Association Of Insulin Resistance With Other Cv Risk Factors

In addition to being a precursor of type 2 diabetes and an independent risk factor for CVD, insulin resistance is also closely associated with several other CV risk factors. The interrelatedness of insulin resistance with the other factors is discussed below. Obesity is frequently associated with several of the components of the IRS and may be critical for the development of the syndrome. The contemporary view is now centered on visceral adiposity Several mechanisms have been proposed for the...

Carbohydrate and Type Diabetes

The recommended intake of carbohydrate for people with diabetes is 45 to 60 of total energy intake (Table 2). Provided that foods rich in fiber and with low-glycemic index predominate, there are no known deleterious effects with this range of carbohydrate intake. When carbohydrate intakes are at the upper end of the proposed range, restriction of carbohydrate to around 45 of total energy and a partly replacement of carbohydrate by monounsaturated fat may be tried for some patients with...

Clinical Diagnosis Of Hypoglycemia

It is not possible to specify a plasma glucose concentration that defines clinical hypoglycemia in people with diabetes because the glycemic thresholds for the manifestations of hypoglycemia shift to higher than normal glucose levels in poorly controlled diabetes and lower than normal glucose levels in well controlled diabetes. The diagnosis is made most convincingly by Whipple's triad symptoms consistent with hypoglycemia, a low plasma glucose concentration and relief of those symptoms after...

Effects On Adipose Tissue

In all clinical studies to date, type 2 diabetic patients treated with thiazolidinediones tend to gain weight and accumulate adipose tissue (55). It would appear paradoxical that a drug which improves insulin sensitivity and glucose and lipid profiles would at the same time increase adiposity and body weight. Considerable research has focused on the reasons for this paradox, especially the sites and nature of thiazolidinedione-induced weight gain. The thiazolidinediones, through PPAR-y...

Evaluation Of Diabetic Renal Disease And Classification

It is now widely accepted that patients with type 1 diabetes exhibit a very characteristic evolution of renal changes (Table 1). Initially, there may be hyperfiltration and renal hypertrophy, but normal albumin excretion rate unless the normal are or have been badly controlled with respect to glycemia. The reservation is, however, that many type 2 diabetic patients have had undiagnosed diabetes for several years. In contrast to type 1 diabetes, patients with type 2 diabetes quite often have...

Female Sexual Dysfunction

Female sexual dysfunctions (FSD) include persistent or recurrent disorders of sexual interest desire, disorders of subjective and genital arousal, orgasm disorder, pain and difficulty with attempted or completed intercourse. The scientific knowledge on sexual dysfunction in women with diabetes is rudimentary. Sexual dysfunction was observed in 27 of type 1 diabetic women. FSD was not related to age, BMI, HbA1c, duration of diabetes, and diabetic complications. However, FSD was related to...

Glucose Monitoring Self Blood Glucose Monitoring

In order to obtain blood glucose control and to maintain this on a daily basis, it is essential for patients with diabetes to do SBGM. The DCCT and other studies clearly demonstrated the importance of this approach and it is now considered as one of the cornerstones of therapy. However one of the findings of the DCCT was that with intensive therapy the number of severe hypoglycemic episodes increase. The data obtained from monitoring are used to assess the efficacy of the treatment program and...

Hypoglycemia in Type Diabetes

Washington University School of Medicine, St. Louis, Missouri, U.S.A. Comprehensive treatment, including glycemic control, makes a difference for people with diabetes. Glycemic control prevents or delays the microvascular complications retinopathy, nephropathy and neuropathy of both type 1 diabetes (1) and type 2 diabetes (2) it may also reduce macrovascular events (3,4). However, because of the imperfections of all current treatment regimens, iatrogenic hypoglycemia is the limiting factor in...

Management Of The

The use of insulin sensitizers and lifestyle modifications to improve insulin resistance in the treatment of type 2 diabetes is discussed elsewhere in the book. Any therapeutic maneuver that improves insulin sensitivity should also have beneficial effects on all the metabolic and CV abnormalities associated with the IRS. In this section we will concentrate on management of the syndrome as a whole particularly its link with CVD. Since obesity and physical activity are important precursors of the...

Nafld As A Cardiovascular Risk Factor

Data is emerging that NAFLD is an independent risk factor for vascular disease, which is the most common cause of death among patients with diabetes (1). Patients with NAFLD have a greater carotid intima-media thickness as well as a higher prevalence of carotid atheromatous plaques (51). The presence of NAFLD among patients with type 2 diabetes is associated with an increased risk of developing vascular disease, which is only partly associated with the presence of the metabolic syndrome...

Obesity And Glycemic Control

It is noteworthy that BMI is the most important predictor of deterioration in glycemic control, regardless of the treatment regimen, according to a study from Finland (25). Moreover, in this study, there was significantly greater decrease in HbA1c levels in patients whose baseline weight was below the mean in those whose weight was above this cutoff value (1.7 vs. 0.5 , p< 0.01). For this reason, there is now agreement that prevention of weight gain is an important target when drug treatment...

Oral Hypoglycemic Agents

Oral hypoglycemic agents are not approved or recommended in the US for treatment of GDM. Older sulfonylureas, such as tolbutamide and chlorpropramide, cross the placenta and cause fetal hyperinsulinemia and macrosomia. They also have the potential to cause prolonged neonatal hypoglycemia. Minimal amounts of glyburide, however, cross the placenta (97). In a study of 404 women with mild GDM randomly assigned to receive either glyburide or insulin, the results demonstrated that the groups achieved...

Other Nutritional Factors

There are no firm epidemiological data with regard to the role of dietary protein in the etiology of type 2 diabetes. Although vegetarians present with lower rates of type 2 diabetes compared with persons who eat meat, it is impossible to disentangle the association of animal protein with the risk of type 2 diabetes from other dietary factors, such as saturated fat and fiber intake (11). The relationship between alcohol and other dietary variables similarly complicates attempts to evaluate a...

