Home Remedies for Hyperglycemia

Blood Sugar Miracle

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Blood Sugar Miracle Summary


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Control of Hyperglycemia

Several studies demonstrate the importance of intensive glycemic control in preventing or reducing microvascular complications of DM. The effect of intensive glycemic control on macrovascular complications in type 1 and type 2 DM is not as convincing. The Diabetes Control and Complications Trial (DCCT) demonstrated compelling evidence in support of a major reduction in chronic microvascular complications among type 1 diabetics under tight glycemic control. In the same study, tight glycemic control was associated with a reduction in major macrovascular events by approximately 50 compared with that in those in whom glycemic control was conventional or less stringent. This difference did not achieve statistical significance. Similarly, the United Kingdom Prospective Diabetes Study (UKPDS) has shown that during 10 years of follow-up intensive glycemic control with either insulin or sulfonylureas decreased the risk of microvascular complications by 25 in non-insulin-requiring diabetics....

Diabetes Mellitus and Stress Hyperglycemia

Stress hyperglycemia at the time of MI is strongly correlated with mortality rates. In a meta-analysis conducted by Capes et al. (20), data from 15 trials reporting admission glucose concentrations in relation to in-hospital mortality or heart failure rates after AMI were reviewed. In the patients without known diabetes, those with a glucose concentration 109-143 mg dL had a 3.9-fold higher risk of death compared to patients with lower glucose concentrations. At glucose concentrations of 143-180 mg dL, the risk of cardiogenic shock or heart failure was increased 3-fold. In patients with frank diabetes, glucose concentrations 180-196 mg dL were associated with a moderate risk of death (relative risk 1.7).


The so-called traditional cardiovascular risk factors account for only about 25 to 50 of the increase in risk for developing CAD among diabetic patients. Thus, the pivotal role of glycemic control in the management of diabetic patients with CAD cannot be overemphasized. Further, hyperglycemia and dyslipidemia associated with DM are central to the pathogenesis of CAD development in these patients. Several prospective studies have emphasized that poor glycemic control predicts CAD risk among diabetic subjects. Lehto et al. demonstrated that the concomitant presence of fasting hyperglycemia and abnormal blood lipids were associated with a threefold higher risk of CAD morbidity and mortality in over 1000 diabetic patients who were followed for up to 7 years. Hyperglycemia induces several abnormalities that may accelerate atherosclerosis. It decreases endothelium-dependent vasodilatation in humans and produces adverse changes in lipid and coagulation factors. Chronic hyperglycemia

Selected Metabolic Aspects Of Diabetesg

A lay person would describe diabetes as too much sugar in the blood. So would most medical students and physicians. However, hyperglycemia is simply the tip of the iceberg, albeit one of profound pathogenetic impact. Type 2 diabetes is, in fact, a syndrome in which resistance to insulin in peripheral tissues is present for years, if not decades, before hyperglycemia becomes evident. As compensatory pancreatic secretory mechanisms in response to the insulin resistance begin to fail, relative and

The Nature Of Complications

The discovery that metabolic consequences of type 1 diabetes (insulin deficiency attributable to failure of pancreatic beta cells, generally induced by autoimmune phenomena) could be corrected by administration of pancreatic extracts and ultimately purified insulin gave rise to a powerful belief system in which insulin deficiency is embraced as the cause of diabetes under all circumstances. We now know that more than 90 of individuals with diabetes have type 2 diabetes, a condition in which insulin resistance is among the primary defects. However, the evolution of diabetes is such that at any given level of insulin resistance the pancreatic compensatory mechanism is inadequate to meet demands and insulin deficiency is a relatively late manifestation of the disorder. Surprisingly, this dichotomy was anticipated in the 1930s. Himsworth was interested in the causes of hyperglycemia in patients with diabetes and performed what Gerald Reaven described as ''a series of simple, but elegant...

Some Therapeutic Considerations

The prevention or retardation of coronary artery disease and its sequelae in subjects with type 2 diabetes provides opportunities and challenges. Stringent gly-cemic control is an imperative. Amelioration of insulin resistance is paramount as well. The armamentarium for treatment of diabetes has expanded recently with the addition to the classical armamentarium of sulfonylureas and insulin of insulin sensitizing agents (glitazones). These agents augment glucose utilization and consequently diminish hyperglycemia, thereby reducing prevailing concentrations of insulin directly and in response to the lowered concentrations of glucose. Other additions include the biguanides, particularly metformin, rapidly acting insulins such as lispro, agonists of first-phase insulin secretion such as Repaglinide, and agents that decrease absorption of glucose from the gastrointestinal track such as a-glucosidase inhibitors. The foundation of effective management of type 2 diabetes includes diet,...

Cardiovascular Disease In Type 1 Diabetes

Hyperglycemia Hyperinsulinemia Central obesity Diabetic dyslipidemia T plasma triglycerides plasma HDL cholesterol small, dense LDL pattern Procoagulant state T plasma fibrinogen T plasma PAI-1 Hypertension as a consequence of the development of obesity, which appears to be a result of intensive insulin treatment (12) or poorly controlled glycemia that leads to hypertriglyceridemia, excessive activation of vascular cell protein kinase C, increased production of advanced glycosylation end products (AGEs), endothelial dysfunction, and oxidative stress (13). Type 1 diabetic patients have increased cardiovascular risk factors as a consequence of their hyperglycemia and its treatment and not as an intrinsic part of the disease itself. The development of cardiovascular disease is thus a very late complication of type 1 diabetes and manifests itself after age 35 in those with onset of type 1 diabetes prior to age 20 (as shown in Figs. 1 and 2) (14). In cross-sectional studies, the prevalence...

Endothelial Dysfunction

It has been shown that endothelial dysfunction may be secondary to insulin resistance and hyperinsulinemia, in addition to the multiple other components of the cardiovascular dysmetabolic syndrome. Hyperlipidemia, hyperglycemia, hypertension, smoking, and homocysteine have all been reported to damage the endothelium. The resulting endothelial dysfunction leads to an imbalance in the endothelial production of the vasoconstrictors versus the vasodilators. Studies have evaluated clinical intervention, both pharmacological and nonpharmacologi-cal, in the treatment of endothelial dysfunction. In particular, the role of an insulin sensitizer was evaluated in individuals felt to have impaired glucose tolerance and insulin resistance and who had attenuated brachial artery vasoactivity (97). After 2 months of therapy, vasoactivity was shown to improve with glitazone treatment and appeared to normalize after 4 months (97). Although this demonstrates that pharmacological treatment of insulin...

Contraindications Precautions And Interactions

This drug is contraindicated in individuals who have had previous hypersensitivity reactions to pentamidine isethionate. Pentamidine isethionate is used cautiously in patients with hypertension, hypotension, hyper-glycemia, renal impairment, diabetes mellitus, liver impairment, bone marrow depression, pregnancy (Category C), or lactation.

The Coagulation System And Diabetes Mellitus

Decreased activity of antithrombotic factors in blood can potentiate thrombosis. Of note, concentrations in blood of protein C and activity of antithrombin are decreased in diabetic subjects. Unlike changes in concentrations of prothrom-botic factors, altered concentrations and activity of antithrombotic factors appear to be reflections of the metabolic state typical of diabetes such as hyperglycemia, regardless of whether type 1 or type 2 diabetes is responsible. In fact, decreased antithrombotic activity has been associated with nonenzymatic glycation of anti-thrombin. To recapitulate, functional activity of the prothrombinase complex and of thrombin itself are increased consistently in blood of subjects with diabetes. The increased activity is likely to be a reflection of increased procoagulant activity of platelets and monocytes in association with increased concentrations of fibrin-ogen, von Willebrand factor, and factor VII. Diminished activity in blood of antithrombotic factors...

