How I Healed my Diabetes

Reverse Diabetes Now

The creator of this program is Matt Traverso who has proven himself to be one of the best health specialists and fitness experts in the world. He is the man who knows how to use the best of natural ingredients to improve chronic diseases like diabetes. In this guide, you can learn the roots of diabetes to eliminate it rather than making use of prescription drugs or other medications to lessen the diabetes signs and symptoms. With reverse your diabetes today, you can discover the way to protect yourself from terrible signs and symptoms of diabetes type 2 or type 1. Reverse Your Diabetes is a very simple and easy to follow guide. The facts in the book are presented in an easy to understand manner. This guide is suitable for everybody. When creating this program, Matt Traverso came up with a system that is aimed at anyone with diabetes, regardless of their race. It is effective for men as well as women, for the old as well as young. Read more here...

Reverse Diabetes Now Overview

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My Reverse Diabetes Now Review

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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.

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...

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...

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...

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...

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...

Gestational Diabetes Mellitus

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

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...

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...

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...

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...

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

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...

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

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

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...

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...

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...

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...

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...

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...

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...

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...

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

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,...

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...

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...

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...

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...

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...

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.

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

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

Changes Blood Glucose

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...

Diabetes Mellitus

What can now be recognized as diabetes was described in the ancient civilizations of Egypt, Greece, and India. The sweet taste of urine in those with the condition was noted in the 1600s and the term mellitus meaning honeylike was introduced (13). Diabetes mellitus is a major public health problem worldwide. It ranks sixth as a primary cause of death in the United States, but when its complications are included, it ranks third. These complications can be very serious and involve, in the United States, 50 of the amputations of all lower extremities in adults and 25 of all kidney failure and are also a leading cause of blindness. Non-insulin-dependent diabetes (NIDDM, or type II) is the form of diabetes characterized as a chronic nutritionally related condition (Table 6) and is a disorder showing abnormalities in glucose, fat, and protein metabolism. The onset of type II diabetes can be triggered by dietary and lifestyle factors similar to those associated with cardiovascular diseases....

Type 2 Diabetes

Type 2 diabetes is associated with elevated oxidative stress (especially lipid peroxidation) and declines in antioxidant defense. This is thought to be due in part to elevated blood glucose levels (hyperglycemia), but severe oxidative stress may also precede and accelerate the development of type 2 diabetes and then of diabetic complications (CVD and microvascular complications such as retinopathy, neuropathy, and nephropathy). Small-scale human trials have shown administration of high doses of vitamin E to reduce oxidative stress and improve some CVD risk factors, such as blood glycated hemoglobin, insulin, and triglyceride levels, in people with diabetes. Such trials have also indicated benefit from vitamin E in improving endothelial function, retinal blood flow, and renal dysfunction. However, the findings of large clinical trials investigating the role of individual or a combination of antioxidant nutrients in reducing the risk of CVD and microvascular complications in people with...

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...

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...

Insulin

As two major types of diabetes (1 and 2) differ, so the use of insulin differs for each. As described earlier, in type 1 diabetes the insulin doses must be closely matched to the meals ingested. Too much insulin or too little ingested carbohydrate can cause serious hypoglycemia. Frequently, patients are on intensive insulin regimens, sometimes four doses per day, and sometimes using an insulin pump. People with well-controlled type 1 diabetes have usually learned to pay close attention to their carbohydrate intake, recognize portion sizes, or even count grams of carbohydrate. They often adjust insulin dose or carbohydrate intake, but this can be done effectively only if they have a good, quantitative understanding of both. Meals skipped or eaten late can be a problem. Intensive insulin regimens may involve the use of an insulin pump or insulin doses based on a 'sliding scale.' Ordinarily, sliding scales are developed for the patient based on the self-monitored blood glucose at the...