Pcos And The Metabolic Syndrome

Insulin resistance and hyperinsulinemia have been extensively studied in PCOS. While obese patients have a more pronounced phenotype, even lean PCOS patients have a reduced insulinmediated glucose disposal and elevated basal hepatic glucose production (38). The hyperinsulinemia first described by Burghen et al. (12) was subsequently confirmed, including studies showing higher fasting insulin levels resulting from a higher basal insulin secretion rate (39), higher insulin responses during an...

Perioperative Management Of The Type Diabetic Outpatient Surgery

Post operative glucose levels are often increased above 250 mg dL when insulin or oral agents are withheld in type 2 diabetics undergoing outpatient surgery. This data has led to the recommendation that insulin therapy be considered for all type 2 diabetics managed with an oral hypoglycemic agent. Alternatively, type 2 diabetics well controlled by diet and exercise can be managed without insulin in the ambulatory surgical setting (61,62). Patients previously treated with insulin should receive...

Ramachandiran Cooppan

Joslin Diabetes Center, Boston, Massachusetts, U.S.A. Diabetes mellitus is a chronic disease that results in major morbidity and mortality. As with any chronic illness the goals of therapy are to alleviate the acute symptoms and complications and then focus on preventing the long-term consequences. While the initial goals can be reasonably achieved in most instances, the long-term complications can prove to be more of a challenge. This is in part due to the fact that the disease is not a single...

Safety And Side Effects

AGIs are the safest oral antidiabetics, but are associated with a rather high frequency of gastrointestinal side effects because they inhibit digestion of carbohydrates. With > 1 million patients having taken acarbose for > 1 year, no serious adverse event has been reported. As antihyperglycemic agents they carry no risk of causing hypoglycemia. When given in combination with oral insulin secretagogues, the frequency of hypoglycemic episodes was reduced (52) and there was no increase in...

Summary

Combined oral agent therapy offers superior efficacy and an opportunity to minimize side effects. In selecting oral combinations, an important objective is minimizing the number of tablets needed and their cost, and this practical imperative has led to various formulations, including several with two agents in a single tablet. Early use of combination therapy is recommended in consensus algorithms (67). Combining oral agents even with the addition of incretin mimetics may delay the need for...

Treatment Of Hypoglycemia

Obviously, prevention of iatrogenic hypoglycemia, as just discussed, is preferable to treatment of hypoglycemia. Episodes of asymptomatic hypoglycemia (detected by self-monitoring of blood glucose) and most episodes of mild to moderate symptomatic hypoglycemia, are effectively self-treated by ingestion of glucose tablets or carbohydrate in the form of juices, soft drinks, milk, crackers, candy or a meal. A glucose dose of 20 g is reasonable (26). However, in the setting of ongoing...

Conclusions On Treatment

Although considerable improvement in the quality of controlled trials has recently been achieved, no major breakthrough in slowing the progression of diabetic neuropathy in the long run has been achieved with drugs used on the basis of present pathogenetic concepts. Some of the newer drugs have shown promising results in phase II trials which require confirmation from large phase III trials. It is conceivable that drugs interfering with the pathogenesis of diabetic neuropathy may be most...

Protease Inhibitors PI

The introduction of highly active antiretroviral therapy (HAART) has significantly improved the survival and quality of life of HIV-infected individuals. However, HARRT-regimen, especially those including PIs have also resulted in increased incidence of metabolic syndrome and diabetes. Eleven PIs are now available in US and at least eight of them are clearly associated with disturbance in glucose homeostasis. It is estimated that up to 40 of patients receiving Pi-based regimen show glucose...

Treatment Goals of Therapy

The goals of therapy in GDM are to decrease both maternal and fetal morbidity and mortality attributed to the disease. In particular, to limit macrosomia, intrauterine demise and neonatal morbidity. Preventing macrosomia has been found to decrease birth trauma, and cesarean-section rate (51). Maternal hyperglycemia conclusively poses a threat to the well-being of the fetus. Fasting hyperglycemia (FPG > 105 mg dL) is associated with increased risk of fetal death (17,18). Higher postprandial...

Increased Aldose Reductase Activity

The aldose reductase pathway has been extensively studied because of the presence of the enzyme in the retina, kidney, and nerves. These are all targets for the long-term complications and would present a unified model for the damage caused by chronic hyperglycemia. The enzyme increases its activity in the presence of high blood glucose levels and causes increased levels of sorbitol. Sorbitol dehydrogenase metabolizes the sorbitol that is then postulated to lead to other metabolic changes that...

Introduction

Diabetes mellitus (DM) has emerged as one of the most common diseases of this century. Its incidence is on the rise and the numbers are projected to reach a dreaded level by the year 2030 (1). In the United States alone, 4000 cases of diabetes are diagnosed every day (2). Most of them are type 2 diabetes mellitus (T2DM), and overall 8 of the population carries this diagnosis (3). Hyperglycemia is the sine qua non for diabetes. It results from the disturbance of normal glucose homeostasis. Under...

Prevention Of Diabetes

Several large studies were published on prevention of diabetes type 2 by exercise combined with other interventions such as weight loss and intensified medical treatment. In one study 3234 nondiabetic patients with impaired glucose tolerance were randomly assigned to either placebo, metformin (850 mg twice daily), and lifestyle-modification program with the goals of a minimum of 7 weight loss and 150 min physical activity per week (52). Physical activity was only recommended, not supervised...

Impact Of Hypoglycemia

There is little published information about the clinical impact of hypoglycemia in type 2 diabetes. While it is reasonable to extrapolate from the experience in type 1 diabetes, there are obvious differences. As noted earlier, episodes of hypoglycemia become familiar events early in the course of type 1 diabetes. They are infrequent early in the course of type 2 diabetes, even during treatment with insulin secretagogues or insulin, but become progressively more frequent as the patient...