Conclusions And Implications For Practice

Subjects with diabetes mellitus have a high prevalence and rapid progression of cardiovascular, peripheral vascular, and cerebral vascular disease secondary and in part attributable to (1) increased platelet reactivity (2) increased prothrom-botic activity reflecting increased concentrations and activity of coagulation factors and decreased activity of antithrombotic factors and (3) decreased fibrinolytic system capacity resulting from overexpression of PAI-1 by hepatic, arterial, and adipose tissue in response to hyperinsulinemia, hypertriglyceridemia, and hyperglycemia. The macrovascular disease appears to be accelerated by an insulin-dependent imbalance between concentrations of plasminogen activators and PAI-1 in blood and in vessel walls. Therapy designed to reduce insulin resistance decreases concentrations in blood not only of insulin but also of PAI-1. -o Thus, the treatment of subjects with diabetes, and particularly type 2 diabetes, should be designed to achieve stringent...

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...

Medical Complications of Glucose Intolerance and Diabetes Mellitus

Hyperglycemia and diabetes mellitus are associated with acute and chronic complications associated with significant morbidity and mortality. Diabetic ketoacidosis (DKA), an acute complication of diabetes mellitus, is seen more often in patients with type I than in patients with type II diabetes mellitus and is a serious and potentially fatal complication. Ketoacidosis is defined by low serum pH (

Case Study For Chapter

A moderate elevation of blood glucose concentration after a carbohydrate meal can happen, but it should not exceed 140 to 150 mg dL. Such a high blood glucose represents a major loss in the regulation of glucose metabolism. The patient is seriously overweight and is likely insulin-resistant. He has ample insulin but the cellular response to insulin is inadequate. The suppressed insulin response develops after repeated and sustained high insulin concentrations associated with excessive carbohydrate intake.

Relationship Between Obesity And Type 2 Diabetes Mellitus

We tend to think of insulin sensitivity, or its converse, insulin resistance, as a single entity, regardless of how or where it is measured. This is unfortunate and has resulted from the paucity of studies in which whole body insulin-resistance and resistance at each of the major insulin sensitive tissues have been measured simultaneously. Most commonly, so-called 'normals' (usually age and or weight matched) are compared to so-called diabetics (individuals with significant hyperglycemia). Under these groupings, normals are normal in both whole body and tissue determinations and diabetics are 'resistant' at both the whole body and at various tissues. More detailed analysis has shown in rhesus monkeys that whole body insulin resistance, probably principally reflective of skeletal muscle insulin

Gerontologie Alert

The hydantoins may affect the blood glucose levels. In some patients these drugs have an inhibitory effect on the release of insulin in the body, causing hyperglycemia. The nurse closely monitors blood glucose levels, particularly in patients with diabetes. The nurse reports any abnormalities to the primary health care provider.

Generating recombinant DNA molecules

To illustrate how recombinant DNA is made, let's consider the cloning of the gene for human insulin, a protein hormone used in the treatment of diabetes. Diabetes is a disease in which blood sugar levels are abnormally high either because the body does not produce enough insulin (type I diabetes) or because cells are unable to respond to insulin (type II diabetes). In mild forms of type I, diabetes can be treated by dietary restrictions but, for many patients, daily insulin treatments are necessary. Until about 20 years ago, cows were the major source of insulin protein. The protein was harvested from the pancreases of animals slaughtered in meat-packing plants and purified at large scale to eliminate the majority of proteins and other contaminants in the pancreas extracts. Then, in 1982, the first recombinant human insulin came on the drug market. Human insulin could be made purer, at lower cost, and on an industrial scale because it was produced in bacteria by recombinant DNA...

Regulating Other Functions

The islets of Langerhans in the pancreas secrete two antagonistic protein hormones, insulin and glucagon. In response to high glucose levels in the blood (as in hyperglycemia), genes in beta cells produce and secrete insulin, which directs body cells, especially liver cells, to absorb glucose and store it as a polysaccharide called glycogen. Insulin production will stop once blood glucose levels are reduced to normal. An insulin deficiency leads to prolonged hyperglycemia, a serious and often fatal disorder called diabetes melli-tus. When blood glucose levels are too low (as in hypoglycemia), genes in the alpha cells of the islets of Langerhans produce and secrete glucagon, which directs body cells to break down their gly-cogen reserves and begin releasing glucose back into the bloodstream until normal blood glucose levels are reached, upon which glucagon production ceases.

Summary And Conclusions

In healthy individuals, blood glucose concentration is tightly regulated. Insulin is secreted in a basal rate between meals that is sufficient to constrain the rate of hepatic glucose release to match the rate of glucose uptake. After meal ingestion, the insulin secretion rate is promptly increased and leads to further suppression of hepatic glucose release, increased glucose uptake by insulin-sensitive tissues, and restoration of blood glucose levels to fasting levels. In patients with diabetes, the mechanism of hyperglycemia in the fasting and fed states is excess hepatic glucose release. This is due to inadequate insulin delivery to the liver along with hepatic insulin resistance. Treatment strategies to restore the blood glucose concentration to normal require provision of an adequate amount of insulin to appropriately inhibit hepatic glucose release in the basal fasting state and after meal ingestion.

Therapeutic Manipulation Avoidance of Hypoglycaemia

Very strict glycaemic control, and blood glucose targets may have to be higher when faced with these problems. Frequent blood glucose monitoring is essential to identify biochemical hypoglycaemia, and the use of basal-bolus insulin regimens (which predominantly use short-acting insulins) may be beneficial in avoiding recurrent hypoglycaemia. However, frequent blood glucose monitoring alone can sometimes exacerbate the problem, unless the patient is instructed in how to use the data to adjust insulin regimens prospectively to avoid problems, rather than to react by immediate treatment of the inevitable occasional high reading. There have been few detailed behavioural studies in people with impaired awareness of hypoglycaemia but it may be a particular problem where the links between high blood glucose and risk of vascular complications have been very well accepted by the patient, who may need convincing that transient hyperglycaemia is not a problem. Clinical experience suggests that...

Impact On Cardiovascular Disease The Dcct And Ukpds Studies

Clinical atherosclerosis results largely from acute embolic or thrombotic events that arise from long-term changes in the arterial wall. The pathogenesis of the arterial wall changes in relation to the metabolic abnormalities that attend poorly controlled diabetes are not well known in humans. Epidemiological studies indicate that both hyperglycemia and hyperinsulinemia increase the risk of atherosclerosis and of the acute clinical complications of that condition. The high triglyceride and low HDL cholesterol concentrations that frequently attend hyperglycemia may contribute as well. Animal studies suggest that good blood glucose control can mitigate the effects of diabetes on the arterial wall. Cross-sectionally, worsening glycemia is associated with thickening of the intima and media layers of the common carotid arteries. Intervention studies to test the impact of improved glycemic control on this or other measures of atherosclerosis are lacking. However, there is mounting evidence...

Roberta D Laredo RD CDE

Diabetes nieilitus is a chronic disease resulting Iront absolute or relative insulin deficiency that occurs in both children and adults. Approximately one of every 600 children in the United States has diabetes, making it one of the most common chronic childhood illnesses. Diabetes occurs when insulin, normally produced by the beta cells of the pancreas, is cither absent, insufficient, or not used properly by the target tissues. Glucose builds up in the blood stream when insulin is unavailable to allow it to enter the cells. Long-term elevated blood glucose levels can lead to the chronic complications of diabetes, including retinopathy, nephropathy, neuropathy, and macrovas-cular disease. Type 1 diabetes is an autoimmune disease in which the beta cells of the pancreas eventually produce little or no insulin. Type I diabetes generally occurs in children and young adults. The body's immune system attacks and destroys the beta cells of the pancreas. Initial therapy involves medical...

Acute and Chronic Complications

The major acute complications of diabetes occuring in children are hypoglycemia, hyperglycemia, and diabetic ketoacidosis. Hypoglycemia is caused by too little food, delayed or missed meals and snacks, increased exercise, excessive insulin, or alcohol intake without food. Hyperglycemia is caused by increased food intake, inadequate insulin dose, or a decrease in usual exercise. Diabetic ketoacidosis results from an absolute lack of insulin and the build-up of ketoacids in the blood.

Diagnosis of T1D in NOD Mice

A mouse is diagnosed diabetic when blood glucose values are greater than 200 mg dL for two consecutive measurements. Blood glucose is conveniently monitored by applying a drop of blood, usually from the tail vein, to a glucose test strip and it is read with a small portable spectrometer.