Diabetes

Although controversy continues to exist regarding the optimal diet for individuals with diabetes, most health care diabetes specialists use the nutrition recommendations issued by the American Diabetes Association. These latest guidelines (57) specify that protein supply 10 to 20 of total caloric intake, saturated fatty acids less than 10 of total calories, and polyunsaturated fatty acids less than 10 of total calories. Thus, 60 to 70 of total calories remain to be divided between carbohydrate (CHO) and monounsaturated fatty acid (MUFA) intake. The distribution is individualized based on nutritional assessment and treatment goals. Nevertheless, individuals who are at a healthy weight and have normal lipid levels are encouraged to use the nutrition recommendations of the National Cholesterol Education Program, in which individuals over 2 years of age are advised to limit fat intake to < 30 of total calories (58,59). The rationale for these recommendations is the desire to lower...

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...

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.

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...

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...

Type 1 Diabetes

Genetic and immunologic risk factors for type 1 diabetes include having a parent with type 1 disease, especially the father (three times more likely than if the mother has type 1). Certain HLA antigens (HLA-DR3 and HLA-DR4) located on chromosome 6 are present in 95 percent of type 1 diabetics. Type 1 diabetics also have a higher prevalence of islet cell cytoplasmic antibodies (ICAs), antibodies to insulin, and antibodies to the enzyme glutamic acid decarboxylase (GAD). Since concordance of type 1 diabetes occurs in only about 36 percent of monozygous twins, environmental factors must also play a role in the development of type 1 disease. Dietary factors such as breast-feeding for less than 3 months or not breast-feeding at all exposure to cow's milk proteins, casein, and bovine serum albumin at age younger than 3 months and exposure to food additives such as nitrates and nitrosamines have also been associated with increased risk for development of type 1 diabetes. Viral infections,...

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

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.

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...

Contemporary Cardiology

Platelet Function Assessment, Diagnosis, and Treatment, edited by Martin Quinn, mb bch bao, phd and Desmond Fitzgerald, md, frcpi, fesc, app, 2005 Diabetes and Cardiovascular Disease, Second Edition, edited by Michael T. Johnstone, md, cm, frcp(c) andAristidis Veves, md, dsc, 2005 Diabetes and Cardiovascular Disease, edited by Michael T.

Cardiovascular Disease

Classification of Diabetes Mellitus Spontaneous Diabetes Mellitus (DM) Insulin-dependent (IDDM, or type I) Non-insulin-dependent (NIDDM or type II) Nonobese NIDDM Obese NIDDM Maturity onset diabetes of young people Secondary diabetes Gestational diabetes The risk of heart disease increases with a rise in cholesterol levels especially when other risk factors are present (17-19). Plasma total cholesterol was accepted as a causal factor (among multiple factors) by the World Health Organization (WHO) expert committee in 1982 and by the U.S. National Institute of Health Consensus Development Conference in 1985 (17). Diet and its effects on plasma cholesterol levels are discussed in the next section. Plasma triglyceride levels have also been correlated with increased risk of heart disease (17) and are associated with increased low-density lipoprotein (LDL) cholesterol levels. High blood pressure increases the risk of a stroke, heart attack, kidney failure, and congestive heart...

Role Of Diet In Cardiovascular Disease

Improper eating habits accompanied by the lack of exercise increase the risk of gaining excess weight, a major risk factor for heart disease, high blood pressure, and diabetes (14). Diet also affects plasma cholesterol levels. Cholesterol is carried in the blood associated with two major types of lipoproteins LDL and HDL. LDL cholesterol has been Diabetes mellitus

Studies In Renal Disease

The individual response to treatment with ACE inhibitors is highly variable. 20 Therefore, several studies have been conducted in which the efficacy of ACE inhibitor therapy was studied in relation to ACE genotype in patients with kidney diseases (Table 2). Yoshida et al. 21 studied the response to ACE inhibitor therapy in 21 Japanese patients with IgA-nephropathy, who were treated with lisinopril (10 mg day). After 4 years of therapy, only patients with DD genotype showed a significant reduction in proteinuria. These results were confirmed by Moriyama et al. 22 in patients with various renal diseases and by Ha et al. 23 in patients with diabetic nephropathy. Those results are also consistent with a study performed by Perna et al. 24 Proteinuria, change of glomerular filtration rate, and progression to end-stage renal disease were effectively reduced by treatment with ramipril in patients with the DD genotype. Interestingly, ethnic background may play a very important role as...

