benfotiamine. Advantages of these compounds appear to be increased absorption, but by the diffusion mechanism only, and greatly increased transketolase activity. Transketolase is the rate-limiting enzyme of the nonoxidative branch of the pentose phosphate pathway. Benfotiamine has been shown to be useful for the management of rare genetic disorders in thiamin transport and may also prove useful to prevent damage from diabetic hyper-glycemia. One study demonstrated that benfotia-mine prevented experimental retinopathy. Diabetic hyperglycemia is accompanied by an increase in the potentially pathogenic glycolytic metabolites glyceraldehyde-3-phosphate and fructose-6-phosphate. Benfotiamine, by increasing transketolase activity, stimulates the pentose phosphate pathway to metabolise these glycolytic intermediates into pentose-5-phosphates and prevent the intracellular increase of...

Pancreatitis and Enteral Nutrition

The authors concluded that hypocaloric enteral feeding is better than TPN. This study is similar to many others, showing that EN providing less than estimated energy intake is associated with reduced hyperglycemia and sepsis. The conventional interpretation is that the EN route reduces sepsis. The trial by van den Berghe et al. showed that irrespective of the route of nutritional support, control of hyperglycemia reduced mortality in the ICU. Their findings support the alternative explanation that the EN route protects the patient because it results in hypocaloric feeding, which prevents hyper-glycemia. The study shows that EN can be given as a cheaper source of nutrition, but since EN was needed only for 6.7 days with less than adequate energy intake, it raises the question as to whether any nutritional support was required. Another important question is whether TPN should be hypo-caloric rather than meet target energy intake in patients who are unable to take oral...

Prevention or Control of Comorbidities

Morbidity and mortality among people with diabetes are rarely due to acute hyperglycemia or diabetic ketoacidosis. Rather, the long-term complications are either specific to diabetes (e.g., diabetic retinopathy or nephropathy) or accelerated by diabetes (e.g., atherosclerosis). Diabetes significantly increases the risk of coronary artery, cerebro-vascular, and peripheral vascular disease, with these cardiovascular complications accounting for approximately 80 of deaths in diabetes. Prudent dietary management of diabetes therefore requires consideration of what can be done to prevent or control the various comorbidities of this disease. For example, all people with diabetes should be on a diet that minimizes the risk of atherosclerosis. At the first clinical sign of hypertension, dietary methods should be implemented to lower blood pressure.

Genetic Susceptibility to Complications

As mentioned above, diabetes is associated with complications involving the eyes, kidneys, blood vessels, and heart. However, not all individuals with diabetes develop these complications. There is increasing evidence that there are genes other than those that increase susceptibility to developing the disease that may influence susceptibility to developing its complications. These genes are not yet identified, but they are likely to interact with other known risk factors for complications, including poor blood-sugar control and increased blood-pressure and blood-cholesterol levels. see also Complex Traits Disease, Genetics of Gene and Environment Gene Discovery Immune System Genetics Mitochondrial Diseases.

Chapter References

Pulsinelli WA, Levy DE, Sigsbee B, et al Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus. Am J Med 74 540, 1983. 18. Longstreth WT, Inui TS High blood glucose level on hospital admission and poor neurological recovery after cardiac arrest. Ann Weurol 15 59, 1984. 19. Lam AM, Winn HR, Cullen BF, et al Hyperglycemia and neurologic outcome in patients with head injury. J Weurosurg 75 545, 1991. 20. Young B, Ott L, Dempsey R, et al Relationship between admission hyperglycemia and neurologic outcome of severely brain-injured patients. Ann Surg 210 466, 1989.

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...

Specific Issues That Impact Evaluation And Treatment

Many comorbid medical conditions may adversely affect wound healing in the extremities. Patients with diabetes mellitus are more prone to wound infection as a result of peripheral vascular disease and hyperglycemia. Other medical conditions that can hamper wound healing include chronic renal insufficiency, end-stage liver disease, anemia, chronic corticosteroid use, obesity, and connective tissue diseases such as Ehlers-Danlos and Marfan syndromes and osteogenesis imperfecta.

Dextrose Prescription

Dextrose in PN solutions generally provides 40-60 of total energy requirements. Hyperglycemia is a common complication of PN due to diabetes, medications, or stress response, so the dextrose load is often initiated below goal until tolerance is demonstrated. The maximum glucose utilization rate is 5-7mg kg minute. Doses that exceed this may result in glucose intolerance or hepatic steatosis. Studies have demonstrated that aggressive blood glucose management is associated with fewer septic complications in critically ill patients.