Does Stress On Its Own Increase The Risk For Heart Disease

Stress is thought to be an independent cardiovascular risk factor. This means that people who are stressed, even if they do not have any other risk factor, are more likely to develop heart disease than those people who are not stressed. It has taken many years for stress to be identified as an independent risk factor, because it is difficult to measure and the effects of stress acting alone were difficult to separate from the other well-established risk factors. Stressed people may have high blood pressure, may smoke, may eat fatty food and be inactive and overweight, and therefore have high cholesterol and high blood sugar, or come from a family affected by heart disease at a young age.

Thiazides and Related Diuretics

Concurrent use of the thiazides with allopurinol may increase the incidence of hypersensitivity to allopurinol. The effects of anesthetics may be increased by thiazide administration. The effects of anticoagulants may be diminished when they are administered with a thiazide diuretic. Because thi-azide diuretics may raise blood uric acid levels, dosage adjustments of antigout drugs may be necessary. Thiazide diuretics may prolong antineoplastic-induced leukopenia. Hyperglycemia may occur when the thiazides area administered with the antidiabetic drugs. Synergistic effects may occur when the thi-azide diuretics are administered concurrently with the loop diuretics, causing profound diuresis and serious electrolyte abnormalities. There is an increased risk of glycoside toxicity if the patient experiences hypokalemia while taking the thiazide diuretics.

Effects of Diabetes on LDL Oxidation

Diseases that enhance LDL oxidation include diabetes and hypertriglyceridemia (115). Hyperglycemia increases LDL oxidation, in part, through an increase in glycation products, which subsequently enhances free radical production in stimulated inflammatory cells (115). Insulin and IGF-I cause an upregulation of LDL receptor and down regulation of HDL receptor (281). Insulin increases uptake and esterification of

Clinical Focus Box 321

The insulin-opposing actions of GH can produce serious metabolic disturbances in individuals who secrete excessive amounts of GH (people with acromegaly) or are given large amounts of GH for an extended time. They may develop insulin resistance and an elevated insulin level in the blood. They may also have hyperglycemia caused by the underutilization and overproduction of glucose. These disturbances are much like those in individuals with non-insulin-dependent (type 2) diabetes mellitus. For this reason, this metabolic response to excess GH is called its diabetogenic action.

Adverse Reactions

The two major adverse reactions seen with insulin administration are hypoglycemia (low blood glucose or sugar) and hyperglycemia (elevated blood glucose or sugar). The symptoms of hypoglycemia and hyper-glycemia are listed in Table 49-1. Hyperglycemia may occur if there is too little insulin in the bloodstream in relation to the available glucose (hypoinsulinism). Hyperglycemia may occur

Ongoing Assessment

The nurse must assess the patient for signs and symptoms of hypoglycemia and hyperglycemia (see Table 49-1) throughout insulin therapy. The patient is particularly prone to hypoglycemic reactions at the time of peak insulin action (see the Summary Drug Table Insulin Preparations) or when the patient has not eaten for some time or has skipped a meal. In acute care settings, frequent blood glucose monitoring is routinely done to help detect abnormalities of blood glucose.

Gerontologic Alert

Although elderly patients taking the oral antidiabetic drugs are particularly susceptible to hypoglycemic reactions, these reactions may be difficult to detect in the elderly. The nurse notifies the health care provider if blood sugar levels are elevated (consistently 200 mg dL) or if ketones are present in the urine. MANAGING HYPERGLYCEMIA AND KETOACIDOSIS. Capillary blood specimens are obtained and tested in the same manner as for insulin (see Patient and Family Teaching Checklist, p. 497). The nurse notifies the health care provider if blood sugar levels are elevated

TABLE 501 Activity of Glucocorticoids in the Body

Action is decreased, and blood pressure falls. Facilitates the breakdown of protein in the muscle, leading to increased plasma amino acid levels. Increases activity of enzymes necessary for glucogenesis producing hyperglycemia, which can aggravate diabetes, precipitate latent diabetes, and cause insulin resistance A complex phenomena that promotes the use of fat for energy (a positive effect) and permits fat stores to accumulate in the body, causing buffalo hump and moon- or round-shaped face (a negative effect).

Quality Of Life And Obstacles To Care

Sense of failure associated with elevated blood glucose readings despite a sincere effort, and the frustrations of needing medication when self-image associates pill taking with the sick role are a few examples of the psychosocial complexities. Effective diabetes education begins with listening to the patient and his perception of life with diabetes.

Monitoring and Managing Adverse Reactions

When the androgens are administered to a patient with diabetes, blood glucose measurements should be done frequently because glucose tolerance may be altered. Adjustments may need to be made in insulin dosage, oral antidiabetic drugs, or diet. The nurse monitors the patient for signs for hypoglycemia and hyper-glycemia (see Chap. 49).

Functions of the Adrenal Medulla

Produces an effect similar to continuous sympathetic nerve stimulation. The symptoms of this condition are hypertension, elevated metabolism, hyperglycemia and sugar in the urine, nervousness, digestive problems, and sweating. It does not take long for the body to become totally fatigued under these conditions, making the patient susceptible to other diseases.

Combined antiretroviral treatment

From its introduction in 1997, HAART has become the cornerstone of HIV therapy 84 . Lipodystrophy, hyperlipidemia, hypertriglyceridemia, insulin resistance 85 , hyperglycemia, cardiovascular symptoms 86 , and hypothyroidism have been described as long-term side effects of HAART. From

Type 1 Diabetes Mellitus

Type 1 diabetes mellitus results when the beta cells of the islets of Langerhans are progressively destroyed by autoimmune attack. Recent evidence in mice suggests that killer T lymphocytes (chapter 15) may target an enzyme known as glutamate decarboxylase in the beta cells. This autoimmune destruction of the beta cells may be provoked by an environmental agent, such as infection by viruses. In other cases, however, the cause is currently unknown. Removal of the insulin-secreting beta cells causes hyperglycemia and the appearance of glucose in the urine. Without insulin, glucose cannot enter the adipose cells the rate of fat synthesis thus lags behind the rate of fat breakdown and large amounts of free fatty acids are released from the adipose cells. symptoms of diabetes may result from high glucagon secretion as well as from the absence of insulin. The lack of insulin may be largely responsible for hyperglycemia and for the release of large amounts of fatty acids into the blood. The...

External insulin infusion pumps

At a much slower rate compared to insulin delivered via CSII. Therefore, any interruption of insulin flow from CSII can result in rapid hyperglycemia and DKA. In addition, even though hypoglycemia is less common with CSII use, the proper use of an insulin pump requires a highly motivated patient who is able to monitor blood glucose frequently, operate the device, and work with a diabetes team. Infrequent blood glucose monitoring, poor cooperation with the patent's treatment team, and inability to program the device properly can result in severe adverse events including hypoglycemia, hyperglycemia or DKA.

Pathology Of Cortisol Metabolism

Wadati Plots Seismic

Excessive glucocorticoid exposure of the fetus results in growth retardation. In retrospective studies, birthweight has been found to be low in patients with 11 -HSD2 deficiency (133,139). In some (140), but not all (14,141), studies there is an inverse relationship between placental 11 -HSD activity and birthweight in otherwise healthy individuals. Extensive epidemiological studies have linked low birthweight with subsequent adverse risk factors for cardiovascular disease, including hypertension and insulin resistance (142). Prenatal treatment of rats with either dexamethasone, which is a poor 11 -HSD2 substrate and so directly accesses the fetus, or carbenoxolone which inhibits 11 -HSD, lowers birthweight and programs permanent hypertension and hyperglycemia in the adult offspring (143-145). However, while the hypertension and insulin resistance in low birthweight babies may be amplified by subsequent obesity (146), current data do not suggest that obesity itselfis programmed...

