Home Remedies for Hyperglycemia

Blood Sugar Miracle

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Increased Oxidative Load in Diabetes the Role of Hyperglycemia

Chronic hyperglycemia can also promote oxidative stress through interference with antioxidant defense systems. Diabetic individuals, especially those who are poorly controlled, are likely to develop multiple micronutrient deficiencies some of which have antioxidant activities 3, 11 . Of all the potential antioxidant deficiencies, depletion of the intracellular content of ascorbate can occur because of direct inhibition of the cellular uptake of dehydroascor-bate by glucose 12 . Nevertheless, the effect of uncontrolled hyperglycemia on antioxidant defense capacity extends beyond individually known micronu-trients 13 . The precise metabolic pathway by which hyperglycemia reduces the antioxidative defense capacity is not completely clear, but appears to be at least partly secondary to overconsumption of antioxidants in the presence of increased production of ROS.

Hyperglycemia in the critically ill

Hyperglycemia can be either the primary problem, as in diabetic emergencies, or a result of other processes, such as hyperglycemia secondary to sepsis. Diabetic emergencies Diabetic ketoacidosis hyperglycemia, acidosis, and ketosis. The pathophysiology results in the clinical picture of hyperglycemia, acidosis, dehydration, polyuria, polydipsia, and electrolyte disturbance. Hyperosmolar non-ketotic coma hence ketone body production, but not enough to prevent hyperglycemia ( Cefaju 1991). Hyperosmolarity may also inhibit lipolysis. Patients with hyperosmolar


Firmed previous studies demonstrating glycemic control to be the most important predictor for the development and severity of complications in T1DM. In patients with T1DM more severe endothelial dysfunction is present when they have poor glycemic control compared with patients with better glycosylated hemoglobin. There is evidence that vasodilatation mediated by endothelium-derived NO is altered in patients with both T1DM and T2DM DM. Moreover, impaired NO-mediated vasodilatation during acute hyperglycemia has been documented in nondiabetic humans. Other studies, however, were not able to demonstrate a correlation between HbA1c values and degree of endothelium-dependent vasodilatation.

General brainoriented life support

Minimizing arrest (no-flow) time and external cardiopulmonary resuscitation (low-flow) time with emergency control of airway, pulmonary oxygenation and ventilation, and high or normal perfusion pressures are basic requirements for cerebral recovery. This requires the earliest possible restoration of spontaneous circulation since the hypotension and hypoperfusion produced by standard external cardiopulmonary resuscitation is inadequate for cerebral resuscitation as the injured brain is very vulnerable. Therefore even mild postarrest hypotension, hypoxemia, and hyperthermia must be avoided. A spontaneous or induced hypertensive bout during or immediately after restoration of spontaneous circulation is associated with better cerebral outcome in dogs and humans. Titrated high-dose epinephrine (adrenaline) during cardiopulmonary resuscitation increases the chance of restoration of spontaneous circulation and of a spontaneous hypertensive bout. If it does not occur spontaneously, we...

Adipose tissuederived proteins

Resistin was identified in 2001 (Steppan et al. 2001), and rodent studies confirmed its adipose tissue-specific expression. Circulating resistin is increased in obese rodents (Rajala et al. 2004) and it appears to increase insulin resistance (Steppan et al. 2001 Banerjee and Lazar 2003). Mice lacking resistin have similar body weight as wild-type mice, but they exhibit lower blood glucose levels after fasting, due to reduced hepatic glucose production (Banerjee et al. 2004). Recently, Graveleau et al. (2005) demonstrated that resistin directly impaired glucose transport in primary mouse cardiomyocytes. All these findings suggest that resistin contributes to the development of insulin resistance in obese rodents. Nevertheless, whether resistin also plays a role in human obesity and diabetes is still unclear (Banerjee and Lazar 2003).

Neurosurgical Intensive Care

In patients with severe head injury and stroke, as well as SAH, the presence of hyperglycemia is associated with a poor prognosis. Although stress is clearly a contributing factor, hyperglycemia itself can contribute to poor outcome. Thus hyperglycemia should be treated vigorously.

With Type 1 Diabetes Mellitus

Currently, the prevalence of Type 1 diabetes in the United States is estimated to be 1,000,000 individuals, and 30,000 new cases are diagnosed each year. Presently there is no practical mechanical insulin-delivery method coupled with an effective glucose-sensory device that could replace the function of the impaired cells to administer insulin with a degree of control to produce a near constant euglycemic state without risk of hypoglycemia. Therefore, persons with Type 1 diabetes are resigned to manually regulate blood glucose levels by subcutaneous insulin injection, and as a consequence, typically exhibit wide deviations of plasma glucose levels from hour to hour and from day to day. Since hypoglycemia is intolerable, glucose control must error on the high side and patients live with relative chronic hyperglycemia as evidenced by elevated HgbA1c levels. Hyperglycemia is the most important factor in the development and progression of the secondary complications of diabetes. These...

Importance of Glycemic Control in Diabetes

Recently the American Diabetes Association (ADA) stated that the 'regulation of blood glucose to achieve near-normal levels is a primary goal in the management of diabetes, and, thus, dietary techniques that limit hyper-glycemia following a meal are likely important in limiting the complications of diabetes' 29 . The ADA added that 'a recent analysis of the randomized controlled trials that have examined the efficacy of the glycemic index on overall blood glucose control indicates that the use of this technique can provide an additional benefit over that observed when total carbohydrate is considered alone' 29 . However, with reference to the glycemic index, the ADA concluded that 'the relationship between glycemic index and glycemic load and the development of type-2 diabetes remains unclear at this time' 29 . So while there is general agreement on the importance of glycemic control in controlling diabetes and preventing its associated complications and some recognition of the...

Pathophysiology of remote organ dysfunction

Metabolic sequelae include an increase in resting energy expenditure averaging 125 per cent of predicted values, elevated protein catabolism, unsuppressed hepatic gluconeogenesis, and peripheral insulin resistance. Hepatic and peripheral insulin resistance, b-cell dysfunction, and hyperglucagonemia result in hyperglycemia. Diabetic ketoacidosis or non-acidotic diabetic coma may be presenting features, particularly in patients with hyperlipidemia. Hypocalcemia and hypertriglyceridemia are also seen.

Side Effects And Dosimetric Considerations

Other side effects may arise from allergic reactions to the contrast medium or local anesthetics, thrombosis as a result of immobilization, or flush symptoms or hyperglycemia in diabetic patients owing to systemic resorption of the intra-articularly applied steroids. In diabetic patients, the dose of intra-articular steroids may be reduced, and the patients should be instructed to regularly check their blood glucose levels for the next two days. In patients with a history of thrombosis or other disorders with an increased risk of blood clotting, antithrombotic measures are recommended and the patients should be carefully instructed to watch for any signs of thrombosis after treatment and immobilization of joints of the lower limbs.

Human growth hormone in critical illness

Human growth hormone is a 191-amino-acid protein produced by the anterior pituitary. Its effects can be summarized as a protein-sparing effect which protects lean body mass, a reduction in body fat (lipolysis), improvement in immunocompetence, sodium and water retention, hyperglycemia, and (potentially) increased incidence of neoplasia.

Local Complications After Radiation Synovectomy

Radiation exposure and future malignancy Other risks associated with the procedure are allergic reactions to contrast medium and local anesthetics, hyperglycemia in diabetic patients and flush symptoms from steroids, thyreotoxicosis as a result of iodine-containing contrast medium, and thrombosis due to immobilization Patients should be advised to report any worsening or other uncommon changes in the treated joint, and the patient should be given a contact he can reach at any time

Insulin administration and adjuvant therapies

Insulin is useful for controlling and avoiding hyperglycemia. If it is added to the parenteral nutrition bag, the suggested intake ranges from 1 IU per 10 g glucose in malnourished minimally stressed patients to 1 IU per 4 to 5 g of glucose in severely catabolic patients. When resistance is severe, it is safer to administer insulin (1-3 IU h) with a syringe pump. Several anabolic agents are effective in, or should improve the efficacy of, the conventional nutritional-metabolic approach to protein metabolism in stress conditions. Hormones like insulin, growth hormone, and insulin-like growth factors are particularly promising ( Wllmoie nd Carp ntjer 1994.).

Observed in Certain Categories of Patients

It should be firmly stressed that none of the clinicians convinced by the practical utility of the above concept are claiming that it is the only way to improve metabolic control. Rather, most of us consider the use of low GI foods as only part of a more general strategy to correct abnormal postprandial hyperglycemia where all the means should be considered as not excluding each other.

