How I Healed my Diabetes

The Big Diabetes Lie

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The Big Diabetes Lie Summary

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I usually find books written on this category hard to understand and full of jargon. But the author was capable of presenting advanced techniques in an extremely easy to understand language.

All the modules inside this book are very detailed and explanatory, there is nothing as comprehensive as this guide.

Pathophysiology of Uncontrolled Diabetes

Pathophysiology Loss Weight

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

Developmental Origins of Cardiovascular Disease Type 2 Diabetes and Obesity in Humans

Fetal Origins Adult Disease

Fetal growth restriction and low weight gain in infancy are associated with an increased risk of adult cardiovascular disease, type 2 diabetes and the Metabolic Syndrome. The fetal origins of adult disease hypothesis proposes that these associations reflect permanent changes in metabolism, body composition and tissue structure caused by undernutrition during critical periods of early development. An alternative hypothesis is that both small size at birth and later disease have a common genetic aetiology. These two hypotheses are not mutually exclusive. In addition to low birthweight, fetal 'overnutrition caused by maternal obesity and gestational diabetes leads to an increased risk of later obesity and type 2 diabetes. There is consistent evidence that accelerated BMI gain during childhood, and adult obesity, are additional risk factors for cardiovascular disease and diabetes. These effects are exaggerated in people of low birthweight. Poor fetal and infant growth combined with recent...

Gestational Diabetes Mellitus

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

Biomedical Anthropology and Obesity The Primary Risk Factor for Type 2 Diabetes

More than 80 of new cases of type 2 diabetes are associated with obesity. This association has been demonstrated in many populations worldwide. Furthermore, risks correlate not only with the degree of adiposity but with the duration and distribution of body fat. A centripetal distribution of fat is a separate risk factor for both cardiovascular disease and diabetes and occurs more frequently in populations with high diabetes prevalence (Harris, 1991 Joos et al., 1984 Lieberman et al., 1999 Mueller et al., 1984). The risk occurs for both adults and Obesity and diabetes are linked to each other, and both are linked to dietary acculturation that involves the consumption of a surfeit of energy regardless of the food source (Kuhnlein & Receveur, 1996 Popkin, 2001 Teufel, 1996). Obesity has been extensively studied in populations with high diabetes prevalence. Overweight and obesity are in excess of 60 of the adults among Native Americans (ADA, 2002b Hall et al., 1992 Hanley et al., 2000...

TABLE 2098 Cutaneous Disorders and Infections Associated with Diabetes Mellitus Disposition And Indications For

Guidelines for admission considerations are listed in Table209 9. These guidelines may result in admissions for diabetic patients for conditions that may be treated on an outpatient basis in the nondiabetic population. 26 Patients who present with new-onset type 2 diabetes, type 1 diabetes without evidence of metabolic decompensation, acute hypoglycemia or hyperglycemia, and do not meet the aforementioned criteria for admission should see their primary care provider within 24 to 48 h as a general rule to arrange for general education and dietary evaluation and to initiate appropriate therapy for glycemic control. General discharge instructions for all diabetics, new or established, are detailed in Table 1. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20 1183, 2. Zimmet PZ, McCarty DJ, de Courten MP The global epidemiology of non-insulin dependent diabetes...

Principles of Dietary Management of Diabetes

Individualization Individualization is a cardinal principle of medical nutrition therapy for diabetes, facilitating individual lifestyle and behavior changes that will lead to improved metabolic control. Since no one diet fits all, the standard, printed diabetic diet is inadequate. Rather, people with diabetes need to consult a person trained in dietetics, one able to develop and teach an individualized nutritional prescription. Table 2 indicates the range of goals that may need accommodation among different people with diabetes. Developing the diabetes nutrition plan With the emphasis on individualization, the meal plan is driven by the diagnosis, pharmacologic treatment, lifestyle, and treatment goals. Important consideration is given to dietary preferences, socioeconomic factors, and the patient's ability to understand and implement instructions. Some patients will need instruction on fine points such as carbohydrate counting others will benefit from the crudest of prescriptions,...

Dietary Transitions Lifestyle Factors and Diabetes

Anthropologists have explored cultural models of illness and the experience of being a person with diabetes. Cultural etiological models often include dietary elements, especially sugar and processed foods, that represent a departure from traditional, ethnically important diets (Kuhnlein & Receveur, 1996). Although many studies discuss the historical trends in type 2 diabetes as a result of modernization, Westernization, or even cokacolization and McDonaldization as creating obeseogenic and diabetogenic environments (Drewnowski & Popkin, 1997 Eaton, Eaton, & Konner, 1999 Popkin 1998, 2001 Wickelgren, 1998), only a few anthropological studies have explicitly documented these changes. Szathmary et al. (1987) found that the Dogrib of Canada retained traditional dietary items and added new foods, thereby increasing diet breadth and caloric intake. The Sandy Lake Cree classified foods and illnesses into Indian and White Man's groups with the notion that the consumption of White...

Maturity Onset Diabetes of the Young MODY

MODY are a group of monogenic disorders inherited in an autosomal dominant pattern. MODY is characterized by early onset (usually before the age of 25 years) of T2D fi cell dysfunction and there being a family history (at least two generations) of early onset diabetes. The defect is in insulin secretion due to mutations in the glucokinase and fi cell transcription factor genes (Table 2). Hepatocyte nuclear factors (HNF) 1a, 1fi, and 4a, insulin promoter factor (IPF1), and neurogenic differentiation (NEUROD1) play an important role in the normal development and function of the fi cells of the pancreas. In the UK mutations in HNF1a is the commonest cause of MODY accounting for 63 of cases, followed by mutations in the glucokinase gene (20 of cases). The clinical presentation and progression of diabetes is Table 2 Maturity onset diabetes of the young Table 2 Maturity onset diabetes of the young

The effect of insulin and IGF1 on the cytoskeleton in relation to SMC migration

Actin Cytoskeleton And Insulin

10 min after insulin 10 imin after insulin + diltiazem FIG. 2. Insulin-induced F-actin reorganization near the membrane of human vascular smooth muscle cells showing a ruffling which does not appear when Ca2+ channels of these cells are blocked by diltiazem. The results are similar in the case of IGF1 (unpublished). 10 min after insulin 10 imin after insulin + diltiazem FIG. 2. Insulin-induced F-actin reorganization near the membrane of human vascular smooth muscle cells showing a ruffling which does not appear when Ca2+ channels of these cells are blocked by diltiazem. The results are similar in the case of IGF1 (unpublished). cytoskeletal types, the actin filaments are primarily responsible for many cell movements, for example for SMC migration (Alberts et al 1994, p 787 803). According to Bretscher's model of fibroblast locomotion, actin filaments depolymerize ahead of the nucleus, generating actin subunits which diffuse to the cell's front where actin filaments polymerize at the...

Insulinoma Clinical Features

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

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

Healthy Pancreas And Insulin

When glucose enters the bloodstream from the intestine after a carbohydrate-rich meal, the resulting increase in blood glucose causes increased secretion of insulin (and decreased secretion of glucagon). Insulin release by the pancreas is largely regulated by the level of glucose in the blood supplied to the pancreas. The peptide hormones insulin, glucagon, and somatostatin are produced by clusters of specialized pancreatic cells, the islets of Langerhans (Fig. 23-24). Each cell type of the islets produces a single hormone a cells produce glucagon 3 cells, insulin and 8 cells, somatostatin. 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...

Diabetes Mellitus Arises from Defects in Insulin Production or Action

Diabetes mellitus, caused by a deficiency in the secretion or action of insulin, is a relatively common disease nearly 6 of the United States population shows some degree of abnormality in glucose metabolism that is indicative of diabetes or a tendency toward the condition. There are two major clinical classes of diabetes mellitus type I diabetes, or insulin-dependent diabetes mellitus (IDDM), and type II diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), also called insulin-resistant diabetes. In type I diabetes, the disease begins early in life and quickly becomes severe. This disease responds to insulin injection, because the metabolic defect stems from a paucity of pancreatic 3 cells and a consequent inability to produce sufficient insulin. IDDM requires insulin therapy and careful, lifelong control of the balance between dietary intake and insulin dose. Characteristic symptoms of type I (and type II) diabetes are excessive thirst and frequent urination (polyuria),...

Biomedical Anthropology and the Evolution of Diabetes Thrifty Genotypes and Phenotypes

Anthropologists have been interested in evolutionary models of type 2 diabetes that explain the vastly different prevalence rates among worldwide populations. Of interest is the current epidemic in populations with multiple generations of high diabetes rates (i.e., Pima Indians), in newly designated populations with rapidly increasing incidence rates (i.e., urban South African populations), and in children and adolescents in populations that have had a history of high prevalence rates among adults (i.e., African American youth) (Lieberman, 1993,2000). Geneticist J. V. Neel first proposed a thrifty genotype for glucose utilization among Native American populations as an evolutionary explanation for their high prevalence rate of type 2 diabetes (Neel, 1962, 1982 Neel, Weder, & Julius, 1998). He hypothesized that a feast and famine existence conferred a selective advantage and increased reproductive fitness for those individuals who had the ability to release insulin quickly, to...

Fibrocalculous Pancreatic Diabetes

In tropical countries there is a form of nonalcoholic chronic pancreatitis characterized by pancreatic exocrine and endocrine insufficiency and associated with pancreatic calcification. This disease, tropical calcific pancreatitis, affects young individuals who are malnourished and present with abdominal pain, extreme emaciation characteristic of protein-energy malnutrition, glucose intolerance, and at a later stage diabetes. The diabetic stage of the illness is referred to as fibrocalcific pancreatic diabetes (FCPD). Several reports of FCPD have been reported from the tropical countries and many cases have been reported from the Indian subcontinent. The pathogenesis of the disease is still unclear and is attributed to various possible causes -malnutrition, cassava toxicity, oxidant stress due to micronutrient deficiency, genetic and environmental factors. Recently, a study showed the N34S variant of the SPINK1 trypsin inhibitor gene as a susceptibility gene for FCPD in the Indian...