Factors Predisposing Patients to Severe Hypoglycaemia in Intensified Insulin Therapy

As mentioned earlier, the first indication that strict glycaemic control might cause abnormal responses to hypoglycaemia was observed when controlled hypoglycaemia was induced in a small group of patients with type 1 diabetes before, and after, they had been treated with intensified insulin therapy (Simonson et al., 1985a). Following the improvement in glycaemic control, the magnitude of the counterregulatory hormonal response to an abrupt lowering of blood glucose to 2.8 mmol l was significantly less than observed previously. This study had been planned to investigate the potential of better glycaemic control to restore some of the defects of normal counterregulation that develop in people with type 1 diabetes (see Chapter 6), so these results were unexpected. The importance of these preliminary observations was underlined by a subsequent study in which patients with type 1 diabetes receiving intensified insulin treatment were found to have impaired glucose counterregulation (Amiel...

Diabetes Mellitus and Hypoglycemia

Inadequate secretion of insulin, or defects in the action of insulin, produce metabolic disturbances that are characteristic of diabetes mellitus. A person with type 1 diabetes requires injections of insulin a person with type 2 diabetes can control this condition by other methods. In both types, hyperglycemia and glycosuria result from a deficiency and or inadequate action of insulin. A person with reactive hypoglycemia, by contrast, secretes excessive amounts of insulin and thus experiences hypoglycemia in response to the stimulus of a carbohydrate meal. Chronic high blood glucose, or hyperglycemia, is the hallmark of diabetes mellitus. The name of this disease is derived from the fact that glucose spills over into the urine when the blood glucose concentration is too high (mellitus is derived from a Latin word meaning honeyed or sweet ). The general term diabetes comes from a Greek word meaning siphon it refers to the frequent urination associated with this condition. The...

Digestion And Absorption Of Carbohydrates

Structure Glycogen

Humans can digest most carbohydrates those we cannot digest constitute the dietary fiber that forms roughage. Carbohydrate is present in food as monosaccharides, disaccha-rides, oligosaccharides, and polysaccharides. The monosaccharides are mainly hexoses (six-carbon sugars), and glucose is by far the most abundant of these. Glucose is obtained directly from the diet or from the digestion of dis-accharides, oligosaccharides, or polysaccharides. The next most common monosaccharides are galactose, fructose, and sorbitol. Galactose is present in the diet only as milk lactose, a disaccharide composed of galactose and glucose. Fructose is present in abundance in fruit and honey and is usually present as disaccharides or polysaccharides. Sorbitol is derived from glucose and is almost as sweet as glucose, but sor-bitol is absorbed much more slowly and, thus, maintains a high blood sugar level for a longer period when similar amounts are ingested. It has been used as a weight-reduction aid to...

The Somogyi Phenomenon The Concept Of Rebound Hyperglycaemia

Rebound Hyperglycaemia

Although fasting glucose concentrations were frequently high in the patients they studied, this was related directly to a waning of circulating plasma insulin concentrations. Some investigators have demonstrated that when hypoglycaemia is experimentally-induced during the night, this can raise blood glucose on the following morning, even if circulating plasma insulin concentrations are maintained (Perriello et al., 1988). However, the additional increase in the fasting blood glucose concentration is modest (around 2.0mmol l) and its clinical relevance is questionable. Other researchers have found no effect on daytime concentrations of blood glucose after lowering blood glucose to hypoglycaemic levels during the night (Hirsch et al., 1990). Careful analysis of data collected both by self-monitoring of blood glucose (Havlin and Cryer, 1987) and by continuous glucose monitoring (Hoi-Hansen et al., 2005) (Figure 4.3) during everyday activities, has also shown that nocturnal hypoglycaemia...

The Liver Is Important in Carbohydrate Metabolism

Carbohydrate Metabolism Liver

Both glycogenolysis and glycogenesis are hormonally regulated. The pancreas secretes insulin into the portal blood. Therefore, the liver is the first organ to respond to changes in plasma insulin levels, to which it is extremely sensitive. For instance, a doubling of portal insulin concentration completely shuts down hepatic glucose production. About half the insulin in portal blood is removed in its first pass through the liver. Insulin tends to lower blood glucose by stimulating glycogenesis and suppressing glycogenolysis and gluconeogenesis. Glucagon, in contrast, stimulates glycogenolysis and gluconeogenesis, raising blood sugar levels. Epinephrine stimulates glycogenolysis. Gluconeogenesis is important in maintaining blood glucose concentrations especially during fasting. The red blood cells and renal medulla are totally dependent on blood glucose for energy, and glucose is the preferred substrate for the brain. Most amino acids can contribute to the carbon atoms of the glucose...

Case Study - Medical Terminology - 78 Steps Health Journal

M.G. has managed her disease with meticulous attention to her diet, exercise, preventative health care, regular blood glucose monitoring, and twice-daily injections of regular and NPH insulin, which she rotates among her upper arms, thighs, and abdomen. She continues in a smoking cessation program supported by weekly acupuncture treatments. She maintains good control of her disease in spite of the inconvenience and time it consumes each day. She will be married next summer and would like to start a family. M.G.'s doctor suggested she try an insulin pump to give her more freedom and enhance her quality of life. After intensive training, she has received her pump. It is about the size of a beeper with a thin catheter that she introduces through a needle into her abdominal subcutaneous tissue. She can administer her insulin in a continuous subcutaneous insulin infusion (CSII) and in calculated meal bolus doses. She still has to test her blood for hyperglycemia and hypo-glycemia and her...

Mechanisms by Which the Atypical Antipsychotic Agents May Cause Diabetes Mellitus

There are a number of ways in which the atypical antipsychotic medications could lead to hyperglycemia and diabetes mellitus. As discussed Another mechanism by which the atypical antipsychotic agents may lead to hyperglycemia and diabetes mellitus is antagonism of the serotonin 5-HT1A receptors. Antagonism of the 5-HT1A receptors may decrease pancreatic beta cell responsiveness to blood sugar levels, resulting in disturbances in glucose metabolism secondary to decreased insulin secretion (Wirshing et al. 1998). Melkersson and colleagues, however, found that patients treated with olanzapine had higher fasting insulin levels on comparison of baseline to 5-month follow-up, suggesting that impaired beta cell function is an unlikely cause for olanzapine-associated diabetes mellitus (Melk-ersson et al. 2000). Their group found that although 11 of 14 olanzapine-treated patients (79 ) were normoglycemic, and only 3 showed increased blood glucose values, the majority of patients (10 of 14, or...

Take Advantage of the Technology

Medical Laboratory Crossword Puzzle

Jessica, a student of physiology, is constantly drinking from a water bottle yet claims to be constantly thirsty. During her physiology laboratory exercise involving urinalysis, she discovers that she has a significant amount of glucose in her urine. Alarmed, because urine normally should contain little or no glucose, she seeks medical attention.As a result of a later medical examination, she learns that she has hyperglycemia, hyperkalemia, and a high plasma osmo-lality.When she shows the doctor her EKG that she recorded in the physiology lab, he remarks that it has some abnormalities.

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

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.

Type 2 Diabetes Mellitus Primarily Originates in the Target Tissue

Acute Complications Diabetes Mellitus

The nature of acute complications that develop in type 1 and type 2 diabetics differs. Persons with poorly controlled type 1 diabetes often exhibit hyperglycemia, glucosuria, dehydration, and diabetic ketoacidosis. As blood glucose becomes elevated above the renal plasma threshold, glucose appears in the urine. As a result of osmotic effects, water follows glucose, leading to polyuria, excessive loss of fluid from the body, and dehydration. With fluid loss, the circulating blood volume is reduced, compromising cardiovascular function, which may lead to circulatory failure. Persons with type 2 diabetes are generally not ketotic and do not develop acidosis or the electrolyte imbalances characteristic of type 1 diabetes. Hyperglycemia leads to fluid loss and dehydration. Severe cases may result in hyperosmolar coma as a result of excessive fluid loss. The initial objective of treatment in these individuals is the administration of fluids to restore fluid...

Nutrition Strategies For Type 1 Diabetes

Insulin Therapy

Patients often experience difficulty in achieving weight loss and maintaining a reasonable body weight through traditional nutrition strategies, such as calorie-restricted diets. Therefore, the focus of nutrition therapy for type 2 diabetes is on achieving target blood glucose levels and improving metabolic control. Type 2 diabetic patients should be encouraged to monitor blood glucose levels because nutrition therapy and lifestyle changes often have a positive effect on blood glucose levels before weight loss goals are achieved. The focus of nutrition assessment and therapy for type 2 diabetes is to identify a reasonable body weight for the patient, and to encourage diet and lifestyle changes to achieve and maintain weight loss goals, blood glucose targets, and blood-pressure levels, and to improve metabolic control. Nutrition strategies encourage a moderate reduction in daily calorie intake, usually a reduction of 250-500 calories per day from the patient's usual daily intake, as...