Oxidative Stress Antioxidants And Lipid Peroxidation

Interestingly, in nerve and dorsal root ganglia of the streptozotocin-induced diabetic rat, no changes occur in the levels of antioxidant enzyme mRNAs, including glutathione peroxidase, and both Cu-Zn- and Mn-dependent superoxide dismutase (the cytosolic and mitochondrial forms, respectively, of this enzyme), whereas the expression of catalase mRNA is increased (Kishi et al. 2000). Several of the antioxidant enzyme genes undergo upregulation of expression in non-neural diabetic tissues and in endothelial cells cultured in high glucose (Ceriello et al. 1996 Khanna et al. 1996 Reddi and Bollineni 1997). This increase of gene expression could reflect an effort to mount an adaptive response to hyperglycemia-mediated oxidative stress and resultant nonenzymatic protein glycation or other free-radical-mediated damage, which causes inactivation of the existing antioxi-dant enzyme population.

Accelerated Atherosclerosis

Essentially the same nutritional approaches to the prevention of atherosclerosis apply whether or not a person has diabetes. However, they are even more important for the patient with diabetes since hyper-glycemia is a risk factor, and most people with diabetes die of atherosclerotic cardiovascular disease. Therefore, anyone with diabetes should follow a 'heart healthy' diet that focuses on lowering low-density lipoprotein (LDL) cholesterol level, which is a major contributor to the progression of atherosclerosis. Total fat intake can be held to 25-35 of total calories, less than 7 saturated fat and the remainder divided between monounsaturated fat and polyunsaturated fats. The recommendation allows for increased intake of unsaturated fats in place of carbohydrates in people with diabetes. In addition to the antiatherosclerotic diet, there should be routine screening for other specific risk factors, notably hypertension and dyslipidemia. If found, these risk factors, which are even...

Counterregulatory Hormones

The response to cellular starvation seen with insulin insufficiency is increased levels of glucagon, catecholamines, cortisone, and growth hormone. Glucagon is the primary counterregulatory hormone. The catabolic effects of these hormones includes increased gluconeogenesis and glycogenolysis, breakdown of fats into free fatty acids and glycerol, and proteolysis with increased levels of amino acids. Increased levels of glucogenic precursors, such as glycerol and amino acids, facilitate gluconeogenesis, worsening hyperglycemia. Free fatty acids released in the periphery are bound to albumin and transported to the liver where they undergo conversion to ketone bodies. The primary ketone bodies b-hydroxybutyric acid (bHB) and acetoacetic acid (AcAc) account for the metabolic acidosis seen in DKA. The two are in equilibrium AcAc + NaDh 2 bHB + NAD. AcAc is metabolized to acetone, another major ketone body. Depletion of baseline hepatic glycogen stores tends to favor ketogenesis. Low insulin...

Definition and Impact of Glucose Tolerance

A most important factor underlying the morbidity in diabetes, its complications and concurrent cardiovascular diseases, is hyperglycemia. Importantly, even at such a low degree as not to reach the limit criteria for diabetes, hyperglycemia is related to morbidity. Lifestyle changes and pharmacological interventions to reduce or even normalize the hyper-glycemia exist, and consistent adherence to such regimen will reduce the morbidity. However, hyper-glycemia is initially without symptoms and therefore usually remains undetected for a long period of time. Therefore, it is important to have reliable methods for the detection of hyperglycemia in its initial stages for proper actions to be taken. Such detection relies on analysis of the circulating glucose in the fasting state or after a challenge. Thus, it is important to recognize that hyperglycemia is subdivided into two different entities. The first entity is fasting hyperglycemia. This is mainly due to inappropriately high release of...

TABLE 1043 Treatment Regimens for Vulvovaginal Candidiasis

Self-medication should only be advised in women with previously diagnosed VVC and recurrence of similar symptoms. If symptoms persist or recur within 2 months, the patient should be seen so that vaginal and microscopic examinations can be performed. Cultures should be considered for patients with frequent recurrences. All possible precipitating factors, such as high blood glucose levels, should be controlled. However, the majority of women with recurrences do not have obvious precipitating causes.