How Is a Hormone Discovered The Arduous Path to Purified Insulin

Millions of people with type I (insulin-dependent) diabetes mellitus inject themselves daily with pure insulin to compensate for the lack of production of this critical hormone by their own pancreatic 3 cells. Insulin injection is not a cure for diabetes, but it allows people who otherwise would have died young to lead long and productive lives. The discovery of insulin, which began with an accidental observation, illustrates the combination of serendipity and careful experimentation that led to the discovery of many of the hormones. In 1889, Oskar Minkowski, a young assistant at the Medical College of Strasbourg, and Josef von Mering, at the Hoppe-Seyler Institute in Strasbourg, had a friendly disagreement about whether the pancreas, known to contain lipases, was important in fat digestion in dogs. To resolve the issue, they began an experiment on fat digestion. They surgically removed the pancreas from a dog, but before their experiment got any farther, Minkowski noticed that the...

Glycogen Synthase Kinase 3 Mediates the Actions of Insulin

As we saw in Chapter 12, one way in which insulin triggers intracellular changes is by activating a protein ki-nase (protein kinase B, or PKB) that in turn phosphor-ylates and inactivates GSK3 (Fig. 15-29 see also Fig. 12-8). Phosphorylation of a Ser residue near the amino terminus of GSK3 converts that region of the protein to a pseudosubstrate, which folds into the site at which the priming phosphorylated Ser residue normally binds (Fig. 15-28b). This prevents GSK3 from binding the priming site of a real substrate, thereby inactivating the enzyme and tipping the balance in favor of dephosphor-ylation of glycogen synthase by PP1. Glycogen phosphorylase can also affect the phosphorylation of glycogen synthase active glycogen phosphorylase directly inhibits PP1, preventing it from activating glycogen syn-thase (Fig. 15-27). Although first discovered in its role in glycogen metabolism (hence the name glycogen synthase kinase), GSK3 clearly has a much broader role than the regulation of...

Medical Anthropology and Diabetes

Since the 1960s anthropologists have published on a diversity of topics related to type 2 diabetes. Weidman (2001) cites over 130 articles, chapters, and books published from 1975 to 2001 by anthropologists. These articles have appeared in anthropology, medical, epidemiology, and nutritional science journals Diabetes research is multifold evolutionary and genetic aspects lifestyle factors, especially dietary factors traditional and contemporary explanatory models of illness and interactions with the biomedical healthcare system. Research has been spurred by the wide range of differences in the prevalence of type 2 diabetes among populations, its devastating societal impact, and its rapidly increasing worldwide incidence and prevalence. In addition to Weidman's (2002) review, there are other comprehensive reviews by anthropologists. Eaton was the first to present a biocultural overview of diabetes in Medical Anthropology (Eaton, 1977). In 1989 Medical Anthropology devoted an entire...

Insufficient insulin production

Glucose is the major stimulus for insulin secretion, which in turn prevents rises in glucose levels. Therefore an elevated glucose level implies a lack of sufficient insulin to maintain normoglycemia. Such a lack of sufficient insulin may occur in the presence of both low and high absolute levels of insulin, depending on the degree of insulin resistance. A number of observations support the possibility that insufficient insulin secretion may be related to cardiovascular disease. Patients with both type 1 diabetes (with no endogenous insulin secretion) and type 2 diabetes (who are not able to make sufficient insulin to prevent hyperglycemia) are at high risk for cardiovascular disease. Intensified insulin therapy may decrease this risk, and certainly does not seem to worsen it (see below). Patients with hypertension and other cardiovascular risk factors are resistant to the antilipolytic effects of insulin 50 any decrease in the secretory capacity of insulin would accentuate this and...

Diabetes Epidemiology

In 2000 the worldwide estimate by the International Diabetes Federation (IDF) was 151 million adults (20-79 years) with type 2 diabetes. This is an increase from 30 million in 1985 and 135 million in 1995. There is a projected global estimate of 300 million people in 2025 (IDF, 2001). Because higher energy intakes and lower energy expenditures are having differential impacts on developed and developing countries, the prevalence of type 2 diabetes in developing countries is expected to increase by 170 compared with a rise of 41 in developed countries between 1995 and 2025 (IDF, 2001). Approximately half this increase will be Asian and Pacific Islander populations. China is predicted to have a prevalence increase of 68 , followed by India (59 ) and other Asian countries and the Pacific Islands (41 ) (Joslin Diabetes Center, 2002). By comparison, the worldwide estimate for type 1 diabetes was 4.9 million in 2000 and is not expected to show a major increase in prevalence. The Diabetes...

Definition and epidemiology of diabetes and impaired glucose tolerance

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

The incretin effect in ageing and in type 2 diabetes

Incretin is the umbrella term to cover the multiple gut factors (now known to be hormones) which augment insulin response above that which can be attributed to glucose alone. This insulinotropic effect has been demonstrated by matching the time course of the plasma glucose excursion following an OGTT with both an i.v. infusion of glucose (Perley & Kipnis 1967) and during a hyperglycaemic clamp. In the hyperglycaemic clamp, plasma glucose was increased to * 11 mmol l for 2 h on two different occasions. In one, only glucose was infused, while in the second, an OGTT was administered at 60 min and the exogenous glucose infusion rate was adjusted during the second hour as the ingested glucose was being absorbed in this manner the plasma glucose level remained at the same plateau level in the second hour as in the first hour (Andersen et al 1978). During the second hour in the study, despite the constancy of the plasma glucose concentration, a marked potentiation of insulin secretion was...

Glucose tolerance glucose utilization and insulin secretion in ageing

Ageing is associated with an increased incidence of hypertension, macrovascular disease and type 2 diabetes (non-insulin-dependent diabetes). It has been suggested that a common mechanism may be responsible for all of these pathological states since all of these conditions often cluster in the same individual. Epidemiological and clinical data have consistently demonstrated an association between insulin resistance and or hyperinsulinaemia and glucose intolerance, dyslipidaemia and elevated systolic blood pressures. Therefore, insulin resistance and hyperinsulinaemia have been proposed as the causal link among the elements of the clusters. The elderly are more glucose intolerant and insulin resistant, but it remains controversial whether this decrease in function is due to an inevitable consequence of 'biological ageing' or due to environmental or lifestyle variables, noticeably increased adiposity altered fat distribution and physical inactivity. An increase of these...

Large Scale Community Coronary Heart Disease and Diabetes Prevention Trials

Conducting large-scale, communitywide trials to address the prevention of obesity is a very expensive and difficult process consequently, evidence of this nature is very limited. However, a number of large CVD and diabetes prevention trials have included weight as an intermediary outcome, which can also provide useful information about effective strategies to address obesity, and have demonstrated that it may be possible to prevent weight gain if not reduce weight at a population level. Strong and consistent evidence of the success of large-scale weight gain prevention initiatives has been obtained from diabetes prevention trials that have addressed the progression to diabetes in people identified as glucose intolerant. Four large-scale trials have produced significant reductions in the rate of diabetes by focusing on exercise and diet, which resulted in small weight losses of approximately 3 or 4 kg on average. The largest trial conducted in the United States found that advice to...

Insulindependent Diabetes Mellitus Experimental Models

Ji-Won Yoon and Hee-Sook Jun, Department of Microbiology and Infectious Diseases, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada Institute for Medical Science, Ajou University School of Medicine, Suwon, Korea Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM), results from the destruction of insulin-producing pancreatic (3 cells, culminating in hypoinsulinemia and hyperglycemia. IDDM appears to be a disease of autoimmunity. Genetic susceptibility is believed to be a prerequisite for the development of IDDM and environmental factors, such as viruses, diet and toxins are also considered to at the BioBreeding Laboratories in Ottawa, Canada. The cumulative incidence of diabetes in DP-BB Wor rats is greater than 80 . The pattern of disease in the DP-BB rat is, in many ways, similar to human IDDM, with the exception of the association of T cell lymphopenia with the DP-BB rat (Table 1). The NOD mouse was...

Diabetes in Pregnancy

For women with diabetes, nutritional counseling should include adequate dietary intake, frequent glucose monitoring, insulin management to meet the growth needs of the fetus, maintaining optimal blood glucose levels, and preventing ketosis and depletion of the mother's nutrient stores. The demands of pregnancy may impose a need for insulin in pregnant women whose condition was controlled through diet alone in the nonpregnant state. Because of hormonal changes during the first and second half of pregnancy, changes to the diet and the insulin dosage may be necessary. Gestational diabetes occurs only during pregnancy and usually resolves after pregnancy. It occurs in 5-10 of pregnancies and most commonly arises after 20 weeks of gestation. Gestational diabetes can be treated largely through nutritional care and moderate exercise to achieve weight control. Nutritional recommendations are to limit protein intake to 15 of total calories, consume 55 of total calories as carbohydrate, and...

Insulin Resistance and Hyperinsulinemia

'Insulin resistance' refers to the phenomenon of insensitivity of the cells of the body to insulin's actions. Different tissues may have different insulin sensitivities. For example, adipose tissue may be more sensitive to insulin than muscle tissue, thus favoring the deposition of fatty acids in adipose tissue and diminished fatty acid oxidation in muscle. Insulin resistance is usually associated with hyper-insulinemia. Hyperinsulinemia is an independent marker that predicts the development of atherosclerosis. A causal relationship between hypertension and hyperinsulinemia has not been well established. Hypertension associated with hyperinsulinemia could be due to increased renal sodium retention, increased intracellular free calcium, increased sympathetic nervous system activity, or increased intraabdominal pressure due to increased visceral fat deposition. The mechanisms of insulin resistance with increasing obesity are not clear, but increased production of cytokines such as tumor...

