Homeopathic Treatment for Diabetes

The Diabetes Loophole

Diabetes Loophole is a step- by-step manual, your complete guide to reverse diabetes naturally and without any side effects.It was created by Reed Wilson who is an alternative health researcher. And has led his team to find answers to the diabetes epidemic that's been silently ravaging the nation.The secrets in this program helped a 10-year-old's life to begin when his diabetes ended, they also helped an elderly woman reduce her blood sugar level from 450 to normal levels and so many people to reduce their diabetic symptoms.The secrets will help you to reduce your risk of cancer by an incredible 67%, reduce cholesterol by 25 to 30% (as much as statin drugs and without the risky side-effects), reduce high blood pressure by as much as half and reduce the risk of a fatal heart attack by 70%The book by reading the book you will learn things like foods that will help you overcome diabetes and exercizes that will improve your health.When you order for this manual you get other books for free like: Super foods, the antiinflammatory diet, the top 20 inflammatory food and others.Everything in this program is focused on giving you exactly what you need in order to get the kind of freedom you've been denied You'll get results like so many others have before you. All you have to do is order. Read more...

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Multifactorial Intervention in Type Diabetes mellitus

Steno Diabetes Centre, Copenhagen, Denmark The prevalence of type 2 diabetes mellitus is rapidly increasing. Patients with type 2 diabetes suffer from micro- as well as macrovascular complications, the latter causing the excess mortality seen in these patients compared to the background population. Several risk factors for the outcome of type 2 diabetes have been identified in prospective epidemiological studies. However, until recently the treatment of type 2 diabetes has been empirical rather than evidence based from randomized intervention studies. Although the diagnosis of diabetes is based on blood glucose levels, it is important to realize that patients with type 2 diabetes mellitus share many clinical features with the metabolic syndrome such as dyslipidaemia, hypertension, hyperinsulinaemia and an increased risk of cardiovascular disease. In cardiovascular medicine a multifactorial treatment approach of several risk factors for cardiovascular disease is generally accepted. We...

Managing Diabetes and Pregnancy

Pregnancy produces major changes in metabolic fuels and hormones and in this way affects the management of diabetes. Basal hepatic glucose production increases significantly with advancing gestation in lean or obese controls, but increased basal insulin secretion and fetal-placental utilization of glucose result in slightly lower fasting blood glucose levels. Fat deposition is accentuated in early pregnancy, but lipolysis is enhanced later in gestation, and more glycerol and free fatty acids (FFA) are released in the postabsorptive state (distant from meals). The increased FFA may contribute to the insulin resistance on glucose utilization by skeletal muscle during pregnancy. Ketogenesis is also accentuated in the postabsorptive state during pregnancy, probably due to increased provision of substrate FFA and hormonal effects on the maternal liver cells. Despite increased first- and second-phase insulin release after a carbohydrate load in normal pregnancy, in the fed state there is a...

Unphysiological insulin delivery

Insulin treatment is designed to mimic the physiology of the islet b-cell, delivering substantial and precise amounts of insulin to cover the hyperglycaemia that follows meals, yet ensuring much lower but stable basal concentrations in between. However, current subcutaneous insulin preparations are inadequate to this task even when administered in multiple small doses. The use of rapid-acting insulin analogues delivered via continuous subcutaneous infusion using an external electromechanical pump perhaps provides the closest approximation to physiological insulin replacement. However, even this form of insulin delivery produces inadequate insulin concentrations during meals and inappropriately raised plasma insulin concentrations when absorption from the gastrointestinal tract is complete. This leads to a combination of

Current insulin regimens fall short of normal physiology thereby presenting the risk of hypoglycaemia

The limitations of intermittent subcutaneous insulin delivery arise partly because insulin enters the systemic rather than the portal circulation. The inability to deliver the insulin directly to the liver, as happens when insulin is secreted from the b-cells, causes higher insulin levels in the peripheral circulation. In addition, short-acting insulin preparations tend to self-associate into hexamers, delaying the rate of absorption of insulin into the bloodstream from subcutaneous depots. Different approaches have been tried to develop a basal insulin preparation, i.e. that mimics normal background low-level insulin secretion, that has stable and consistent characteristics. However, lente and isophane preparations not only produce an undesirable peak of insulin but have considerable inter- and intra-subject variability. Recently introduced rapid-acting and so-called basal insulin analogues have improved pharmacokinetics that may prove more useful than conventional insulin...

Does the species of insulin affect the risk of hypoglycaemia

The question of whether human insulin might contribute to hypoglycaemia unawareness was raised during the 1980s. The development of recombinant insulin of human structure resulted in its widespread introduction to many patients who previously been using animal insulin without problems. A minority complained vociferously of different problems including a major reduction in hypoglycaemic warning signs, which improved when they were transferred back to animal insulin. However, repeated studies have failed either to confirm a consistent reduction in physiological responses and symptoms in those on human insulin or identify any convincing mechanisms. Furthermore, the concerns were confined to only a few countries such as the UK and Switzerland. The introduction of human insulin in others such as the USA and Germany produced few problems. To some, the most likely explanation is that the time of transfer coincided with attempts to tighten glycaemic control, and it was this that led to a loss...

Diabetes and labour

Buchanan TA, Metzger BE, Freinkel N and Bergman RN. Insulin sensitivity and B-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes. Am J Obstet Gynecol 1990 162 1008-1014. Girling J and Dornhorst A. Pregnancy and Diabetes Mellitus, in Textbook of Diabetes 3rd ed, Pickup JC, Williams G, Editors. 2003, Blackwell Oxford. pp. 65.1-65.39. Greene MF, Hare JW, Krache M, Phillippe M, Barss VA, Saltzman DH, Nadel A, Younger MD, Heffner L and Scherl JE. Prematurity among insulin-requiring diabetic gravid women. Am J Obstet Gynecol 1989 161 106-111.

Insulin Analogues in Children and Teens with Type Diabetes Advantages and Caveats

Type 1 diabetes mellitus (T1D) is a chronic, metabolic disorder that most commonly presents during childhood and is characterized by absolute insulin deficiency. T1D is caused by selective immune-mediated autoreactive T-cell destruction of beta cells in the pancreatic islets of Langerhans 1 . Insulin deficiency leads to chronic hyperglycemia and other disturbances of intermediary metabolism. As a result, individuals who have diabetes are at risk of developing progressive long-term microvascular (eg, retinopathy, nephropathy, and neuropathy) and macrovascular (eg, cerebral, coronary, and peripheral vascular disease) complications 2 . The seminal trial in T1D, the Diabetes Control and Complications Trial, proved in adults and adolescents that the onset and progression of the microvascular complications can be prevented or delayed by tight control of blood glucose levels 2-4 . Although advanced complications are rare in youth, the demonstration of glycemic memory in follow-up studies of...

Global And National Prevalence Of Type Diabetes

The prevalence of diabetes has now been described in many different countries and settings, enabling a good understanding of global disease patterns. Interestingly, most of these large population-based studies do not differentiate between type 1 and type 2 diabetes and simply report the prevalence of all cases of diabetes. However, on the assumption that type 2 diabetes accounts for approximately 90 of all cases of diabetes, these data can be accepted as providing reliable information on type 2 diabetes. The large numbers of published prevalence reports has allowed several estimates to be made of the global and country-specific burden of diabetes. Recent publications from the World Health Organization (1) and from the International Diabetes Federation (2) have provided data on the current numbers of people with diabetes, and projections for the year 2025 (Fig. 1 and Color Plate 1, following p. 34). Table 1 indicates that although the methods of the 2 estimates are somewhat different,...

Effects of FFAs on local and systemic inflammation and link to insulin resistance

Elevated FFAs cause ectopic lipid deposition in nonadipose tissue, and this lipotoxicity may induce a pro-inflammatory response, which in turn may negatively interfere with insulin signalling. Supporting this concept, the use of high dose salicylate has been proven to decrease plasma glucose in type 2 diabetic patients (236). The molecular basis of this observation relies on decreased activity of a serine kinase called IkB kinase p (IKKP) of the NFkB signalling pathway (237), and subsequent impaired phosphorylation of IRS-1 and PI3Kinase (238). The link between IKKp and FFAs in insulin resistance has been further supported by the report that, in rats, salicylate prevents the deleterious effects of lipid infusion on muscle glucose metabolism and insulin secretion (238). In a recent report Cai and colleagues showed that obesity- or high fat-induced hepatic lipid deposition is accompanied by increased NFkB activity in the liver (239). Studies of genetically modified mice with either...

Why do I have to inject insulin several times a day

The object of insulin therapy is to imitate the body's natural supply of insulin as closely as possible. In a person who does not have diabetes, insulin is released by the pancreas in response to food. As the blood glucose level falls between meals, so the insulin level drops back towards zero. It never quite gets there, however, and there is no time in the 24 hours when there is no detectable insulin in the bloodstream. What you are trying to do when you give yourself insulin injections is to reproduce the normal pattern ofinsulin production from the pancreas. There are several ways of doing this using different types ofinsulin and numbers of injections per day. For example, many people follow a system which comprises three injections of short-acting insulin before the three main meals of the day, plus a night-time injection of a medium- or long-acting insulin to control blood glucose while they are asleep. Another popular and equally successful system involves two injections a day...

Longterm Diabetes Complications As Used For Defining Diabetes Thresholds

Diabetes mellitus is characterised by hyperglycaemia, which is associated with long-term damage, dysfunction and failure of various organs. Several studies30,31 have confirmed relationships between hyperglycaemia and the risk of developing such micro- and macrovascular complications as retinopathy, neuropathy, nephropathy and cardiovascular disease. However, many have compared the rates of each condition in subjects already classified according to the diagnostic criteria as having diabetes or not. Few studies consider whether the current diagnostic glucose levels represent the best level for predicting an increased risk of such complications, and no formal statistical threshold for any complication has been consistently demonstrated. The relationships of FPG and 2 h PG with the development of retinopathy were evaluated in a study undertaken in the Pima Indian population over a wide range of plasma glucose cutpoints23. Both variables were similarly associated with retinopathy,...