Management Of The Disease Process

Atherosclerosis should be treated by correction of risk factors such as hyperlipidaemia, smoking, hypertension, diabetes, and polycythaemia. In the presence of classic symptoms and appropriate carotid stenosis a decision to intervene can be based on duplex scan alone. Unless there is a contraindication, aspirin 300 mg day will significantly reduce the incidence of further neurological events. The role of new antiplatelet agents such as clopidogrel and ticlopidine have not been subjected to trial. Anticoagulants are unproven and carry significant side effects, but may be useful when other treatment modalities have failed.

Introduction Normal Adolescent Growth and Diets

Adolescence is a unique time of rapid growth, with half of eventual adult weight and 45 of peak bone mass accumulated during adolescence. Adolescence is a time when peak physical muscular development and exercise performance is reached. However, adolescent diets are often notorious for their reliance on snacks and 'junk foods' that are high in calories, sugar, salt, and saturated fat, which could provide extra energy for high-activity demands of teenagers, but often risk becoming part of bad habits leading to obesity and increased risk of atherosclerotic heart disease in later life. Although most studies have been on older subjects, it is now clear that many Western diseases, especially heart disease, stroke, diabetes, hypertension, and many cancers, are diet related, and that diets high in saturated fat and low in fruits, vegetables, and fiber may increase risks of heart disease. Indeed, autopsy reports of atherosclerotic plaques already present in adolescents who died accidentally...

The Dietary Guidelines forAmericans

Research clearly shows that being overweight greatly increases your risk for many diseases, including heart disease, cancer, and diabetes. If you are overweight, combining a healthful eating plan with regular physical activity is the most effective way to lose weight and to sustain Consult with a physician before beginning a new physical activity program if you have or are at risk for a medical condition (such as heart disease, high blood pressure, or diabetes), or if you are a man older than 40 years or a woman older than 50.

Immunogenetics and disease association

HLA-DR3 and or DR4, except when the disease occurs as part of type 1 autoimmune polyglandular syndrome. A high prevalence of other autoimmune diseases (ovarian failure, Graves disease, Hashimoto's disease, hypothyroidism and insulin-dependent diabetes mellitus) is associated with Addisons disease (see Table 1).

History and Physical Examination

Past Medical History (PMH) Past diseases, surgeries, hospitalizations medical problems history of diabetes, hypertension, peptic ulcer disease, asthma, myocardial infarction, cancer. In children include birth history, prenatal history, immunizations, and type of feedings.

Neuroendocrine Effects of Alcohol

Alcohol activates the sympathetic nervous system, increasing circulating catecholamines from the adrenal medulla. Hypothalamic-pituitary stimulation results in increased circulating cortisol from the adrenal cortex and can, rarely, cause a pseudo-Cushing's syndrome with typical moon-shaped face, truncal obesity, and muscle weakness. Alcoholics with pseudo-Cushing's show many of the biochemical features of Cushing's syndrome, including failure to suppress cortisol with a 48-h low-dose dexamethasone suppression test. However, they may be distinguished by an insulin stress test. In pseudo-Cushing's, the cortisol rises in response to insulin-induced hypoglycemia, but in true Cushing's there is no response to hypoglycemia.

Coordination Of Cellular Activity With Changing Demands Of The Internal And External Environment

Cells perceive a variety of chemical and physical factors as indicators of environmental change and respond to them in coordinated and characteristic ways. The final response, or output, of any specific cell and the signals, or inputs, to which it responds are determined by its particular differentiated state. Thus, a pancreatic beta cell perceives glucose and secretes insulin, a muscle cell perceives acetylcholine and contracts, and a retinal cell perceives light and stops releasing inhibitory neurotransmitter. Despite their different specialized functions, however, all cells draw upon a surprisingly limited set of molecular mechanisms to connect input and output.