Insulin Counters High Blood Glucose

Insulin stimulates glucose uptake by muscle and adipose tissue (Table 23-3), where the glucose is converted to glucose 6-phosphate. In the liver, insulin also activates glycogen synthase and inactivates glycogen phosphory-lase, so that much of the glucose 6-phosphate is channeled into glycogen. Insulin also stimulates the storage of excess fuel as fat (Fig. 23-26). In the liver, insulin activates both the oxidation of glucose 6-phosphate to pyruvate via gly-colysis and the oxidation of pyruvate to acetyl-CoA. If not oxidized further for energy production, this acetyl-CoA is used for fatty acid synthesis in the liver, and the fatty acids are exported as the TAGs of plasma lipoproteins (VLDLs) to the adipose tissue. Insulin stimulates TAG synthesis in adipocytes, from fatty acids released from the VLDL triacylglycerols. These fatty acids are ultimately derived from the excess glucose taken up from the blood by the liver. In summary, the effect of insulin is to favor the conversion of...

Atherogenity of insulin

Clinical studies have demonstrated that those processes linked to hyperinsulinaemia, such as type 2 diabetes or obesity, show a higher mortality due to coronary or cerebral atherosclerosis (Pyorala et al 1985). Furthermore, experimental results show that insulin acts on the vascular wall, either producing hypertension and endothelial changes, or influencing the smooth muscle cells (SMCs) to proliferate. It is well known that endothelial lesions and SMC proliferation are basic steps of atherogenesis (Ross 1993). For a better understanding of the role of SMCs in atherosclerosis, it is worth mentioning that these cells and collagen represent the main content of the atheroma plaque. SMCs migrate from the media crossing the intima to accumulate and release collagen. Two distinctive phenotypes of SMC are known contractile and synthetic. Contractile SMCs respond to agents inducing vasomotor changes, whereas the synthetic SMCs are capable of expressing genes for growth regulators and collagen...

Diabetes And Endocrine Disorders

Diabetes Mellitus Diabetes mellitus is one of the most common metabolic diseases encountered. The prevalence of diabetes mellitus in both adults and children has been steadily rising in the past 20-30 years. Improved glycemic control has a beneficial effect on microvascular and neuropathic complications in type 2 diabetes, but has no effect on the incidence of macrovascular disease. However, light control of blood pressure (with an ACE inhibitor or a beta-blocker) in patients with type 2 diabetes and hypertension reduces the risk of diabetes-related death, including that secondary to macrovascular complications, as well as the risk of other diabetes-related complications and eye disease.10 Good control of diabetes also decreases the potential for postoperative infection. Diabetic patients need careful treatment with adjusted doses or infusions of short-acting insulin based on frequent blood sugar determinations. The main concern for the anesthetist in the perioperative management of...

Insulin Acts in the Arcuate Nucleus to Regulate Eating and Energy Conservation

Insulin secretion reflects both the size of fat reserves (adiposity) and the current energy balance (blood glucose level). Insulin acts on insulin receptors in the hypothalamus to inhibit eating (Fig. 23-33). Insulin receptors in the orexigenic neurons of the arcuate nucleus inhibit the release of NPY, and insulin receptors in the anorexigenic neurons stimulate a-MSH production, thereby decreasing fuel intake and increasing thermo-genesis. By mechanisms discussed in Section 23.3, insulin also signals muscle, liver, and adipose tissues to increase catabolic reactions, including fat oxidation, which results in weight loss. Leptin makes the cells of liver and muscle more sensitive to insulin. One hypothesis to explain this effect suggests cross-talk between the protein tyrosine kinases activated by leptin and those activated by insulin (Fig. 23-35) common second messengers in the two signaling pathways allow leptin to trigger some of the same downstream events that are triggered by...

Growth and hypertension and type 2 diabetes

Increased susceptibility to hypertension and type 2 diabetes, two disorders closely linked to CHD.14-17 Table 22.4 is based on 698 patients being treated for type 2 diabetes and 2997 patients being treated for hypertension. It again shows odds ratios according to birthweight and quarters of BMI at age 11 years. The two disorders are associated with the same general pattern of growth as CHD. The risks for each disease fall with increasing birthweight and rise with increasing BMI. The odds ratio for type 2 diabetes is 0-67 (95 CI 0-58-0-79) for each kilogram increase in birthweight and Table 22.4 Odds ratios (95 CI) for hypertension and type 2 diabetes according to birthweight and BMI at 11 years

Secondary Diabetes Mellitus Other Specific Types

This broad category includes multiple disorders that are associated with either extensive pancreatic destruction or significant insulin resistance. Secondary diabetes as a consequence of decreased insulin production can occur following pancreatectomy, chronic pancreatitis, cystic fibrosis, or hemochro-matosis. In the absence of pancreatic damage, secondary diabetes can result from extreme insulin resistance induced by glucocorticoids (Cushing's syndrome) growth hormone (acromegaly) adrener-gic hormones (pheochromocytoma) other medical conditions, such as uremia, hepatic cirrhosis, or polycystic ovary syndrome or medications (diuretics or exogenous glucocorticoids). Included in this category of secondary diabetes are patients who appear to have type 2 diabetes but in whom monogenic molecular defects in either the glucose-sensing or insulin action pathways have been defined. The best established molecular defects are mutations in the gene coding for the enzyme glucokinase, which has a...

Conclusions revascularization in patients with diabetes

In both trials and observational data sets, diabetes mellitus is clearly a marker for high risk and, in comparison with non-diabetic patients, the prognosis is worse after either PTCA or CABG. In the largest randomized trial of PTCA versus CABG, patients with diabetes who received internal mammary artery grafts had better outcomes than those treated with PTCA. However, large non-randomized registry data suggest equivalent outcomes after either procedure as long as the sicker patients are triaged to surgery. One conclusion that may resolve the apparent dilemma is that selected patients with diabetes, such as those with favorable angiographic characteristics, may do as well with PTCA and CABG, whereas those with more diffuse or advanced coronary artery disease do better with CABG as initial therapy. Because 5200 patients have been enrolled in trials of PTCA versus CABG surgery, collaborative meta-analysis based on individual patient data may allow more definitive characterization of...

Insulin Changes the Expression of Many Genes Involved in Carbohydrate and Fat Metabolism

In addition to its effects on the activity of existing enzymes, insulin also regulates the expression of as many as 150 genes, including some related to fuel metabolism (Fig. 15-31 Table 15-3). Insulin stimulates the transcription of the genes that encode hexokinases II and IV, PFK-1, pyruvate kinase, and the bifunctional enzyme PFK-2 FBPase-2 (all involved in glycolysis and its regulation), several enzymes involved in fatty acid synthesis, and two enzymes that generate the reductant for fatty acid synthesis (NADPH) via the pentose phosphate pathway (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase). Insulin also slows the expression of the genes for two enzymes of gluconeoge-nesis (PEP carboxykinase and glucose 6-phosphatase). These effects take place on a longer time scale (minutes to hours) than those mediated by covalent alteration of enzymes, but the impact on metabolism can be very significant. When the diet provides an excess of glucose, the resulting rise...

Plasma Glucose and Insulin Responses

The 'glycemic index' approach has been used to classify foods according to their ability to raise the level of glucose in the blood. Foods are tested in equivalent carbohydrate portions according to standardized methodology. On a scale where glucose 100, the glycemic index of refined sucrose ( 65) is similar to that of white bread ( 70). Table 3 shows the glycemic index of a range of common foods. Refined sucrose elicits an insulin response commensurate with its glycemic response, i.e., it does not stimulate inappropriately high insulin secretion. See also Carbohydrates Chemistry and Classification Regulation of Metabolism Requirements and Dietary Importance. Dental Disease. Diabetes Mellitus Classification and Chemical Pathology Dietary Management. Fructose. Glucose Chemistry and Dietary Sources Metabolism and Maintenance of Blood Glucose Level. Glycemic Index.

Insulin Resistance Introduction

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

Proposed Mechanism by which Dietary Carbohydrates Glycemic Index Influence Insulin Resistance

Adipocyte metabolism is central to the pathogenesis of insulin resistance and dietary carbohydrates influence adipocyte function. The previous simplistic view that insulin resistance resulted from the down-regulation of the insulin receptors in response to hyperinsulinemia is being replaced by the hypothesis that high circulating NEFA levels both impair insulin action and reduce pancreatic fi cell secretion. It is plausible that low glycemic index carbohydrates reduce insulin resistance by their ability to reduce adipocyte NEFA release. There is evidence of a loss of suppression of hormone-sensitive lipase (HSL), an enzyme that breaks down triglyceride to free fatty acids and glycerol, to small physiological amounts of insulin and, to a lesser extent, insulin insensitivity of lipoprotein lipase. HSL is normally very sensitive to small increases in insulin levels and is totally suppressed at much lower concentrations than those required for glucose uptake. In insulin-resistant...

Other Health Outcomes Bone Status Cancer and Diabetes

Finally, a number of studies have examined associations between weight cycling and diabetes and have yielded little evidence of a relation. According to findings from the Nurses Health Study, no association was found between weight fluctuation and diabetes incidence. In another study, glucose tolerance and weight fluctuations were directly monitored in obese patients, and no deterioration was observed to be directly associated with weight cycling. Interestingly, the Diabetes Prevention Program Research Group found that the diabetes reduction achieved over 4 years with a lifestyle intervention was not diminished with the gradual regaining of more than half of the weight lost. This observation is an indication that a period of weight reduction may exert a net benefit for diabetes, even if weight is subsequently regained.