Assessment Of Diabetesrelated Symptoms

The clinical diagnosis of diabetes is often prompted by symptoms such as polyuria and polydipsia, recurrent infections, unexplained weight loss and, in severe cases, drowsiness and coma. In such cases a single blood glucose determination in excess of the diagnostic values indicated in Figure 2.2 (black zone) establishes the diagnosis. Figure 2.2 also defines levels of blood glucose below which a diagnosis of diabetes is unlikely in non-pregnant individuals. These criteria are unchanged from the 1985 WHO report7. For clinical purposes, an OGTT to establish diagnostic status need only be considered if casual blood glucose values lie in the uncertain range (i.e. between the levels that establish or exclude diabetes) and fasting blood glucose levels are below those which establish the diagnosis of diabetes. Diabetes mellitus likely Diabetes mellitus uncertain Diabetes mellitus likely Diabetes mellitus uncertain Diabetes mellitus unlikely Figure 2.2. Unstandardised (casual, random) blood...

Diabetes Classification Beyond Stamp Collecting

Humans appear to have a powerful instinct to classify. In part this may spring from a purely intellectual and aesthetic requirement to create some sort of order from the bewildering chaos of observable natural phenomena. This inbuilt taxonomic imperative is likely, however, to have more utilitarian roots. To be able to manipulate the natural world to improves one's comfort and or survival, one needs to understand its nature. The classification of natural phenomena into related groups is an essential first step towards this comprehension. Given the powerful threat represented by illness, it is not surprising that the classification and reclassification of disease has been a continued obsession of the healing professions since their earliest recorded history. In Chapter 2, Max de Courten provides a balanced and thorough account of how we have reached the currently accepted glycaemic criteria for the diagnosis of diabetes mellitus, and its classification into sub-types. In this short...

Rationale For The Prevention Of Type Diabetes

Several observations align to indicate the increasing need to prevent type 2 diabetes, rather than simply treat it, once established. Chapter 1 has mentioned the increasing prevalence and incidence, excess mortality and limited effectiveness of interventions. In addition to these, diabetes, and particularly type 2 diabetes, incurs high health care costs. Estimates of costs vary depending on the methods used17, but from 6018 to 100 billion19 in health care costs were spent on diabetes in the USA in 1995, which is variously estimated to be 6-17 of all health care costs. The majority of health care costs for diabetes are spent in developed countries, whereas estimates suggest that the majority of disability-adjusted life years (DALYs) are lost in developing countries, where limited health care budgets are available to deal with the problems of diabetes18. Recent studies from US health maintenance organizations (HMOs) have shown approximately two-fold increases in medical care expenses...

Definition Of Type Diabetes Mellitus

The studies reviewed here use a variety of criteria to define type 2 diabetes. This is inevitable, given the long time period included. It was not possible to identify consistent criteria for all studies. However, the 1985 WHO criteria24 were used as a reference when possible since the majority of modern studies used them. In prevention trials, the development of any clinical diagnosis of diabetes or measured hyperglycemia meeting defined criteria was usually the outcome of the trial. No studies published to date have tested for autoimmune markers that would identify subjects developing type 1 diabetes. Since over 90 of people developing diabetes over the age of 50 years will have type 2 diabetes30, this is a minor limitation. However, proper diagnosis of the etiological type of diabetes as an outcome will become increasingly important in trials in the future, since specific interventions aimed at defined metabolic and immunological pathways will increasingly be tested.

Natural History And Risk Factors For Type Diabetes

Primary prevention of diabetes requires a thorough knowledge of the natural history of the development of glucose intolerance and risk factors. Once these have been established from observational studies, it is at least theoretically possible that interventions aimed at any of the factors could reduce diabetes risk. A number of recent reviews of risk factors exist8,31-39, and are summarized in Table 6.2 for individual level risk factors, that is, those that operate on or within a person. This table does not include group-, societal-, or populationlevel risk factors such as Westernization, commercialization of the food supply, increased motorized transport, television and computer time replacing group and individual activity and interaction, and changes in social mores which alter individual factors over large numbers of people simultaneously. The information about possible genes related to or causing type 2 diabetes is not included here, since, in the short term, gene-based...

Treatment of Prediabetes IGTIFG

Intensive lifestyle behavior change programs that include monitoring of regular physical activity recommendations and nutrition counseling can reduce the risk of type 2 diabetes in this population by about 50 . The following treatments are recommended for people with prediabetes (IGT or IFG) Regular follow-up and reassessment of risks including re-screening for diabetes every 1-3 years (American Diabetes Association, 2003i Chiasson, 2002 Eriksson, 1999 HOPE Study Investigators, 2002 Kelly, 2002 Miles, 2002). There is some evidence of prevention of diabetes through pharmacotherapy with biguanides, alpha glucosidase inhibitors, ACE inhibitors, and thiazolidinediones. However, none of these treatments have proven to be as effective as lifestyle change.

Diagnosis Type Diabetes

Diagnosis of type 2 diabetes (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, Casual plasma glucose greater than or equal to 200 mg dL plus typical symptoms of diabetes. In the absence of unequivocal hyperglycemia associated with acute metabolic decompensation, the results should be confirmed by repeat testing on a different day. At the present time A1C should not be used to diagnose diabetes.

Initial Stabilization for Outpatients Requiring Immediate Insulin Treatment

If the patient presents and is considered stable enough for outpatient care but meets indications noted above for starting insulin, there are several acceptable ways of initiating insulin. One example is to calculate the total daily dose of insulin at 0.3 units kg and start bedtime glargine at 50 of the total dose, splitting the remaining 50 with short-acting insulin before meals. A third example is to calculate the total daily dose of insulin at 0.3 U kg and use pre-mixed insulin with 2 3 the dose in the a.m. and 1 3 in the p.m. At presentation, all patients should be instructed on blood glucose monitoring hypoglycemia recognition and treatment and how when to contact health care support. Patients should check blood sugars frequently when insulin is initiated. Patients should receive daily phone or visit contact for at least 3 days and have 24-hour emergency phone support if needed. Patients should be referred for nutrition and diabetes education and be seen in a timely way after...

Consider Referral to Diabetes Care Team or Specialists Diabetes Care Team

Consultation with a diabetes educator is suggested if the patient is having difficulty adhering to a nutrition and exercise regimen and the patient is having difficulty adhering to, or accurately completing, blood glucose monitoring or may need answers to some questions. Every primary care physician must develop a relationship with a diabetes education program to provide other options for management. The American Diabetes Association publishes a list of recognized educational programs in each state. These programs may be staffed with endocrinologists or primary care providers plus diabetes educators including dietitians, nurses, and other health care providers who are Certified Diabetes Educators (CDE) or have didactic and experiential expertise in diabetes care and education.

Intensive Insulin Therapy

Randomised trials, most notably the DCCT, have provided substantial data on the epidemiology of hypoglycaemia in adults with type 1 diabetes and, in particular, on the impact of intensive insulin therapy. The Diabetes Control and Complications Trial (DCCT) The DDCT was a landmark study and provided diabetes specialists with the long-awaited proof that strict glycaemic control limited the incidence and severity of microvascular complications in people with type 1 diabetes. A total of 1441 patients with type 1 diabetes Table 3.3 Risk factors for severe hypoglycaemia in adults with type 1 diabetes Insulin This table examines the risk factors for severe hypoglycaemia that have been most commonly examined in adults with type 1 diabetes. Studies examining predominantly mild hypoglycaemia were not included. + positive association between risk factor and severe hypoglycaemia no association between risk factor and severe hypoglycaemia. * only a risk factor if awareness of hypoglycaemia not...

Human Insulin And Counterregulation

At present there is no consistent evidence that the species of insulin is an important determinant of the counterregulatory response to hypoglycaemia. Over 25 clinical laboratory studies have examined the effect of insulin species on the counterregulatory response to hypogly-caemia induced by an intravenous bolus, intravenous infusion, or subcutaneous injection of insulin (Fisher and Frier, 1993 Jorgensson et al., 1994). Most of the studies showed no significant differences between the hormonal responses. Two studies showed a reduction in the epinephrine response to hypoglycaemia, and both of these studies also reported diminished autonomic symptoms to hypoglycaemia after human insulin (Schluter et al., 1982 Heine et al., 1989). A meta-analysis comparison of the effects of human and animal insulin as well as of the adverse reaction profiles did not show clinically relevant differences between species especially in terms of risk and responses to hypoglycaemia (Richter and Neises, 2005).

Factors Predisposing Patients to Severe Hypoglycaemia in Intensified Insulin Therapy

The relationship between impaired symptomatic awareness of hypoglycaemia and an increased rate of severe hypoglycaemia is well established (Hepburn et al., 1990 Gold et al., 1994 Clarke et al., 1995), although affected patients in these studies were not subject to strict glycaemic control. The association between counterregulatory failure and increased risk of severe hypoglycaemia is also well recognised (Ryder et al., 1990). Indeed, counterregulatory failure was proposed as a predictor of risk of severe hypoglycaemia in the subsequent application of intensified therapy (White et al., 1983), and it was not until later that the ability of intensified therapy to cause counterregulatory failure was suggested (Simonson et al., 1985a). It is indeed very important to appreciate that neither asymptomatic nor severe hypoglycaemia are restricted to people using intensified insulin therapy. Apart from a previous history of severe hypoglycaemia, the greatest risk may be the degree of insulin...

Other Risks Of Intensified Insulin Therapy Diabetic Ketoacidosis and Hyperinsulinaemia

Although severe hypoglycaemia was indisputably the major metabolic side-effect of intensive insulin therapy in the DCCT, concerns have been expressed that some intensive treatment regimens may also increase the risk of developing ketosis. This was primarily related to the use of CSII (with insulin pump therapy) and was thought to relate to the absence of any intermediate-acting or background insulin in the event of pump failure. In insulin pump therapy, soluble or fast-acting analogue insulin is delivered steadily by a slow infusion of very low doses throughout the day. The insulin delivery is accelerated before meals to deliver boluses, akin to giving intermittent subcutaneous injections of short-acting insulin. Because the basal insulin is delivered in a very low volume and there is no depot of intermediate-acting insulin in the subcutaneous tissues to act as a reservoir, an interruption in the delivery of insulin can rapidly lead to hyperglycaemia and even ketosis, especially if...