Glandular Extracts Hormones And Enzymes

Glandular extracts, hormones, and enzyme collections are specific to the species, age, and sex of respective animals. Major products such as pepsin, rennin and other digestive enzymes, lipase and trypsin enzymes extracted from the pancreas, bile from the liver, adrenocortical steroids from the adrenal glands, and female reproductive hormones from the ovary are all medically significant products. Though insulin has been referenced as one of the prime pharmaceutical products derived from animal by-products, it is now synthesized by other procedures. This is true for a number of other pharmaceuticals, but reliance on the natural production and extraction is still an important source of medical treatment and prevention compounds.

Descent rules See rules of descent

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

Age and Risk Factor Profile

A few studies have indicated that subjects already at high risk of coronary disease experience a greater beneficial effect of drinking alcohol moderately conversely, only in those with a high risk level is coronary heart disease prevented. Hence, the large Nurses Health Study found that the J-shaped relation was significant only in women older than 50 years of age, whereas younger women who had a light alcohol intake did not differ from abstainers with regard to mortality. Fuchs et al. found that women at high risk for coronary heart disease (due to risk factors such as older age, diabetes, family history of coronary heart disease, high cholesterol, and hypertension) who had a light alcohol intake were at a lower risk of death than women who were at the same risk level but did not drink alcohol. In a study by the American Cancer Society, the finding by Fuchs et al. was confirmed among men,

Pancreatitis and Pancreatic Insufficiency

Pancreatitis occurs less frequently than liver disease in chronic alcoholics, and is characterized by severe attacks of abdominal pain due to pancreatic inflammation, while pancreatic insufficiency is due to the eventual destruction of pancreatic cells that secrete digestive enzymes and insulin. This destructive process is associated with progressive scarring of the pancreas together with distortion and partial blockage of the pancreatic ducts, which promote recurrent episodes of acute inflammatory pancreatitis. Since the pancreas is the site of production of proteases and lipases for protein and lipid digestion, destruction of more than 90 of the pancreas results in significant malabsorption of these major dietary constituents, as well as diabetes secondary to reduced insulin secretion. Consequently, patients with pancreatic insufficiency exhibit severe loss of body fat and muscle protein. Since the absorption of fat-soluble vitamins is dependent upon pancreatic lipase for...

Table 3D 1 Risk factors for pneumonia

Smoking, alcohol, COPD, cystic fibrosis, chronic bronchitis, viral infections Acute illness and antibiotic use AIDS*, diabetes, transplant, steroid use, asplenia, sickle cell disease, uremia, neoplasia, chemotherapy, extremes of age, complement deficiency Indwelling catheters, intrathoracic devices American southwest (Valley Fever), Ohio MississippiValleys (histoplasmosis, blastomycosis), Southeast Asia (tuberculosis), pigeon droppings (psittacosis), bovinesources (Q fever), buildings with contaminated water supply Dormitory, prison, barracks, nursing home

Electrolyte Disturbances

Chronic changes in plasma potassium are well tolerated but acute changes are associated with electrocardiogram (ECG) changes and cardiac arrhythmias (Figure PR.4). It is the ratio of intracellular to extracellular potassium that is relevant to myocardial excitability. Where the disturbance is chronic, this ratio will be nearly normal. Hypokalaemia may be treated by giving potassium either orally or intravenously. Care must be taken in the presence of renal insufficiency or low cardiac output states as hyperkalaemia may result. A flow controlled pump should be used to control the intravenous infusion rate if the concentration of potassium exceeds 40 mmol l and ECG monitoring will be required as ventricular fibrillation may occur if hypokalaemia is corrected too quickly. Hyperkalaemia should be treated over several days by the administration of calcium resonium. If ECG changes are noted or more rapid correction of acute changes is required pre-operatively insulin, 20 units in 100 ml of...