Cell Biology Of Insulin Secretion

The islet nerves and their neurotransmitters alter islet hormone secretion through surface-located receptors, which affect the cell biology of exocytosis of the islet hormones via signaling systems. Several transduction mechanisms are operative in b cells, transmitting signals for the stimulation or inhibition of insulin secretion. A primary mechanism underlying insulin secretion involves b cell metabolism of glucose, which increases the cytosolic ratio of ATP ADP. This depolarizes the plasma membrane through the closure of ATP-regulated K+ channels, which causes the opening of voltage-sensitive Ca2+ channels and the uptake of extracellular Ca2+ to raise the cytosolic concentration of Ca2 + . Another signaling pathway is initiated by phosphoinositide hydrolysis using phos-pholipase C (PLC) and phospholipase D (PLD), which produces diacylglycerol (DAG) and activates protein kinase C (PKC). PLC also induces the formation of inositol 1,4,5-triphosphate (IP3), which stimulates the...

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

Endocrinology & Diabetes Research Unit, Schneider Children's Medical Center of Israel and Sackler Faculty of Medicine, Tel Aviv University, Israel Abstract Present knowledge on the effects of growth hormone (GH) insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGF1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding...

Regulation of Insulin Secretion

There are several agents regulating the secretion of insulin (Figure EP.14) but the major factors are CONTROLLING FACTORS IN INSULIN SECRETION Insulin Somatostatin (identical to growth hormone releasing inhibiting hormone) is released by 5 cells in response to increases in plasma glucose, amino acids and fatty acids. It slows down gastro-intestinal function and so protects against rapid increase in plasma nutrients during the absorptive phase after a meal. Somatostatin inhibits release of both insulin and glucagon. Only abnormalities of insulin secretion, particularly insulin deficiency, will be considered here. Insulin Deficiency Inadequate release of insulin leads to diabetes mellitus. This condition may occur in several forms, which include A primary deficiency of insulin due to auto-immune destruction of the P cells - type 1, insulin-dependent or juvenile onset diabetes Unimpaired insulin secretion but with an attenuated metabolic effect at a cellular level. This condition is seen...

Effects of insulin and IGF1 on SMCs

More than a decade ago different publications showed that insulin stimulates SMC proliferation in vitro (Stout 1990). We have observed that in non-cultured cells, SMCs directly taken from the human artery, insulin stimulates collagen secretion. This effect was probably produced by activation of the IGF1 receptors, because addition of insulin receptor-blocking antibodies did not show any inhibition. On the contrary, antibodies blocking IGF1 receptors inhibited the insulin-induced collagen secretion. We concluded that insulin is able to change the SMC phenotype by acting as a growth factor (Ruiz-Torres et al 1998). Moreover, insulin stimulates the chemotaxis of SMCs directly dispersed from the human artery (Mu oz et al 1998). In these experiments this migration could be inhibited by insulin receptor-blocking antibodies, so we assumed that insulin was acting here through its specific receptors. Nevertheless, these results point out a very close relationship between the stimulating effect...

Glucose levels and the risk for cardiovascular disease in nondiabetic patients

Hyperglycemia occurring at the time of an acute stress may also increase the risk of mortality in non-diabetic individuals. Two meta-analyses of prospective studies concluded that stress hyperglycemia increased the risk of mortality in non-diabetic patients with acute MI (RR 3-9)38 and stroke (RR 3-1).39

Risk of cardiovascular disease in patients with diabetes

As noted above, diabetes is an independent risk factor for cardiovascular disease.2 People with diabetes have a two- to fourfold higher risk of coronary, cerebrovascular, and peripheral vascular disease than non-diabetic people.1 The relative risk is greater for women than for men.1,19 Diabetes is also a poor prognostic factor post myocardial infarction (MI) diabetic patients have a higher inhospital mortality, and postdischarge mortality than non-diabetic patients, and a higher risk of infarct-related complications.20,21 Just as the risk of eye, kidney, and nerve disease increases with the degree of glycemia, a growing number of studies of diabetic patients suggest that the risk of cardiovascular disease also rises with the degree of glycemia. For example, the Wisconsin Epidemiologic Study of Diabetic Retinopathy followed a population-based sample of 1210 patients with diabetes presenting before the age of 30 and 1780 patients with diabetes presenting at or after the age of 30.22 In...

Glycemic Index and the Prevention of Type 2 Diabetes

Changes in diet and physical activity levels, both alone and in combination, reduce the progression of impaired glucose tolerance to diabetes. Two large US prospective population studies have demonstrated a doubling of the relative risk of developing type 2 diabetes for both men and women when the habitual diet is characterized by a high glycaemic index and high fat content. A similar protective effect against diabetes has been reported

Type 2 Diabetes Mellitus

This is a heterogeneous disorder in which there is both resistance to the action of insulin and relative insulin insufficiency. In contrast to type 1 diabetes, endogenous insulin secretion is at least partially preserved and thus most patients are not insulin dependent for acute survival (hence the former name, non-insulin-dependent diabetes). The circulating insulin levels are adequate to protect these patients from ketosis, except during periods of extreme stress. Some patients in this category can be treated with oral agents (sulfonylureas, metfor-min, and thiazolidinediones), but many are managed with insulin because their pancreases are unable to produce sufficient insulin to overcome their tissue insulin resistance. Obesity is a frequent contributing factor to the insulin resistance in this disorder. Occasionally, it is difficult to determine whether a patient has type 1 or type 2 diabetes. This is particularly likely in a nonobese person older than 35 years of age who has never...

Insulinlike Growth Factor

Neurogenic effects of insulin-like growth factor (IGF) have been identified in cultures of embryonic neural stem cells as well as in vivo using transgenic models overexpressing or lacking specific IGF encoding genes. In proliferative cultures of embryonic precursors, insulin and IGFs promote the proliferation of neural stem cells and the acquisition of a neuronal phenotype. In mice and humans, disruption of the IGF-I gene is associated with profound retardation of brain growth. In contrast, overexpression of IGF-I results in larger brains marked by greater numbers of neurons. Similar effects on proliferation and neuronal lineage appear conserved in adulthood, as peripheral IGF-I infusion (for 6 days) increases the number of proliferating cells and the fraction of new cells exhibiting neuronal characteristics in the adult hippocampus of rodents.

IGF1 and insulin secretion during ageing

In a similar defined population of healthy individuals (as mentioned earlier) insulin levels are usually increased with advancing age (Ruiz-Torres et al 1996). FIG. 1. IGF1 serum levels and insulin secretion of young (20 39 years old, n 22) and old (70 92, n 33) healthy men with corresponding anthropometrical manifestations. On the right are blood concentrations of the N-terminal peptide of procollagen type III (PIIIP). The figure shows the opposite age-dependent behaviour of the hormones mentioned. IGF1 concentrations were determined after alcohol extraction by radioimmunoassay and PIIIP. Daily insulin secretion was by means of 24 h C-peptide excretion, corrections and normalization of results as described (Ruiz-Torres et al 1996) LBM calculated according to Forbes & Bruining (1976) and adipose mass worked out on the basis of skin fold thickness and body density according to Durnin & Womersley (1974). FIG. 1. IGF1 serum levels and insulin secretion of young (20 39 years old, n...

Type 2 Diabetes Worldwide Prevalence

Type 2 diabetes is one of the most common noncom-municable diseases in the world with an estimated 147.2 million people suffering from this disorder by 2010 this figure is expected to reach 212.9 million. Furthermore, it has been predicted that by the year 2010 over half the people with T2D will be living in Asia. This trend is likely to be due to increasing urbanization and industrialization. According to WHO estimates the figure is likely to double by the year 2025. The prevalence of T2D varies widely from the highest in Pima Indians (almost half of the population affected) to the lowest in Rural Africa (1 ). As with T1D, the incidence of diabetes in different countries is likely to reflect the different genetic architecture as well as the differing environment. A good example is afforded by the population of Nauru. In full-blooded Nauruans over the age of 60 years the prevalence of T2D is 83 , whereas in those with genetic admixture as adduced by HLA typing the prevalence is 17...

Fructose and Diabetes

Historically, in the nutritional management of diabetes mellitus, the ingestion of fructose was recommended as a sweetener for diabetics because it causes smaller increases in blood glucose following ingestion compared to similar amounts of glucose, sucrose, or starches. In fact, fructose, in small quantities, increases the hepatic uptake of glucose and promotes glycogen storage, probably by stimulating the activity of hepatic glucokinase (EC 2.7.1.2). Also, in individuals with type 2 diabetes mellitus, the addition of a small amount of fructose to an oral glucose tolerance test improves the glycemic response, indicating improved glycemic control. It must be emphasized, however, that the consumption of large quantities of fructose is not recommended, particularly for diabetics who, as a group, are at increased risk for cardiovascular disease, because of

Dietary Fiber Obesity and the Etiology of Diabetes

In 1975, Trowell suggested that the etiology of diabetes might be related to a dietary fiber deficiency. This is supported by several key pieces of evidence. Vegetarians who consume a high-fiber lacto-ovo vegetarian diet appear to have a lower risk of mortality from diabetes-related causes compared to nonvegetarians. Consumption of whole grain cereals is associated with a lower risk of diabetes. Importantly, the same dietary pattern appears to lower the risk of obesity, itself an independent risk factor in the etiology of type 2 diabetes. Obesity is emerging as a problem of epidemic proportions in affluent and developing countries. Consumption of whole grain cereal products lowers the risk of diabetes. A report showed that in 91249 women questioned about dietary habits in 1991, greater cereal fiber intake was significantly related to lowered risk of type 2 diabetes. In this study, glycemic index (but not glycemic load) was also a significant risk factor, and this interacted with a...