Modifiable Risk Factors

Hu et al. (39) published results from the Nurses' Heath Study including 84,941 female nurses followed from 1980 to 1996, and who were free of diagnosed cardiovascular disease and diabetes at baseline. During the 16 years follow-up 3300 new cases of type 2 diabetes were diagnosed. As shown in Figure 4 obesity was the single most important predictor of diabetes. Women whose body mass index was at least 35.0 km m2 had almost 40-fold risk of becoming diabetic compared to women whose body mass index...

The Antidiabetic Properties Of Glp In Type Diabetes And Limitations To Its Therapeutic

In patients with type 2 diabetes, the incretin effect is reduced or absent (47). GLP-1 secretion is diminished in type 2 diabetic subjects, possibly contributing to the reduced incretin effect (48). A continuous intravenous GLP-1 infusion stimulates insulin secretion and normalizes both fasting and postprandial blood glucose in patients with type 2 diabetes (29,49). A continuous subcutaneous administration for 6 weeks reduced diurnal glucose concentrations and HbA1c by 1.3 and suppressed...

Pathogenetic Mechanisms

Recent experimental studies suggest a multifactorial pathogenesis of diabetic neuropathy. Most data have been generated in the diabetic rat model, on the basis of which two approaches have been chosen to contribute to the clarification of the pathogenesis of diabetic neuropathy. Firstly, it has been attempted to characterize the pathophysiological, pathobiochemical, and structural abnormalities that result in experimental diabetic neuropathy. Secondly, specific therapeutic interventions have...

Defects In The Incretin Effect In Type Diabetes

The incretin effect is absent or diminished in type 2 diabetes. GLP-1 still stimulates insulin secretion in type 2 diabetic patients at higher plasma concentrations, whereas GIP has lost most of its insulinotropic activity (27-29). The reason for the loss of the insulinotropic action of GIP has not completely been elucidated yet. Specific defects in GIP signaling and general secretory defects of the beta cell are most likely responsible. GLP-1 secretion as well as GLP-1 action is diminished in...

Info

Previous diabetes 3400 New diabetes 580 Non diabetes 10719 FIGURE 3 Kaplan-Meier curves for composite outcome of cardiovascular mortality morbidity at 1 year by diabetic status. p 0.005 for previous versus new diabetes diagnosis p< 0.001 for previous versus no diabetes diagnosis p< 0.001 for new versus no diabetes diagnosis. Significant increases in post-MI mortality have been described in diabetic patients treated with thrombolysis compared to those without diabetes (40). This increase in...

Dan Ziegler

Institute of Clinical Diabetes Research, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, DUsseldorf, Germany CLASSIFICATION, EPIDEMIOLOGY, AND CLINICAL IMPACT OF DIABETIC NEUROPATHY Diabetic neuropathy has been defined as a demonstrable disorder, either clinically evident or subclinical, that occurs in the setting of diabetes mellitus without other causes for peripheral neuropathy. It includes manifestations in the somatic and or autonomic parts of the...

Barriers To Optimal Diabetes Care

Although many effective treatment modalities are available for the control of diabetes, glycemic control is still below national guidelines. Suboptimal treatment of diabetes in ethnic groups may be due to barriers that hinder effective treatment. The barriers at the level of the patient include poor diabetes-specific knowledge, lack of self-management skills and non-adherence to lifestyle modification such as diet and exercise. Others include, negative belief and attitudes about diabetes, low...

Practicalities

Efficacy, side effects, and compliance strongly depend on rational indications, education of patients on how to use the drug, and good dietary advice. Even with good clinical practice, a considerable variation in response and side effects is seen. Side effects depend, among other things, on the dose and time intervals for titration of optimal therapeutic dosage. It is essential to start with low doses of 25 mg of acarbose or miglitol twice a day, with a stepwise increase in 2 to 3 week...

Preoperative Evaluation Of The Diabetic Patient

A surgical procedure cannot be considered successful unless the patient recovers with an equal or improved quality of life and long-term survival. Patients with long standing diabetes are at increased risk for developing complications. The goal of preoperative assessment is to identify patient risk factors and quantify risk, in order to decide the appropriateness of the planned surgical procedure and the timing of surgery. History, physical, and selective tests are used to identify the presence...

References

Metzger BE, Coustan DR., The Organizing Committee. Summary and recommendations of the fourth international workshop-conference on gestational diabetes mellitus. Diabetes Care 1998 21 (Suppl 2) B161-7. 2. Dabelea D, Snell-Bergeon JK, Hartsfield CL, et al. Increasing prevalence of gestational diabetes mellitus (GDM) over time and by birth cohort Kaiser Permanente of Colorado GDM Screening Program. Diabetes Care 2005 28 579. 3. Carpenter MW, Coustan DR, Criteria for screening tests for gestational...

Ace Inhibitors Or Arbs In Early Nephropathy

Furthermore, while it is evident that both classes of drugs inhibiting the RAS appear to be beneficial, an important question remains is one class superior for the prevention of the development of cardiovascular and renal disease This particular issue has now been addressed by the DETAIL trial (66). DETAIL was a much-needed, long-term study comparing an ACE-inhibitor with an ARB head-to-head in a diabetic population. The 5-year, prospective, multicenter, double-blind study directly compared the...

Mutations In The Glucokinase Gene Mody

MODY2 presents with mild, dietary manageable hyperglycemia and in the case of a positive family anamnesis, this MODY form is especially seen in children with the highest prevalence. Usually affected subjects are free of symptoms at diagnosis and are identified in routine health examinations Table 2 . Approximately half of the female mutation carriers present for the first time with gestation diabetes. The molecular causes of MODY2 are mutations in the glucokinase GCK gene and more than 200...