Frequency Of Hypoglycaemia In Type Diabetes

Mild hypoglycaemia is defined by the ability to self-treat, while the need for external assistance denotes a severe episode. The frequency of hypoglycaemia in people with type 1 diabetes is described in Chapter 3. Mild hypoglycaemia occurs on average around twice weekly (Pramming et al., 1991 Pedersen-Bjergaard et al., 2004) and the estimated incidence of severe hypoglycaemia ranges from 1.0 to 1.7 episodes per patient per year (MacLeod et al., 1993 ter Braak et al., 2000 Pedersen-Bjergaard et al., 2004) with an annual prevalence of between 30 (MacLeod et al., 1993 The Diabetes Control and Complications Trial Research Group, 1993 Stephenson et al., 1994) and 40 (ter Braak et al., 2000). The frequency of hypoglycaemia in type 2 diabetes cannot be summarised in an equally succinct manner because of the heterogeneity of this disorder and the range of treatment modalities available. Furthermore, many people with type 2 diabetes are elderly and the frequency of hypoglycaemia is often...

Genetics Of Type Diabetes

The concordance of type 1 diabetes in monozygotic twins is 30-40 , compared with 5 in siblings. This indicates the importance of genetic factors in the development of the disease,50 (Table 2(ii).2) but at the some time this intermediate level of concordance shows that non-genetic or environmental factors must also be involved. Transmission of type 1 diabetes is considered to be polygenic, meaning that several genetic loci are associated with an increased risk of diabetes. Non-Mendelian or polygenic inheritance and the probable heterogeneity of type 1 diabetes have contributed to the complexity of type 1 diabetes genetics. Table 2(ii).2 Lifetime risks of type 1 diabetes in first-degree relatives (proband diagnosed before 20 years of

Growth hormone GH and insulinlike growth factors IGFs

Table 5.2 Growth hormones and cytokines that have been implicated in the pathogenesis of diabetic kidney desease list of different components of the growth hormone-insulin-like growth factor (GH-IGF) axis, transforming growth factor p (TGF-P) system, and vascular endothelial growth factor (VEGF) system and known or potential inhibitors of these systems.

Diagnosis Of Diabetes

The diagnostic criteria for DM have been modified in recent years by the American Diabetes Association (ADA) from previous recommendations made by the National Diabetes Data Group in 1979 and the World Health Organization (WHO) in 1985. In clinical practice, establishing the diagnosis of diabetes is seldom a problem. When symptoms of hyperglycemia exist (thirst, polyuria, weight loss, etc.) a random plasma glucose concentration of > 11.1 mmol l (200 mg dl) or a fasting plasma glucose (FPG) of > 7.0 mmol l (126 mg dl) confirms the diagnosis. Where diagnostic difficulty exists, the precise diagnosis can be established with an oral glucose tolerance test (OGTT) using a 75 g anhydrous glucose load dissolved in water a 2 h value > 11.1 mmol l (200 mg dl) establishes the diagnosis of diabetes. A confirmatory test using one or

Epidemiology Of Diabetes

The epidemiology of type 1 diabetes, a disease of as yet unknown etiology, is complex. The overall incidence rates are comparable in North America and Europe however, this disguises some marked variations in incidence rates between countries and even within countries. Within Europe, particularly high incidence rates are found in Finland, Sweden and Sardinia. Most Asian populations have a low incidence rate. In general, the incidence of type 1 diabetes seems to be increasing with an average increase in incidence of around 3 per year. About half of all cases of type 1 diabetes are diagnosed at an age of < 15 years, with an observed peak in incidence rates in children aged 10-14 years. More recently, many cases are being diagnosed in children of < 5 years of age. In many high-risk populations a male excess of type 1 diabetes is seen, especially after the age of puberty. Cases of type 2 diabetes greatly exceed those of type 1 diabetes accounting for about 85 of cases in Europe and...

Type Diabetes Not On Insulin Therapy

When pre-existing glycemic control is good and minor surgery only is planned, breakfast and oral agents are omitted on the morning of surgery (long-acting sulfonylureas should be omitted on the day prior to surgery). Dextrose infusions should be avoided and blood glucose checked every 2 hours. Postoperatively, oral agents may be recommenced at the time of the next meal. When glycemic control is poor or major surgery is planned, it is desirable to admit the patient before the day of operation to optimize blood glucose control with short- or intermediate-acting insulins. On the day of surgery, breakfast is omitted and the surgery covered with intravenous insulin and glucose (see later). Postoperatively, subcutaneous insulin is continued until blood glucose levels are stable when the patient can restart oral therapy.

Chronic complications of diabetes

The results of the Diabetes Control and Complications Trial in the USA have established unequivocally the relationship between glycemic control and the incidence or progression of diabetic microvascular complications. Such complications occur in both type 1 and type 2 diabetic patients, although the latter patients often die because of major vascular disease before microvascular complications become advanced. More than 40 of type 1 diabetic patients will survive for more than 40 years, half of them without developing significant microvascular complications. The United Kingdom Prospective Diabetes Study (UKPDS) has also provided pivotal information on the relationship between glucose control and complications in type 2 diabetes diabetes mellitus (DM). It has demonstrated, in a significant way, the beneficial effect of an improvement in blood glucose control on subsequent risk of developing specific diabetic complications.

Diabetes Mellitus

Completely revised and updated, this third edition of Atlas of Diabetes Mellitus provides complete coverage of the signs and symptoms of diabetes mellitus and its treatment. Featuring over 120 color plates illustrating the signs and symptoms of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) and their treatment, it also contains an instructive review section that covers Treatments with diet, insulin, and drugs Diabetes and pregnancy. With new chapters that discuss diabetes in the adolescent and the diabetic patient at home, the atlas also includes further up-to-date information on islet cell transplantation, diabetes and surgery, the costs of diabetes to both patient and the health system, and clinical trials. Detailed captions for each illustration, as well as bibliographic references and a full index, enhance the book's value as an atlas-text for teaching, residency training and clinical practice. Introduction Pathogenesis Treatment...

Vitamin E therapy in type II diabetes

A number of studies have looked at the potential of vitamin E therapy in people with type II diabetes. Devaraj and Jialal (2000b) studied the influence of RRR-alpha-tocopherol therapy (1200 IU day for 3 months) on controls and people with type II diabetes (with and without microvascular disease). The vitamin E supplement significantly decreased the monocyte release of O2 , IL-1-beta, tumor necrosis factor-alpha, and decreased monocyte-endothelium adhesion in all three groups. Increased levels of IL-I-beta, O2 , TNF-alpha, and the increased adherence of monocytes to arterial endothelium are all thought to be markers of inflammation and proatherogenic.

Nutritional risk factors in the onset and prevention of type diabetes

Type 1 diabetes is considered an immune-mediated disease, in which signs of beta-cell autoimmunity can be detected at variable times before the diagnosis of clinical disease (Knip 2002). Large geographical differences in incidence and linearly increasing incidence seen in many countries during the last five decades cannot be explained solely by genetic factors (Onkamo et al. 1999 Karvonen et al. 2000 Green et al. 2001). The relatively low concordance of identical twins also confirm the important role of environmental factors in the aetiology of this disease (Barnett et al. 1981). So far there is little firm evidence on the role of nutritional factors. Breastfeeding, vitamins C, D and E, nicotinamide and zinc have been reported as possibly protecting from type 1 diabetes, whereas N-nitroso compounds, cow's milk, some cereals, increased linear growth, and obesity may increase the risk (Virtanen & Knip 2003).

Prevention of Cardiovascular Disease in Patients who have Diabetes

This article examines the evidence in favor or against choosing treatment with insulin secretagogues or sensitizers as the preferred way to prevent cardiovascular events. It should be emphasized that most patients eventually will be treated with a combination of therapies therefore, much of the discussion may not be relevant. Conversely, combination of two sensitizers may have added effects. Also, retrospective data suggest that a combination of sulfonylurea and metformin may be associated with increased cardiovascular events. Nevertheless, it is important to recognize the relative value of these different agents as we choose complex therapeutic regimens.

Grafting in Diabetic Patients

Clinical outcomes in diabetic patients following coronary revascularization procedures with bypass surgery (CABG) or percutaneous coronary intervention (PCI) are worse than in nondiabetics. Current evidence suggests that CABG is preferable to PCI for revascularization in patients who have diabetes and multi-vessel coronary artery disease. Most trials have not used contemporary adjunctive therapies, such as GP Ilb IIIa inhibitors and prolonged dual antiplatelet therapy. It is conceivable that implementation of these evidence-based therapies may improve clinical outcomes significantly in diabetic patients who undergo PCI. In the future, emerging technologies, such as drug-eluting stents and soluble receptor for advanced glycation end products, may further improve outcomes after PCI and make it the preferred revascularization modality in diabetics.

Lipoprotein abnormalities associated with diabetes

Diabetes is associated with multiple disturbances in lipoprotein metabolism that are triggered by insulin deficiency, insulin resistance, and hyperglycemia 6,7 . The diabetic dyslipidemia of type 2 diabetes and insulin resistance is characterized several interrelated abnormalities, including triglyceride-rich lipoproteins (very low density lipoprotein VLDL , intermediate density lipoprotein IDL , and remnant particles), low high-density lipoprotein (HDL) cholesterol, and small, dense low-density lipoprotein (LDL) particles. There is an increase in the lipid-rich, large VLDL upregulation of hepatic sterol regulatory element binding protein-1, which stimulates de novo lipid synthesis and increased availability of free fatty acids, all of which probably are linked with insulin resistance 7 . The activity of lipoprotein lipase is suppressed which leads to reduced catabolism of triglyceride-rich particles, whereas hepatic lipase activity is increased which facilitates the compositional...