Burton E Sobel and David J Schneider

This book was inspired by cogent clinical observations and a rapidly expanding body of knowledge implicating diverse, specific, and sometimes paradoxical or unexpected factors in the pathogenesis of accelerated coronary artery disease associated with type 2 diabetes. A clinical example is the initially astounding observation in the BARI I trial of a fourfold increase in 5-year mortality in patients with type 2 diabetes compared with that in nondiabetic subjects after percutaneous transluminal coronary angioplasty (PTCA), and the threefold increase after surgical revascularization. Examples of the unexpected factors include the emerging information strongly implicating insulin resistance in liver, adipose tissue, and skeletal muscle with consequent hyperinsulinemia as a culprit in acceleration of coronary disease and its sequelae independent of the hallmark metabolic abnormalities of diabetes mellitus, including hyperglycemia, hypertriglyceride-mia, and elevated concentrations of...

David J Schneider and Burton E Sobel

Optimal treatment of patients with diabetes requires an understanding of the mechanisms underlying the disease. Treatment must be designed not only to control hyperglycemia but also to prevent or retard complications that result from diverse processes underlying the development of diabetes. This chapter will focus on the therapeutic promise of elucidation of such processes and their cardiovascular consequences. All diabetic subjects exhibit hyperglycemia. Yet hyperglycemia is only the tip of an iceberg of abnormalities in carbohydrate, lipid, and protein metabolism. Although insulin deficiency is the hallmark of type 1 diabetes, 90 of diabetic subjects suffer from type 2 diabetes, a disorder of dysinsulinemia. For decades before its onset, insulin resistance and compensatory increases in the concentration of insulin and its precursors in blood are present, particularly postprandially. Impaired glucose tolerance occurs eventually as compensatory mechanisms fail. Early treatment may...

The Components Of Blood

Erythrocyte Sedimentation Rate Procedure

The ESR can be an important diagnostic index, as values are often significantly elevated during infection, in patients with arthritis, and in patients with inflammatory diseases. In some diseases, such as sickle-cell anemia, polycythemia (abnormal increase in red cell numbers), and hyperglycemia (elevated blood sugar levels), the ESR is slower than normal. The reasons for alterations in the ESR in disease states are not always clear, but the cells tend to sediment faster when the concentration of plasma proteins increases.

Clinical Relevance

Infections by themselves can destabilize diabetic control. Marked hyperglycemia and or ketoacidosis can, in turn, make the control of infection more difficult. Hyperglycemia and the generalized metabolic imbalance associated with diabetes mellitus are believed to be largely responsible for the disordered immune function seen in this disease. Significant dysfunction of the polymorphonuclear leukocyte (PMNL) chemotaxis, phagocytosis, and intracellular bactericidal capability have been identified (7-9). A recent study has implicated increased levels of cytosolic calcium secondary to hyperglycemia for the phagocytic defect in the diabetic PMNL (10). Improvement of the metabolic control results in improved function of these cells. Similar defects in monocyte function have also been described (11).

Indications For Insulin Therapy In Type 2 Diabetes

Insulin therapy has multiple forms and applications in type 2 diabetes (Table 1). Some of these indications are temporary, such as during an acute illness, in pregnancy, and when those taking metformin are at risk for renal insufficiency or other factors predisposing to lactic acidosis. Insulin is also indicated as initial therapy when individuals present with severe hyperglycemia (fasting glucose over 300 mg dl or random glucose values over 400 mg dl) with significant symptoms such as severe polyuria, severe fatigue, and weight loss. Obviously, insulin is often initiated as permanent therapy after a period of oral agent therapy when the insulin secretory defect has progressed to the point where insulin secretagogues are no longer able to supply adequate insulin to prevent severe hyperglycemia, even in the presence of complementary insulin sensitizers. At other times, insulin may be required earlier than normally expected because of intolerance or contraindications to one or more oral...

Insulin Therapy in Children

Hyperuricemia And Exercise

The traditional goals of treatment of children and adolescents with diabetes were to use insulin, diet, and exercise to minimize symptoms of hypoglycemia and hyperglycemia, promote normal growth and development, and, using intensive education and psychosocial support, maximize independence and self-management in order to reduce the adverse psychosocial effects of this chronic disease. Since the results of the DCCT were published, additional primary aims of therapy are to lower blood glucose and glycosylated hemoglobin values to as close to norma as possible. In pediatric patients, achievement of such stringent treatment goals is best accomplished with a multidisciplinary team of clinicians to provide ongoing education and support of aggressive self-management efforts on the part of parents and patients. Matching the treatment to the patient (rather than vice versa) by taking a flexible and varied approach to insulin replacement, diet, and exercise is critically important. A major...

Immunoassay Of Endogenous Plasma Insulin In Man

Centrations observed in diabetic subjects during the glucose tolerance test are not inconsistent with the less extensive data of Bornstein and Lawrence (1) and Baird and Bornstein (39). Very recently Seltzer and Smith (41), employing the rat diaphragm assay of Vallance-Owen and Hurlock (33), have reported insulin concentrations one hour after glucose, in tolbutamide-sensitive adult diabetics, almost in the normal range, but significantly lower values were observed in juvenile diabetics and adult tolbutamide-insensitive diabetics. To resolve the present finding of a higher than normal integrated insulin output in diabetics during the glucose tolerance test with sustained hyperglycemia in these patients, it must be concluded that the tissues of the maturity-onset diabetic do not respond to his insulin as well as the tissues of the nondiabetic subject respond to his insulin. However, from these observations it cannot be concluded that the early diabetic has the same maximal potential...

Type 2 Diabetes Mellitus

Insulin Resistance Symptoms Weight Gain

Type 2 diabetes is usually slow to develop, is hereditary, and occurs most often in people who are overweight. Genetic factors are very significant people at highest risk are those who have both parents with type 2 diabetes and those who are members of certain ethnic groups, particularly Native Americans of the Southwestern United States and Mexican-Americans. Unlike people with type 1 diabetes, those who have type 2 diabetes can have normal or even elevated levels of insulin in their blood. Despite this, people with type 2 diabetes have hyperglycemia if untreated. This must mean that, even though the insulin levels may be in the normal range, the amount of insulin secreted is insufficient to control blood glucose levels. Figure 19.12 Oral glucose tolerance in prediabetes and type 2 diabetes. The oral glucose tolerance test showing (a) blood glucose concentrations and (b) insulin values following the ingestion of a glucose solution. Values are shown for people who are normal,...

Insulin Therapy in Pregnancy

GLUCOSE TOXICITY AND THE ROLE OF POSTPRANDIAL HYPERGLYCEMIA If a mother has hyperglycemia, the fetus will be exposed to either sustained hyperglycemia or intermittent pulses of hyperglycemia. Both situations prematurely stimulate fetal insulin secretion. Fetal hyperinsulinemia may cause increased fetal body fat (macrosomia), and therefore a difficult delivery, or inhibition of pulmonary maturation of surfactant, and therefore respiratory distress of the neonate. The fetus may also have decreased serum potassium levels caused by the elevated insulin and glucose levels, which may lead to cardiac arrhythmias. Neonatal hypoglycemia may cause permanent neurological damage. After the period of organogenesis, maternal hyperglycemia interferes with normal growth and development during the second and third trimesters. The maternal postprandial glucose level has been shown to be the most important variable in the subsequent risk of neonatal macrosomia. The fetus thus is overnour-ished by the...