Cabg

This was suggested in a report from the BARI trial, which evaluated patients with and without diabetes who had undergone revascularization with CABG or PTCA within three months after study entry 25 . Among the patients with diabetes, CABG significantly reduced the mortality after a subsequent MI relative risk 0.09 compared to angioplasty . BARI trial data and results from three other trials that reported results for patients with diabetes EAST, CABRI, and RITA were...

Antidiabetic Drugs And Body Weight

It has long been recognized that antidiabetic drugs can promote weight gain in subjects with type 2 diabetes. The strongest weight-promoting effect is exerted by insulin. In the diabetes control and complications trial DCCT , intensified insulin treatment was associated with substantial weight gain that resulted in unfavorable changes of lipid levels and blood pressure similar to those seen in the insulin resistance syndrome 24 . In the UKPDS, insulin treatment caused a mean weight gain of...

Diagnostic Criteria For Diabetes And Other Categories Of Abnormal Glucose Tolerance

Diabetes mellitus DM refers to a number of disorders that share the common feature of elevated blood glucose levels. The classification accepted by the World Health Organization WHO 1,2 and the American Diabetes Association ADA 3,4 combines both clinical stages of hyperglycemia and the etiological types. Two main subtypes of diabetes are type 1, either autoimmune or idiopathic, and type 2, attributable to insulin resistance, insulin secretion defects, or both. Although diabetes has been known...

Epidemiology Of Dyslipidemia In Type Diabetes

Given the predicted increase in the prevalence of diabetes worldwide and the progressive Westernization of lifestyles in developing countries, cardiovascular disease, which is increased two to five times in people with diabetes, has and will continue to have major implications for health and healthcare provision. Although the development of atherosclerosis and clinical vascular disease is multifactorial, dyslipidemia is a major contributing risk factor. Dyslipidemia is common in patients with...

Stress And Blood Glucose Control

Psychological stress has significant effects on the metabolism on individuals without diabetes by increasing counterregulatory hormones, which could result in elevated blood sugars, among other impacts. In type 2 diabetes it is thought that stress can exert an effect on blood glucose control, either directly through these hormones or indirectly by disruption of the diabetes self-care regimen. Although the laboratory and clinical research to date does not appear to support a consistent...

Transcutaneous Electrical Nerve Stimulation

Transcutaneous electrical nerve stimulation TENS influences neuronal afferent transmission and conduction velocity, increases the nociceptive flexion reflex threshold, and changes the somatosensory-evoked potentials. In a 4-week study of TENS applied to the lower limbs, each for 30 min daily, pain relief was noted in 83 of the patients compared to 38 of a sham-treated group. In patients who only marginally responded to amitriptyline, pain reduction was significantly greater following TENS given...

Longterm Risk Of Esrd In Diabetic Patients Treated With Different Antihypertensive Drugs

The incidence of ESRD in diabetic patients has continued to increase despite the extensive use of ACEi to prevent DN. Recently, Suissa, et al. 75 have assessed the long-term effect of ACEi on the risk of ESRD in a population-based cohort of all diabetic patients treated with antihypertensive drugs between 1982 and 1986. The cohort of 6102 patients, in which 102 cases developed ESRD until 1997, were matched to 4129 controls. Relative to thiazide diuretic use, the adjusted rate ratio of ESRD...

The Natural History Of The Diabetic Foot

The natural history can be divided into the following stages 9 1. Normal foot. The foot is normal and does not have the risk factors of ulceration namely neuropathy, ischemia, deformity, callus and edema. 2. At-risk foot. The patient has developed one or more risk factors noted in stage 1. 3. Foot with ulcer. There are two main types of diabetic foot, which have characteristic ulceration ulceration in the neuropathic foot develops at the sites of high mechanical pressure on the plantar surface....

Metaanalyses Comparing The Effects Of Acei Or Arb For Preventing The Development And Progression Of Diabetic Kidney

Recently, several meta-analyses 66-69 comparing the effects of ACEi and ARB for preventing the development and progression of DN were published. Surprisingly, these reports reached totally different conclusions indicating the well known discrepancies between meta-analyses and subsequent large randomized, controlled trials 70 . In 2004, Strippoli GF, et al. 66 analyzed 43 trials with a total of 7545 patients 36 of 43 identified trials compared ACEi with placebo 4008 patients , 4 compared ARB...

Lipotoxicity

Lipotoxicity Beta Cell Dysfunction

Although free fatty acids FFA , also termed NEFA, acutely increase insulin secretion, chronic FFA overload diminishes beta-cell function. Type 2 diabetes subjects have often increased FFA due to insulin resistance to adipocyte lipolysis. It is now clear that high glucose inhibits beta-cell fatty acid oxidation, which may lead to accumulation of long-chain FIGURE 6 Schematic representation of possible negative influences of hyperglycemia and increased NEFA, and of various modulators involved in...

Contraindications

AGIs have very few contraindications. They should not be given to patients with diverticulosis, large hernia, acute gastrointestinal diseases, colitis, inclusive and obstructive diseases of the bowel because of their adverse effects on gas production in the bowel, particularly in the colon. Pregnancy and lactation period are contraindications. For acarbose, but not for miglitol, severe renal insufficiency serum creatinine gt 3.5mg dL is a contraindication. Bile acid adsorbents, such as...

Pathogenesis Of Microvascular Disease

From a pathogenic viewpoint a number of different molecular mechanisms have been proposed for the development of the various manifestations of diabetic retinopathy. The underlying abnormalities may also play a role in the microvascular disease that results in nephropathy and possibly neuropathy. Many of these theories have been studied extensively in animals and humans using both in vitro and in vivo methods. The primary goal of these studies was to try and identify the underlying mechanisms...

Tissue Specific Insulin Receptor Knockout Models

In order to better understand whether severe insulin resistance can lead to frank diabetes, and to delineate the roles of the various insulin-sensitive tissues, the question has arisen whether it would be possible to induce diabetes in animal models harboring genetic defects leading to absence of insulin receptors in specific tissues brain, muscle, liver, adipocytes, and pancreas islets . Therefore, animal models with conditional knockouts of the insulin receptor have been studied Fig. 3 ....