Laboratory Assessment

Leukocytosis and hyperglycemia have also been examined for their ability to predict iron toxicity. One early study found that a white blood cell count (WBC) of greater than 15,000 pL with glucose level of greater than 150 mg dL correlated with an iron level of more than 300 pg dL. 7 This study, however, assumed that a serum iron level of greater than 300 pg dL denoted toxicity, which is not true in all cases. Subsequent studies were unable to validate the association between these laboratory values and also did not correlate these laboratory values with clinical illness. 89

Complications And Mortality

The development of cerebral edema during the treatment of DKA, especially in young patients, is a potentially catastrophic complication. 13 Cerebral edema tends to occur during the first 24 h of therapy when the patient appears to be improving clinically and biochemically. 8 The true incidence of clinically apparent cerebral edema is unknown, but estimated to be 0.7 to 1.0 per 100 episodes of DKA in children.8 Cerebral edema complicating DKA has a reported mortality of 70 percent. One hypothesis is that the osmotic diuresis promotes loss of water and sodium from both intra- and extracellular spaces. Hyperglycemia leads to a hyperosmolar extracellular state. Brain cells enzymatically produce osmotically active particles, or idiogenic osmoles that protect cells from further loss of water and shrinkage. During therapy with intravenous fluid and insulin, water moves into brain cells faster then idiogenic osmoles can dissipate, promoting cellular swelling. 814 Subclinical brain swelling...

Pathophysiology And Pharmacology

Intracellular calcium is the primary stimulus for smooth and cardiac muscle contraction and for impulse formation in sinoatrial pacemaker cells. At therapeutic concentrations, organic CCBs bind to the alpha subunit of the L-type calcium channel, causing the channel to favor the closed state and thereby decreasing calcium entry during phase II depolarization. At very high concentrations, some CCBs (verapamil) may occupy the channel canal and completely block calcium entry through the L-channel. The result is profound smooth muscle relaxation, weakened cardiac contraction, and blunted cardiac automaticity. Clinically, these effects are recognized as hypotension and bradycardia. When circulatory shock supervenes with severe overdose, lactic acidosis and hyperglycemia are common manifestations. Hyperglycemia results from a suppressive effect of CCBs on pancreatic beta-cell insulin release, together with whole-body insulin resistance. 23 Severe poisoning also can cause hyperkalemia, which...

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.

Nutritional Support of Bone Marrow Transplant Patients

A review found that although EN is the current standard for nutritional support, it has not found favor for patients undergoing bone marrow transplant because these patients have severe mucositis, often vomit the tube, and do not tolerate nasogas-tric tubes because of discomfort and ulceration. Veno-occlusive disease with encephalopathy may occur in bone marrow patients, which is another indication for TPN with branched-chain amino acids rather than EN. A controlled trial of EN versus TPN in bone marrow transplant patients showed that outcome was no different but body composition and magnesium levels were better maintained on TPN. In contrast, TPN patients had more fluid overload and hyperglycemia. It should be noted that 'enteral nutrition' in this trial was not tube feeding but a combination of snacks, diet counseling, and tube feeding. The authors concluded that TPN should be reserved for patients with severe mucositis. Review of the Cochrane

Neuropeptide Y Receptors

Neuropeptide Y (NPY) is a 36 amino acid neuropeptide that is widely distributed in both the central and peripheral nervous systems. NPY is a member of the pancreatic poly-peptide family, which also includes the structurally related peptides peptide YY (PYY) and pancreatic polypeptide (PP). Neurons containing NPY typically coexpress and cosecrete classical neurotransmitters and or other neuropeptides (e.g., norepinephrine, g-aminobutyric acid, somatostatin, corticotrophin releasing hormone) hence, NPY probably acts in concert with other neurotransmitters and neuro-peptides in either a cotransmitter or modulatory role. As expected from its ubiquitous distribution and colocalization with other neurotransmitters and neuropeptides, NPY has been implicated in a wide variety of physiological effects, including the regulation of body weight, neuronal excitability, circadian rhythms, mood, ethanol consumption, nociception, cognition, endocrine function, cardiovascular function,...