Integration Of Simultaneous Signals

Pathways may run in parallel, intersect, coincide, diverge, and perhaps intersect again before influencing the final effector molecules. Some signaling pathways must compete for common substrates as well as for the final effector molecules that express the final alterations in cellular behavior. Target cells must integrate all inputs by summing them algebraically and sometimes geometrically and then respond accordingly. For example, in the hepatocyte, both glucagon and epinephrine stimulate adenylyl cyclase, each by way of its own G-protein-coupled receptor. The effects of these signals combine to produce a more intense activation of adenylyl cyclase than would result from either one alone. At the same time, these cells may also be receiving some input from insulin, an action of which is activation of cAMP phosphodiesterase, which breaks down cAMP. In the pancreatic beta cell, which secretes insulin, epinephrine binds to two classes of G-protein-coupled receptors a2 receptors, which...

Endocrine aspects of healthy ageing in men

Frailty is characterized by generalized weakness, impaired mobility and balance and poor endurance. Loss of muscle strength is an important factor in the process of frailty, and is the limiting factor for an individual's chances of living an independent life until death. In men, several hormonal systems show a decline in activity during ageing. Serum bioavailable testosterone and oestradiol, dehydroepiandrosterone and its sulfate, and growth hormone and insulin-like growth factor 1 concentrations all decrease during ageing in men. Physical changes during ageing have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. Studies on hormone administration in the elderly appear to be promising. However, until now, hormone replacement has not yet been proven to be beneficial and safe.

Obtaining incremental information from diagnostic tests

A 75 year old male presents with a history of exertional chest pain. The patient describes substernal chest pain that he perceives as a pressure sensation occurring when he walks too fast, uphill, or in the cold. It is relieved by rest within a few minutes. On two recent occasions, he tried a friend's nitroglycerin tablets, and obtained even more rapid relief of his symptoms. His symptoms have never occurred at rest. The patient has a history of diabetes mellitus, hypertension, and hypercholes-terolemia. He smokes one pack of cigarettes a day. Several male family members died of coronary artery disease before the age of 60. The patient underwent carotid artery surgery a year ago for treatment of transient ischemic attacks. A more comprehensive attempt to consider all clinical characteristics, including risk factors for atherosclerosis, was published from the Duke University Medical Center databank.6 In addition to the three parameters previously...

From Antibiotics To Biologics

The extraction and use of animal proteins as roughly human equivalents came next (first bovine insulin from the animal pancreas and then growth hormone from the animal pituitary gland) to treat diseases of deficiency. The discovery of insulin in 1921 by Dr. Banting of Toronto (for which he shared the Nobel prize) set the stage for the mass production of insulin (Lilly IletinTM), which by the spring of 1923 became available to doctors for general administration (52). The widely visible miracle cure that insulin provided to critically ill diabetics solidified the budding disciplines of drug development and parenteral manufacturing. The discovery of penicillin by Alexander Flemingc in the 1920s resulted in the use of microbial fermentation by-products (antibiotics) to treat infection followed by the development of fermentation processes for steroids and was accompanied by the introduction of the concept of randomization in drug clinical trials (59). The control of infectious disease is...

Metabolism in Different Organs

Skeletal and cardiac muscle and adipose tissue are the main sites for transamination of the branched-chain amino acids, and the resulting ketoacids are transported to the liver for oxidation. However, in fasting and diabetes the capacity of muscle to oxidize branched-chain ketoacids increases markedly. In the postabsorptive state there is a net loss of amino acids from muscle, whereas in the fed state there is net uptake, reflecting the changes in net protein deposition and loss. However, at all times there is net output of alanine and glutamine from muscle, representing the disposal of the amino groups from the branched-chain amino acids. Muscle also takes up glucose, which is metabolized to supply the carbon skeletons for alanine and glu-tamine. Thus, there is a well-recognized glucose-alanine cycle between muscle and liver (Figure 11).