Clinical Manifestation

In clinical practice one speaks of diabetic coma even if the patient has not lost conscious. About 10 of patients with coma diabeticum are really unconscious 6 . The causes of these conscious disturbances are cerebral dysfunction in association with severe hypertonic dehydration. The transition from hyperglycemic decompensation with severe ketoacidosis toward coma diabeticum is substantially dependent on the extent of the increase in serum osmolality. The consciousness correlates best with...

Cerebral Edema

A severe, but avoidable complication of therapy is cerebral edema 9 . Brain edema is observed mostly 3 to 13 hours after beginning of therapy. It must be considered especially in patients below 20 years. In one study in children and young adults a total of 55 death cases were investigated 35 . Thirty-six of these patients had a ketoacidosis. A further retrospective study in children investigated searched for risk factors for the development symptomatic brain edema 33 . The prevalence of...

Bicarbonate Therapy

The therapy with bicarbonate is one of the mostly discussed procedures of management in the treatment of diabetic ketoacidosis. In general, acidosis is decreased after adequate rehydration and implementation of insulin treatment. The main indication for bicarbonate is the emergency treatment of serious disturbances of heart rhythm with severe acidosis and hyperkalemia. In such cases a body weight-adjusted amount of sodium bicarbonate e.g., 50-100 mL is infused. Otherwise, bicarbonate therapy...

Pathophysiology Of Hyperglycemia

An enormous amount of research has been dedicated to unraveling the pathophysiology of type 2 diabetes mellitus over the last 30 years. While a large number of reviews have been devoted to its description, this chapter follows the line of our recent seminar 1 . Insulin is the key hormone for regulating blood glucose. In general, normoglycemia is maintained by the balanced interplay between insulin secretion and the efficacy of insulin actions. In the fasting state, the major part of glucose is...

Diabetes Mellitus Type Is A Multifactorial Disease With Strong Genetic Susceptibility

Diabetes mellitus type 2 is the most common endocrine-metabolic disorder and affects at least 5 of Western society. According to the persisting trends for increasing obesity, the amount of newly diagnosed patients will increase dramatically over the next decades. Unfortunately, lifestyle in combination with affluent alimentation does not spare the young, and increasing obesity in this group is already observed. Usually diabetes mellitus occurs at ages over 40 but we now observe a shift in the...

Screening Methods

Profunda And Sfa Arteriogram

The clinical exam and Rose questionnaire are useful though unfortunately fairly insensitive tools for the diagnosis of lower extremity vascular disease 163 . Ancillary modalities include the ABI, toe systolic blood pressure, ultrasound duplex scanning, tissue PO2 measurement, and arteriography. The ABI is a ratio of Doppler recorded systolic arterial blood pressures in the lower and upper extremities, 166 and is normally between 1.00 and 1.40 167 . PAD is defined as an ABI less than 0.9. Lower...

Longterm Implantable Cgm Enzymebased Blood Glucose Electrochemical Sensor

Glucose Electrochemical Sensors

Medtronic Diabetes has developed an electrochemical sensor for long-term implantation in the superior vena cava called the Vascular Glucose Monitoring System http www. medtronicdiabetes.com . The distal tip of the flexible vascular catheter contains an oxygen FIGURE 5 Electrochemical ISF glucose sensor designed for long-term implantation within the subcutaneous tissue. ISF glucose data is transmitted wirelessly to the patient-worn display mg dL versus time www.DexCom.com . FIGURE 5...

Stage The Necrotic Foot Diagnosis

Necrosis has very grave implications, threatening the loss of the limb and is caused by infection or ischemia or by both together. It is classified as either wet or dry, each with its specific management. In the neuropathic foot, necrosis is invariably wet initially and is nearly always due to a septic arteritis secondary to soft tissue infection complicating a digital or metatarsal ulcer. The arterial lumen is often occluded by a septic thrombus. Both wet and dry necrosis can occur in the...

Management

Non-Proliferative Diabetic Retinopathy Management of NPDR relies heavily on patient education, periodic screening and, when necessary, laser treatment. The American College of Physicians American Academy of Ophthalmology has recommended a schedule for ophthalmic evaluation for patients with diabetes Table 1 . Periodic eye examinations enable ophthalmologists to identify patients who would benefit from prophylactic treatment, before serious complications develop. The potential sight-threatening...

Insulin Perfusion

The normal insulin need is about 1 IE hr and should be adapted to the increased needs depending on the extent of ketoacidosis, sepsis, overweight, activation of counter regulatory hormone systems and eventually therapy with catecholamines or glucocorticoids leading to insulin resistance. The guidelines of the German diabetes association recommend the low-dose insulin therapy with a starting dose of 6 IE hr 0.1 IE kg bodyweight until ketoacidosis is controlled and blood glucose is lowered to 14...

Insulin Therapy in Type Diabetes

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, U.S.A. Type 2 diabetes mellitus is defined by hyperglycemia, which is the result of an inability of the pancreas to make enough insulin for an individual's insulin resistance. Once this relative deficiency in insulin develops, the ability to produce insulin is no longer balanced with the insulin resistance and hepatic glucose production, thus the sugar...

Contents

Epidemiology of Type 2 Diabetes 1 2. Pathogenesis of Type 2 Diabetes 13 Michael Stumvoll, Barry J. Goldstein, and Timon W. van Haeften 3. Rationale and Goals for Glucose Control in Diabetes Mellitus and Glucose Monitoring 27 4. The Role of the Diabetes Educator in the Education and Management of Diabetes Mellitus 45 5. Nutrition in the Etiology and Management of Type 2 Diabetes 59 Monika Toeller and Jim I. Mann 6. Diabetes and Exercise 73 Gerhard Schuler and Axel Linke 7. Psychosocial Issues...