Therapeutic Implications

Consideration of the known derangements in platelet function, the coagulation system, and the fibrinolytic system and their probable contributions to exacerbation of macrovascular disease in type 2 diabetes give rise to several therapeutic considerations. Stringent glycemic control is an imperative to protect patients against microvascular complications including nephropathy, retinopathy, and neuropathy. However, we believe it should be achieved under conditions in which prevailing concentrations of insulin in blood are minimized. Furthermore, adjunctive measures are likely to be helpful. Empirical use of aspirin (160 to 325 mg day in a single dose) seems appropriate in view of the high likelihood that covert coronary artery disease is present even in asymptomatic subjects with type 2 diabetes and the compelling evidence that prophylactic aspirin reduces the risk of heart attack when coronary disease is present. Reduction of angiotensin-II and IV levels, known to stimulate PAI-1...

Atherogenesis In The Prediabetic State

Particularly fertile ground for germination of vulnerable plaques. Thus, a focus on treatment in the prediabetic state is likely to be important in preventing cardiovascular events later in ultimately diabetic subjects. One example is women with the polycystic ovary syndrome. These subjects are insulin-resistant and often have postprandial hyperglycemia. They are also often hypertensive. They are at increased risk for coronary artery disease. Accordingly, therapy designed to ameliorate insulin resistance is under intense investigation.

Vcardiomyopathy And Diabetes

Myopathy'' has been extant for decades. Implicated derangements include impaired function of the sarcoplasmic reticulum, an organelle responsible for the uptake and release of intracellular calcium and, therefore, pivotal in modulating cardiac contractility. However, cardiomyopathy changes may not be related exclusively to metabolic derangements typical of insulin deficiency. They occur also in hearts of patients with type 2 diabetes whose hyperglycemia is well controlled.

Monitoring and Screening Recommendations

The development of glucose intolerance and diabetes mellitus may be a very serious comorbid complication of treatment with antipsychotic agents, thus contributing to the morbidity and mortality in schizophrenia patients. The development of hyperglycemia in schizophrenia patients often goes unrecognized, as it does in approximately 50 of the general population who have this condition. Because patients taking antipsychotic medications may be at increased risk for developing diabetes, close monitoring and screening for obesity and hyperglycemia are imperative for individualizing treatment decisions and reducing the risks of morbidity and mortality (Haupt and Newcomer 2001). Before starting treatment with an atypical antipsychotic, the clinician should perform a risk factor assessment for diabetes mellitus and other metabolic disorders. This risk assessment should include baseline serum lipid and glucose values (preferably fasting), weight, body mass index, age, ethnicity, family history...

Conventional Antipsychotic Agents Diabetes and Glucose Intolerance

Conventional antipsychotic agents, which have primarily antidopaminer-gic activity, may alter glucose-insulin homeostasis (Hagg et al. 1998). In particular, the low-potency phenothiazines may induce diabetes mellitus or aggravate existing diabetes mellitus (Hagg et al. 1998 Haupt and Newcomer 2001). Because of this finding, chlorpromazine has been used to prevent hypoglycemia in patients with malignant insulinoma. Furthermore, chlorpromazine has been shown to induce hyperglycemia in healthy volunteers as well as in patients with latent diabetes (Hagg et al. 1998).

Mechanisms Contributing To Diabetic Cardiomyopathy

Hyperglycemia per se may cause myocardial damage by glycation of myo-cardial matrix proteins with formation of advanced glycosylation end-products (AGEs) and associated free-radical-mediated damage that, in the case of collagen, causes increased cross-linking. This may be the mechanism underlying the common histological finding of increased PAS positive material in myocardium from diabetic patients and is an attractive possibility as an explanation for echocardio-graphic Doppler findings consistent with decreased compliance. However, very limited immunohistopathological studies directed specifically at detection of AGEs in myocardium of autopsied patients with diabetes have not shown extensive deposition. In very small studies examining the histological appearance of myocardium obtained by endomyocardial biopsy in diabetic patients with evidence of cardiomyopathy who do not have coronary artery disease or hypertension, only very modest increases in connective tissue have been...

Anorexigenic Peptides

Mice lacking the MC4 receptors (MC4-R-deficient mice). These mice (female and male) exhibit increased food intake and become obese. Both sexes have marked hyperinsulinemia, hyperleptinemia, with either normoglycemia (females) or hyper-glycemia (males), plasma corticosterone levels being normal. These data support the view that MC4 receptors are essential in the cascade of events normally leading to decreased food intake and leanness

Effects or Functions of Specialized Cells

Although they do not immediately kill cells, infections with noncytocidal viruses often interfere with the specialized functions of differentiated cells. For example, lymphocytic choriomeningitis (LCM) virus replicating in somatotropic cells of the pituitary gland of the persistently infected mouse lowers the production of the mRNA for growth hormone in the infected cells, thus impeding the growth and development of the animal. Similarly, LCM virus replicating in 3 cells of the islets ol Langerhans in the pancreas can induce hyperglycemia in the mouse, not dissimilar to insulin-dependent diabetes in humans. (3-Adrenergic receptors and opiate receptors are impaired in brain cells persistently infected with measles virus. Viruses that infect lymphocytes may induce a generalized immunosuppression. Rhinovirus infection of the nasal epithelium results in cilial stasis and later in the destruction of cilia, although the cells are often not killed. This effect can be demonstrated in organ...

Tumor Associated and Pathogen Induced Expression of MIC

MIC are frequently expressed in many, but not all, lung, breast, kidney, ovarian, prostate, gastric, and colon carcinomas and melanomas (Groh et al. 1999 Vetter et al. 2002). There are high degrees of variability in the proportions of tumor cells that are positive for MIC. The physiological reasons are unknown, but they could be related to local stress-inducing conditions such as tumor cell proliferation, hypoxia, and hyperglycemia. Oxidative stress has been shown to increase MIC gene expression in a colon carcinoma cell line (Yamamoto et al. 2001). Modest MIC expression has also been reported in some hematopoietic malignancies (AML, ALL, and CML), perhaps most significantly in multiple myeloma (Salih et al. 2003).

The Pancreas and Diabetes

The most common endocrine disorder, and a serious public health problem, is diabetes mellitus, a failure of the body cells to use glucose effectively. The excess glucose accumulates in the blood, causing hyperglycemia. Increased urination (polyuria) marks the effort to eliminate the excess glucose in the urine, a condition termed glycosuria. The result is dehydration and excessive thirst (polydipsia). There is also weakness, weight loss, and extreme hunger (polyphagia). Unable to use carbohydrates, the body burns more fat. This leads to accumulation of ketone bodies in the blood and a shift toward acidosis, a condition termed ketoacidosis. If untreated, diabetes will lead to starvation of the central nervous system and coma. Diabetic patients are prone to cardiovascular, neurologic, and vision problems, infections, and, sometimes, renal failure. There are two types of diabetes mellitus. Heredity seems to be a factor in the appearance of both. Type 1, also called juvenile-onset or...

Management of Diabetes in Patients with Heart Failure

Poorly controlled diabetes should be managed aggressively in any patient with CHF because the attendant metabolic stress can certainly have adverse effects on myocardial function. Stringent control of blood glucose reduces the incidence of several complications of diabetes, specifically retinopathy, neuropathy, and nephropathy, but no data are available pertaining to the long-term effects of stringent control on diabetic cardiomyopathy or CHF in general in patients with diabetes. To the extent that diabetic cardiomyopathy is caused by hyperglycemia per se (e.g., matrix glycosylation) or the intracellular metabolic effects of reduced glucose transport (e.g., free radical damage to membranes), normalization of carbohydrate metabolism makes intuitive sense. Moreover, stringent control has been shown to modestly reduce event rates after an index myocardial infarction. On the other hand, prolonged hyperinsulinemia may be atherogenic and pro-thrombotic in type II diabetic patients. Thus, it...

Treatment Of The Hormonal And Metabolic Abnormalities Of Diabetes

Control of hyperglycemia retards progression of microvascular disease in both type 1 and type 2 diabetes. Accordingly, stringent glycemic control is imperative. Yet glycemic control exerts only a modest impact in retarding progression of macrovascular disease. Clearly other steps are needed.