Endocrine Pancreas Insulin

As previously mentioned, the pancreas secretes a number of hormones that play an integral role in physiologic equilibrium. The most well known of these is insulin, a product of the b cell that is critical for the maintenance of glucose homeostasis. Insulin was discovered by the Canadian surgeon Frederick Banting for which he was awarded the 1923 Nobel Prize in Physiology Medicine.8,9 Beta cells are stimulated to secrete insulin by glucose as well as hormonal and neural activity. The initial protein synthesized by b cells is proinsulin which is converted into its active form on the proteolytic cleavage of C-peptide. Insulin is released into the portal circulation where at least 50 percent is cleared during this first pass through the liver. The remaining insulin binds to insulin receptors which promote the active transport of glucose across the membranes of most cells, especially of the muscle and adipose tissue compartments. In addition, insulin stimulates the storage of glucose in...

Nerve Fatty Acid Metabolism In Diabetes

The impact of diabetes mellitus causes an inability of tissues to metabolize glucose properly and this, in turn, leads to accelerated triacylglycerol breakdown and enhanced P-oxidation of fatty acids. The resulting increase in fat catabolism, together with a depletion of Krebs cycle intermediates, produces a marked increase in ketone body formation. Glucose is the major metabolic fuel for the normal nerve axon and Schwann cells, although in its absence, the peripheral nerve is able to utilize ketone bodies for at least a portion of its energy needs (Winegrad and Simmons 1987). Under normal circumstances, the blood-brain barrier prevents entry of albumin-bound fatty acids into the tissue. Furthermore, nerve incubated with physiological concentrations of free fatty acid exhibits profound respiratory inhibition. Although fatty acids do not therefore constitute a significant energy source in the nerve, the tissue possess the enzymatic machinery to biosynthesize long-chain saturated and...

Type 1 Diabetes Mellitus

This form of diabetes is defined by insulin deficiency due to destruction of the fi cells of the pancreas. It was formerly designated ''insulin-dependent diabetes,'' but efforts are being made to eliminate this name because many patients with other types of Table 3 Classification of diabetes mellitusa I. Type 1 diabetes (formerly designated insulin-dependent diabetes) II. Type 2 diabetes (formerly designated non-insulin-dependent diabetes) III. Secondary diabetes A. Genetic defects of 0 cell function (e.g., maturity onset diabetes of youth) B. Genetic defects of insulin action pathway IV. Gestational diabetes Classification proposed by the Expert Committee on the Diagnosis and the Classification of Diabetes Mellitus under the sponsorship of the American Diabetes Association (Diabetes Care 27 S5-S10, 2004). diabetes also require insulin for adequate control. The predominant cause is believed to be an autoimmune attack against the insulin-producing 0 cells within the islets of...

Diabetes Educational and Community Based Interventions

A number of Native American and Canadian populations have recognized the importance of lifestyle changes in diabetes prevention (Stolarczyk, Gilliland, Lium, & Owen, 1999). Consequently, Native populations are becoming more actively involved in the planning, implementation, and evaluation of diabetes programs (Gohdes & Acton, 2000 Joe & Young, 1994 Olson, 1999 Wiedman, 2001). Community interventions have developed with the cooperation of tribal and indigenous organizations, public health agencies, and healthcare professional organizations (Young, 2001). These interventions often focus on community rather than individual responses to diabetes preventive activities. A good example is the program among the Sandy Lake Cree that focused on collective responsibility for the burden of diabetes in their community (Gittelsohn et al., 1995, 1996 Hanley, Harris, Gittelsohn, & Andres, 1995). A public health campaign of educating tribal members on low-fat diets, cigarette smoking, and...

Diabetes Complications

Diabetes is the sixth leading cause of death in the United States. Among diabetics heart disease is the primary cause of diabetes-related deaths and is 2-4 times higher in people with diabetes than those without the disease (ADA, 2002a Centers for Disease Control, 2001). A life-threatening consequence of type 1 diabetes is diabetic coma due to ketoacidosis resulting from the exclusive use of fat as an energy source. The most frequent complications of long-term diabetes occur because of abnormalities in the blood vessels and nerves caused by chronic hyperglycemia. Diabetes is the leading cause of blindness, kidney failure, and amputations of the lower limb. There are also abnormalities that occur in the immune, cardiovascular, and digestive systems as well as periodontal disease, sexual dysfunction, and complications of pregnancy (ADA, 2002a Harris, 1995). Diabetes also is associated with psychological and social dysfunction. Because type 2 diabetes often does not have an acute onset,...

Oral Antidiabetic Agents

Oral antidiabetic agents are not insulin insulin is delivered only by injection or infusion. The variety of agents in use has escalated dramatically in recent years, so it is worth knowing how the various classes act and how they may interact with diet. Sulfonylureas (e.g., glyburide, glimepiride, and glipizide) commonly act by stimulation of pancreatic insulin secretion. They therefore can cause hypogly-cemia if taken in excess or without normal food intake. The other most popular oral agent is metformin, which does not stimulate insulin secretion and therefore should not cause hypoglycemia by itself. Metformin can cause bloating and diarrhea, but it can also be mildly weight reducing in conjunction with diet. The drugs called thiazolidinediones (TZDs), pio-glitazone and rosiglitazone, improve insulin sensitivity but do not by themselves cause hypoglycemia. TZDs can, however, cause fluid retention and weight gain, so they are sometimes counterproductive in someone trying to lose...

Diabetes Mellitus

Diabetes mellitus is one of the more common systemic illnesses affecting wound healing. The prolonged elevated levels of blood glucose render an irreversible angiopathy that predominantly involves small vessels. This microangiopathy diminishes blood flow, causing a decrease in oxygen delivery and the supply of vital nutrients and inflammatory cells required for healing. Furthermore, diabetes adversely affects

Diabetes

Diabetes mellitus is characterized by either an absolute or relative lack of insulin, which has short-term and long-term consequences. Diabetic people may develop both microvascular complications (mainly affecting the eyes, kidneys, and nerves) and macro-vascular complications (essentially accelerated development of atherosclerosis presenting mainly as heart attack and peripheral vascular disease). Medical management aims to replace the insulin, or modulate its production or efficacy using oral (hypoglycemic) drugs, in a metabolic environment enhanced by good control of diet and body composition. Medical management also aims to achieve early detection of complications and other risk factors for cardiovascular disease by regular testing of blood and urine biochemical variables and blood pressure and by regular physical examination of the eyes, neurological, and cardiovascular systems. compliance) through to very high-carbohydrate diets (sometimes 60-65 energy from carbohydrate) used in...

New Onset Diabetes

2.Diagnosis New Onset Diabetes Mellitus 7.Diet Diabetic diet with 1000 kcal + 100 kcal year of age. 3 meals and 3 snacks (between each meal and qhs.) Total Daily Insulin Dosage -Divide 2 3 before breakfast and 1 3 before dinner. Give 2 3 of total insulin requirement as NPH and give 1 3 as lispro or regular insulin. 11. Labs CBC, ketones SMA 7 and 12, antithyroglobulin, antithyroid microsomal, anti-insulin, anti-islet cell antibodies. UA, urine culture and sensitivity urine pregnancy test urine ketones.

Insulin

High-dose insulin infusion also has provided benefit in two models of verapamil toxicity. 1820 Insulin appears to improve myocardial mechanical efficiency and contractility by accelerating carbohydrate oxidation. Insulin is also potent a positive inotrope that operates through a mechanism similar to the postreceptor action of the a1 adrenoreceptor. Insulin does not produce a sharp improvement in hemodynamic indexes when bolus infused. Instead, insulin slowly but steadily improves heart contractility. Insulin has no direct effect on cardiac conduction but may lower plasma potassium concentrations and indirectly improve automaticity and conduction. Perhaps the best role of insulin is as an adjunctive therapy for suspected massive overdose, and it is more effective in humans when administered before profound hypodynamic shock supervenes.21 A suggested infusion dose is 1.0 unit kg h for the first hour, followed by 0.5 unit kg h. 21 Depending on the severity of overdose, resistance to...

Type 2 Diabetes

A strong association of obesity with the prevalence of type 2 diabetes mellitus (DM) is well documented. The risk of developing type 2 DM increases with the degree and duration of obesity as much as 50-fold with severe obesity. The US National Diabetes Commission reported that the risk of diabetes doubles for every 20 of excess body weight. The risk of type 2 DM is greater with visceral obesity. Type 2 DM is frequently associated with other complications, such as hypertension and dyslipidemia, resulting in additive risks for atherosclerosis and cardiovascular disease. Poor glycemic control in type 2 DM may lead to severe microvascular complications, including nephropathy, retinopathy, and neuropathy. Weight loss is a very effective treatment for type 2 DM and can prevent the onset of type 2 DM in susceptible individuals. Type 2 DM, once very rare in children, has increased greatly in prevalence with the obesity epidemic.

Type 1 Diabetes

Type 1 diabetes is caused by beta cell destruction, leading to insulin deficiency. T1DM was previously called insulin-dependent diabetes mellitus (IDDM), because patients who have it require insulin for survival. It was also called juvenile-onset diabetes mellitus, because most type 1 diabetics are children or young adults. At the time of diagnosis, about 85 percent to 90 percent of people with type 1 diabetes have antibodies directed against components of their beta cells, indicating that the immune system is responsible for the progressive and irreversible beta cell destruction. cells, but in the case of type 1 diabetes, the body's immune system destroys its own beta cells. Certain types of HLA genes are strongly associated with type 1 diabetes, and other types protect against its development. However, these HLA genes are neither necessary nor sufficient to cause or protect from type 1 diabetes. T1DM is therefore a complex genetic disorder, in which several genes interact with the...

Insulinoma

Insulin is produced by the p-cells of the islets of Langerhans of the pancreas. These tumours are usually solitary, < 3 cm in diameter, and may be situated in any part of the gland. Over 90 are benign. Multiple insulinomata should alert to the possibility of MEN I. Diagnosis is confirmed by hypoglycaemia on fasting (up to 72 h) during which time the patient should have an attack. This can be confirmed by measurement of elevated insulin and lowered blood sugar. Failure to provoke an attack during this time precludes the diagnosis. Provocation tests are unreliable, can be dangerous and are no longer used.