TABLE 1702 Key Diagnostic Features of Calcium Channel Antagonist Overdose

Other clinical manifestations of CCB toxicity stem from multiorgan hypoperfusion and inhibition of metabolic processes and may indicate impending severe shock. Physical examination (and intuition) may provide the best initial evidence of incipient severe toxicity. Most patients with significant toxicity are drowsy and asthenic. However, muscular weakness does not occur from a direct effect of CCBs on skeletal muscle excitation contraction even with massive overdoses. Mydriasis is not a key feature of CCB poisoning, although some patients do exhibit dilated pupils. Mental function is often altered, with behavior ranging from agitation to coma. Noncardiogenic pulmonary edema is sometimes seen. Hypoxemia also has been reported, presumably from intrapulmonary ventilation-perfusion mismatch. Metabolic (lactic) acidosis with hyperglycemia is described in multiple case reports and in laboratory reports. Hypokalemia is observed frequently but carries little prognostic meaning. However,...

Evidence of the Benefits of Enteral Nutrition

EN has not been compared to standard care (SC) in the same systematic way as PN. Systematic reviews of EN compared to PN have consistently shown increased infectious complications with PN. However, all showed significantly elevated blood glucose in the PN group. It is likely that hyperglycemia was more frequent with PN because patients randomized to PN received more energy than those on EN, despite the intent to make both groups isocaloric. Data from a large controlled trial in intensive care unit (ICU) patients showed that keeping blood glucose below 7mmol l irrespective of the route of feeding significantly reduced mortality and multisystem organ failure arising from sepsis. This study indicated that hyperglycemia in the PN arm of the study would have significantly increased the risk of sepsis. None of these studies prove that EN is better than standard therapy they show that it is less likely to cause infection than PN given without regard to the rigid control of blood glucose....

Lipolysis in adipose tissue5 Clinical Features

Ihe typical patient with HHNS is usually elderly, who is often referred by a caretaker for abnormalities in vital signs and or mental status with complaints which include weakness, anorexia, or fatigue. Many will have either undiagnosed or poorly controlled type 2 diabetes. Ihese patients often have some level of baseline cognitive impairment, and self-referral for medical treatment is rare. In general, any patient with hyperglycemia, an impaired means of communication, and limited access to unassisted free water intake is at risk for HHNS. Ihe presence of renal insufficiency or cardiovascular disease is common to this patient population. Ihe medications such as diuretics that are commonly used to treat these underlying chronic problems, predisposes to the development of HHNS. Usually some precipitating event causes a patient to develop an insidious state of progressive hyperglycemia and hyperosmolarity, which goes unchecked. By far, acute infection is the most common precipitating...

Introduction And Definitions

Diabetes mellitus is a group of metabolic diseases characterized by high blood sugar or hyperglycemia. Chronic hyperglycemia results from defects in insulin secretion from the pancreas and or insufficient insulin action in muscle and adipose tissue. Diabetes is characterized by both under- and over-secretion of insulin, the hormone that transports glucose across cell membranes. Diabetes is associated with long-term damage and dysfunction of the pancreas, eyes, kidneys, nerves, heart, and large and small blood vessels (American Diabetes Association ADA , 2002a Harris, 1995).

Individuals with chronic disease

Diabetes leads to susceptibility to infection in later stages of the disease because of persistent hyperglycemia (Umpierrez and Kitabchi, 2003 Maldonado et al., 2004) or loss of microcirculation efficiency (Dinh and Veves, 2005). Salmonella (Acheson and Hohmann, 2001), Listeria monocytogenes (Nolla-Salas et al., 2002 Chougle and Narayanaswamy, 2004) and Toxoplasma gondii (Yamamoto et al., 2003) have been isolated from infected tissues of patients with advanced diabetes. Elderly who are diabetic are especially prone to infections in general (Rajagopalan, 2005), which may include foodborne infections.

Skin and Soft Tissue Complications

Several cutaneous disorders and infections are more common in diabetics (Iable,,2.09-8). Serious infections usually develop due to the combination of poorly controlled serum glucose, vascular insufficiency, and tissue hypoxia. These infections may spread rapidly with dramatic skin changes. The most common sites are lower extremities, but such infections may occur on the peritoneum, scrotum, and abdominal wall (especially at sites of penetrating trauma or surgery). They all require emergent, aggressive medical and surgical treatment. Hemodynamic support and correction of ketoacidosis and or hyperglycemia is often required.