Lipid goals in patients who have diabetes

Diabetes is a CHD-risk equivalent, as defined by the ATPIII recommendations. Based on the evidence from the LDL-lowering clinical trials that were summarized above, most patients who have diabetes should have an LDL goal of less than 100 mg dL (Table 3). If LDL is grater than 130 mg dL, treatment with LDL-lowering drugs should be initiated simultaneously with therapeutic lifestyle changes (TLC) to achieve the LDL goal 1 . The American Diabetes Association (ADA) has the same recommendations for LDL goal 42 . In addition, the ADA recommends a triglyceride goal of less than 150 mg dL and an HDL cholesterol goal of greater than 40 mg dL in men and greater than 50 mg dL in women (see Table 3). According to ATPIII, however, when triglyceride levels are elevated (200-499 mg dL) after achieving LDL goal, non-HDL cholesterol should be the secondary target of therapy. No HDL goal is specified in ATPIII because of the lack of sufficient evidence. It is recommended that if HDL remains low after...

Coronary revascularization in diabetics

Diabetic patients who have coronary artery disease have significantly worse long-term outcomes compared with nondiabetic patients. The reasons for this are complex but relate, in part, to more extensive atherosclerosis, an increased risk of thrombosis, overexpression of mitogenic cyto-kines, higher oxidative stress, glycated end products, larger and more activated platelets, and more rapid progression of disease. Patients who have diabetes experience higher perioperative mortality rates compared with nondiabetics who undergo bypass surgery (CABG) 1,2 or percutaneous coronary intervention (PCI) 3,4 . Although outcomes after revascularization in diabetics are worse after either modality, CABG seems to be preferable to PCI in most patients who have multi-vessel disease (Fig. 1).

Defects of hepatic glucose metabolism in diabetes mellitus

Turning our attention to hepatic glucose fluxes following a normal meal in type 1 and type 2 diabetic patients, studies have revealed significant alterations of hepatic glycogen storage (Figure 11.12), glycogen release and gluconeogenesis in both patient groups (Taylor et al.1996 Hundal et al. 2000 Bischof et al. 2001, 2002 Singhal et al. 2002 Krssak et al. 2004). A defect in hepatic glycogen storage was observed in glucokinase deficient maturity-onset diabetes of the young 2 (MODY-2) patients, in whom the impaired hepatic glucokinase activity is held responsible for a reduction in the contribution of glucose (the direct pathway) to hepatic glycogen synthesis (Velho et al. 1996). Lower glycogen synthesis (Bischof et al. 2001, 2002 Krssak et al. 2004) and unsatisfactory suppression of endogenous glucose production (Sinha et al. 2002 Krssak et al. 2004) contribute to postprandial hyperglycaemia in both pathologies. Increased gluconeogenesis is the key to postabsorptive hyperglycaemia in...

Application of muscle biopsy in diabetes

Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes (Beck-Nielsen & Groop 1994 Beck-Nielsen 1998 Beck-Nielsen et al. 2003). During the past two decades, skeletal muscle biopsies have been increasingly applied in the search for biochemical and molecular abnormalities responsible for insulin resistance. It is evident that type 2 diabetes is caused by a complex interplay between genetic and environmental factors. The latter include intrauterine malnutrition and postnatal factors such as obesity, physical inactivity and modern Western lifestyle, as well as the metabolic milieu associated with type 2 diabetes and prediabetes, including glucose intolerance, hyperglycaemia, hyperlipidaemia and hyperinsulinaemia (Beck-Nielsen & Groop 1994 Beck-Nielsen 1998 Beck-Nielsen et al. 2003). The choice of study design is therefore extremely important for the interpretation of data obtained (Table 14.1). Novel potential markers of insulin resistance and type 2 diabetes...

Major data and relevance to better understanding of diabetes and metabolism

Several studies in diabetic patients revealed the effects of lifestyle modification or physical exercise on endothelial function. In insulin-resistant subjects, lifestyle modification with exercise and weight reduction over six months improved endothelial function (Hamdy et al. 2003). Interestingly, the relationship between percentage weight reduction and improved FMD was linear. A similar result was seen in patients with type 2 diabetes (Maiorana et al. 2001). Likewise, in patients with type 1 diabetes, FMD could be improved by four months of bicycle exercise (Fuchsjager-Mayrl et al. 2002). However, the positive training effect on endothelial function was not maintained after cessation of regular exercise (Figure 15.5). In all studies, GTN-mediated dilation was unaffected by exercise. Another interesting study assessing FMD in 75 children with type 1 diabetes revealed that even children with diabetes have impaired endothelial function compared to healthy controls (Jarvisalo et al....

Relationship between Insulin Sensitivity and Insulin Release

Fluctuations in insulin sensitivity occur during the normal life cycle, with insulin resistance being observed during puberty, pregnancy, and with ageing. On the other hand, increased physical activity and increased carbohydrate intake are associated with enhanced insulin sensitivity. Hence P-cells are markedly adaptable in their ability to regulate insulin release in a very precise manner. Obviously, the P-cell is fundamental to ensuring that in healthy subjects, plasma glucose levels remain within a narrow physiological range for review, see 30 . In healthy individuals, there is a feedback loop between the insulin-sensitive tissues and the P-cells, with P-cells increasing insulin supply in response to demand by the liver, muscles and adipose tissue. The relationship between insulin sensitivity and insulin levels is reciprocal and hyperbolic 31 . In response to changes in insulin sensitivity, insulin release increases or decreases reciprocally to maintain normal glucose tolerance....

Adaptation of pCell Function to Insulin Resistance Increased Insulin Release

Under physiological conditions, glucose-stimulated insulin secretion requires the metabolism of glucose and thereby the generation of ATP. The resulting increase in the ATP ADP ratio triggers the closure of the ATP-sensitive potassium (KATP) channel, depolarization of the cell membrane and influx of calcium through voltage-dependent calcium channels, resulting in insulin granule exocytosis 32 . The p-cell's adaptive response to changes in insulin sensitivity is probably mediated by increased cellular glucose metabolism, NEFA signaling and sensitivity to incretins. Data from animal studies suggest that the increase in p-cell glucose metabolism involves an increase in the activity of glucokinase, the rate-limiting enzyme responsible for glucose phosphorylation after its entry into the cell 33 . Glucose utilization rises as both oxidation and flux of glucose are increased, the latter through pyruvate carboxylase and the replenishment of tricarboxylic acid cycle intermediates in the...

Adaptation of pCell Mass to Insulin Resistance Mechanisms of Growth and Proliferation

Although changes in P-cell function are observed under conditions of increased secretory demand, the volume of P-cells also increases. In rodents fed a high-fat diet for 12 months to induce obesity and insulin resistance, islet size increases as a result of an increase in the number of P-cells rather than a change in P-cell size, and new islets do not form 36 . NEFAs rather than glucose may mediate this increase in P-cell mass for review, see 30, 37 . In contrast, human studies suggest that P-cell volume is increased by about 50 in healthy obese individuals, which, however seems to be more dependent on hypertrophy of existing cells than proliferation 38, 39 . Interestingly, in the long-term increased dietary fat feeding study in rats, P-cell mass increased but glucose-induced insulin release did not, which indicates a dissociation between P-cell mass and the secretory function 36 . Increased signaling by insulin and or insulin-like growth factor 1 (IGF-1) could also underlie the...

Clinical and Scientific Significance of Non Invasive Determination of the pCell Mass in Diabetes

A reliable method for (repeated) non-invasive quantification of p-cell mass in vivo in humans will enhance our understanding of the pathophysiology of both type 1 and type 2 diabetes (T1D, T2D). Progressive p-cell loss is characteristic for T1D, but the natural history of p-cell loss remains to be determined. p-Cell dysfunction is a hallmark of T2D, but it is not known at which stage of the disease this occurs. Individual patients show large differences regarding the relative contribution of insulin resistance or insulin deficiency to the diabetic state. Also the deterioration of p-cell function varies. Development of diabetes is thought to occur in steps 1 . At early stages, p-cell mass may even be increased 2 . Development of p-cell mass and p-cell function in the course of disease do not necessarily show a direct correlation, i.e. in particular stages of the disease, the p-cell function may be impaired while the p-cell mass is not significantly reduced or vice versa 1 . If a...

Glucose Stimulated Insulin Secretion

Glucose uptake into the pancreatic p-cell is the initial step in glucose-stimulated insulin secretion (GSIS). This glucose transport is mediated by GLUT2, a low-affinity (Km 17mmol l) glucose transporter 16 . Glucose is then phosphorylated by the high-KM glucokinase, which is rate-limiting for glucose metabolism and of insulin release and is therefore viewed as a glucose sensor. This sensor couples changes in physiological glucose concentration in the pancreatic p-cells and in the liver to the intermediary metabolism, i.e. glycolysis, the citrate cycle and respiratory-chain phosphorylation and increases the ATP levels in the p-cells. Changes in the ATP ADP ratio within the p-cells inhibits ATP-sensitive K+ channels (subunits Kir6.2 and SUR1), resulting in activation of voltage-gated Ca2+ channels which triggers the release of insulin granules. Exocytosis of insulin-containing secretory vesicles in pancreatic p-cells is crucial to maintenance of plasma glucose levels 17 . Decreased...

Diabetes Mellitus and Cancer A Conclusion

Many studies have suggested that diabetes mellitus type 2 may alter the risk of developing a variety of cancers, and the associations are biologically plausible. One of largest prospective studies worldwide, enrolling 467,922 men and 588,321 women who had no reported history of cancer at the time of enrollment, revealed after 16 years of follow-up that diabetes was significantly associated with fatal colon cancer in men and women, and with PC in men, and significantly associated with liver cancer and bladder cancer. In addition, diabetes was significantly associated with breast cancer in women 61 . These findings strongly suggest that diabetes is an independent predictor of mortality from these cancer entities. When treating cancer patients who have diabetes, clinicians must consider the cardiac, renal, and neurologic complications commonly associated with diabetes continued improvement of cancer outcomes may also depend upon improved diabetes control 62 . Diabetes rates continue to...