Prevention of complications of acute renal failure

In many critically ill patients with ARF, appropriate nutritional support is unnecessarily withheld because of the fear of inducing fluid overload, hyperglycemia which is difficult to control, and rapidly deteriorating uremia. Because of such medical management and the common presence of hypercatabolism in these patients, malnutrition becomes another complication of ARF. Once again the early application of adequate renal replacement therapy is the best form of prevention.

Mechanism of Action

Liver dysfunction (especially at high doses), decreased glucose tolerance, hyperglycemia, and hyperuricemia. Thus, it is contraindicated in patients with hepatic dysfunction, peptic ulcer, hyperuricemia, or diabetes melli-tus. A paradox associated with nicotinic acid is that it is the most widely available hypolipidemic drug (it is sold over the counter), yet its use requires the closest management by the physician.

Neuroendocrine and metabolic effects

The neuroendocrine stress response after painful trauma is characterized by an increased secretion of catabolic hormones (ACTH, cortisol, glucagon, catecholamines) and a decreased secretion of anabolic hormones (insulin, testosterone, growth hormone). This results in hypermetabolism and release of substrates (glucose, amino acids, fat) from peripheral stores (muscle, fat tissue, liver). Hyperglycemia, increased protein breakdown, and a negative nitrogen balance are the consequences. In addition, the release of aldosterone and vasopressin is enhanced and results in sodium and water retention. Nociceptive impulses from the injured area contribute significantly to the initiation and maintainance of these effects, since regional anesthesia can potently reduce the stress response ( Keh.le.t.,,1 9.9.3). Other factors such as cell breakdown products or inflammatory mediators also play a role. Stress-induced activation of the hypothalamopituitary axis may cause suppression of immune functions...

Management Of Hypotension

Neurogenic diabetes insipidus is characterized by polyuria, hyperosmolality with a serum osmolarity greater than 295, a urine osmolarity less than 300 mOsm L and a urine specific gravity less than 1.005. Treatment requires aggressive replacement of urinary output for the previous hour together with hourly maintenance infusions. If urine output exceeds 400 mL h and is not related to diuretic administration, fluid loading, inotropes or hyperglycemia, pharmacologic treatment is required with antidiuretic hormone. If not treated or treated inadequately, diabetes insipidus will result in further metabolic derangements of hypernatremia, hypokalemia, hypomagnesemia and hypocalcemia. Norepinephrine (Levophed) is identical to the endogenous catecholamine which is synthesized in the adrenal medulla and in sympathetic nervous tissue. It acts predominately by a direct effect on alpha-adrenergic receptors increasing total peripheral resistance with increases in systolic and diastolic blood...

Laboratory Data

Basic metabolic panel, glucose, calcium. Electrolyte abnormalities (hypernatremia, hyponatremia, hypocalcemia) and hypoglycemia or hyperglycemia can present with headache. Metabolic acidosis may be seen with underlying metabolic disorder or intoxication respiratory acidosis is seen in other intoxications (alcohol, benzodiazepines, and barbiturates).

Intravenous nutrition

Intravenous nutrition usually includes hyperosmolar glucose solutions to supply calories. The seriously ill patient often has obligatory catabolism and fails to utilize carbohydrate calories normally. Elevation of the blood sugar level is the common sequela. Glucose solutions should not be infused at a rate that will cause blood glucose levels to exceed 12 mmol l. Intravenous nutrition should be commenced at 20 ml h of 25 per cent glucose solution for at least 4 h. If the blood sugar level remains below 12 mmol l, the rate should be increased to 40 ml h. Depending on the blood sugar, the rate can be increased to 60 and then 80 ml h. The latter rate supplies 2000 kcal day. Insulin by infusion may be needed if hyperglycemia develops when the rate of glucose infusion is less than 4 mg kg min (approximately 80 ml h of a 25 per cent glucose solution for a lean body mass of 80 kg). Glucose infusions should not exceed 4 mg kg min ( American Society for Parenteral and Enteral Nutrition 1993)....

Surgical Intervention

Results from the surgical treatment of obesity provide the most convincing evidence of the benefit of weight loss in Type 2 diabetes. The Swedish obese subjects (SOS) study is a recent prospective trial, which has demonstrated the effect of surgically induced weight loss on the incidence of diabetes mellitus (95). The intervention consists of a surgically treated group of severely obese individuals and a matched group of weight-stable obese controls. This study provides overwhelming evidence that weight loss not only helps reduce, treat and eliminate diabetes, but also that losing weight can prevent the onset of diabetes. The surgically treated patients lost an average of about 60 of their body weight, with the incidence of hyperinsulinaemia and high blood glucose significantly decreased compared with the medically treated group. For the 8 years these patients have been followed, one consistent factor has held up -weight loss maintains improvements in insulin sensitivity, helps...

Comments on the Treatment with Biphasic Premix Insulin

The explanation for the results with biphasic pre-mix insulin versus basal insulins is that both postprandial and basal glycaemia are controlled by the biphasic premix insulin. In patients with high HbA1c, basal hyperglycemia plays a greater role for the HbA1c level than in a situation with low HbA1c, where postprandial hyper-glycemia contributes more to overall glycaemic control 44 . The biphasic premix insulin analogues have an advantage over basal insulin alone because they provide the rapid-acting insulin component that covers mealtime hyper-glycaemia. Therefore, it is not surprising that the premix insulin can reduce HbA1c more than intermediate-acting or the long-acting insulin analogues. Conversely, premixed regimens are relatively inflexible with their fixed ratio between the fast- and long-acting components. They can be difficult to intensify, because of risk of hypoglycaemia and weight gain.

Clinical features

Respiratory alkalosis, metabolic acidosis, ketosis, hypoglycemia, and hyperglycemia may all occur. The biochemical pattern of a respiratory alkalosis together with metabolic acidosis is characteristic of salicylate poisoning. The patient usually presents with a combined respiratory alkalosis and metabolic acidosis, with a blood pH in the range 7.40 to 7.46. Later, as metabolic compensation fails, the arterial pH may fall below 7.40. The most important clinical signs of serious toxicity are a falling plasma pH, hypoxemia, and the development of pulmonary edema. Confusion and depressed consciousness are serious signs, usually indicating that salicylate has entered the central nervous system. These symptoms may be improved by correction of metabolic acidosis. The likelihood of respiratory alkalosis increases with age until 12 years, when the adult picture of respiratory alkalosis followed by metabolic acidosis occurs. The underlying mechanisms for these age-dependent differences in...

Comments on Treatment with Basal Bolus Regimen

It is still unknown whether it is essential to address postprandial hyperglycemia by using rapid-acting insulin before the meals to reduce the risk of a cardiovascular event and late diabetic complications. Nevertheless, in many patients, especially with a poor endogenous insulin secretion, treatment of both basal and postprandial hyperglycaemia with a basal-bolus regimen is necessary to reach a target of HbA1c less than 6.5-7.0 . The practical burden imposed by the frequency of injections and glucose testing may be taken into consideration before choosing multiple injections in a subject with type 2 diabetes mellitus.

Electrolytes urea creatinine osmolality glucose and thyroxine

Volume depletion, as indicated by elevated urea, creatinine, and sodium, is frequently present. Adrenergic overstimulation can lead to hypokalemia, while hyperkalemia together with hypocalcemia can be found secondary to rhabdomyolysis when raised serum urea and creatinine may indicate renal failure. Hyponatremia may result from excessive water drinking together with SIADH a low plasma osmolality is accompanied by concentrated urine with a high osmolality. Sympathetic overdrive will often result in hyperglycemia. Transient hyperthyroxinemia may result from heavy amphetamine abuse.

Comments on Inhaled Insulin

Glucose regulation, day-to-day variation in blood glucose control, risk of hypoglycaemia and change in weight have been the main outcome in the clinical randomised studies comparing the new and old insulin preparations. No major difference in HbA1c has been demonstrated between the analogue and human insulin-based regimens. The benefit of the long-acting analogues has been seen in relation to the reduction of risk of hypo-glycaemia and in less weight gain with insulin detemir. It is still unknown whether it is essential to address the postprandial hyperglycemia by use of rapid-acting insulin or a biphasic premix insulin analogue before the meals to reduce the risk of cardiovascular events and late diabetic complications.

The problem with tpn and bowel rest

The cornerstone of management of acute pancreatitis has been pancreatic rest, as the presence of food in the proximal gut is the most potent stimulus for trypsin synthesis and secretion, and continued trypsin synthesis can be expected to perpetuate the inflammatory response. Further studies have shown that acute pancreatitis is one of the most catabolic of illnesses 18, 19 . Consequently, the maintenance of pancreatic rest through starvation is a less than ideal option as an adequate supply of amino acids is essential for the repair process. The development of PN was heralded as a potential major breakthrough as, for the first time, feeding could be maintained without stimulating the pancreas. We, and others, have shown in human studies that PN is efficacious in meeting nutritional requirements without stimulating the pancreas 20 . Unfortunately, its use was also associated with an alarming increase in metabolic (namely, hyperglycemia) and septic complications. Indeed, one study...