Insulin Resistance

As already mentioned the insulin-resistant state associated with hypertension may be aggravated by therapy with potassium wasting diuretics. In this regard, several authors have suggested that the responses are in part explained by insulin resistance. Increased plasma insulin levels can increase hepatic VLDL production, thereby giving rise to both hypertriglyceridemia as well as increased LDL via intravascular catabolism of VLDL by lipoprotein lipase which is stimulated by insulin. Further, hyperglycemia in untreated type II diabetics is associated with increases in dietary cholesterol, cholesterol synthesis, and plasma triglyceride and cholesterol levels. Treatment with insulin has been shown to reverse these abnormalities. A role for hypokalemia-induced insulin resistance in the development of hyperlipidemia has also been suggested. Experimental animal studies of furosemide-induced potassium depletion suggest that insulin resistance is an important factor in the pathogenesis of...

Insulin Therapy

Continuous low-dose short-acting (regular) insulin by intravenous infusion is the method of choice for treating DKA. Continuous intravenous insulin eliminates the problem of poor absorption from other routes. A priming dose of 0.1 U kg of regular insulin is followed by a constant infusion of 0.1 U kg h. Some authorities debate the necessity or efficacy of the initial intravenous bolus and begin with the infusion. If acidosis has not improved in 2 h, the inravenous insulin rate should be increased to 0.15 to 0.2 U kg h.2 Concern that the insulin may adhere to the glass and tubing has proven to be unfounded, and effective delivery of insulin can be provided without the addition of albumin or gelatin to the infusate. 5 When acidosis is corrected, the continuous infusion may be discontinued. Bicarbonate therapy remains highly controversial. With provision of fluids, electrolytes, glucose, and insulin, metabolic acidosis is usually corrected through the interruption of ketogenesis and the...

Insulin controlled

Admit the day before surgery. Half usual dose of short acting insulin the evening before surgery. Fast from midnight for a morning list. No insulin in the morning. Blood glucose result one hour pre-operatively. The evening after surgery give one third dose of short acting insulin with supper. Check blood glucose three hours after supper. Return to usual treatment the day after surgery. Fast from 08-00 for an afternoon list. Half dose of short acting insulin with light breakfast. Start slow infusion of 5 Dextrose (four hours per half litre). Check blood glucose two hourly after breakfast. Half dose of short acting insulin with supper. Check glucose three hours after this. Return to usual treatment the day after surgery. Admit 48 hours pre-operatively for stabilisation on insulin infusion regimen. Monitor glucose two hourly in the first 24 hours of the regimen. Continue insulin infusion regimen until full oral intake is resumed. Return to normal...

Hyperinsulinemia

In non-diabetic people, fasting and 2 hour postload insulin levels rise with fasting and 2 hour glucose levels.58,59 Thus even mildly hyperglycemic patients have higher levels of insulin than normoglycemic controls. Moreover, hyperinsu-linemia is associated with coronary heart disease,60,61 and many other cardiovascular risk factors including hyperten-sion,62 left ventricular hypertrophy,63 elevated levels of triglyceride,64-66 fibrinogen, von Willebrand factor-related antigen, factor VIII activity, plasminogen activator inhibitor-1 (PAI-1) antigen, and PAI-1 activity,64 and depressed levels of HDL65,66 and tPA.64,67 Insulin may promote hypertension and atherosclerosis by stimulating renal sodium, water retention,65 smooth muscle proliferation, and vascular growth factor production,65 and sensitizing smooth muscle to the pressor effects of angiotensin II,68 and increasing norepinephrine release through activation of the sympathetic nervous system.69 Hyperinsulinemia is not a...

Blood Sugar Control

The physiological control of blood glucose is complex. While the major role belongs to insulin, a multitude of other hormonal influences apply. It should also be remembered that insulin has other actions beyond the regulation of blood glucose. Pharmacological control of blood glucose becomes necessary in situations of elevation and depression of blood glucose beyond the homeostatic limits, in other words due to hyperglycaemia or hypoglycaemia. The causes of failure in regulation of blood glucose are given in Figure EN.1.

Diabetes Grade A

Diabetes leads to many long-term complications, including retinopathy, neuropathy, nephropathy and atherosclerosis. However, only recently has control of glucose level been demonstrated to reduce these complications. The DCCT (Diabetes Control and Complications Trial) randomized 1441 insulin-dependent diabetic patients to intensive insulin therapy versus conventional therapy, with a mean follow up of 6-5 years.51 The intensive therapy arm showed significant reductions in retinopathy, neuropathy and nephropathy. However, as there were few cardiovascular events in this primary prevention study the lower rate of cardiovascular events in the intensive therapy arm was not significant (P 0-08). A Monte Carlo simulation model based on the reduction of renal, neurological and retinal complications estimated that the cost effectiveness of lifetime intensive insulin therapy compared with conventional therapy was 28 661 per life year added.52

Gestational Diabetes

Gestational diabetes (GDM) is defined as glucose intolerance first recognized in pregnancy. This therefore, excludes those women with either type 1 diabetes or type 2 diabetes diagnosed before conception. GDM is a relatively common occurrence in pregnancy affecting 1-14 in White European and North American populations and higher in certain ethnic groups such as South Asian and Afro-Caribbean populations. GDM increases the risk to both mother and fetus although the levels of maternal glycemia that leads to an adverse outcome are not well defined. Furthermore, there is controversy as to who should be screened in pregnancy and the best available diagnostic test that has high sensitivity and specificity and the timing of the test during gestation. This is reflected in the lack of international agreement on diagnostic criteria ranging from the WHO critieria to a more pragmatic approach based on fasting and post prandial glucose levels. Those at particular risk for GDM are ethnic groups...

Diabetic patients

Although aggressive control of blood glucose levels in type 2 diabetic patients reduces microvascular clinical outcomes, its effect on macrovascular disease outcomes remains unknown. Other traditional CHD risk factors are believed to increase dramatically the risk for clinical CHD events in these patients. Inherent in the diabetic disease process is an abnormality of lipoprotein lipase activity that is partially but not completely corrected by optimal glucose control. Any additional lipid and lipoprotein disorder(s) present in diabetic patients because of either inherited or secondary causes (obesity, alcohol consumption, etc.), accelerate atherosclerotic progression and increase the risk of clinical CHD events. Treatment of lipid disorders in diabetic patients with commensurate lowering of blood cholesterol levels suggests a similar treatment benefit in diabetic as in non-diabetic patients.2,3,5 The use of niacin in diabetic patients has traditionally not been recommended because of...

Effects Of Acyl Chain Composition On Membrane Protein Function

Several different receptor systems in the heart have been examined in this kind of detail. The amount of 22 6n-3-containing phospholipid in the sarcolemmal membranes of rats was elevated by injections of hydrocortisone, and this was accompanied by a downregulation of -adrenergic receptors (Skuladottir et al., 1993). This finding is supported by the results of a detailed examination of 22 6n3-supplemented cardiomyoctes (Grynberg et al., 1995). Fatty acid enrichment produced cells in which 20 of the total fatty acids were 22 6n3. The a-adrenergic system was unaffected, but the -adrenergic receptors had a decreased affinity for ligand. In a study of streptozotocin-induced diabetes mellitus, the sarcoplasic reticulum membranes of treated rats showed a loss of arachi-donic acid, 20 4n6, acyl chains and an increase in 22 6n-3 (Kuwahara et al., 1997). This was accompanied by decreased sodium potassium-ATPase activity and a reduction in calcium uptake.

Cause of Death The Bottom Line

In many trauma cases, the cause of death is well defined (e.g., massive craniocerebral trauma caused by motor vehicle collision 104,113-117 ). In other cases of injury with survival, the cause of death can be multifactorial (114). Each of these factors make some contribution to the death of that individual (113,116). Other conditions and diseases could have precipitated the event and influenced the course of the illness but are not directly related to the immediate cause of death. These significant factors may or may not contribute to the cause of death (e.g., cause of death subdural hemorrhage significant factors acute ethanol intoxication, diabetes mellitus 113 ).

Absorption Transport and Storage

Ascorbate and dehydroascorbate circulate in the bloodstream both in free solution and bound to albumin. About 5 of plasma vitamin C is normally in the form of dehydroascorbate. Ascorbate enters cells by sodium-dependent active transport dehy-droascorbate is transported by the insulin-dependent glucose transporter and is accumulated intracellu-larly by reduction to ascorbate. In poorly controlled diabetes mellitus, tissue uptake of dehydroascorbate is impaired because of competition by glucose, and there may be functional deficiency of vitamin C despite an apparently adequate intake.

The Impact of Critical Medical Anthropology Studies

As Morsy (1996) observes, a review of the CMA literature shows that this genre of medical anthropology spans a range of both substantive and analytical concerns. Critical medical anthropologists have worked on a growing number of health-related issues and health conditions, including mental health, illicit substance abuse, smoking, AIDS, homelessness, reproduction, folk healing, infant care and mortality, diabetes, medical pluralism, immunology, nutrition, health policy, health care disparities, the pharmaceutical industry, rural health services, doctor-patient relationships, the role of the state in primary health care, and medical hegemony. As this (quite partial) list suggests, CMA theory has fostered numerous research and explanatory efforts and proven to be particularly fertile ground for the development of new explanatory concepts and new research questions. Consequently, the CMA perspective has not only strongly influenced the work of many medical anthropologists who define...