Diabetes Mellitus and Breast Cancer Possible Associating Mechanisms

Four major mechanisms may contribute to the association between type 2 diabetes mellitus and breast cancer (fig. 2) activation of the insulin pathway, activation of the insulin-like growth factor (IGF)-1 pathway, altered regulation of endogenous sex hormones, altered regulation of adipocytokines. The Insulin Pathway and Breast Cancer Insulin is a polypeptide hormone secreted from pancreatic p-cells in response to elevation in glucose levels 7 . The first step in activation of the insulin pathway is binding of insulin to the insulin receptor (IR). The primary targets for insulin are skeletal muscle, adipose tissue and the liver, however many other tissues, including normal breast tissue and breast cancer, express the IR. The IR is a tyrosine kinase receptor, composed of two extracellular a-subunits and two transmembrane p-subunits. Insulin binding leads to autophosphorylation of tyrosine residues in the intracellular subunits and thus activates the tyrosine kinase. Once activated, the...

Diabetes Mellitus and Clinical Aspects of Breast Cancer

Diabetes Mellitus and Breast Cancer Screening Screening mammography has been shown to reduce breast cancer mortality and is recommended by clinical practice guidelines for all women between the ages of 50 and 69 years. With current antidiabetic treatment, many patients with diabetes do not have additional comorbidity and thus may benefit from screening, yet in several countries diabetes may adversely affect attendance to screening mammography. Beckman et al. 38 found that American diabetic patients were less likely to undergo screening mammography, probably due to compromised attitude of their primary care physicians to preventive medicine and to high costs of mammography. Lipscombe et al. 39 investigated mammography rates in a large Canadian cohort, consisting of 69,168 women with diabetes and 663,519 women without diabetes. Although all patients were fully insured, diabetic patients had about one-third lower chances to perform screening mammography. On the other hand, a study from...

Diabetes Associated With Other Factors

Type 2 diabetes can also be associated with the following other clinical states, drugs, and chemicals US regulators have determined that six antipsychotic medications can increase the risk of impaired glucose tolerance and diabetes. These medications are Recent studies involving almost 20,000 schizophrenic patients across the United States showed that patients taking Risperdal had an increase in diabetes of 49 a 27 increase for Zyprexa, and patients taking Seroquel had 3.34 times as many cases of diabetes as those on older antipsychotic medications. It is important to consider that schizophrenic patients have a greater tendency to be overweight, and weight gain can increase the risk for type 2 diabetes (9). In a recent study in the Journal of Clinical Pharmacology, diabetic patients with psychoses had a 3 higher risk of developing diabetes within 1 month of first taking olanzapine and a 42.6 increase risk within 12 months of treatment, compared with controls. Thus, management of...

Diabetes Prevention Study

The Diabetes Prevention Study involved 3234 patients with IGT and BMI greater than 24 kg m2. There were three groups for assignment placebo, metformin (850 mg twice daily), or intensive lifestyle changes. The lifestyle modifications included dietary instruction, 150 minutes of exercise weekly, and a calorie-restricted, low-fat diet. These patients were followed for an average of 2.8 years. The study demonstrated a 58 relative risk reduction in progression to diabetes with diet and exercise compared with a 31 relative risk reduction with metformin. The number of patients needed to treat was seven for 3 years for lifestyle modification and 14 for metformin. The metformin seemed to be more effective in the younger patients with higher BMI and higher fasting-glucose levels than in patients more than 60 years of age, who showed the least benefit with the drug (14).

Finnish Diabetes Prevention Study

In the Finnish Diabetes Prevention Study (15), 522 patients with IGT and a mean BMI of 31 kg m2 were evaluated. A control group was compared with a lifestyle-changes group with the same exercise as the Diabetes Prevention Study and similar fat- and calorie-restricted diets, with a fiber intake of at least 15 g 1000 cal. Once again, a 58 relative risk reduction was seen. The number of patients needed to treat to prevent diabetes was 22 for 1 year and five for 5 years with this study.

The Troglitazone in the Prevention of Diabetes Study

The Troglitazone in the Prevention of Diabetes (TRIPOD) study evaluated 236 Hispanic women with gestational diabetes and a mean BMI of 30 kg m2. This trial used 400 mg day of troglitazone, and demonstrated a 55 relative risk reduction of diabetes with a number needed to treat of 15 patients for 2.5 years. The 121 women on placebo developed diabetes at a rate of 12 yearly, compared with 5 among the 114 that received troglitazone. Additionally, lowered plasma insulin levels were found in 89 of individuals on troglitazone. The decreased secretory demands on the P-cells caused by the reduction in insulin resistance not only delayed the development of diabetes, but preserved P-cell function (14). In an analysis of the 84 women who were still nondiabetic 8 months after the study medications had to be stopped, the rate of progression to type 2 diabetes was 21 in the placebo group and 3 in the troglitazone group, for a 92 risk reduction. This would not have been seen if the glitazone was...

Malnutritionassociated Diabetes

Diabetes associated with malnutrition usually presents in young individuals between the ages of 10 and 40. These patients do not get diabetic ketoacidosis but require insulin for glycemic control. Three different approaches can be used for glucose testing in order to diagnose diabetes The fasting plasma glucose test is the most popular choice and is currently used to diagnose approximately 90 of all individuals with type 2 diabetes. However, it is important to understand that postprandial hyperglycemia will precede fasting hypergly-cemia and should be strongly considered to screen patients, particularly those at risk. An oral glucose tolerance test can serve this purpose by giving excellent postprandial data and can also be used to concomitantly measure insulin levels to ascertain the patient's insulin sensitivity. It is recommended that, regardless of the type of test used, laboratory values that are abnormal should be documented at least twice to avoid missed diagnoses by laboratory...

Human Insulin Preparations

Although undergoing some major improvements over the past several years, human insulin still has some limitations. The human insulins have variable and inconsistent absorption rates that cause erratic and unpredictable blood-glucose-lowering effects, resulting from the varying onset of actions, peak, and duration of action of these products. This is because when regular insulin is administered subcutaneously, its absorption into the circulation is slow, with a subsequent slow onset of action. Therefore, regular insulin should be administered 30-40 minutes before a meal to avoid a potential physiological mismatch, with subsequent hypoglycemia. This advance administration can become inconvenient or somewhat hazardous at times, particularly if the patient is unable to eat and has taken insulin (e.g., if the meal becomes surprisingly delayed or is not palatable to the patient). Additionally, when larger doses of regular insulin are given subcutaneously, the duration of action is...

Prescribing of Antidiabetic Drugs for Type Diabetes

Although hard end-point studies are somewhat sparse in diabetology, little doubt exists that near-normal blood glucose levels are beneficial, relieving symptoms and preventing long-term vascular complications. Guidelines are legion, and treatment goals are becoming increasingly ambitious. For example, the latest IDF guidelines for the treatment of type 2 diabetes 10 aim for HbA1c levels lower than 6.5 . Since this goal is rarely achieved through lifestyle measures alone, oral antidiabetic agents are usually required. Initially, monotherapy is commenced with the most appropriate drug, based on the clinical and biochemical profile of the patient, and in the light of safety considerations. For most patients, drugs from different classes are required in varying combinations, insulin being ultimately necessary in many patients. Current guidelines recommend metformin and sulphonylureas as first-line therapy. Other regimens may be equally effective or even more so. However, comparative...

Insulin Glargine Lantus

Insulin glargine (Lantus) was the first available long-acting human insulin analogue 12 . Glargine is a clear solution and there is no need to thoroughly mix it before injection. Insulin glargine (21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin) differs from native insulin in that the 21 amino acid residue aspargine on the A chain has been substituted with a glycerine residue and 2 arginine residues have been added to the C terminus of the B chain, making glargine soluble in the acidic environment at pH of 4 12 . Glargine precipitates in the neutral pH of subcutaneous tissue, which prolongs its absorption to the blood. The addition of zinc as a hexamer-stabilising agent further prolongs the duration of action. Insulin glargine must not be mixed with other insulins 12 . Clamp studies in normal subjects and type 1 diabetic patients have confirmed that the duration of glargine is longer than NPH insulin and the action profile is flatter. Median duration of action is 23 h for glargine versus...

Treating Subjects with Type Diabetes with Multiple Injections Basal Bolus Therapy

Multiple injections with fast-acting insulin before the meals and intermediate or long-acting insulin at bedtime (basal-bolus regimen) is the first choice insulin regimen in most type 1 patients, but is not used very much in patients with type 2 diabetes. Nevertheless, prandial glucose regulation is an emerging concept, since epidemiological and mechanistic studies indicate that postprandial glucose contributes significantly to overall glycaemic exposure and also contributes to the vascular complications in type 2 diabetes 34,45 . Adding prandial insulin to basal insulin is a logical approach when the target of HbAlc cannot be achieved by the combination of basal insulin and oral therapy. Basal-bolus therapy represents the most physiological insulin regimen, but is more complex and the patient needs to be more educated and motivated for glucose monitoring. A few studies have evaluated the efficacy of multiple injections in type 2 diabetic patients. In the first study the efficacy and...

Treatment of Subjects with Type Diabetes Using Pulmonary Inhalation of Insulin

Several pharmaceutical companies have developed inhaled insulin, and exubera from Sanofi aventis and Pfizer has been approved in several countries. The lungs with their large surface area and the thin alveolar epithelium allow rapid absorption of inhaled insulin 52 . The bioavailability has a range of 15-25 52 . The exubera insulin is a fine powder insulin in doses of 1 or 3 mg, corresponding to approximately 3 and 9 units of human insulin. The clinical trials have shown that the insulin antibody levels increase with the use of inhaled insulin, but this has not been linked to any changes in glycemic control and episodes of hypoglycaemia or allergic reactions 53 . The pharmacokinetic profile of exubera is quite similar to that of rapid-acting insulin analogues, but with a duration of action between that of rapid-acting analogues and fast-acting human insulin 54 . The development of inhaled insulin must be seen in the light of a substantial resistance to insulin therapy in patients with...