Organ Specific Issues

Hyperglycemia is common in the organ donor. The etiology is multifactorial and likely due to a combination of catecholamine induced insulin resistance and rapid infusions of large volumes of glucose containing fluids. The goal of treating hyperglycemia is to minimize fluid losses secondary to the resultant obligatory osmotic diuresis. Donor hyperglycemia does not adversely affect posttransplant pancreatic allograft function and unless fluid losses are the issue, requires no treatment. As noted above, donor hyperglycemia is not a contraindication to pancreatic procurement unless the donor has a previous history of diabetes mellitus. Donor hyperamylasemia also does not preclude consideration of the pancreas. At the time of recovery, the donor surgeon must assess the pancreas for any evidence of trauma or pancreatitis. The pancreas is vulnerable to ischemia. Significant and prolonged hypotension in the donor coupled with the requirement for high dose vasopressor administration is a...

Immediate Questions

What are the vital signs Does patient have any mental status changes Children with hyperglycemia due to diabetic ketoacidosis (DKA) can have mental status changes, including coma. F. Does patient have signs of sepsis or shock Shock can result from sepsis or trauma. Patients can also develop hyperglycemia postoperatively.

Differential Diagnosis

Low or absent levels of endogenously produced insulin. New-onset and poorly controlled type 1 DM can both lead to hyperglycemia. C. Stress-Induced Hyperglycemia. Sepsis, trauma (especially head injury), and postoperative states can cause a stress reaction leading to decreased metabolism of glucose. D. TPN-Induced Hyperglycemia. Glucose is one of the major calorie sources in TPN solutions. A higher concentration of glucose is present in the solution when it is received centrally. Hyperglycemia can occur when the solution is advanced too quickly or an excessive amount is administered. E. Medications. Pulse steroids, thiazide diuretics, theophylline, and phenytoin can induce hyperglycemia. F. Factitious Hyperglycemia. Be sure the specimen was not drawn from or above an IV line that is infusing a solution that contains glucose. If in doubt, repeat the test.

Enteral feeding without pancreatic stimulation distal jejunal feeding

Activation of the ileal brake in this way may have the additional benefit of inhibiting gastric acid secretion 62 and the need for NG decompression. Finally, it must be remembered that although the glycemic response to enteral feeding is lower than that to PN 29 , hyperglycemia can still occur due to islet cell damage, and that the more effective the mode of enteral feeding, the greater the risk of hyperglycemia. Consequently, all forms of feeding must be closely monitored, with judicious use of insulin to control hyperglycemia.

Pathophysiology of Diabetes

Type-2 diabetes is characterised by a combination of insulin resistance and defective insulin response that results from it 21 . Blood insulin concentrations are raised, at least initially, but are never sufficient to meet the resistance that entrains them. Like type-1, type-2 diabetes also presents after a variable period of prediabetes, whose presence might be revealed by high fasting insulin glucose ratios and later by glycosuria or hyperglycemia in circumstances which temporarily increase insulin resistance - typically pregnancy, thyrotoxicosis or a course of anti-inflammatory steroids. Between 17 and 63 of women whose glycosuria during pregnancy is attributable to glucose intolerance will subsequently become diabetic, depending on the series quoted 22 . Of these, a proportion (around 20 according to one study 23 ) will develop type-1 diabetes, underscoring the principle to be established here that the prediabetes of type 1 and type 2 differs only in tempo, not in outcome. Both...

Good Glycaemic Control Improves Prognosis

Good glycaemic control as indicated by near-normal HbA1c levels has been shown to reduce the risk of developing microvascular complications in both Type 1 and Type 2 diabetes (2,3). In addition, there is increasing evidence that it also reduces the development and progression of macrovascular disease (1,4,5). People with diabetes are two to four times more likely to die of coronary heart disease than people without diabetes, even when total cholesterol level and blood pressure are the same. Thus, preventing the excess cardiovascular morbidity and mortality associated with diabetes is arguably the most pressing treatment goal. However, this does not mean that normalising blood lipid or clotting factors is more important than normalising blood glucose. Indeed, high blood glucose levels are now recognised to contribute directly to the pathogenesis of macrovascular disease in both diabetic and non-diabetic subjects (6,7).

Trace Elements That Have Recommended Daily Dietary Allowances

Chromium plays a pivotal role in all macronutrient (protein, carbohydrate, and lipid) metabolism. It is, however, crucial in the synthesis of glucose tolerance factor (GTF), a cofactor in insulin action. Trivalent chromium is an essential nutrient and has a key role in lipid and glucose metabolism. Supplementation with chromium does not appear to reduce glucose levels in euglycemia. It may, however, have some efficacy in reducing glucose levels in hyperglycemia. The effects of chromium on lipid levels are variable. Chromium in doses less than 1000 mcg or 1 mg d appear to be safe for short-term administration to type 2 diabetic patients.69

Ts and Microcirculatory Flow Alterations

Hemodynamic alterations in diabetes are believed to arise as a result of hyperglycemia-induced metabolic abnormalities and elaboration of vasoactive factors including ETs. There is great heterogeneity in findings from microcirculation studies in humans. Study of nailfold microcirculation has revealed elevated as well as reduced blood velocity in diabetic patients when compared to healthy subjects. Reduced blood velocity has also been observed in gastric mucosal blood flow studies. Much of the inconsistency in such studies can be attributed to duration of diabetes, interstudy variability, and limitations of techniques used for measurement of blood flow.

Ts in Organ Specific Microvascular Alterations in Diabetes

Diabetic retinopathy (DR) predominantly affects the vascular components of the retina. Early in the disease course, diabetes causes functional alterations such as reduced retinal blood flow 2 . With sustained hyperglycemia structural changes such as capillary BM thickening, loss of pericytes, and breakdown of intracellular endothelial cell junctions occur. Diabetic nephropathy (DN) remains the most common cause of renal failure. Sustained hyperglycemia leads to

Lessons from Genetically Modified Diabetic Animals

A rat model of experimental diabetic retinopathy, Ang-2 is upregulated manyfold prior to the onset of pericyte dropout. The upregulation of Ang-2 persists over time, suggesting a nontransient effect of hyperglycemia on Ang-2 transcription. Confirmatory data come from a mouse model in which a reporter construct is expressed under the control of the Ang-2 promoter (Ang-2 LacZ knockin mice). Intravitreal application of Ang-2 mimics the pericyte-depleting effect of hyperglycemia without affecting retinal capillary diameters or endothelial cell survival. When Ang-2 LacZ knockin mice were maintained hyperglycemic for 6 months, they did not develop pericyte loss, as did the wild-type controls, suggesting that Ang-2 plays a significant role in the early peri-cyte loss by hyperglycemia. Preservation of pericytes in this diabetic model was accompanied by a partial reduction of acellular capillaries compared with nontransgenic diabetic mice. Pericytes partially protect endothelial cells in...

Polyol Pathway and Protein Kinase C Activation

Hyperglycemia activates the polyol pathway, resulting in the formation of sorbitol by aldose reductase. As aldose reductase utilizes NADPH for the reduction of glucose to sorbitol, cellular stores of NADPH may be depleted (55). NADPH is required for the functioning of several enzymes, such as NO, synthase for NO generation, and cytochromes P450, and for the activity of glutathione reductase that replenishes glutathione, one of the most important endogenous antioxidant systems. Increased polyol pathway activity is associated with the occurrence of long-term complications in patients with diabetes. This is demonstrated by the efficacy of aldose reductase inhibitors in the restoration of impaired endothelium-dependent vasodilatation, as well as in the prevention of diabetic neuropathy, albuminuria, and cataracts in animal models but so far not in humans.

Advanced Glycosylation End Products AGEs

Glucose binds to amino groups on proteins or to lipids, leading to the generation of weak bonds or Schiff bases by Maillard's reaction. These early nonenzymatic glycosyla-tion products are reversible and are known as Amadori products. Through several oxidative and nonoxidative reactions, including glycoxidation and auto-oxidative glycosylation, they are converted to irreversibly modified cross-linked condensation products of glucose and lysine or arginine residues, so-called advanced glycosylation end products (AGEs). AGEs formation normally occurs at a low rate during the normal aging process, whereas it is accelerated by hyperglycemia thus plasma levels of AGEs are increased in patients with T1DM and may precede the occurrence of microangiopathy. AGEs carry out their harmful effects by accumulating in tissue and generating ROS. AGEs bind to their respective cellular receptors (RAGEs), activate endothelial cells, monocytes, and mesangial cells, and increase oxidative stress. AGEs...