Recommended readings

The overall strategy for assessing food additives has received strong endorsements from the scientific community, and only the details have been modified to keep pace with scientific advancements. Figure 4.1 gives a schematic representation of the safety decision tree protocol proposed by the U.S. Food Safety Council. The first step involves the careful selection and characterization of the substance to be tested. Preliminary evaluations of the substance are made by assessing physical and chemical properties of the test substance. A literature search is done to collect any available information regarding the toxicity testing of the substance. Exposure assessment involves gathering information on probable human exposure, i.e., estimated intake levels for the population as a whole or any subpopulation that might be vulnerable to significant levels of the substance. An example of a subpopulation is diabetic patients when the test substance is a new sugar substitute.

Human Aldose Reductase

Inhibition of AR provides a therapeutic means for the prevention of complications associated with chronic diabetes. Kraemer et al. (2004) performed a virtual screen based on the high-resolution crystal structure of the inhibitor IDD594 in complex with human AR. AR operates on a large scale of structurally different substrates. To achieve this pronounced promiscuity, the enzyme can adapt rather flexibly to its substrates. Likewise, it has a similar adaptability for the binding of inhibitors. The authors applied a protocol of consecutive hierarchical filters to search the Available Chemicals Directory. In the first selection step, putative ligands were chosen that exhibit functional groups to anchor the anion-binding pocket of AR. Subsequently, a pharmacophore model based on the binding geometry of IDD594 and the mapping of the binding pocket in terms of putative hot spots'' of binding was applied as a second consecutive filter. In a third and final filtering step, the remaining...

Membranous Glomerulopathy

Membranous Glomerulopathy

Membranous glomerulopathy is a major cause of the nephrotic syndrome in adults (1,2). Only in the past decades has it been surpassed by focal and segmental glomerulosclerosis as the main cause of the nephrotic syndrome (3-5). Membranous glomerulopathy develops mostly idiopathically, but can also be seen in relation with and possibly secondary to, among others, hepatitis B, Sjogren's syndrome, transplantation, lupus erythematosus, diabetes mellitus, sarcoidosis, syphilis, exposure to certain drugs and heavy metals (penicillamine, bucillamine, gold, mercuric chloride), and malignancies (10 ), including carcinomas, carcinoids, sarcomas, lymphoma's, and leukemias (2,6-10). The possibility of a malignancy must be considered especially in older patients with membranous glomerulopathy. In these patients it is also imperative to perform urinary immunoelectropho-resis routinely to rule out myeloma and renal primary amyloidosis (AL) (2). Finally, idiopathic membranous glomerulopathy, of which...

Protein Tyrosine Phosphatase1B PTP1B

Protein tyrosine phosphatase-1B (PTP-1B) is a tyrosine phosphatase that has been implicated as a key target for type 2 diabetes (M0ller et al., 2000). This phosphatase hydrolyzes phosphotyrosines on the insulin receptor, thus deactivating it. Doman et al. (2002) defined the site targeted in the docking calculations by the positions of the two phosphotyrosine molecules observed in the complex with PTP-1B (Puius et al., 1997). The closed, ligand-bound conformation of the active site was used in the docking studies. Molecules were docked into the active site of PTP-1B in multiple conformations using the Northwestern University version of DOCK3.5. Two databases of molecules were used as follows about 152,000 compounds from the ACD98.2 database and about 82,000 compounds from the BioSpecs 1999 and the Maybridge 1999 catalogs. Only molecules that had at least 17 and no more than 60 nonhydrogen atoms were docked. This amounted to 165,581 molecules docked in total. The atomic properties of...

Dupuytrens contracture

There appears to be a familial susceptibility. Diabetes, epilepsy or its treatment are also associated. The palmar and plantar fascia undergo thickening and contracture. In the foot the pressure of walking and standing maintain the foot's normal shape. In the hand, the medial side is most affected so that the little finger is held flexed. The condition can usually be considerably improved by excising the palmar fascia and carrying out Z-plasty on the overlying skin, since the tendons are not shortened.

Shortcomings of Small Molecular Contrast Media for Characterizing Tumor Vessels

To understand the biology underlying the kinetics of MRI contrast media, it is essential to recognize that tumor microvascular hyperpermeability is relatively specific to macromolecular solutes. Small molecular solutes such as insulin, glucose, or paramagnetic gadolinium chelates are known to be readily diffusible across the endothelial barrier of both normal and neoplastic vessels (Crone and Levitt 1984 Jain 1987). There is no basis from previous invasive studies to anticipate that tumor vessels will leak SMCM while normal vessels in the same organ will not be permeable to the same bio-probes. Two notable

Dha Membrane Proteins And Leukocyte Function 71 Introduction to DHA and Proteins

In addition to rhodopsin and protein kinase C, the activity of numerous other proteins has been shown to be altered by nonlamellar phase-preferring lipids, including DHA. Included in the long and growing list of likely targets for DHA-enzyme interactions are the phospholipases A2 (Huang et al., 1996) and C (Sanderson & Calder, 1998), CTP phosphocholine cytidyltransferase (Arnold & Cornell, 1996), mitochondrial ubiquinone-cytochrome-c reductase (Li et al., 1995), Ca2+-ATPase (Hui et al., 1981), GDP mannose-dolicolphosphate mannosyl transferase (Jensen & Schutzbach, 1988), cytochrome P450SCC (Schwarz et al., 1997), adenine nucleotide translocator (Streicher-Scott et al., 1994), the insulin receptor (McCallum & Epand, 1995), Na,K-ATPase (Mayol et al., 1999), the y-aminobutyric acid type A receptor (Nabekura et al., 1998), lecithin cholesterol acyltransferase (Parks et al., 1992), K+ (Poling et al., 1995), Na+ (Kang & Leaf, 1996) and Ca2+ (Pepe et al., 1994) channels, gap...

Lower Extremity Lacerations

Lacerations of the lower extremity are under greater tension than those of the upper extremity. Fascia may be loosely approximated with buried sutures of 4-0 absorbable material. Any lower extremity laceration under significant tension should be repaired with a multiple-layered closure first using buried deep 4-0 absorbable sutures followed by simple interrupted 4-0 nonabsorbable sutures. Simple interrupted sutures of 4-0 nonabsorbable suture material may be used for skin closure in lacerations under minimal tension, and horizontal mattress sutures are ideal for wounds under moderate tension in the lower extremity. Wounds proximal to the knee and in areas that are usually covered (i.e., where cosmesis is not an issue) can be closed with skin staples. In patients with diabetes or those with stasis changes, deep sutures should be avoided because they markedly increase the risk of wound infection. Skin staples or horizontal mattress sutures are an excellent alternative in these patients.

Water Channel Blockers

By homology to the red cell water channel CHIP 28 or, by its more recent designation, Aquaporin 1, a second water channel, Aquaporin 2, was cloned and demonstrated to function as the ADH-dependent water channel of the collecting duct 21, 60 . This protein is abundant in apical membranes and subapical vesicles of collecting ducts. It is inserted into and removed from the apical membrane in response to the addition or removal of ADH, respectively 36,60 . Moreover, some patients with congenital nephrogenic diabetes insipidus were recently shown to possess normal ADH V2 receptors, but lacked functional Aquaporin II molecules 17 . Like Aquaporin I, this protein has cysteine residues at sites likely to be near the active site, and therefore its water channel function is inhibited by mercuric chloride and organic mercurials such as para-chloromercuribenzoate (pCMBS) 21, 59 . At present, however, there are no compounds which selectively inhibit the function of this channel. Such compounds...

Determinants Of Perioperative Morbidity And Mortality

Surgical risk is influenced by a number of patient related factors such as age, severity of coronary artery disease, left ventricular function, and the presence of comorbid conditions (for example, diabetes, renal insufficiency, pulmonary and peripheral vascular disease, obesity). On the basis of these demographic and clinical determinants, risk models have been developed which can be used to either calculate the surgical risk or to stratify patients into low, medium or high risk subgroups.3 4 Off-pump surgery on the beating heart also offers the opportunity to reduce the surgical incision and trauma to skin, soft tissue, and bone. Smaller access by means of various forms of minithoracotomy may reduce the risk of perioperative infection and enhance the speed of recovery. Sternotomy requires 6-12 weeks to heal and prevents early return to normal daily activities. 19 Deep sternal wound infection occurs in 1-4 of the patients and is associated with a 25 mortality.3 The determinants of...

Control of Carbohydrate Metabolism Hormonal Regulation

Insulin When a meal is ingested, glucose is liberated as a result of the hydrolysis of dietary carbohydrate in the small intestine, and it is then absorbed into the blood. Increased glucose concentrations stimulate the production and secretion of insulin by the fi cells of the pancreas. Insulin promotes the transfer of glucose into the target cells (i.e., skeletal muscle, liver, and adipose tissue) for use as energy and for storage in the form of glycogen, primarily in the liver. Insulin also stimulates glycolysis by increasing the activity of glycogen synthase (Figure 3) and the transcription of glycolytic enzymes (Figure 4). Insulin inhibits gluconeogenesis by decreasing the transcription Fasting results in a decrease in insulin concentration and a reduction in glucose uptake by the muscle and adipose tissue, which use alternate forms of energy (e.g., free fatty acids). Glucose then becomes available for uptake by the brain, red blood cells, and renal medulla, which are strongly...

Renal Anatomy and Basic Concepts and Methods in Renal Pathology

Lesions are often in the form of intracellular accumulations, manifestations of either local metabolic abnormalities or systemic processes. For example, lipid inclusions in proximal and, less commonly, distal tubular cells result from hyperlipidemia and lipiduria of nephrotic syndrome, and protein reabsorption droplets (hyaline droplets) accumulate in proximal tubular cells in association with albuminuria and its reabsorption by tubular epithelium. Additional locally induced abnormalities include uniform fine cytoplasmic vacuolization consequent to hypertonic solution infusion (e.g., mannitol, sucrose). Tubular cells may be sites of storage of hemosiderin in patients with chronic intravascular hemolysis, high iron load, or glomerular hematuria. Few metabolic storage diseases affect tubular epithelium among others are cystinosis with crystals and glycogen storage diseases and diabetes mellitus with abundant intracellular glycogen. Vacuoles, especially large and irregular, may be...