Comments on Inhaled Insulin

In type 2 patients the effect of inhaled insulin before meals on HbA1c did not seem to differ from that of fast-acting human insulin. Adding three times inhaled insulin to existing oral therapy is generally more effective than adding another oral hypoglycaemic agent. In the trials, subjects have been more satisfied with inhaled insulin than with subcutaneous insulin treatment. Whether this outcome will be borne out in clinical practice remains to be determined. Inhaled insulin seems to be most suitable in patients with controlled fasting blood glucose using a basal insulin. Smoking is a contraindication for inhaled insulin and inhaled insulin is not recommended in patients with asthma or chronic obstructive pulmonary disease. All candidates for inhaled insulin should have their lung function checked before and after 6 months and then every year. If lung function has declined more than 20 or by more than 500 ml from baseline, inhaled insulin should be discontinued. The long-term effect...

Activity of the Entero Insular Axis and Incretin Hormones in Type Diabetic Patients

Reduced Incretin Effect in Patients with Type 2 Diabetes In healthy human subjects oral glucose elicits a considerably higher insulin secretory response than does intravenous glucose (even if leading to the same glycemic increments). This incretin effect is substantially reduced or even completely lost in patients with type 2 diabetes 86 . The reduction in the incretin effect probably is an acquired defect, since it is also found in patients with diabetes secondary to chronic pancreatitis, whereas chronic pancreatitis without diabetes is characterized by a normal incretin effect 87 . Secretion of Incretin Hormones in Patients with Type 2 Diabetes Cross-sectional analyses of larger cohorts suggest that there is a slight reduction in postprandial GLP-1 secretion following the ingestion of a mixed meal in patients with type 2 diabetes. Subjects with impaired glucose tolerance display intermediate results between healthy controls (normal response) and type 2-diabetic patients (reduced...

Choosing Between Pancreas And Islet Transplantation As Treatments For Diabetes

Since pancreas transplantation has been shown to be very effective in controlling acute and chronic complications of diabetes over long periods of time, and islet transplantation has not, pancreas transplantation must be viewed as the more effective option. However, individual recipients who do not want to undergo the extensive surgery and potentially complicated postoperative course of organ transplantation may logically choose islet transplantation. This should be done, however, with the full knowledge that the majority of islet recipients need to return to insulin-based treatment and that intrahepatic islet transplant recipients do not have restored glucagon secretion during hypoglycemia. The latter is a significant issue given the number of islet transplant recipients who return to insulin treatment and are once again at-risk for hypoglycemia. There are few data that address the impact of islet transplantation on the secondary complications of diabetes mellitus. However, it can be...

Expression of the Renin Angiotensin System in Diabetes

The production and action of Ang II is regulated at multiple levels, including the availability of angiotensinogen, levels and activities of angiotensin-processing enzymes, angiotensin receptor isotype expression, and postreceptor signaling (Fig. 1). Although quantitation of Ang II levels would provide a direct measure of extracellular RAS activation, these measurements are complicated by the rapid degradation of this peptide (46,47) and its tissue-specific production (26,27,48). Reports on the effects of diabetes on plasma and tissues Ang II levels are controversial. Studies of streptozotocin (STZ)-induced diabetes in rats have reported no effect of diabetes on Ang II levels in plasma, kidney, aorta, and heart (49), reduced renal Ang II but normal levels in plasma Ang II (50), and decreased plasma Ang II in diabetes (51). Similar controversies appear for the effects of diabetes on changes in upstream components of the RAS. For example, recent studies have reported that plasma renin...

Outcomes in Diabetic Patients

Meta-analyses of ACE inhibitor trials provide compelling evidence that ACE inhibitors reduce cardiovascular events and mortality related to acute myocardial infarction (MI) and heart failure (90,91). Because diabetes is an independent risk factor for CVD (92) and the RAS and diabetes appear to interact at multiple levels, it is possible that diabetes may affect the efficacy of ACE inhibition on CVD. Several recent reports have provided retrospective analyses of data from diabetic subgroups, which participated in large ACE inhibitor trials. Although some of these trials were not designed to specifically address the effects of ACE inhibition in diabetes, comparison of the relative effects of ACE inhibition in the diabetic and nondiabetic subgroups may provide important insight into the role of the RAS in CVD in diabetes. An underlying question regarding the vascular protective effects of antihypertensive therapies is whether these effects are mediated via the reduction in BP or whether...

Effect of Angiotensin Converting Enzyme Inhibition Following Acute Myocardial Infarction on Cardiovascular Outcomes in

The GISSI-3 study examined the short-term effects of ACE inhibition when administered within 24 hours following an acute MI in a population of more than 18,000 patients, including 2790 patients who reported a history of diabetes (10). Retrospective analysis of results from this study revealed that ACE inhibitor treatment provided greater protective effects against 6-week mortality in diabetic patients compared with nondiabetics. The overall risk reduction by ACE inhibitor treatment for the diabetic group was 32 , compared with a risk reduction of 5 for nondiabetic patients. Within the diabetic group, ACE inhibitor treatment reduced mortality rates for both insulin-dependent (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) patients by 49 and 27 , respectively. Although this report indicates that the benefit of ACE inhibitor treatment in the diabetic group was greater than that for the nondiabetic group, the basis for this difference is unclear. Although the baseline...

Renin Angiotensin System Inhibition and New Onset Diabetes

Several large clinical studies have reported that ACE inhibitor treatment is associated with a reduction in the incidence of new-onset diabetes. The MICRO-HOPE study reported that the relative risk for new diagnosis of diabetes in the ramipril ACE inhibitor-treated group was 0.66 (p < 0.001) compared with the placebo-treated controls (96). The Captopril Prevention Project trial reported that the relative risk of developing diabetes in the ACE inhibitor treated group was 0.86 (p 0.039) compared with the conventionally (diuretics, -blockers) treatment group. Recently, the LIFE trial reported that ATI receptor antagonism using Losartan was associated with a 25 lower incidence of new-onset diabetes compared with patients treated with atenolol, which were similarly matched for initial clinical characteristics and BP control (154). Consistent with the clinical finding on the effects of RAS inhibition on the onset of diabetes, experimental studies have also indicated that ACE inhibition...

Diabetes and vascular disease

Complications of macrovascular disease are responsible for 50 of the deaths in patients with type 2 diabetes mellitus (DM), 27 of the deaths in patients with type 1 diabetes for 35 years or less, and 67 of the deaths in patients with type 1 diabetes for 40 years or more (1,2). The rapid progression of macroangiopathy in patients with type 2 diabetes may reflect diverse phenomena some intrinsic to the vessel wall angiopathic factors such as elevated homocysteine and hyperlipidemia deleterious effects of dysinsulinemia and excessive or persistent microthrombi with consequent acceleration of vasculopathy secondary to clot-associated mitogens (3,4). As a result of these phenomena, cardiovascular mortality is as high as 15 in the 10 years after the diagnosis of DM becomes established (5). Because more than 90 of patients with diabetes have type 2 diabetes and because macrovascular disease is the cause of death in most patients with type 2 as opposed to type 1 (insulinopenic) diabetes, type...

Mechanisms responsible for hyperreactivity of platelets in people with diabetes

Increased expression of the surface GPs Ib and IIb IIIa has been observed in platelets from subjects with both type 1 and type 2 diabetes (43). GP Ib-IX binds to von Willebrand factor in the subendothelium and is responsible for adherence of platelets at sites of vascular injury. Interaction between GP Ib-IX and von Willebrand factor leads to activation of platelets. Activation of GP IIb IIIa leads to the binding of fibrinogen and aggregation of platelets. Thus, increased expression of either or both of these two surface glycoproteins is likely to contribute to the increased reactivity that has been observed platelets from people with diabetes. Winocour and his colleagues have shown an association between decreased membrane fluidity and hypersensitivity of platelets to thrombin (34). Reduced membrane fluidity may be a reflection of increased glycation of membrane proteins. A reduction in membrane fluidity occurs following incubation of platelets in media containing concentrations of...

Antiplatelet therapy and diabetes

Beneficial cardiovascular effects of aspirin are particularly prominent in people with diabetes. In the Physicians Health Study, prevention of MI was greater in those with compared with those without diabetes (65). Treatment with aspirin decreased mortality in the Early Treatment Diabetic Retinopathy Study (66). Because of the marked beneficial effects of aspirin, the American Diabetes Association has recommended treatment with aspirin of all patients with type 2 diabetes without specific contraindications. Considered together, data acquired in vitro and in vivo suggest that platelets from subjects with diabetes are hypersensitive to diverse agonists. Unfortunately, currently available antiplatelet therapy does not restore normal responsiveness to platelets from subjects with diabetes. In animal preparations simulating selected aspects of diabetes, platelets remain hypersensitive to thrombin despite administration of aspirin (67). This observation suggests that the hypersensitivity is...

The coagulation system and diabetes mellitus

The increased concentrations of FPA seen in association with diabetes reflect an altered balance between prothrombotic and anti-thrombotic determinants in subjects with DM favoring thrombosis. This interpretation is consistent with other observations suggesting that generation of thrombin is increased with diabetes resulting in increased concentrations in blood of thrombin-anti-thrombin complexes (75). The steady-state The increased generation of thrombin in people with diabetes is likely to be dependent on increased activity of factor Xa. This has been observed in patients with type 1 diabetes (76). Factor Xa, a major component of the prothrombinase complex, is formed from components including circulating coagulation factor X assembled on phospholipid membranes in association with the tissue factor Vila complex. Thrombin is generated by the prothrombinase complex comprising factors Xa, Va, and II assembled on phospholipid membranes. The activity of this complex is reflected by...