Routes of administration

In patients who are alert and orientated, tube positioning may be confirmed by aspiration of gastric contents and auscultation of the epigastrum. If aspiration or auscultation is unsuccessful, radiograph confirmation of the position of the tube is essential, and must be undertaken routinely in all such susceptible patients. In some patients (e.g. diabetics with neuropathy, head injuries, postabdominal surgery and ITU ventilated patients), nasogastric delivery of nutrients may not be appropriate because of increased risk of regurgitation and or pulmonary aspiration of feed. All such patients and others with gastric atony or gastroparesis should be considered for postpyloric nasoduo-denal or nasojejunal feeding. For the surgical patient for whom postoperative nutritional support is anticipated, placement at laparotomy is advised. In other cases a fine-bore tube may be introduced pernasally and, if spontaneous passage has not occurred after 12-24 h, endoscopic or...

Endocrinology of ageing

The third endocrine system that gradually declines in activity with ageing is the growth hormone (GH) insulin-like growth factor 1 (IGF1) axis (Corpas et al 1993). Mean pulse amplitude, duration, and free fraction of GH secreted, but not pulse frequency, gradually decrease during ageing. In parallel, there is a progressive fall in circulating IGF1 levels (Corpas et al 1993). The IGF1

Changing Perspectives On Contaminants

The lines of disease causation have become blurred at the genetic level by the discovery of microbe-induced disease processes not originally associated with microbial causes and only recently identified by genotypic approaches. The latter include viral-induced cancerso (83-85), schizophrenia (86), and diabetes mellitus (87). Borrelia burgdorferi DNA incorporated in the genome of arthritic mice (88) and detected in humans (89) and a list of organisms referenced by Relman (87) have been found using genotypic approaches to detect microbial genes inserted into the genome of man and animals and therefore associated with specific diseases. These include Helicobacter pylori (peptic ulcer disease), hepatitis C virus (non-A, non-B hepatitis), bartonella henselae (Bacillary angiomatosis), Tropheryma whippelii (Whipple's disease), sin nombre virus (Hantavirus pulmonary syndrome), and Kaposi's sarcoma-associated herpes virus (Kaposi sarcoma). In this context Fredricks and Relman have called for...

Clinical Assessment Of Volume Status

Volume loss can often be suspected from the history. Poor oral intake or history of vomiting, diarrhea, poorly controlled diabetes, renal disease, or adrenal disease are suggestive. With moderate volume loss, there may be postural hypotension and possibly a resting tachycardia. There may be narrowing of the pulse pressure. Jugular venous pressure will be difficult to appreciate clinically (assuming no right heart disease). Patients with moderate to severe volume loss may be weak and

Thyroid Hormone Effects

T3 has multiple effects on carbohydrate metabolism. It increases intestinal absorption of glucose and increases muscle and adipose tissue uptake of glucose. T3 enhances the glycogenolytic and hyperglycemic effects of adrenaline, and enhances insulin's effects on glycogen production and glucose utilization. However, T3 speeds up the degradation of insulin. This becomes clinically important in those who cannot produce their own endogenous insulin (type I diabetics). Hyperthyroidism leads to a worsening of blood glucose control in type 1 diabetics and conversely, hypothy-roidism leads to an improvement of their glucose regulation.

Preoperative Management Of Specific Problems

Duration of the procedure correlates with higher rate of wound infection, and therefore in procedures lasting more than 4 h a second dose of the antibiotic should be administered intraoperatively. Recent work suggests that better glycemic control with insulin infusions may reduce the incidence of deep sternal wound infections in diabetic patients who have undergone cardiac surgery. This observation is supported by a study demonstrating better preservations of neutrophil function with aggressive glycemic control using an insulin infusion compared with intermittent therapy, in diabetic cardiac patients.

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