Initial and Preoperative Management

Anemia should be corrected to a hemoglobin greater than 10 g dl. Coagulopathy (raised international normalized ratio INR , PT and PTT, or platelets < 100,000) should be diagnosed preoperatively and platelets should be given intraoperatively if the patient is severely thrombocytopenic. Diabetic patients usually have severe hyperglycemia, which should be corrected with a glucose-insulin sliding scale. Electrolyte abnormalities must be corrected as far as possible, without incurring unnecessary delay of surgical debride-ment.

Adrenergic Agents

The most common side effect of b-adrenergic drugs is skeletal muscle tremor. Patients may also experience nervousness, anxiety, insomnia, headache, hyperglycemia, palpitations, tachycardia, and hypertension. Despite earlier concerns over potential cardiotoxicity, especially when these drugs were used in combination with theophylline, clinical experience has not revealed significant problems. Arrhythmias and evidence of myocardial ischemia are rare, especially in patients without prior history of coronary artery disease.

Maternal Nutrition

Prolonged starvation, as well as nutritional deprivation in experimental animals, indicate that even severe limitations in maternal nutrition only limit fetal growth by 10-20 . Restriction of caloric and protein intakes to less than 50 of normal for a considerable portion of gestation are needed before marked reductions in fetal growth are observed such severe conditions often result in fetal loss before the impact on late gestation fetal growth rate and fetal size at birth are manifested. Similarly, fetal macrosomia is only common in pregnancies complicated by gestational diabetes mellitus in which maternal plasma hyperglycemia and hypertri-glyceridemia, plus fetal hyperinsulinemia, combine to produce excessive fetal adiposity.

Islet pathology

The DP-BB rat and the NOD mouse have many features that make them advantageous models of human autoimmune diabetes (Table 1). These models develop diabetes spontaneously their symptoms characterized by hyperglycemia, glucosuria, keto-nuria, polyuria, polydipsia, weight loss and death if insulin is not administered. In the BB rat, mononuclear cell infiltration, known as insulitis, of the pancreatic islets usually occurs at an age of 60-120 days in both males and females and lymphocytes are scattered throughout the islets. In contrast, lymphocytes are detected in the peri-islets at 4 weeks of age in the NOD mouse and these mononuclear cells appear to migrate toward the islets as the NOD mouse matures. Diabetes develops at 120-200 days of age in the NOD mouse. Insulitis often precedes or accompanies the onset of hyperglycemia in these animal models. The progressive and selective loss of pancreatic (3 cells is an important characteristic of IDDM. This destructive process excludes other...

Therapy

Because the ultimate extent of injury observed following ischemia largely reflects damage incurred during reperfusion (reperfusion injury), effective therapy must not only limit ongoing mechanisms of damage but also facilitate repair of the damage that has already occurred. Optimum therapy to obviate continuing injury and salvage viable brain tissue is unknown.16 Most therapeutic studies use animal models, use pretreatment, or contain small numbers of patients. However, a few general principles can be stated. Perfusion should be maintained at normal levels. It does not appear that intracranial pressure is increased in the postresuscitation period, and therefore therapies directed at increased intracranial pressure (hyperventilation and osmotic agents) are unnecessary. Hypotension should be avoided for obvious reasons. Oxygenation should be maintained at or near normal levels. Hyperoxia should be avoided, since it is toxic to the lungs and may increase brain damage. Prearrest...

Thiazolidinediones

Troglitazone, a thiazolidinedione, offers the theoretical advantage of reducing hyperglycemia without increasing insulin secretion. Troglitazone effectively reduces plasma glucose concentrations both when given alone and in combination with either a sulfonylurea or insulin. 10 Troglitazone reduces insulin resistance as well as decreasing endogenous glucose production, and its effects are evident in both the liver and the skeletal muscle. Troglitazone exerts its antihyperglycemic effect only in the presence of insulin and does not cause hypoglycemia in nondiabetics. Troglitazone has been demonstrated to improve glycemic control in patients with type 2 diabetes mellitus.11

Endocrine System

Pregnancy-related hormonal changes and feedback mechanism adjustments are incompletely understood. Characteristic changes in carbohydrate metabolism lead to hyperinsulinemia and fasting hypoglycemia. The altered response to glucose ingestion produces postprandial hyperglycemia and ensures a sustained glucose supply to the fetus. Mineral (especially iron), protein, and fat metabolism are also changed. Thyroid alterations include increased vascularity and mild hyperplasia, but clinically detectable goiter is not a normal finding in pregnancy. To assess thyroid function during pregnancy, free thyroxine and thyroid-stimulating-hormone concentrations should be measured, since they are not affected by physiologic changes of normal pregnancy.