Oxidative and Nitrosative Stress in Diabetes Induced Vascular Dysfunction

Various neurohumoral mediators and mechanical forces acting on the innermost layer of blood vessels, the endothelium, are involved in the regulation of the vascular tone. The main pathway of vasoregulation involves the activation of the constitutive, endothelial isoform of NO synthase (eNOS) resulting in NO production (53). Endothelium-depen-dent vasodilatation is frequently used as a reproducible and accessible parameter to probe endothelial function in various pathophysiological conditions. It is well established that endothelial dysfunction, in many diseases, precedes, predicts, and predisposes for the subsequent, more severe vascular alterations. Endothelial dysfunction has been documented in various forms of diabetes, and even in prediabetic individuals (52,54-58). The pathogenesis of this endothelial dysfunction involves many components including increased polyol pathway flux, altered cellular redox state, increased formation of diacylglycerol, and the subsequent activation of...

Endothelial dysfunction and diabetes mellitus

Although the link between diabetes and cardiovascular disease is not well understood, endothelial dysfunction may be implicated in the pathogenesis of diabetic vascular disease. The evidence of endothelial dysfunction in diabetes comes largely from studies measuring the endothelial substances that mediate fibrinolysis and coagulation. Chapters 2 and 6 give detailed descriptions of these studies. For example, plasminogen activator inhibitor-1 levels are increased, whereas fibrinolytic activity and prostacyclin levels are decreased in both type 1 and 2 diabetes (42-45).

The Epidemiology of Diabetes Mellitus

The Epidemiology of Diabetes Mellitus An International Perspective International Diabetes Institute, Caulfield, Victoria, Australia The epidemiology of diabetes mellitus an international perspective edited by Jean-Marie Ekoe, Paul Zimmet, Rhys Williams. p. cm. 1. Diabetes-Epidemiology. I. Ekoe, J.M. II. Zimmet, Paul. III. Williams, D.R.R. (David Robert Rhys)

Diabetes Mellitus Diagnosis and Classification

Centre de Recherche CHUM, Montreal, Canada 2International Diabetes Institute, Melbourne, Australia Diabetes mellitus may present with clear and classical symptoms (thirst, polyuria or ketoacidosis) or may be accompanied by specific complications. The lack of sensitivity and specificity of some of these 'diabetic symptoms' has already been discussed (see previous chapter). However, when the symptoms and or specific complications are present, the diagnosis of diabetes is confirmed by a single, unequivocally elevated blood glucose measurement as shown in Figure 3.1 (1). Severe hyperglycemia found under conditions of acute infective, traumatic or other stress may be transitory and should not in itself be regarded as diagnostic of diabetes. If a diagnosis of diabetes is made, one must feel confident that the diagnosis is fully established since the consequences for the individual are considerable and lifelong (2). For the asymptomatic persons at least one additional plasma blood glucose...

Drug or Chemicalinduced Diabetes

Insulin secretion may be impaired by many drugs. They may not, by themselves, cause diabetes but may precipitate diabetes in persons with insulin resistance (71,72). Classification is ambiguous in such cases as the primacy of -cells destruction or where insulin resistance is unknown. Pancreatic -cells destruction may occur with the use of certain toxins such as Vacor (a rat prison) and pentamidine (73-75). There are also many drugs and hormones which can impair insulin action. The list shown in Table 3.3 is not all-inclusive, but reflects the more commonly recognized drug-, hormone-, or toxin-induced forms of diabetes and hyperglycemia.

Primary Prevention Of Type Diabetes

Prevention of diabetes can be considered at three different levels. Primary prevention covers activities aimed at preventing diabetes from occurring in susceptible populations or individuals. Secondary prevention is aimed at early diagnosis and effective control of diabetes in order to avoid or at least delay the progress of the disease, and tertiary prevention includes those measures undertaken to prevent complications and disability due to diabetes (6,11). Studies in a number of populations, including Europeans, Native Americans, Indian, Chinese and African-born Mauritians, Samoans, Nauruans and Melanesian Papua New Guineans have shown that individuals with IGT have a higher risk of progressing to Type 2 diabetes (between 2- and 7fold higher) than persons with normal glucose tolerance (3,11). Therefore, persons with IGT have formed the target group for interventions aimed at preventing Type 2 diabetes in several studies. These have been of two main types behavioural interventions...

Type Diabetes Incidence Worldwide

Incidence rates reported over a period of 20 years, from the late 1970s to the early 1990s (Table 7A.2) (17,25,27,39-84) show the vast geographical variation in Type 1 diabetes incidence. This large variation worldwide was also seen in small 'pockets' of countries, e.g. around the Baltic Sea. In North America the range of the intraconti-nental variation in Type 1 diabetes incidence was also large ranging from < 1 per 100 000 in Mexico to 24 per 100 000 on Prince Edward Island and incidence overall seemed to be higher in the northern than the southern part of the continent (25). The incidence data from South America (57-59) and Oceania (25,64,65) were sparse and sporadic. According to the available data, Type 1 diabetes incidence in the southern hemisphere, in Oceania and South America, seemed to be low and there was no noticeable variation in incidence. Also in Asia the within-continent variation was smaller than in Europe and North America and the incidence did not correlate to the...

Temporal Trends In Type Diabetes Incidence

Most of the Type 1 diabetes registries have been using consistent case definitions and registration practices for a relatively short time, and only a few registries have been active for a longer period, e.g. 20 years or more. Therefore temporal trends in Type 1 diabetes incidence have been difficult to study in detail. In some countries temporal changes in Type 1 diabetes incidence have been reported (Table 7A.3). Several registries (17, 27, 43, 56, 62, 71, 86-93, 101-103) have reported a change in Type 1 diabetes incidence in North America, Europe and Oceania during various periods between 1966 and 1992. During these years an increase in Type 1 diabetes incidence has been observed in several European countries, whereas in the North American continent occasional peaks Table 7A.3 Reported increase in Type 1 diabetes incidence from 1960 to 1996 The greatest temporal increase was found in Europe, especially in the northern part of the continent. For instance, in Finland the increase in...

Seasonal Variation In Type Diabetes Incidence

Seasonal variation in Type 1 diabetes incidence was already reported in the 1920s when higher rates of 'acute diabetes' were found during the late autumn, winter and early spring (1). Peaks in incidence, with one peak in the winter months and the other during the late summer, were detected in northern Sweden among children aged 0-14 registered during 1938 to 1977 (106). Several other epidemiologic studies have described seasonal patterns in the onset (or better at diagnosis) of new cases of insulin-dependent diabetes in children Most studies have reported higher occurrence of insulin-dependent diabetes during the cold autumn and winter months than during the warmer spring and summer months, but these findings are difficult to compare because of differences in The months seasons of highest incidence have varied across populations however, the low incidence during the warm months has been consistent. There were some exceptions in the seasonal pattern in Europe in France (89) and in...

Type Diabetes And Possible Association With Viral Infections

Seasonal variation in the diagnosis of Type 1 diabetes has been considered as indirect evidence for environmental exposure in the development of Type 1 diabetes. Recent studies have provided more indirect evidence for an association between viral infections and the pathogenesis of insulin-dependent diabetes, but the final evidence for viruses causing insulin-dependent diabetes is still missing (114). Some communicable diseases occur more frequently during the cold winter months in areas where the climate changes during the year. Therefore infectious diseases could play a role, at least as a triggering factor in the onset of clinical symptoms of insulin-dependent diabetes. development of Type 1 diabetes, this disease is not a common consequence of viral infection. Even though it was suggested in the last century that there might be a connection between mumps and Type 1 diabetes (115), the part that viruses play in Type 1 diabetes is still not clear. Many reports have shown a temporal...

The Aetiology Of Type Diabetes Evidence Of A Nongenetic Contribution

The most striking evidence of a non-genetic contribution to Type 1 diabetes relates to the fact The Epidemiology of Diabetes Mellitus. An International Perspective. Edited by Jean-Marie Ekoe, Paul Zimmet and Rhys Williams. 2001 John Wiley & Sons Ltd. that the concordance rate in monozygotic twins is far below unity (1,2,3). Since monozygotic twin partners have identical genes, this difference can only be attributed to the influence of non-genetic exposures. Two additional lines of evidence provide support for the non-genetic contribution. First, the huge variation in the incidence of Type 1 diabetes between Caucasian populations (16) cannot be explained by the geographical distribution of susceptibility genes. Second, the rising incidence of Type 1 diabetes, as observed in many European populations (17), cannot possibly be explained by increased size of the pool of susceptibility genes (18) and must be attributed to increased susceptibility in individuals at genetic risk and or the...

The Aetiology Of Type Diabetes Summary

With all currently available information considered together, there seems to be no doubt that Type 1 diabetes develops as the consequence of interaction(s) between genetic factors and non-genetic determinants, leading to an immunemediated process of ,3-cell destruction which may be ongoing for several years before Type 1 diabetes presents clinically. This is schematically illustrated in Figure 7B.1. Many details of the aetiological determinants remain to be established, particularly how genetic factors interact with non-genetic determinants in the activation of the immune system. Possibly, each of several distinct combinations of genetic markers may, when exposure to relevant environmental factors takes place, induce the disease process that represents the unique pathogenetic feature of Type 1 diabetes. Possibly, other factors ( stress, infections) The main reason for predicting Type 1 diabetes is the provision of possible intervention before clinical disease develops (45,46,47,48)....

Prediction Of Type Diabetes Available Markers

The current appreciation of the aetiology and pathogenesis of Type 1 diabetes has important implications for prediction of the disease. Until immune markers appear in the circulation, the only available and reasonably well-established markers of Type 1 diabetes are represented by genetic determinants (Figure 7B.1). The appearance of immune markers signifies an activation of the immune system which to a high degree correlates with an ongoing destruction of the -cells of the pancreas. When a sufficiently large part of the cells has been destroyed metabolic decompensation develops, with clinical presentation of Type 1 diabetes as the consequence. This may be preceded by the demonstration of reduced response in insulin secretion to a glucose challenge. The scenario provides for the establishment of several types of markers in predicting Type 1 diabetes. As mentioned above, Type 1 diabetes tends to cluster in families due to sharing of genetic susceptibility factors. A positive family...