Dietary Approaches

The gold standard in the dietary treatment of obese patients with type 2 diabetes is a balanced moderately energy-restricted diet. The energy deficit is between 500 and 800 kcal day. The most important single measure is the reduction in fat intake, particularly in saturated fatty acids. It is generally recommended to prefer a high-carbohydrate low-fat diet. As shown TABLE 5 Obesity Prevention and Treatment Flowchart 18.5-24.9 Normal weight BMI 18.5-24.9 plus risk factors s and or comorbidity...

Rhuna Shen Susan E Wiegers and Ruchira Glaser

Department of Medicine, Cardiovascular Medicine Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A Cardiovascular disease is a leading cause of death in the diabetic population, accounting for close to 80 of the mortality in diabetic patients in North America 1,2 . Patients with diabetes mellitus have both a significantly higher risk for, and a higher mortality from, coronary artery disease CAD . The diabetic patient has a two-to four-fold increase in the...

Intracavernosal Injection Therapy

Intracavernosal therapy requires some specialist knowledge and the ability to treat priapism should it occur. Many specialists used to regard this as the standard treatment and use it for both diagnostic and therapeutic reasons although its role as first-line therapy has been replaced by less invasive treatment modalities. Patients need to be taught how to perform self-injection and the dose needs to be chosen carefully to avoid prolonged erections or priapism. Some patients find it helpful to...

Diagnostic Procedures

The following basic diagnostic steps are needed usually during the first 24 hours clinical history, physical examination, clinical chemistry including TSH, parameters of sepsis, blood gases, urine status, blood and urine cultures in case of signs of infection, ECG, ultrasound of the abdomen, chest X-ray and eventually echocardiography. Especially in the beginning of the therapy of diabetic ketoacidosis, regular control of capillary blood glucose, potassium, and blood gases is needed. Initially,...

Physiology and Pathophysiology

Guanil Cyclase

Penile erection is a neurovascular event modulated by psychological factors and hormonal status depending on appropriate trabecular smooth muscle and arterial relaxation in the corpus cavernosum Fig. 1 . On sexual stimulation, nerve impulses cause the release of cholinergic and non-adrenergic non-cholinergic NANC neurotransmitters that mediate erectile function by relaxing the smooth muscle of the corpus cavernosum. A principal neural mediator of erection is NO which activates guanil cyclase to...

Figure

Glycemic Neovascular Tissue And Vitreous

Features of diabetic retinopathy, including microaneurysms, cotton wool spots CWS , retinal edema, exudates, venous abnormalities and neovascularization, are all secondary to compromised capillary endothelium, which leads to increased capillary permeability and fragility. Widespread small vessel damage leads to areas of ischemia, which can promote intraocular angiogenesis. Numerous hypotheses explaining the microvascular complications of diabetes have been investigated, including the role of...

Mody Modyx

Diabetes, microvascular complications often reduced serum concentrations of triglycerides, Apolipoprotein AII ans CIII, and Lp a lipoprotein Impaired fasting glucose tolerance, diabetes, normal proinsulin-insulin ratio in serum Diabetes, microvascular complications often renal glucosuria, increased sensitivity to sulfonylurea drugs increased proinsulininsulin ratio in serum Diabetes Diabetes, renal cysts and other abnormalities of renal development progressive non-diabetic renal dysfunction,...

4. V. Emanuele N F. Swade T And Ann Emanuele M. Consequencies Of Alcohol Use In Diabetics. Alcohol Health And Research

Diabetes Statistics. Alexandria, VA American Diabetes Association, 2006. 2. American Diabetes Association. Medical Management of Type 2 Diabetes. Alexandria, VA American Diabetes Association, 1998. 3. Diabetes Research Working Group. Congressional report on National Institutes of Health implementation of the recommendations of the Congressionally-directed Diabetes Research Working Group, 1998. 4. Mokdad AH, Ford ES. Diabetes trends in the U.S. 1990-1998....

1 Haffner Sm Et Al. Insulin Sensitivity In Subjects With Type 2 Diabetes. Diabetes Care 1999 22 562-8

Nathan DM, Singer DE, Godine JE, Perlmuter LC. Non-insulin-dependent diabetes in older patients. Complications and risk factors. Am J Med 1986 81 837-42. 2. United Kingdom Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS 33 . Lancet 1998 352 837-53. 3. United Kingdom Prospective Diabetes Study Group. Effect of intensive blood-glucose control...

Historical Aspects And Introduction

The glucose-lowering potential of guanides was first described in medieval times when extracts of Galega officinalis goat's rue or French lilac were used as treatment of diabetes in Europe 1 . In 1957, metformin, a dimethylated biguanide, and phenformin, a phenetylated biguanide were introduced for the therapy of type 2 diabetes mellitus Fig. 1 . Because of the strong association with lactic acidosis, phenformin was withdrawn in the 1970s in most countries including the United States 2 . In...

Hyperglycemia

Acute hyperglycemia reversibly influences upper-gut motor and sensory function. In situations where postprandial insulin release is defective type 2 diabetes or absent type 1 diabetes , the rate of gastric emptying is a major determinant of postprandial blood glucose concentrations. Therefore, altered gastric emptying can contribute to GI symptoms as well as poor glycemic control 24 . Patients with type 2 diabetes mellitus and without neuropathic complications have been shown to exhibit...

Dpp Inhibitors

Endogenous GLP-1 concentrations can be raised two- to threefold by inhibiting GLP-1 degradation via DPP-4. Support for this approach to therapy also comes from the observations that glucose tolerance is improved in animals in which the enzyme has been genetically deleted 75 and in animals treated with DPP-4 inhibitors 76 . Various substances with DPP-4 inhibition properties are currently being tested in preclinical and clinical trials. The two compounds have reached approval in several...