Problems of Establishing the Cause of Death at Postmortem

In attempting to establish a post-mortem diagnosis of hypoglycaemia, the pathologist needs to perform biochemical tests, examine the brain for evidence of hypoglycaemic brain damage, and exclude any other possible cause of death (Tattersall and Gale, 1993). Carbohydrate metabolism continues after death, and post-mortem changes in blood glucose can cause difficulties in confirming a hypoglycaemic death forensically. The continuing breakdown of glycogen (glycogenolysis) increases the blood glucose concentration in the inferior vena cava, so that the presence of a normal or high blood glucose concentration on the right side of the heart does not exclude ante-mortem hypoglycaemia (a false negative result for a diagnosis of hypoglycaemia). In the peripheral circulation, glucose continues to be utilised by red blood cells, so that the presence of a low glucose concentration does not necessarily indicate ante-mortem hypoglycaemia. Indeed low blood glucose is often found after death in those...

Developing the Full Hormonal Picture

Isolated hormones have been injected into experimental organisms and organ extracts, followed by observation and recording of the animal's physiological responses. For example, injection of vasopressin reduces an animal's urine output while simultaneously producing a slight blood pressure rise. Injection of insulin lowers blood sugar levels, which is why diabetics are prescribed insulin. Such experiments require the use of experimental animals, and extracts from these animals, which has sparked considerable controversy and debate concerning animal rights. These studies are important in understanding the physiology of the human body.

Harold E Lebovitz

Diabetes mellitus has many etiologies, all of which cause high plasma glucose as defined above (hyperglycemia) and carry a risk for the development of both microvascular and macrovascular complications. Disorders of glucose metabolism are defined as impaired fasting plasma glucose (IFG), impaired glucose


Insulin resistance, defined as an attenuation of normal insulin action, is a key pathogenic phenomenon observed in the natural history of type 2 diabetes (1,2). Development of this condition in insulin-sensitive peripheral tissues (e.g., muscle and fat) results in hyperinsulinemia, a compensatory mechanism required to maintain normal or near-normal glucose levels. This ''compensated'' state may be maintained for many years. Once pancreatic P-cell dysfunction occurs, however, inability to compensate for the increased insulin resistance results in clinical hyperglycemia and the diagnosis of type 2 diabetes is then apparent and can be made on clinical grounds. As such, insulin resistance can be considered an initial pathophysiological event leading to, and premonitory of, type 2 diabetes (3-5). Intensive research has been aimed at identifying the cellular mechanisms responsible for insulin resistance and providing a framework for designing pharmacological therapies to alleviate the...


It is important to note that this increased predisposition for the development of peripheral vascular disease among diabetic patients is not true in patients who have simple glucose intolerance. Other studies have investigated the incidence in prevalence of peripheral vascular disease among patients with glucose intolerance, but not frank diabetes (16-17). In all cases, the incidence of peripheral arterial disease was no different among those who have glucose intolerance compared to age-matched controls. In the Casteldaccia study (18) that involved 102 healthy volunteers and 102 predominately male patients with peripheral arterial disease, factors such as arterial hypertension, hypercholesteremia, hypertriglyceridemia, smoking habits, and hyperglycemia were correlated with the incidence of peripheral arterial disease. This study showed that smoking and hypercholesterolemia were the most important risk factors for the development of peripheral arterial disease. Moreover, this and other...

Urine Ketone Testing

Positive urinary ketones do not always indicate sickness. Ketones are a byproduct of fat metabolism, and their presence with normal blood sugars can indicate fat mobilization in a patient who is actively trying to lose weight by restricting calories. However, patients with type 1 diabetes who are restricting their calories for weight management may also restrict their insulin, resulting in metabolic decompensation and DKA in the absence of marked hyperglycemia. This is especially common in teenage girls who desire rapid weight loss such as during prom season. Thus, patients should carefully monitor urinary ketones and glycemia during periods of caloric restriction.

Type 2 Diabetes

Accordingly, in the Leiden 85-Plus Study66 it has been demonstrated that low production of IL-10 by stimulated peripheral blood cells, associates with the metabolic syndrome and type 2 diabetes. It was found that individuals with raised blood glucose tended to have a low capacity to produce IL-10. A similar association was shown between high plasma triglyceride concentrations and low production capacity of IL-10. Even if this study does not consider the possibility that the elevation of blood glucose concentration itself could have a direct effect upon cellular IL-10 production, it seems to confirm the role of inflammation in the aetiology of type 2 diabetes.


There are three general levels of glycemic control that can be set as goals in the management of patients with type 1 or type 2 diabetes (1) keep patients out of ketoacidosis and hyperosmolar coma (2) prevent symptoms of hyperglycemia (e.g., polyuria) and catabolism (fatigue, weight loss, and hyperphagia) and (3) prevent long-term complications associated with diabetes. In the absence of extenuating social or medical circumstances that make prevention of long-term complications irrelevant (e.g., terminal illness) or infeasible (e.g., inability of the patient to cooperate with a complex care program), the third level should be the standard of care for people with diabetes. The effectiveness of good glycemic control in slowing or preventing the development of diabetic retinopathy, ne-phropathy, and neuropathy has been demonstrated in several well-controlled clinical trials and is beyond question. Whether good glycemic control has a beneficial effect on the risk of atherosclerosis and...

Control Improves

Improved blood glucose control is associated with a number of effects that could contribute to a reduction in the risk of clinical cardiovascular events such as myocardial infarction and stroke. Improved glycemia lowers PAI-1 concentrations and reduces platelet adhesiveness and aggregability. Chronic amelioration of hyperglycemia reduces glycation of proteins in the arterial wall and in circulating lipoproteins. Improved glycemia is associated with an amelioration of the circulating lipid abnormalities, especially the elevated triglycerides and low HDL cholesterol that are typical of poorly controlled type 1 or type 2 diabetes. No clinical trial has been conducted exclusively in patients with diabetes to determine the effects of lipid lowering per se on cardiovascular events. However, several lipid-lowering trials have included patients with type 2 diabetes. Post hoc analysis of those trials is informative about the potential role of hyperlipidemia in the genesis of atherosclerosis in...


Hypertriglyceridemia associated with increased concentrations of the atherogenic small, dense LDL cholesterol and low levels of HDL cholesterol are the most frequently observed lipid and lipoprotein abnormalities associated with type 2 diabetes. Baseline triglyceride levels change with the development of DM and correlate well with levels of fasting hyperglycemia. Control of hyperglycemia ameliorates but does not normalize these abnormalities. There is no consensus on the best method to assess CAD in diabetics or whether diabetics with CAD should have a more aggressive target for LDL cholesterol reduction (and HDL cholesterol augmentation) than nondiabetics. Nevertheless, strategies based essentially on LDL reduction in these patients do provide a basis for treatment of the elevated LDL in facilitating diabetic vasculopathy and, hence, indirectly support a more aggressive approach to dyslipidemia management in diabetic subjects with CAD.


Another example of a condition with claims of treatment by magnets is diabetic neuropathy, a painful and disabling complication of high blood glucose, which is treated with drugs, including antidepressants, anticonvulsants, and analgesics, with mixed results. A small single-site pilot study of the effectiveness of magnetic foot insoles for the treatment of pain due to diabetic neuropathy reportedly showed a reduction in symptoms of burning and numbness and tingling 30 . Consecutive patients (14) with diagnosed advanced chronic peripheral neuropathic pain secondary to diabetes, who had failed conventional pharmacologic treatments, and 10 patients with peripheral neuropathies not related to diabetes, were recruited for this study. These patients wore active (475 Gauss) or sham magnetic insoles on opposing feet (in shoes). They rated the level of pain on a continuous five-point visual analog scale twice daily for each foot. After 30 days, the active and sham insoles were switched and...


In a case control study, there was some trending supporting evidence that, in the absence of DM, homeostatic glycemic control (HbAlC) was a risk factor for atherosclerosis (117). Also, subjects from the general population with mild to moderate hyperglycemia following oral glucose load, but not in the fasting state, showed increased CVD risk (reviewed inref. 118).