Posttransplant Diabetes Mellitus

Anywhere from 5-40 of recipients of renal allografts will develop posttransplant diabetes mellitus (PTDM). This hyperglycemia is generally medication-related. Corticosteroids increase gluconeogenesis, and produce end organ resistance to insulin effect. Both CsA and Tacrolimus directly inhibit islet cell release of insulin and are additive in their effect on blood glucose with corti-costeroids. It appears that increase in age, a positive family history for diabetes, and African American race all predispose to the development of PTDM. Clinically, Tacrolimus appears to produce more hyperglycemia than CsA.

Maintenance of normoglycemia

Hyperglycemia is associated with a worsened outcome after ischemic cerebral injury. In conditions of insufficient oxygen supply, cellular energy requirements may be partially met by anaerobic glycolysis which leads to an accumulation of lactic acid. Since this is virtually all ionized at physiological pH an intracellular acidosis develops, leading to deregulation of ionic membrane pumps and the formation of other mediators of neuronal injury. This intracellular acidosis is the probable mechanism of the adverse effects of hyperglycemia in brain injury, although the evidence in focal ischemia is not as clear. Thus hyperglycemia enhances injury in the ischemic core, whereas damage in the penumbra may be reduced due to collateral flow. Significant hyperglycemia (> 10 mmol l) should always be corrected with insulin infusion in neurosurgical patients. The administration of glucose-containing solutions does not produce a significant increase in blood glucose, but may predispose patients to...

Monitoring the grafted liver

Survival of the patient is dependent on normal function of the graft. Good clinical prognostic features include evidence of normal cerebral function, the production of bile from the T-tube, normal to high blood sugars, the need for intravenous potassium supplements, and a normalizing prothrombin time. Progressive organ system dysfunction in the absence of another cause indicates graft failure.

Biological Effects

Animals have developed highly adaptive and redundant mechanisms to maintain energy balance by matching caloric intake to caloric expenditure. A role for a-MSH in the regulation of energy homeostasis is suggested by several lines of evidence. Regulation of signaling by melanocortin 3 and melanocortin 4 receptors in the CNS are controlled via neuronal cell bodies in the arcuate nucleus that produce a-MSH. Increased melanocortin signaling via pharmacological or genetic means in the CNS causes potent reductions in food intake and weight loss, whereas decreased melanocortin signaling results in increased food intake and weight gain. Injection of a-MSH into the lateral ventricle of rodents leads to suppression of food intake in a dose-dependent manner. In contrast, intraventricular (icv) administration of the melanocortin agonist MTII inhibits food intake in fasted mice. Moreover, the icv injection of a pharmacological antagonist of a-MSH (SHU9119) at sites containing MC-4 receptors results...

Cardiovascular system

C, C, D This is a patient with acute hemorrhagic pancreatitis. Potential complications are hypocalcemia, hyperglycemia, ARDS, and shock. Appropriate interventions would include volume resuscitation, management of the hypocalcemia, and appropriate management of the respiratory dysfunction. Surgical exploration is not indicated at this time. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition pp. 1175-1178.)

Specialized Nutrition Support

Studies indicate EN has advantages over PN. An early meta-analysis indicated cost benefits of EN over PN 81 . Subsequent meta-analyses confirmed this economic advantage and also indicated a decreased risk of infection associated with EN in comparison to PN 64, 82 . Studies also indicate decreased intestinal permeability and lower incidence of hyperglycemia in comparison to the PN 83 . American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines recommend that perioperative EN is indicated in patients anticipated to be unable to meet nutritional needs orally for a period of 7 to 10 days whose GI tract is functional 64 .

The Use Of Antiretroviral Drugs In Pregnancy

The teratogenic risk associated with administration of antiretroviral drugs during the first trimester of pregnancy is not clear. Women who have not begun therapy prior to becoming pregnant may consider waiting until after 10 to 12 weeks' gestation to begin antiviral treatment. If a woman decides to discontinue antiretroviral therapy during pregnancy, all drugs should be stopped and reintro-duced simultaneously to avoid the development of resistance. Pregnant women may be particularly susceptible to hyperglycemia caused by protease inhibitors.

Sepsis and should be considered in all acutely sick neonates In

Most often caused by enzyme or cofactor deficiencies in the catabolism of branched chain amino acids (valine, leucine, and isoleucine). Organic acid and a positive gap acidosis develop from metabolites built up behind the enzymatic block. Other effects of metabolite excess include inhibition of enzymes of the urea cycle with secondary hyperammonemia. Many of these metabolites have direct CNS toxicity. Marrow suppression and altered glucose metabolism (hyperglycemia or hypoglycemia) also can occur as secondary effects.

Radiographic and Other Studies

With large amounts of glucose used to stop catabolism, patients may develop hyperglycemia and associated fluid losses. Hyperglycemia may be a presenting feature of some organic acidemias. To ensure that glucose given is being used to stop or prevent catabolism and promote anabolism, an insulin drip may be used. Insulin and growth hormone have both been used to promote anabolism in patients who are not responding to the usual measures.

Clinical presentation and outcome

Prominent laboratory findings include leukopenia (especially lymphopenia), thrombocytopenia and elevated liver transaminases (Tab. 3). Most pediatric patients do not manifest hemoconcentration this finding and the prominent respiratory symptoms help distinguish the illness from dengue virus infection in dengue-endemic areas. Renal failure, hyperglycemia and hemophagocytosis have been noted in some patients. Most have abnormal chest radiographs at presentation. Many patients develop complications such as respiratory failure requiring assisted ventilation, ARDS, shock and multiorgan system dysfunction. Severe infections have typically progressed rapidly, with a median duration of symptoms prior to death of 9 days (range 2-31 days). The proximate cause of death is usually respiratory failure.

How Does Triple Therapy Improve Glucose Metabolism

First of all, insulin aspart given at the initiation of the meal was in fact able to reconstruct the necessary fast and high insulin peaks compared with non-diabetic subjects (Fig. 3). This seems to be important since the insulin concentration obtained (24-h area under the curve) is much lower in triple therapy despite much lower blood glucose values. This indicates that the insulin profile is more important than the absolute amount of insulin given. We were able to measure insulin aspart with a specific antibody and thereby, for the first time in insulin-treated subjects, measure the amount of endogenous insulin

Endocrine system

D An increased anion gap (AG) is usually present with greater prerenal azotemia, and is not directly related to hyperglycemia. The shift of extracellular phosphate into the intracellular space does not occur until diabetic ketoacidosis is reversed by the administration of insulin and fluids. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition pp. 1263-1264 Adrogue H, Wilson H, Boyd A. N Engl J Med 1982 307 1603.) 5. C It is not uncommon to have hyperglycemia in association with a head-injured child. Most likely, as a result of an increase in catecholamines and corticos-teroids, there is an increase in blood sugar. Hyper-glycemia has already been shown to be associated with the degree of severity in brain injury. Some data suggests that ischemic brain injury may be worse in those patients who have hyperglycemia in their recovery phase as opposed to those patients who had normo-glycemia. Any coagulopathy that may exacerbate an ischemic picture also may worsen the...

Murine Model of Accelerated Atherosclerosis in Mice Infected with a Periodontal Pathogen

Toward that end, our laboratory employed mice deficient in apolipoprotein E (apo E null). In these animals, spontaneous atherosclerosis develops on a normal chow diet driven primarily by hypercholesterolemia. We, and others, have shown that induction of superimposed stresses, such as hyperglycemia or hyperhomocysteinemia, accelerates atherosclerosis in this model. To test the premise that oral infection may accelerate vascular inflammation and macrovascular disease, male apo E null mice were inoculated with the human periodontal pathogen Porphyromonas gingivalis, strain 381, by oral gavage and oral anal topical application, beginning at age 6 weeks. Control animals received vehicle (phosphate buffered saline PBS). In parallel with accelerated alveolar bone loss in infected mice versus those animals receiving PBS, P. gingivalis-infected mice displayed a significant 40 percent increase in atherosclerotic lesion area at the aortic root versus vehicle at age 17 weeks (Figure 1). Although...

Somatostatin Analogue

Octreotide is useful in inhibiting the secretion of various autacoids and peptide hormones by metastatic carcinoid tumors (serotonin) and islet cell carcinomas of the pancreas (gastrin, glucagon, insulin, vasoactive intestinal peptide). The diarrhea and flushing associated with the carcinoid syndrome are improved in 70 to 80 of the patients treated with octreotide. Its side effects, which are usually mild, include nausea and pain at the injection site. Mild transient hypoglycemia or hyper-glycemia may result from alterations in insulin, glucagon, or growth hormone secretion.