Koda Et Al Diabetes 1995

Biologic actions and therapeutic potential of the proglucagon-derived peptides. Nat Clin Pract Endocrinol Metab 2005 1 1 22-31. 2. Edelman SV, Weyer C. Unresolved challenges with insulin therapy in type 1 and type 2 diabetes potential benefit of replacing amylin, a second -cell hormone. Diabetes Technol Ther 2002 4 175-89. 3. Koda JE, Fineman M, Rink TJ, et al. Amylin concentrations and glucose control. Lancet 1992 339 1179-80. 4. Koda JE, Fineman MS, Kolterman OG, et al. 24 hour...

DSME Coordinator Role

Diabetes educators often find themselves faced with the challenge of starting a diabetes education program service or they are hired to manage one. For many educators with varying levels of clinical competence, starting, coordinating or managing a diabetes self-management program poses many challenges, and the development of additional skills for diabetes educators has become as important as clinical skills. These skills include Strategic and business planning Continuous quality improvement CQI...

Hormonal Control

Numerous peptide hormones play a role in the regulation of intestinal motility and gastric emptying and also directly, or indirectly, in the control of satiety and caloric intake. Some of these peptides are also involved in glycemic control. These hormones may also influence the neural control of gut motility. Glucagon-like peptide-1 GLP-1 arises from the differential post-transcriptional processing of the proglucagon gene that occurs in the intestinal L cells and in the hypothalamus. It is an...

Thiazolidindiones

Thiozolidindiones TZDs-Rosiglitazone and Piogitazone induce peripheral tissue sensitization to insulin by binding to nuclear peroxisome proliferators-activated receptor-y or PPAR-y, thus stimulating the transcription of genes that regulate carbohydrate and lipid metabolism. Studies have shown reduction of insulin resistance by up to 33 49 with the use of TZDs. Furthermore, recent data suggest that TZDs improve P-cell function by as much as 65 48 . Remarkable response to the metabolic effects of...

Perioperative Management Of The Type Diabetic Major Surgery

Type 2 diabetics unable to increase endogenous insulin secretion may behave metabolically in the perioperative period similar to the classic patient with type 1 diabetes 1,14,44 . Insulin therapy and frequent blood glucose monitoring are required to minimize the risk for ketoacidosis and hypoglycemia 16,17 . A variable-rate insulin infusion fixed-rate glucose infusion method provides the greatest flexibility, safety, and degree of glycemic control. Surgery should be scheduled as early in the...

Transition From Intravenous To Subcutaneous Insulin Therapy

The transition from i.v. insulin therapy to subcutaneous insulin and oral nutrition can be initiated in an awake patient when significant improvement and a pH-value of gt 7.2 have been reached. It is recommended to pursue a primary intensified therapy with pre-prandial applied doses of short acting insulin analogs combination with the prolonged acting insulin two or three times per day, or alternatively very long acting insulin analog once or twice a day. The first dose of long acting insulin...

Strategies For Management And Prevention Of Diabetes In Highrisk Ethnic Populations

The ethnic disparity observed in the rates of diabetic nephropathy, neuropathy and retinopathy disappears when the ethnic groups are maintained at a comparable level of glycemic control. Response to lifestyle or pharmacological intervention was also similar among the ethnic groups in the DPP study 46 . These findings raise hope and confidence that the high morbidity of diabetes in the ethnic minority groups can be ameliorated provided the barriers to the delivery of optimal care are identified...

Approach To The Surgical Patient With Hyperglycemia

Diabetic and non-diabetic patients develop hyperglycemia during surgery and medical illness due to enhanced hepatic gluconeogenesis, relative insulin deficiency, and decreased sensitivity of the liver, skeletal muscle, and adipose tissue to the actions of insulin 1-3 . While clinical evidence suggests a direct association between hyperglycemia and adverse outcome in patients undergoing vascular and cardiac surgery, there is little prospective data available to indicate that glucose control...

Osteomyelitis

Classically, the treatment of osteomyelitis is surgical removal of bone. But long-term suppressive antibiotic therapy is also used. As osteomyelitis is usually associated with an infected ulcer and cellulitis, wide spectrum antibiotics should be initially given. On review, antibiotic selection is guided by the results of cultures. Ideally percutaneous bone biopsy should be carried out but this is not always practical especially in ischemic feet. Bone fragments in the base of the wound should be...

Ebenezer A Nyenwe and Samuel Dagogo Jack

Division of Endocrinology, Diabetes, and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee, U.S.A. Diabetes mellitus is a chronic debilitating disease currently estimated to affect 7 over 20 million of the total population of the United States 1 . Type 2 diabetes accounts for 90 to 95 of all cases of diabetes. Studies show that the prevalence of diabetes is disproportionately higher among ethnic minority groups, including African Americans, Asian Americans, Pacific...

Minimally Invasive Cgm Dialysis Cathetertype Isf Glucose Sensor

Dialysis catheter-type glucose sensors consist of a flexible catheter that the patient inserts through the skin into the sc tissue. The small pore dialysis catheter is connected to a fluidics system that transports a salt solution dialysate into and out of the body. Glucose-free dialysate is infused into the dialysis catheter previously inserted into the sc tissue, and allowed to equilibrate with ISF glucose. Glucose containing dialysate is pumped out of the body to an external electrochemical...

Clinical Efficacy Of Metformin In Patients With Type Diabetes Mellitus

The glucose-lowering effect of metformin, monotherapy or in combination, has been extensively reviewed 70-72 . In a meta-analysis 73 all randomized, controlled clinical trials comparing metformin with placebo 29,62,74-80 and sulfonylurea 62,74,81-87 were evaluated. The weighted mean difference between metformin and placebo after treatment median treatment duration 4.5 months for fasting blood glucose was -2.0 mM and for HbA1c -0.9 . Body weight was not significantly changed after treatment....