Metabolism and utilisation of energy substrates

The catabolic phase of severely injured patients is characterised by the mobilisation of fuel stores, that is, increased glycogenolysis, gluconeogenesis and lipolysis, and breakdown of proteins. The main stimulus for the breakdown of glycogen in both skeletal muscle and liver is adrenaline, although glucagon and vasopressin may also have a role in the liver. This glycogenolysis leads to hyperglycaemia either directly due to liberation of glucose from the liver, or indirectly, via the Cori cycle, from lactate released from skeletal muscle. It should always be remembered that raised plasma lactate concentrations can reflect this increase in skeletal muscle glycogenolysis as well as tissue hypoxia. The hyperglycaemia, which is directly related to the severity of the injury, is potentiated, after severe injuries, by the reduction of glucose utilisation in skeletal muscle following the inhibition of insulin secretion by raised adrenaline levels and by the development of intracellular...

Protein Modification in the Golgi

The Golgi apparatus consists stacks of flattened cister-nae that contain enzymes and other proteins involved in the further modification and processing of newly made proteins. It is separated into cis, medial, and trans cisternae, followed by a meshwork of tubules and vesicles called the trans Golgi network (TGN). The process of N-linked glycosylation is completed through the action of glycosidases and glycosyltransferases localized in specific cisternae. Likewise, the glycosyla-tion of serine and threonine residues (O-linked glycosy-lation) is accomplished by other glycosyltransferases. Additional modifications also occur in the Golgi. For example, proteins and carbohydrate are sulfated by sulfotransferases and some proteins are phosphorylated on serine and threonine residues by Golgi kinases. In addition, proteins like digestive enzymes (trypsin, carboxypeptidase) and hormones (insulin) are made as inactive precursors that must be proteolytically processed to their active forms in...

Absorption Transport Storage and Excretion

Chromium absorption in young and old normal subjects is similar, but people with type 1 DM absorb two- to fourfold more Cr than other groups tested. People with diabetes appear to have an impaired ability to convert inorganic Cr to a useable form. Diabetic mice also lose the ability to convert Cr to a useable form. People with diabetes require additional Cr and the body responds with increased absorption, but the absorbed Cr cannot be utilized effectively and is excreted in the urine. Chromium content in tissues of people with diabetes is also lower. Tissue Cr is an accurate method to assess Cr absorption and utilization and is also a measure of Cr storage. The kidney, which is one of the primary sites of tissue Cr storage, is also one of the best sources of insulin potentiating forms of Cr. Chromium is transported to the tissues primarily bound to transferrin, the same protein that transports iron. There are two metal binding sites on transferrin one primarily for iron and a second...

Finding And Validating Modelbased Biomarkers

The endocrinology literature is replete with examples of this, in particular when considering the glucose-insulin system, which we will cover in some detail. The attempt to describe one individual's metabolic identity, or the state of an individual's regulatory pathways, with a relatively small set of parameters was a major thrust for this area of research, and has generated intriguing and important results. The basic approach undertaken may be extensable to other areas with little modification. appreciated is that the analysis of PET experiments has always required a mechanistic model of blood-tissue exchange to maximize the information extracted from this kind of study. The model was developed over many years (30) and has been subject to many modifications (31) and updates that extended the application of the technology to a variety of organs (32). Disease states have also been a focus, with studies demonstrating the interplay between transport and phosphorylation of glucose...

Ischaemic burden myocardial ischaemia

Occasionally these ischaemic changes may be established from ambulatory, 24hr Holter monitoring. These data are particularly useful in those individuals with 'silent ischaemia', i.e. absence of pain. Silent ischaemia has been found to occur in 2.5 of the male population (McMurray and Stewart, 2000) and represents impaired myocardial perfusion. A number of patients, diabetics especially, may have silent ischaemia. This can present the exercise professional with an additional challenge when risk stratifying and prescribing exercise, unless information on ischaemic threshold is available. In general, the greater degree of ST depression, the greater the likelihood of the patient experiencing chest pain.

Proteinprotein interactions and posttranslational modification

Post-translational modifications (PTMs) are protein processing events in which the nascent (translated) protein is modified covalently in order to confer or abstract functionality, allowing for diversity in the regulation of protein function. These include proteolytic cleavage (e.g., active insulin from proinsulin), phosphorylation (e.g., kinase mediated signalling cascades), glycosylation (e.g., excreted proteins, transcription factors), ubiquitinisation, acetylation, methylation, etc. Although over a few hundred PTMs have been documented, methods for monitoring them on a proteomic scale are still in early days of development. Four basic strategies that can be used with varying degrees of success have been identified (Mann and Jensen, 2003) as being currently available for monitoring PTMs. These are (a) 2D-GE based separations followed by MS identification, (b) affinity-based enrichment of modified proteins followed by MS of protein mixtures, (c) LC-MS MS of enzymatically digested...

Burden of illness

Approximately 15 of over 150 million people worldwide with diabetes mellitus will develop foot ulceration at some time in their life.41 Although rates as high as 11 have been reported in Africa,41 a community-based study in the Netherlands estimated the mean incidence of active foot ulceration amongst people with type 2 diabetes to be 2-1 per year 42 23 of those had an amputation before or after ulceration. The risk of amputation before healing in an established deep foot infection is 44 .43 As these data are drawn from different sources, extrapolation is risky, but an indicative estimate of the risk of developing a deep infection from an active ulcer appears to be up to 50 . It is estimated that contiguous soft-tissue infection preceded by skin ulceration accounts for 90 of cases of osteomyelitis in the feet of diabetics.44 Thus, risk factors for ulceration are, indirectly, risk factors for osteomyelitis. In a prospective cohort study of 749 diabetic veterans,45 independent risk...

Current Research and Its Applications

Evidence suggests that multinodular goiter is a non-neoplastic, hyperplastic proliferation of thyroid cells. Thyroid cells proliferate and form large follicles. The rate of proliferation is not uniform and as one follicle develops, matures and ceases to grow, new follicles develop from new cells. This form of growth explains why a partial resection of a goiter may be followed by a recurrence. Failure of thyroxine therapy to prevent recurrence of the goiter following partial resection has stimulated research for identification of growth factors other than TSH several growth factors have been identified as possible stimuli for thyroid cell proliferation. Epidermal growth factor (EGF) and an insulin-like growth factor (IGF-1) have been implicated in the pathogenesis of the goiter. While the precise molecular events controlling the thyrocytes' growth have not yet been completely established, transformation of a normal thyroid cell to a proliferative cell is probably secondary to an...

Environmental Factors

Many viruses have been implicated in the patho-genesis of T1D they may have a direct effect on 0 cells by infection and cell lysis, or alternatively they may act as triggers to the autoimmune process. Among the viruses that have been implicated in humans are coxsackie A, coxsackie B, rubella, cytomegalovirus, mumps, and Epstein-Barr viruses. The enteroviruses (Coxsackie A, Coxsackie B, and Echovirus) are the most commonly associated viruses with diabetes and serve as a major trigger for T1D in the young possibly by induction of islet cell antibodies. The evidence for viral involvement in type 1 diabetes came from several sources, including anecdotal case reports, epidemiological studies, seasonal incidence studies, and animal models. There is data to support the theory that enterovirus infection either accompanies or precedes the development of T1D in young people in many instances. Coxsackie B was first implicated in the early 1970s by Gamble, who found an increased titer of...

Cost of heart failure

In western developed countries, coronary artery disease, either alone or in combination with hypertension, seems to be the most common cause of heart failure. It is, however, very difficult to be certain what is the primary aetiology of heart failure in a patient with multiple potential causes (for example, coronary artery disease, hypertension, diabetes mellitus, atrial fibrillation, etc). Furthermore, even the absence of overt hypertension in a patient presenting with heart failure does not rule out an important aetiological role in the past, with normalisation of blood pressure as the patient develops pump failure. Even in those with suspected coronary artery disease the diagnosis is not always correct and in the absence of coronary angiography must remain presumed rather than confirmed. In this context, even coronary angiography has its limitations in identifying atherosclerotic disease. The initial cohort of the Framingham heart study was monitored until 1965 hypertension...

Fasting Plasma Glucose Determination

Nondiabetic individuals have fasting plasma glucose levels below 5.6 mmol l. The diagnosis of diabetes mellitus can be made when fasting plasma glucose levels are significantly elevated (> 7.0mmol l) on at least two occasions. Fasting glucose below 7.0mmol l but above 5.6mmol l, although not normal, does not meet the criteria for definite diagnosis and is classified as impaired fasting glucose. Although not absolutely predictive of diabetes, individuals with impaired fasting glucose progress to overt diabetes at a rate of approximately 5 per year. Plasma or serum measurements are generally more reliable than whole blood glucose determinations (in which the normal range is lower) because they are independent of the hematocrit and are appropriate for accurate, automated analysis. For accurate measurement, blood samples must be put into tubes containing sodium fluoride (which prevents glycolysis) or be centrifuged within 30 min to remove cells. Fasting plasma glucose is considered the...

Infections in the ICU

Infections are common in the ICU and are a significant cause of mortality. Critically ill patients are particularly vulnerable to infection because their immune responses may be impaired (trauma, burns, malignancy, diabetes) or suppressed (cytotoxic agents, steroids). Extremes of age, malnutrition, and co-morbid diseases also render patients more susceptible to infection. Finally, ICU care involves invasive procedures and indwelling devices which disrupt anatomic and physiologic barriers further predisposing patients to infection.

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