Chapter s nutrition and gastrointestinal system

B During hypermetabolism, which is characterized by an initial ebb phase followed by a flow phase, there is usually an associated hyperglycemia owing to decreased sensitivity to the effect of insulin, although the level of insulin may actually be higher than usual. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition pp. 1145-1148.) 17. C Acute pancreatitis is a medical condition characterized by inflammation of the pancreas with subsequent release of the enzymes amylase and lipase. The degree of serum amylase does not seem to be proportional to the severity of acute pancreatitis. Serum lipase levels seem to be elevated for a longer period of time than serum amylase. Pancreatic trypsinogen serum levels seem to rise early in the course of pancreatitis and remain elevated for up to 5 days. In a clinical situation where amylase and lipase are normal and there is a high suspicion of pancreatitis, one could look at the level of trypsinogen. Some of the bad prognostic signs...

Carbohydrate Protein and Fat Metabolism

Glucocorticoids not only break down protein but also stimulate the catabolism of lipids in adipose tissue and enhance the actions of other lipolytic agents. This occurrence results in an increase in plasma free fatty acids and an enhanced tendency to ketosis. The mechanism of this lipolytic action is unknown. The net effect of the biochemical changes induced by the glucocorti-coids is antagonism of the actions of insulin. These biochemical events promote hyperglycemia and glycosuria, which are similar to the diabetic state.

Antidiabetic Actions of GLP1

Short-term intravenous infusions of GLP-1 (approximately 1.2 pmol kg min, leading to pharmacological plasma concentrations of total GLP-1 of approximately 100 pmol L, and intact biologically active GLP-1 of approximately 15 pmol L) lower blood glucose in human subjects with type 2 diabetes through a transient glucose-dependent stimulation of insulin and suppression of glucagon secretion and gastric emptying 110-113 . A 6-week subcutaneous infusion of GLP-1 in patients with type 2 diabetes achieving plasma levels of total GLP-1 of around 65 pmol L 114 was followed by a substantial improvement in insulin secretory capacity, insulin sensitivity, a reduction in HbA1c by 1.2 , and weight loss 114 . Although intravenous or subcutaneous GLP-1 infusions may be useful for the short-term control of hyperglycemia under a variety of clinical conditions 115,116 , the long-term treatment of type 2 diabetes requires a more feasible approach for achieving sustained GLP-1 receptor activation. The...

Hyaline Replacement Amyloid of Islets of Langerhans

In animals, the vagus nerve is involved in insulin secretion 26, 27 because vagotomy is performed in most gastric operations, this may contribute to postprandial hyperglycemia. Vagotomy may alter the release of gastrointestinal peptides from the mucosa of the small intestine, which, in turn, affects absorption and glucose tolerance 24 . After total or partial gastrectomy, dumping syndrome followed by secondary hypoglycemia may occur. Early dumping syndrome is due to the rapid passage of ingested food, which causes distension of the jejunum. The rapid absorption of carbohydrate produces marked hyperglycemia, an excessive stimulus 28 that causes the islets to became hyperactive, and this, finally, results in their hyalinization.

Metabolic Disturbances And Complications Of The Diabetic State

There are only two major sources of blood glucose exogenous, or the ingestion of dietary carbohydrate, and endogenous, which is contributed by hepatic and renal gluconeogenesis and hepatic glycogenolysis. Diabetes mellitus is a metabolic disorder in which carbohydrate metabolism is reduced while that of proteins and lipids is increased. In diabetics, exogenous and endogenous glucose is not used effectively, and it accumulates in the blood (hyperglycemia). As blood glucose levels increase, the amount of glucose filtered by the glomeruli eventually exceeds the reabsorption capacity (Tm, transport maximum) of the proximal tubule cells, and glucose appears in the urine (glucosuria). Protein catabo-lism and the rate of nitrogen excretion are increased when blood insulin falls to low levels stimulation of hepatic gluconeogenesis converts amino acids to glucose. The catabolism of lipids and fatty acids is also accelerated in the absence of insulin, leading to the formation of ketone bodies,...

The Molecular Endocrinology Of Diabetes Mellitus

Diabetes mellitus is a metabolic syndrome characterized by hyperglycemia resulting from variable defects in insulin secretion and action. Traditionally, diabetes mellitus has been divided into four categories Type 1 diabetes, characterized by absolute insulin deficiency and requirement of insulin therapy to sustain life Type 2 diabetes, characterized by variable defects in insulin secretion and action, without an absolute need for insulin therapy (although insulin might be necessary for adequate control of hyperglycemia) other specific types of diabetes and gesta-tional diabetes. Type 1 diabetes is further subdivided into Type 1A, or autoimmune, diabetes and Type 1B, or idiopathic diabetes. The other category is very large, encompassing diabetes resulting from other illness or medications (such as cystic fibrosis-related diabetes) as well as many genetic syndromes that include diabetes (101). It is becoming increasingly apparent, however, that these categories are artificial and that...

Concluding Remarks

Experimental and clinical studies over the past few years indicate that ETs are of significance in several human diseases. Their predominant expression in vascular tissues and their multifunctional nature do indeed suggest that alteration of ETs may be involved in diseases affecting both the micro-and macrovasculature. In both animal and human diabetes, ETs have been shown to be upregulated. Hyperglycemia-induced biochemical anomalies such as PKC activation, nonenzymatic glycation, oxidative stress, augmented polyol pathway, and elaboration of various growth factors and cytokines may contribute to alteration of ETs. ETs, in turn, may regulate other vasoactive factors and growth factors leading to changes in both hemodynamic and structural parameters. A schematic outline of ET alteration and its consequences has been depicted in Figure 1. In support of a central role of these multifunctional peptides in diabetes-induced pathogenetic changes, it has been shown that ET-receptor...

Other Systemic Diseases and Acceleration of Microvascular Dysfunction and Atherosclerosis

What is the link to oral pathology Epidemiologic studies have strongly suggested that diabetes increases the prevalence and severity of periodontitis. Our laboratory developed a murine model with which to test these concepts. Oral anal inoculation with P gingivalis of mice rendered diabetic with streptozotocin enhanced alveolar bone loss in hyperglycemic animals, in parallel with increased expression of inflammatory and gelatinolytic mediators in the gingival tissue. Multiple pathogenic mechanisms underlie diabetes-accelerated periodontal disease, including the chronic accumulation of advanced glycation end products (AGEs), the products of nonenzymatic glycation oxidation of proteins lipids that may form in settings of hyper-glycemia, oxidant stress, and inflammation. AGEs engage a central receptor in the vasculature, receptor for AGE (RAGE). Our previous studies have shown that pharmacological blockade of this receptor, using the extracellular soluble form of RAGE, suppresses...


The cardiac toxicity is owing to massive cate-cholamine (release of epinephrine and norepinephrine) stimulation of the myocardium and is aggravated by hypokalemia, hypercalcemia, and hypophosphatemia. P-Adrenergic stimulation is responsible for the electrolyte abnormalities, acid-base disturbances, and vasodilation. Metabolic acidosis, hypokalemia, and hyperglycemia are recognized features. The hypokalemia is from a transcel-lular shift (into the skeletal muscles).

Effecs Of Irr On Wound Healing

In addition to insulin, the adipocyte-derived hormones leptin and adiponectin are involved in fatty acid metabolism, as well as the recently identified acylation-stimulating protein (ASP). Leptin directly inhibits fatty acid synthesis4445 and increases the release and oxidation of fatty acids by activating hormone-sensitive lipase.46 Leptin also has multiple additional metabolic and endocrine functions. Leptin functions in immunoregulation, inflammation, and hematopoiesis,47 and regulates food intake by communicating with the hypothalamus about the degree of fat stores and changing eating behavior accordingly to maintain a level of homeostasis.48 It may also regulate TAG homeostasis by restricting TAG storage primarily to adipocytes and sparing nonadipocytes.49 Leptin deficiency may lead to hyperglycemia, hyperinsulinemia, and insulin resistance.50 A review of the role of leptin in lipid metabolism provides more information on this topic.51 A possible role for leptin in wound healing...