Laboratory

Total body potassium is depleted by renal losses. However, measured serum potassium is normal or elevated in most patients 10 because of two important factors extracellular shift of potassium secondary to acidemia and increased intravascular osmolarity caused by hyperglycemia. 11 Prerenal azotemia also contributes by interfering with kaliuresis. Osmotic diuresis leads to excessive renal losses of sodium chloride in the urine. However, the presence of hyperglycemia tends to artificially lower the serum sodium levels. The standard correction is by adding 1.6 meq to the reported sodium value for every 100 mg of glucose over 100 mg dL. Osmotic diuresis also causes urinary losses and total body depletion of phosphorous, calcium, and magnesium. Be aware that hemoconcentration frequently leads to initial artificially elevated levels. As therapy progresses lower serum levels of each will be evident.

Physical Findings

Ihe physical manifestations associated with HHNS are nonspecific. Generally, clinical signs of volume depletion such as poor skin turgor, dry mucous membranes, sunken eyeballs, and orthostatic hypotension, will correlate with degree of hyperglycemia and hyperosmolality and duration of physiologic imbalance. Other central nervous system (CNS) symptoms may include tremor, clonus, hyperreflexia or hyporeflexia, a positive plantar response, reversible hemiplegia, or hemisensory defects (without CVA or structural intracerebral lesion). Ihe degree of lethargy and coma is proportional to the level of osmolality. 78 Ihose with coma tend to have higher osmolarity, hyperglycemia, and greater volume contraction. In view of the age of the patient population, it is not surprising that the misdiagnosis of stroke or organic brain disease is common.

Diabetes Mellitus

Hyperglycemia Clin.ic.al . .Features Diagnosis, .oLUMerlyingL Causes Therapy Chronic .Therap.y for Hyperglycemia Complications.oi .Diabetes Mellitus Cardiovascular. Complications Diabetes mellitus is a group of metabolic diseases characterized by deficiency of insulin production, deficiency of insulin action, or a combination of the two deficiencies resulting in hyperglycemia. Chronic hyperglycemia is a final common pathway leading to long-term complications involving the eye, the nervous system, the kidneys, and the immune system that collectively can be grouped as microvascular complications. These complications are leading causes of blindness, chronic renal failure, and lower extremity amputation. Diabetes mellitus also predisposes individuals to accelerated atherogenesis, and the resultant hypertension leads to macrovascular complications of atherosclerotic cardiovascular, cerebrovascular, and peripheral vascular disease. Emergency physicians are frequently called on to...

Nephropathy

Diabetic nephropathy is one of the leading causes of end-stage renal disease. Approximately one-third of new cases of renal failure each year are due to diabetic nephropathy. Incidence approaches 40 percent lifetime in type 1 diabetes and 4 to 20 percent in type 2 diabetes. Since the overwhelming majority of diabetics are type 2, most patients with nephropathy will have this form of the disease. Hyperglycemia leads to glomerular hypertension and hyperfiltration, which in turn lead to deposition of protein in the mesangium. These protein deposits ultimately lead to sclerosis of the glomerulus and to renal failure. Intensive insulin therapy as practiced in the DCCT reduced by 60 percent the frequency of microalbuminuria, the clinical herald of diabetic nephropathy. In addition to being a marker for nephropathy, albuminuria has also been shown to correlate with high risk for coronary ischemic events. Angiotensin-converting enzyme (ACE) inhibitors have been shown to delay both the onset...

Cyclic PN

PN therapy may be infused continuously 24-h daily, or the same volume may be infused over a shorter period of time, such as a cycle of 12-h PN infusion and 12-h free of infusion. Infusion pumps can be programmed to adjust infusion rates according to the desired volumes and administration times. Continuous infusion is generally selected when PN is first initiated for an acutely ill patient. Benefits for a cyclic total PN regimen are particularly notable for long-term patients. A cycled PN regimen allows more mobility for the patient, thus enabling the patient to achieve a more active lifestyle. Limitations to a cycled PN regimen include fluid intolerance or glucose intolerance. When initiating a PN cycle, blood glucose concentrations should be checked to ensure that hyperglycemia or hypoglycemia is not an issue for the patient. Because of the potential for 'rebound hypoglycemia' upon abrupt cessation of infusion,