Diagnostic Strategy

Diagnostic Strategy For Diabetes

Islet cell autoantibody testing is not always reliable, and the results are not immediately available. Thus, the physician must depend on clinical judgment in classifying new-onset diabetes patients. The pathways in bold in the decision trees provided in Figure 1 indicate the most likely outcomes. Classification may only be possible after months or longer of follow-up. In African American children with new, acute-onset diabetes, islet autoantibody testing can identify many of the children who...

Implantable Insulin Pumps Continuous Peritoneal Insulin Infusion

The safety and efficacy of continuous peritoneal insulin infusion CPII therapy using a programmable implantable insulin pump have been demonstrated in patients with type 1 and type 2 diabetes. An external programmer is used to control the basal rate and timing amount of a regular insulin bolus infused prior to meals. Peritoneal insulin delivery significantly reduces the risk of hypoglycemia, an advantage that may be due to portal delivery of insulin and a more physiological ratio of portal to...

Laboratory Criteria Of Coma Diabeticum

The criteria in clinical chemistry of a diabetic coma are summarized in Table 2 8 approximately 15 of patients with diabetic ketoacidosis have glucose concentration in plasma lt 350mg dL. In these cases one speaks of euglycemic diabetic ketoacidosis. This appears in situations in which gluconeogenesis appears to be disturbed, e.g., liver disease, alcoholism, prolonged fasting or in cases where insulin-independent glucose consumption is very high i.e., in pregnancy . In cases where blood glucose...

The Discovery Of The Incretin Hormones Gastric Inhibitory Polypeptide And Glucagonlike Peptide

Early in the first half of the 20th century it was already hypothesized that gastrointestinal hormones are important for glucose homeostasis and stimulation of insulin secretion after a meal 1,2 . In the late 1960s it was finally shown that orally administered glucose leads to a greater insulin response than intravenously administered glucose dosed to lead to identical serum glucose excursions 3 . This difference in insulin secretion is termed the incretin effect. The gastrointestinal hormones...

Pathophysiology Of Macrosomia

Pathophysiology Undernutrition

The epidemic of obesity, and the difficulty in losing accumulated weight suggest that there may have been an advantage to this metabolic phenotype during human evolution. The development of type 2 diabetes in susceptible individuals would not have been a disadvantage in the absence of opportunities to become obese. The thrifty genotype hypothesis was first advanced by JV Neel 24 nearly 40 years ago and recently updated 32,33 . This hypothesis explains the insulin resistance and relative beta...

Cgm Trend Data Used To Minimize Postprandial Hyperglycemia And Avoid Hypoglycemia

Insulin Pump Catheter

Patients use the real-time glucose trend data displayed on the hand-held CGM monitor to make more appropriate clinical decisions regarding BG control 20,22,23 . The Food and Drug Administration FDA , however, does not currently allow the patient with diabetes to initiate a change in medical therapy insulin or oral hypoglycemia medication based solely upon CGM glucose sensor data. Diabetic patient are therefore required to adjust drug therapy according to traditional SMBG measurements. This...

Anti Hypertensive Medications Thiazides

Thiazides have been associated with glycemic disturbance for many decades. In 1981, a randomized, controlled trial from the Medical Research Council suggested that patients receiving bendrofluazide developed more impaired glucose tolerance IGT than those receiving propranolol 15.4 vs. 4.8 cases patient-years, respectively 13 . This study was criticized for using extremely high dose of bendrofluazide. There are, however, many prospective clinical trials that have demonstrated definite adverse...

Rationale For Combination Therapy

In the context of two major physiologic defects, insulin resistance and insulin secretory failure, combination treatments with differing actions are entirely logical. Several different advantages of combining agents can be distinguished. The first rationale for combination therapy either with oral agents alone or with oral agents and insulin or oral agents with other injectable medicine such as incretin mimetics is its superior efficacy. One principle that emerges from randomized controlled...

Contributors

Adams School of Medicine, The University of Western Australia, Sir Charles Gairdner Hospital, Perth, Australia Intekhab Ahmed Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A. William E. Benson Retina Service, Wills Eye Hospital, Philadelphia, Pennsylvania, U.S.A. David John Betteridge Department of Medicine, University College Hospital, London, U.K. Christina Bratcher Department of...

Clinical Evaluation Of Patients With Suspected Diabetic Enteropathy

The evaluation of upper GI symptoms in patients with diabetes by means of esophagogas-troduodenoscopy may document the presence of intercurrent conditions such as peptic ulceration, peptic stricture or Mallory-Weiss tears a result of repeated retching and vomiting . The presence of bezoars suggests delayed gastric emptying. Confirmation of the diagnosis of gastroparesis requires documentation of delayed gastric emptying. Scintigraphic transit studies are typically used to measure gastric...

Longterm Implantable Cgm Optical Blood Glucose Sensor

Animas Corporation is developing a long-term implantable sensor that uses near-infrared spectroscopy to measure the concentration of glucose in blood. The system resembles a pacemaker with an sc electronics optical module and a miniature sensor head that is surgically implanted around a blood vessel. A universal calibration algorithm has been developed that allows glucose to be accurately predicted from the optical spectra. The system has been designed to overcome the biocompatibility...

Glycosylated Hemoglobin Hbac

The development of the glycosylated hemoglobin assay has become one of the major advances in taking care of patients with diabetes mellitus. The glycohemoglobin measurement correlates with fasting blood glucose, postprandial glucose, the glucose peak during an oral glucose tolerance test and the mean glucose levels over many weeks. Currently most laboratories use the HbA1c measurement but this is not universal. After the results of the DCCT were published the use of the HbA1c level in setting a...

Etiology and Clinical Presentation

Pcos Diagnosis

The etiology of PCOS, most likely a combination of genetic disposition and environmental factors, is not completely understood 23,24 . While familial clustering of PCOS has been well documented, even including a male factor with higher androgen levels in first degree relatives of affected patients 25,26 , the search for candidate genes has not come up with obvious culprits 27,28 . While not its cause, insulin resistance plays a pathogenic role in the development of PCOS. Hyperinsulinemia...