Sulfonylurea Sensitivity and MODY

Group of disorders with wide variability in the severity of the hyperglycemia and the age at which it becomes clinically manifest. Several genetic subtypes of MODY have now been described, and these are all characterized by mild fasting hyperglycemia in otherwise normal individuals (Table 3) (47). Mutations in six genes have been shown to cause MODY, with two different types of monogenic mutation (48). Glucokinase MODY is caused by mutations in the gene for the glycolytic enzyme glucokinase, and transcription factor MODY is caused by mutations in transcription factors (such as hepatocyte nuclear factor genes HNF-1a, HNF-4a, and HNF-1b and insulin promoter factor-1) (49). There are clear clinical differences between these two different types of MODY, reflecting quantitative and qualitative differences in pancreatic b-cell dysfunction. Glucokinase MODY is relatively mild and characterized by nonprogressive hyperglycemia, which is caused by a stable defect and resetting of the pancreatic...

Lactic Acid and Insulin

Some natural compounds have also been reported to inhibit the cancer-promoting effects of insulin. For example, genistein inhibited insulin-induced proliferation of human breast cancer cells in vitro.132 This likely occurred via inhibition of PTK activity. In addition, some natural compounds may be able to reduce insulin production by reducing insulin resistance. Insulin resistance occurs when cells are no longer sensitive to insulin and thus more is produced in an effort to reduce blood glucose levels. Insulin resistance has been implicated as a risk factor for breast cancer.133,134,135 Diets high in omega-6 fatty acids promote insulin resistance, possibly via chronic activation of PKC.136,137,138 Natural compounds that can reduce insulin resistance include omega-3 fatty acids and other PKC inhibitors.139-142

The Natural Course of Human Diabetic Retinopathy

The two most characteristic features of incipient diabetic retinopathy are increased vascular permeability and progressive vascular occlusion. The method of retinal digest preparations, developed by Kuwabara and Cogan, allowed inspection and quantitation of changes in the affected retina liberated from neuroglial tissues due to differential susceptibility against trypsin digestion. As a result of their work and that of others presented later, pericyte loss was identified as the earliest change in the diabetic retina. With time, microvascular endothelial cell loss, in part due to programmed cell death, and progressive capillary occlusion occur. Acellular capillaries are the most significant lesions in the diabetic retina, as they (1) represent the phenotype of hyperglycemia-induced vascular cell damage, which is a general feature of diabetic complications, and (2) are the likely harbingers of all subsequent changes. Micro-aneurysms, which are the first clinically detectable lesions in...

AGlucosidase Inhibitors

The a-glucosidase inhibitors primarily act to decrease postprandial hyperglycemia by slowing the rate at which carbohydrates are absorbed from the gastrointestinal tract. They act by competitively inhibiting a-glucosi-dases, a group of enzymes in the intestinal brush border epithelial cells that includes glycoamylase, sucrase, mal-tase, and dextranase. The prolongation of the intestinal absorption of carbohydrates results in a blunted insulin response, keeping postprandial hyperglycemia under control. To be effective, a-glucosidase inhibitors must be taken before or with meals. Theoretically, the a-glucosidase inhibitors are most beneficial in patients

Carbohydrates energy metabolism and wound healing

Carbohydrates have been shown to impact wound healing in a variety of ways. Historically, carbohydrates have been viewed as an energy source for patients who are recovering from wounds. Differences have been noted in regards to carbohydrate requirements of patients who suffer from acute traumatic wounds (i.e., burns), acute iatrogenic wounds (i.e., incisions), and chronic wounds (i.e., diabetic wounds) (2). Under normal circumstances, the body increases glucose production via the liver and kidneys. This increase in gluconeogenesis is stimulated by a variety of hormones, including glucagons, epinephrine, and norepinephrine. Skin cells are glucose dependent for energy in cutaneous wound healing (3). Although adequate glucose levels are vital for wound healing, excessively high levels (hyperglycemia) have a negative impact on this process.

Linking Biochemistry to Cell Biology of Diabetic Retinopathy The Unifying Hypothesis

The Biochemistry Diabetes

The causal link between diabetes and microvascular complications is chronic hyperglycemia. Large prospective clinical studies in both type 1 and type 2 diabetics have demonstrated a strong relationship between glycemia and diabetic microvascular complications. The link between hyperglycemia and endothelial cell damage in diabetes has been intensively studied during the past 20 years. Biochemically, four independent pathways were investigated and led to the development of pharmacological inhibitors Figure 3 Biochemistry of diabetic vascular damage Mitochondrial overproduction of reactive oxygen species (mt-ROS) induces upregulation of poly(ADP-ribose)polymerase (PARP), which inhibits a central enzyme of glycolysis (GAPDH) with subsequent effects on major pathways of hyperglycemia-induced damage. The initiator of mt-ROS is increased transport of glucose into endothelial cells followed by increased flux through glycolysis and the tricarbon cycle. (From Brownlee, Claude Bernard Lecture...

Neurological Disorders and Neurodegenerative Diseases

ACTH-dependent hypersecretion of glucocorticoids induces Cushing's syndrome. Cushing's syndrome is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. The symptoms of Cushing's syndrome vary, but most people show upper body obesity, a rounded face, an increase in the neck region and thinning arms and legs. Children tend to be obese with slowed growth rates. Additional symptoms afflict the skin, which becomes fragile and thin. Most patients suffer from severe fatigue, weak muscles, high blood pressure and high blood sugar. Irritability, anxiety and depression are common.

Metabolic disorders

C With adrenocortical insufficiency, hypotension is associated with low levels of stress hormones. Thus, hypoglycemia is more of a possibility than hyper-glycemia. (DiAeage AM, Levine LS. Nelson's Textbook of Pediatrics, 15th Edition pp. 1613-1617 Kaplan SA. Clinical Pediatric Endocrinology, 1990 pp. 181-223.) 8. C Diabetic ketoacidosis in the pediatric patient is a potentially life-threatening event. Ketosis and hyperglycemia result from an imbalance of glucagon and insulin levels with an increase in catecholamines, growth hormones, and glucocorticoids. An increase in somatostatin is not associated with diabetic ketoacidosis, but it down regulates the production and release of glucagon and growth hormones. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition pp. 1261-1270 Kaplan SA. Clinical Pediatric Endocrinology, 1990 pp. 127-164.)

Mechanism of ET Alteration in Diabetes

The mechanisms by which sustained hyperglycemia leads to upregulation of ETs include activation of PKC, augmented polyol pathway and pseudohypoxia, oxidative stress, elaboration of growth factors, and alteration of vasoactive factors such as NO. Mechanisms and consequences of ET alteration in diabetes are diagrammed in Figure 1. We will briefly describe the possible mechanism by which these biochemical anomalies may lead to alteration of the ET system in diabetes. Hyperglycemia Figure 1 Putative mechanisms and consequences of ET alteration in diabetes. A schematic outlining various hyperglycemia-induced pathways leading to upregulation of endothelin levels is shown in the upper panel. Some of the major effects of increased ET levels are also presented. (see color insert) Figure 1 Putative mechanisms and consequences of ET alteration in diabetes. A schematic outlining various hyperglycemia-induced pathways leading to upregulation of endothelin levels is shown in the upper panel. Some...

Physiological factors influencing food intake

Chemoreceptors in the gastrointestinal tract detect the chemical presence of nutrients, and provide information on the composition of the foods consumed. Factors such as cholecystokinine (CCK) and glucagon-like peptide 1 (GLP-1) are released in response to the chemical presence of food in the gastrointestinal tract. CCK is a hormone released in the duodenum in response to consumption of fat (i.e. long-chain fatty acids) or protein (i.e. amino acids). GLP-1 is a hormone released in the blood by mucosal cells of the gut in response to the presence of carbohydrates and fat (Macintosh et al., 2001). CCK and GLP-1 suppress appetite by decreasing gastric emptying - by affecting the pyloric pressure, stomach motility and stomach muscle relaxation. By decreasing stomach emptying, the stomach distension increases, leading to sensations of fullness (Geliebter et al., 1988 Rolls et al., 1998). GLP-1 stimulates the islet B-cells in the pancreas to secrete insulin, thereby lowering blood glucose...

Peritraumatic and perioperative concepts of neuroprotection

Studies in laboratory animals and humans have shown that hyperglycemia is associated with worsened outcome following stroke or neurotrauma. The mechanisms by which normoglycemia may protect neuronal tissue include decreases in intracellular lactic acidosis and in membrane permeability with reduced cellular edema. Therefore plasma glucose concentration should be monitored closely and adjusted within the range of 100 to 150 g dl (5.5-8.5 mmol l).

Study of Glucose Transporters by Use of Transgenic and Knock Out Mice

The b cells of the pancreas first sense, then respond to, elevated blood glucose levels by secreting insulin. The glucose transporter in their cell membranes is GLUT 2 circumstantial evidence suggests that it may be involved in the glucose-sensing mechanism. However, studies in transgenic mice created to express a transforming ras protein in the b cells showed that these animals respond normally to a glucose load, even though their b cells do not express GLUT 2 ( 26). It is thus difficult to consider GLUT 2 part of the sensing apparatus.