Sex Hormones Effects

Progesterone is an inhibitor of human VSMC proliferation induced by hyperglycemia and hyperinsulinemia in vitro (333). However, in The Heart and Estrogen Progestin Replacement Study (HERS) carotid B-mode ultrasound examinations substudy, there were no significant treatment effects on carotid IMT (334). Also, in the Los Angeles Atherosclerosis Study the common carotid artery IMT was significantly related to years since bilateral oophorectomy, even though 90 of this group had a history of HRT. This finding which conflicts with a concept that such therapy reverses the adverse effect of bilateral oophorectomy on CHD (335). HRT significantly increased antibodies against Hsp 65 and against LDL with a low degree of oxidative modification. The hormonemediated immune response may trigger an inflammatory response within the vessel wall and potentially increase plaque burden (336). Also, oral

Antidiabetic Drugs

Hyperglycemia hypoglycemia insulin Diabetes mellitus is a complicated, chronic disorder characterized by either insufficient insulin production by the beta cells of the pancreas or by cellular resistance to insulin. Insulin insufficiency results in elevated blood glucose levels, or hyperglycemia. As a result of the disease, individuals with diabetes are at greater risk for a number of disorders, including myocardial infarction, cerebrovascular accident (stroke), blindness, kidney disease, and lower limb amputations. Those with type 1 diabetes mellitus produce insulin in insufficient amounts and therefore must have insulin supplementation to survive. Type 1 diabetes usually has a rapid onset, occurs before the age of 20 years, produces more severe symptoms than type 2 diabetes, and is more difficult to control. Major symptoms of type 1 diabetes include hyperglycemia, polydipsia (increased thirst), polyphagia (increased appetite), polyuria (increased urination), and weight loss....


Insulin is a hormone manufactured by the beta cells of the pancreas. It is the principal hormone required for the proper use of glucose (carbohydrate) by the body. Insulin also controls the storage and utilization of amino acids and fatty acids. Insulin lowers blood glucose levels by inhibiting glucose production by the liver.


Metformin (Glucophage), currently the only biguanide, acts by reducing hepatic glucose production and increasing insulin sensitivity in muscle and fat cells. The liver normally releases glucose by detecting the level of circulating insulin. When insulin levels are high, glucose is available in the blood, and the liver produces little or no glucose. When insulin levels are low, there is little circulating glucose, so the liver produces more glucose. In type 2 diabetes, the liver may not detect levels of glucose in the blood and, instead of regulating glucose production, releases glucose despite blood sugar levels.


Like the sulfonylureas, the meglitinides act to lower blood glucose levels by stimulating the release of insulin from the pancreas. This action is dependent on the ability of the beta cell in the pancreas to produce some insulin. However, the action of the meglitinides is more rapid than that of the sulfonylureas and their

Metabolic Syndrome

The metabolic abnormalities associated with DM are well recognized and include insulin resistance (or, more appropriately, dysinsulinemia), hyperglycemia, hypertension, and dyslipidemia. These factors are associated with a panoply of biological perturbations that result in endothelial dysfunction with impaired coronary flow reserve, increased platelet activity, increased thromboxane A2 secretion,

Otitis Externa

Otitis externa is observed in the summer months more frequently, as the maceration of the skin lining the externa auditory meatus is facilitated by heat, humidity, and perspiration. Swimming may lead to otitis externa (swimmer's ear) by introducing moisture into the ear canal. Malignant otitis externa is typically seen in elderly diabetics in whom chronic hyperglycemia, tissue hypoperfusion due to microangiopathy, altered cell-mediated immunity, and impaired phagocytic function all play a pathogenetic role. Occasionally, malignant otitis externa has been noted after the syringing of the ear canal (4) and in patients infected with human immunodeficiency virus (HIV) (5). Complications that may be life threatening could result from the spread to the temporal bone, sigmoid sinus, jugular bulb, base of the skull, meninges, and the brain.


A person with type 1 diabetes mellitus depends on insulin injections to prevent hyperglycemia and ketoacidosis. If inadequate insulin is injected, the person may enter a coma as a result of the ketoacidosis, electrolyte imbalance, and dehydration that develop. An overdose of insulin, however, can also produce a coma as a result of the hypoglycemia (abnormally low blood glucose levels) produced. The physical signs and symptoms of diabetic and hypoglycemic coma are sufficiently different to allow hospital personnel to distinguish between these two types.


The endocrine portions of the pancreas are the pancreatic islets, small clusters of cells within the pancreatic tissue. The term islet, meaning small island, is used because these cells look like little islands in the midst of the many pancreatic cells that secrete digestive juices (Fig. 16-5). The islet cells produce two hormones, insulin and glucagon, that regulate sugar metabolism. Insulin increases cellular use of glucose, thus decreasing sugar levels in the blood. Glucagon has the opposite effect of increasing blood sugar levels.

Glycerol Transport

The coordinated regulation of the expression and activity of HSL, FATP and AQPap (during fasting, see above) will benefit the effective release of FA and gly-cerol from adipocytes. Physiologically coordinated regulation of the AQPap and FATP1 genes by insulin should be efficient for supplying glycerol and NEFA in accordance with nutritional conditions. However, the suppression of AQPap (as well as FATP1) mRNA expression by feeding was impaired in obese mice with insulin resistance despite high concentrations of plasma insulin leading to higher glycerol and NEFA plasma levels 308 . Consistent with this finding, using micro-dialysis the interstitial glycerol concentration in subcutaneous fat tissue was found to be elevated in obese mice and increased glycerol production in fat tissue was reported for obese humans 312 . Hyperglycerolemia and increased glycerol turnover rate in combination with increased NEFA influx into the liver in obesity contributes to elevated hepatic glucose...


Driving is a common and everyday activity that demands complex psychomotor skills, including good visuo-spatial functions, rapid information processing, vigilance and satisfactory judgment. Because hypoglycaemia rapidly interferes with cognitive functions, even modest degrees of neuroglycopenia may affect driving skills, without necessarily provoking symptomatic awareness of hypoglycaemia. Seminal studies using a sophisticated driving simulator have examined the driving abilities of drivers with type 1 diabetes at different blood glucose concentrations, maintained by a glucose clamp (Cox et al., 1993 Cox et al., 2000). Driving performance started to deteriorate when blood glucose declined below 3.8mmol l, and typical driving deficiencies included speeding and inappropriate braking, driving off the road, crossing the centre line, ignoring 'STOP' signs and causing an increased number of 'crashes'. Allowing for the artificial conditions of a driving simulator, it is evident that...

Diagnostic Tests

With bacterial meningitis, the CSF generally has the characteristics shown in Table 3 and, in surveys of this disease in older adults, no differences were noted in the diagnostic criteria including pleocytosis, hypoglycorrhachia, or positive cultures. Additionally, the rate at which blood cultures were positive also seemed similar to that in younger patients. The determination of hypoglycorrhachia may be more difficult in patients with peripheral blood hyperglycemia or hypoglycemia. A serum glucose drawn at approximately the same time as the lumbar puncture is mandatory ratios of CSF glucose to serum glucose of less than 0.31 are consistent with hypoglycorrhachia and bacterial meningitis (20). A minority of patients with bacterial meningitis may demonstrate atypical CSF parameters, particularly a lymphocytic response or lower percentage of neutrophils or a Gram stain without organisms (19). This scenario is especially seen with L. monocytogenes meningitis in which the Gram stain is...

Insulin Storage

Improperly stored insulin is a common cause of erratic or high blood sugars, and should be considered if there is a change in the patient's glycemic control, or if a patient does not seem to be responding to his insulin as usual, especially when traveling. Patients should be given the following instructions

Materials 21 General

Mice mice can be maintained in conventional housing. Because infection can influence tolerance induction, it may be preferable to use a specific-pathogen free facility. Ideally animals should be 6-8 wk old at the time of transplantation. Mice up to 12 wk old may be used. The strains selected will depend on the degree of antigenic mismatch required. Definitive information concerning the MHC genotype of available mouse strains can be found on the Jackson website (www.jax.org). For study of immunological mechanisms resulting in rejection of islet transplants (as opposed to the autoimmune disease process) it is not necessary to use spontaneously diabetic mice (i.e., NOD mice). Diabetes can be induced by injection of streptozotocin (STZ), allowing monitoring of graft function by the measurement of blood sugar levels. NOD mice may reproduce some unique features of the diabetic genetic background. If it is considered desirable to use this strain, development of autoimmune diabetes may...