P2Adrenoceptor Agonists

Ability to stimulate (2-receptors elsewhere in the body (see Chapter 2). The side effects include palpitations, tremor, nausea, vomiting, nervousness, anxiety, chest pain, shortness of breath, hyperglycemia, hypokalemia, and hypotension. Serious complications of drug therapy are pulmonary edema, cardiac insufficiency, arrhythmias, myocardial ischemia, and maternal death. Terbutaline is frequently used in the management of premature labor, although it has not been marketed for such use. Its effectiveness, side effects, precautions, and contraindications are similar to those of all ( 2-adrener-gic agonists. Terbutaline can cause tachycardia, hypotension, hyperglycemia, and hypokalemia. It can be given orally in addition to subcutaneous or intravenous administration.

Valproic Acid Sodium Valproate

Valproic acid causes hair loss in about 5 of patients, but this effect is reversible. Transient gastrointestinal effects are common, and some mild behavioral effects have been reported. Metabolic effects, including hyperglycemia, hyperglycinuria, and hyperammonemia, have been reported. An increase in body weight also has been noted. Valproic acid is not a CNS depressant, but its administration may lead to increased depression if it is used in combination with phenobarbital, primi-done, benzodiazepines, or other CNS depressant agents.

Lipid complexation with starch

Apart from lipid-starch complexation that could modify the glycemic response, several studies have shown that co-intake of fat along with carbohydrates in a mixed meal could affect postprandial glucose response. It is believed that fat may reduce postprandial glucose by decreasing the rate of gastric emptying, at least in part related to increased stimulation of the gastrointestinal hormones such as glucose-dependent insulin-releasing polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1) (Morgan, 1998). Several issues, including dosage levels of fat affecting glucose response, have been described by Owen and Wolever (2003). The authors showed that fat intake along with carbohydrates in normal healthy subjects, in a dose-dependent relationship, could decrease the glycemic response however fat consumption in a normal range (17-44 energy) does not significantly affect glycemic response. As pointed out by Owen and Wolever (2003), it is important to note that individuals with diabetes...

Current Medical Treatments For Hypertension

Attention is now paid to health-related quality of life (HR-QOL) issues in health services. The most common areas of inquiry on patient-completed questionnaires are cognitive function, symptomatic well-being, adverse effects, sexual function, psychological well-being, sleep dysfunction, social participation, and general health perception.16 A recent goal of treatment for hypertension, in addition to lowering blood pressure, is to reduce the adverse side effects of medications in order to increase patient compliance.33 Side effects include nausea, vomiting, muscle twitching, headaches, flushing, hypotension, tachycardia, aggravation of angina pectoris, hyperglycemia, renal failure, bowel and bladder paresis, blurred vision, dry mouth, bronchoconstriction, heartblock, drowsiness, and increased risk of glaucoma.15

Secretion and Action of Incretin Hormones in Physiology

GIP and GLP-1 exert their actions via engagement of structurally distinct G protein-coupled receptors. GIP receptors are predominantly expressed on islet P-cells, and to a lesser extent, in adipose tissue and in the central nervous system 50-53 . In contrast, GLP-1 receptors are expressed in pancreatic endocrine P-cells 54,55 and in several peripheral tissues including the central and peripheral nervous system, heart, kidney, lung, and the gastrointestinal tract 56,57 . Activation of both incretin receptors on P-cells leads to rapid increases in levels of cyclic AMP and intracellular calcium, followed by insulin exocytosis, in a glucose-dependent manner 58 . Incretin receptor signaling is associated with protein kinase A activation, induction of gene transcription, enhanced levels of (pro-)insulin biosynthesis 59 , and the stimulation of P-cell proliferation 60,61 . GLP-1 and GIP receptor activation protect P-cells against toxin-induced apoptosis (elicited by glucotoxicity...

Subrata Chakrabarti and JZia Ali Khan

Diabetes is the leading cause of blindness, renal failure, and limb amputation in the North American population 1, 2 . In spite of improvements in therapeutic modalities, this disorder accounts for significant morbidity and mortality in diabetic patients. Long-standing diabetes leads to structural and functional alterations in both micro- and macrovascula-ture. The most devastating complications in terms of morbidity are, however, of microvascular origin. The determinant of these complications is sustained hyper-glycemia, which leads to biochemical and structural anomalies in the eye, kidney, heart, and peripheral nerves. Microvascular endothelial damage may be a key factor in the pathogenesis of chronic diabetic complications. Endothelins, by virtue of multifunctional capability and widespread tissue distribution, may affect function and structure of microvasculature in several target organs of diabetic complications. Early events in small vessel disease include functional deficits...

Central nervous sysytem

D In experimentally induced status epilepti-cus, which is divided into phase I and phase II, it has been shown that phase I is characterized by hypertension, lactic acidosis, hyperglycemia, and hyper- or normokalemia, whereas phase II is characterized by hypoglycemia, hyperkalemia, hyperthermia, and respiratory compromise. (Lothman E. Neurology 1990 40 13.)

Ischemic Stroke And Carotid Endarterectomy

Close monitoring of fluid status, electrolytes and blood sugar is necessary in the ischemic stroke patient. Normovolemia and euglycemia is the goal, since hyperglycemia is associated with increased morbidity and mortality after stroke 14 . Maintenance of normo- or hypothermia provides brain protection, since hyperthermia can worsen outcome in cerebral ischemia 15 . Fever after a stroke is a common occurrence. Acetaminophen and cooling blankets help in reducing acute increases in temperature. An infectious source for the fever should always be sought and treated with appropriate anti-microbial agents. Fever in the chronic phase of stroke is usually the result of aspiration pneumonia or urinary tract infection 16 .

Carbohydrate requirementsenergy metabolism

Hyperglycemia is a complication of excessive carbohydrate (glucose) provision and must be addressed in reference to the higher percentages of carbohydrate need suggested. Clearly, there is a hyperglycemic effect in the flow phase of burn injury as well as in critically ill patients who may also have a wound. Although short-term hyperglycemia accompanies the stress response to injury, persistent hyperglycemia is a problem that has commonly been associated with poor wound healing and immunity (7). Pediatric burn patients with poor glucose control experienced reduced skin graft take and subsequent mortality. Total caloric intake should be evaluated, as hypercaloric feeding may be associated with hyperglycemia. Further, because carbohydrate is a key substrate in burn wound healing, internal insulin production may be enhanced. Insulin, an anabolic hormone, has positive effects on nitrogen utilization. The use of exogenous insulin has been shown to lead to a decrease in peripheral muscle...

Metabolic Effects of Cytokines in Burns Trauma and Sepsis

Independent co-identification of a small polypeptide molecule present in the plasma of rabbits infected with Trypanosoma brucei which led to hypertriglyceridemia, hyperglycemia, and cachexia (hence, cachectin) 11 with the same molecule that induces hemorrhagic necrosis of tumors in animals after exposure of macrophages to endotoxin (tumor necrosis factor) has rapidly increased the understanding of metabolism following injury 12,13 . In healthy individuals, plasma TNF levels are less than 35 pg ml however, in both animals and humans, peak levels of TNF (240 pg ml) occur after 90 to 120 min of exposure to endotoxin or Gram-negative bacteria and are positively correlated with mortality 14-16 . TNF induces hyper-triglyceridemia, weight loss, and cachexia, in part by inhibition of endothelial lipoprotein lipase, but also by increased lipolysis and mobilization of fat stores. Administration of TNF to animals and humans induces proteolysis, hepatocyte amino acid uptake, by increasing the...

Conservative management

Percutaneous peritoneal lavage (usually 1-2 l h of dialysis fluid or normal saline) should be considered early whenever dark brown ascitic fluid is obtained. Lavage is usually discontinued when the returned fluid is clear. Striking reduction of early cardiorespiratory dysfunction and early mortality has been demonstrated, in particular for alcohol-induced pancreatitis. These benefits are ascribed to the early removal of toxic substances before they reach the systemic circulation. Peritoneal lavage is also useful in patients with coexisting renal failure and or fluid overload. However, it seems unlikely that enough lavage fluid gains access to the lesser sac where the concentration of toxic agents must be greatest. This therapy neither slows progression of local tissue injury nor prevents the development of necrosis and infection, and thus fails to influence overall mortality. A dramatic reduction in the incidence and subsequent mortality from pancreatic infection has been obtained by...

Capillary Basement Membrane Thickness in Health and Disease

Several mechanisms are implicated in the pathogenesis of microangiopathy leading to diabetic CBM thickening. These have been reviewed recently 3 and include hyper-glycemia-induced increases in Type IV collagen synthesis, decreased expression of matrix metalloproteinases (MMP-2 and 3), and increased tissue inhibitors of metalloproteinase (TIMP). Vascular endothelial growth factor (VEGF) also may be involved because treatment with anti-VEGF antibodies reduces glomerular BM thickening. Also, oxygen radicals oxidative stress and advanced glycation end products (AGEs) may play a role because aminoguanidine (which inhibits AGE formation, but also has antioxidant properties) attenuates diabetic nephropathy. In addition, the polyol enzymatic pathway is stimulated by hyperglycemia and has been implicated in the chronic sequelae of diabetes. In this regard, hyperpermeability is an early feature of diabetic microangiopathy and is reduced by aldose reductase inhibitors. Because hyperglycemia...

Caspases in Wallerian Degeneration

Accumulation of mitochondrial mutations. There is an increasing body of evidence suggesting that persistent hyperglycemia may lead to mitochondrial dysfunction and apoptotic cell death in tissue culture and animal models of diabetic neuropathy (Russell et al., 1999 Srinivasan et al., 2000 Schmeichel et al., 2003). It is likely that localized mitochondrial dysfunction may also lead to axonal degeneration before any evidence of cell death occurs. However, this remains speculative at this moment, as there is no firm experimental evidence.

Status epilepticus

Since hypoglycemia may be associated with status epilepticus, either as an etiology or as a consequence of prolonged seizure activity with autonomic failure, the blood glucose should be rapidly determined. Since the techniques employed for bedside determination lose accuracy outside the normal range, 'borderline' hypoglycemic values should be treated (along with thiamine administration). Non-ketotic hyperglycemia frequently presents with epilepsia partialis continua, which does not typically respond to antiseizure agents, but which usually remits with rehydration and control of the blood sugar.

Type 1 Diabetes

T1D is an autoimmune disease caused by the T cell-mediated destruction of insulin-producing P cells in the pancreatic islets of Langerhans (Tisch and McDevitt, 1996 Delovitch and Singh, 1997). T1D pathology begins with the development of peri-insulitis as a result of recruitment of a heterogeneous population of leukocytes comprising T cells, B cells, macrophages (M ), and dendritic cells (DCs) to the perivascular region of the islets, which slowly progresses to an invasive and destructive insulitis (Pankewycz et al., 1991 Dahlen et al., 1998 Hussain et al., 2004). The period of insulitis varies between individuals (years in humans, months in rodents) before it finally progresses to overt T1D manifested by hyperglycemia (Delovitch and Singh, 1997 Mathis et al., 2001). Both CD4+ and CD8+ T cells are required for islet P cell destruction (Christianson et al., 1993 Delovitch and Singh, 1997). CD8+ T cells function as effector cells but also require help from CD4+ T cells (Christianson et...


These vitamins have been isolated in foods and their chemical structures identified as part of the B group, although the activity of para amino benzoic acid (PABA) is quite different from other B vitamins. Biotin acts as a coenzyme in the metabolism of fats, carbohydrates, and protein. Prolonged use of antibiotics and antiseizure medicines interfere with its production. It is destroyed by raw egg white. The vitamin strengthens brittle nails and lowers blood glucose levels preventing diabetic neuropathy. Deficiency symptoms include fatigue, lack of appetite, dermatitis, hair loss, anemia, nausea, and depression.

Role of Inflammation

In molecular and animal studies, hyperinsulinemia and hyperglycemia132,133 have been shown to be independent risk factors of colorectal carcinogenesis. Insulin and IGF-1 receptors are expressed by both normal colorectal epithelial cells and colon cancer tissue.134,135 Therefore, both premalignant and cancerous stages can be affected by IGF-1. In a recent review, Chang and colleagues136 summarize the epidemiologic literature with respect to hyperinsulinemia and hyperglycemia as risk factors for colorectal cancer. According to the authors, epidemiologic findings to date indicate a slightly increased risk of colorectal cancer for patients with diabetes however, there are some inconsistencies across the study results. Possible explanations for these inconsistencies might include inadequate information about patients' diabetic disease and treatment status. A greater attention toward medical history, staging and treatment for hyperinsuline-mia and hyperglycemia might be helpful to further...

Metabolic Effects

Epinephrine, the most potent stimulant of hepatic glycogenolysis, gives rise to glucose, which readily enters the circulation isoproterenol produces relatively weak hyperglycemia. Administration of both a- and ( -adrenoceptor blocking agents is necessary for complete antagonism of glycogenolysis in this tissue.


A synthetic class of compounds known as thiazolidinediones (TZDs) selectively bind PPARy with high affinity (nanomolar range) and potently enhance transcriptional activity.59 Interestingly, these compounds were developed and used as lipid-lowering and insulin-sensitizing agents before the discovery that they are also potent ligands for PPARy. As antidiabetic agents, TZDs appear to work by either mimicking or enhancing insulin action without stimulating P-cell insulin secretion60 and have been demonstrated as very effective in improving insulin sensitivity and glucose tolerance in diabetic patients.61-63 Studies using various animal models of obesity and diabetes have also reported that these synthetic compounds are effective in lowering hyperglycemia and hyperinsulinemia and improving insulin sensitivity.64-66 The notion that TZDs produce these effects through


Excessive quantities of carbohydrates can also have a negative impact in the hospital setting. Even moderate degrees of hyperglycemia may result in an increased incidence of infection and adverse outcomes (42). Persistent hyperglycemia has been associated with poor wound healing and immunity (7). Excessive amounts of glucose have been positively correlated with increased carbon dioxide production and hepatic steatosis in traumatized and septic patients (12,13). Diabetic subjects who suffer from wounds need to be especially careful in regard to the regulation of glucose intake and the maintenance of euglycemia (17).


Insulin-mediated glucose disposal varies widely in the population at large, with approximately 50 of the variability in insulin action resulting from differences in lifestyle variables with degree of adiposity and physical fitness each accounting for approximately (25 ). The remaining 50 is familial, likely to be of genetic origin, with powerful ethnic differences. Type 2 diabetes develops when insulin-resistant individuals cannot secrete the increased amounts of insulin needed to overcome the insulin resistance. However, the majority of insulin-resistant individuals are able to maintain the degree of hyperinsulinemia required to prevent manifest decompensation of glucose homeostasis. Although compensatory hyperinsulinemia prevents the development of frank hyperglycemia in insulin-resistant persons, insulin-resistant hyperinsuline-mic individuals are at greatly increased risk of being somewhat glucose intolerant, with a dyslipi-demia characterized by a high plasma TG and low HDL-C...

Acute pancreatitis

The gold standards are direct inspection at laparotomy and microscopic examination. However, routine diagnostic cornerstones remain abdominal pain, nausea, vomiting, and hyperamylasemia. Clinical signs, although suggestive, are notoriously non-specific. Remote organ failure and metabolic disturbances such as hyperglycemia and hypocalcemia, although rarely present at the onset, should alert the clinician.

Discrete seizures

Seizures occurring during another critical illness usually represent a central nervous system manifestation of a systemic disorder. In a prospective study of neurological complications of critical medical illnesses, seizures were the second most common problem encountered (and were almost as frequent as metabolic encephalopathy). The most frequent causes were cerebrovascular disease, central nervous system infections, metabolic encephalopathies, neoplasms, hypoglycemia, and osmolar disorders (including non-ketotic hyperglycemia). A retrospective analysis found that drug withdrawal was the most common etiology of seizures. Table 1 summarizes common causes of seizures in ICU patients. Acute metabolic disturbances commonly produce seizures in ICU patients, but one must consider that seizures may be symptoms of structural disorders which are made manifest by metabolic disorders. Generalized convulsions are typical of metabolic disturbances, but two common exceptions are seizures due to...


Side effects were reported in two of the systematic reviews and two RCTs. These included herpes simplex, herpes zoster, severe ankle oedema, fractured neck of femur, acute anxiety and severe depression 117 weight gain, oedema, gastrointestinal symptoms and psychological symptoms 119 raised blood glucose 126 infection and raised blood pressure.121 One review reported that the major side effects were significantly more frequent in the intervention group compared to the control group. The frequency of minor side effects was high in all the studies.

Endocrine changes

Hyperglycemia Hyperglycemia is a frequent complication of brain death because of the administration of glucose-containing fluids to replace large urinary losses, reduced insulin secretion, and increased levels of catecholamines. The consequent increase in extracellular osmolality may lead to intracellular dehydration, an osmotic diuresis, and electrolyte disturbances hyperglycemia may be associated with decreased pancreatic allograft survival. Therefore it is important to control blood glucose levels with intravenous insulin infusions.

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