Prediction Of Type Diabetes Methodological Considerations

Prediction of a chronic disease like Type 1 diabetes involves a quantitative assessment of the risk of developing the disease. At the most basic level, ignoring specific markers, the disease risk may be estimated from the population incidence by the relationship where Rt 12 represents the cumulative risk of developing Type 1 diabetes over the period (usually in years) from t 1 to t 2 in the general population, and INC represents the population incidence (expressed as number of new cases per person-year at risk) applicable to this period and assumed constant. For a relatively rare disease like Type 1 diabetes the quantity INC (t2 11) is usually small (< 0.05) under these circumstances, the relation approximates the more simple expression Thus, if the population incidence of Type 1 diabetes among children aged 0-14 years is 16 per 100 000 person-years, the cumulative risk of developing Type 1 diabetes over a period of five years may be estimated to 0.08 ( 0.00016 year-1 5 years)....

Prediction Of Type Diabetes A Hypothetical Example

Numerous recent studies have illustrated how combined marker information enhances the prediction of Type 1 diabetes (58), particularly in connection with preventive trials (48). The approach is most conveniently illustrated by a numerical example. In this section we use a positive family history of Type 1 diabetes (FH) as the first step marker which is combined with the presence of a genetic susceptibility marker (GM) as the second step marker. We apply hypothetical data which we, however, consider to be fairly representative for a country such as England with well-established traditions in epidemiological and clinical diabetology (48,54,55, 56,58). First of all, we consider a population of unaffected children aged 0-14 years. For convenience, the population size will be fixed at 1 000 000 subjects which we assume to follow during a period of 5 years. The incidence of Type 1 diabetes (ignoring marker status) may be set at 0.00016 per person-year at risk, corresponding with an absolute...

The Range Of Diabetes In Youth

Surveys for diabetes among children and young adults from many geographic locations reveal a spectrum of clinical characteristics. The majority of young European-origin patients appear to fit the clinical picture of Type 1 diabetes, while the prevalence of Maturity-onset Diabetes of Youth (MODY) is estimated at 1-3 (9). In other ethnic groups Type 2-like syndromes are reported more frequently among children, although no consensus on defining characteristics has yet emerged. Winter's classic case-series, published in 1987 (1), described 12 of 129 African American patients with an atypical disease course, an absence of the Type 1 diabetes-associated HLA variants and no detectable islet cell antibodies (ICA). C-peptide levels in these patients were intermediate between those of Type 1 diabetes patients and non-diabetic subjects. Additional characteristics resembling Type 2 diabetes were observed, such as obesity and a high prevalence of diabetes among relatives. These patients were...

Intermediate Syndromes Double Diabetes

Correctly distinguishing the etiology of childhood diabetes has been an issue for many investigators. An incidence study of diabetes among Swedish youth aged 15 -34 demonstrated that even in this relatively homogeneous population with few structural barriers to diagnosis and optimal treatment, confusion as to the clinical type and etiology of diabetes can occur (42). Patients diagnosed in 1983-84 (n 281) were followed for 3 years. Initially, 75 were classified as Type 1, 19 were Type 2, and 6 were unclassifiable or their diabetes was secondary to another disease process. By 3 years duration, 87 of the Type 1 diabetes patients were still classified as Type 1, and 72 of the initial Type 2 diabetes patients were still in that category. Thus, 13 of Type 1 diabetes and 28 of Type 2 patients (n 43 in all) exhibited an atypical clinical course. Of these, six patients were designated Type 1 at onset on the basis of glycemia, ketonuria and other clinical characteristics. At followup, these...

Genetic Associations With Diabetes

Recent advances in the genetic epidemiology of Type 1, Type 2 and MODY may soon make it possible to distinguish them based on genetic markers. Inheritance in European-origin MODY families usually follows that of an autosomal dominant pattern, with vertical transmission of disease from one generation to the next, and approximately 50 of siblings affected (28). Reports of non-Type 1 in other ethnic groups show vertical transmission in only a subset of such families (4). Work in Europeans and US whites has identified several associations of MODY with specific mutations (29) the HLA-DR and -DQ alleles linked to Type 1 diabetes are not found in MODY patients (27, 65). Indeed, some investigators suggest that patients with early-onset Type 2 diabetes can be distinguished from MODY patients on the basis of inheritance patterns (66). There is widespread consensus that Type 2 diabetes, in contrast to MODY, is a genetically heterogeneous condition (45, 67). Familial aggregation is common,...

Risk Factors The Epidemiology Of Obesity And Hyperinsulinemia In Children

It is well accepted that overweight as a child is a risk factor for obesity in adulthood. Using data from the Fels Longitudinal Study, Guo et al. (76) correlated girls' percent ideal body weight aged 10-18 with their percent ideal weight at age 35 all coefficients exceeded 0.6. We know that obesity, impaired glucose tolerance and insulin resistance are important metabolic risk factors for Type 2 diabetes mellitus (77, 78), and they are also suspected to be important etiologic components of youth-onset disease. among youth aged 12-19 years (82). Cross-sectional anthropometric surveys of Mexican American children were conducted in Brownsville, Texas in 1972 and again in 1983 (83). Mean BMI and triceps skinfold increased significantly over the 11-year interval except among boys > 15 years old. In preparation for an intervention study in 4th grade Mexican American children in Texas, baseline data were collected in 1997-98 on 173 subjects 21 of boys and 18 of girls were overweight,...

Insulin Resistance And Hyperinsulinemia In Healthy Children And Adolescents

A reasonably comprehensive literature is emerging on puberty and insulin metabolism. In a study of normal, European-origin children (14 prepubertal and 19 pubertal), Amiel et al. showed them to exhibit selective insulin resistance which may have served to enhance the anabolic effect of insulin in proteins (89). A much larger study of insulin resistance (357 healthy children, ages 10-14 73 were African American) demonstrated a significant decrease in insulin sensitivity through puberty, resolving to near prepubertal levels by Tanner stage 5 (90). Girls were more insulin resistant than boys at every pubertal stage approximately 50 of this difference could be accounted for by adiposity as reflected by skinfold thickness. Non-Hispanic white boys were more insulin resistant than African Americans, and there was no significant ethnic difference among girls, controlled for BMI, adiposity and blood pressure. The authors suggest that the initial reports of greater insulin resistance among...

Insights From The Chicago Childhood Diabetes Registry

The population-based Chicago Childhood Diabetes Registry has been ascertaining diabetes with onset < age 18 since 1985 among African American and Hispanic children (100). During the first 10 years of the study, 1985-94, there were 735 incident cases of insulin-treated diabetes among 520 non-Hispanic blacks and 215 Hispanics. Overall, the average annual risk for non-Hispanic blacks, 15.3 10,5 was significantly higher than that for Hispanics (10.8 105). The average yearly incidence among non-Hispanic black males was 13.7 105 persons, while among non-Hispanic black females it was 16.8 10.5 Among Hispanic males the average annual risk was 10.8 105 and among Hispanic females it was 10.7 105 per year.

Age Sex and Family History of Diabetes

Both age and sex are risk factors for diabetes, with African American women having a greater risk than men and both sexes having a greater risk with increasing age, Figure 9A.3 (1-3,6-8). Family history of diabetes was determined in NHANES II among previously and newly diagnosed African American diabetic subjects, age 20-54 years, 25 had a parent and 50 had a sibling with diabetes. In contrast, in individuals without diabetes, 19 had a parent with diabetes and 8 had a sibling with diabetes. The age-standardized prevalence of diabetes increased with numbers of diabetic first-degree relatives (Table 9A.2). African American individuals with 0, 1 and > 2 relatives with diabetes had prevalence rates of diabetes of 7.8 , 11.8 and 23.3 respectively corresponding rates for whites were 4.6, 8.4 and 16.3 (9). This supports a possible dose effect for inherited diabetes risk factors (10).

Is There A Metabolic Insulin Resistance Syndrome In African Americans

Insulin resistance, glucose intolerance, hyper-insulinemia, central obesity, dyslipidemia, hypertension and macrovascular disease are components of the metabolic insulin resistance syndrome (68). If the syndrome exists in a population and the components are causally related, then targeting the primary defect might eliminate the cascade of abnormalities. Selective reporting of the components makes assessment difficult in African Americans the association of hyperinsulinemia and hypertension is weakest (Table 9A.4).

Remission in Diabetes

African American subjects with Type 2 diabetes who present with severe hyperglycemia may develop long-lasting remissions (92, 93). At the time of presentation, these individuals require hospitalization for severe symptomatic hypergly-cemia (mean glucose 600 mg dl, 33.3 mM) and following a period of treatment, with anti-diabetic pharmacologic agents they are able to discontinue The development of remission is not associated with (1) marked weight loss (2) reversal of stressful illness or (3) a 'transient honeymoon', or variant of immunologically mediated Type 1 diabetes as evidenced by absent islet cell and glutamic acid decarboxylase antibodies (92). The clinical characteristics of 72 individuals who developed remission were mean age 48 years, BMI 27.6 kg m2 (range 21-35) two-thirds were men. All had newly diagnosed Type 2 diabetes and remission developed within 12 months. Most patients participated in intensive glycemic monitoring and regulation. Although the hemoglobin AlC was...

Diabetic Ketoacidosis DKA in African American Adults with Type Diabetes

Adult African Americans may present with DKA as their initial manifestation of diabetes, often without any precipitating events. A series of 21 cases (80 were newly diagnosed) showed that following treatment these individuals had a clinical course of Type 2 diabetes (104). Their mean presenting plasma glucose was 693 mg dl (38.5 mM), ph 7.18, age 45 years and BMI 28.7 kg m2. Metabolic studies performed several months after the episode found all were insulin-resistant with significant residual C-peptide levels (but less than normal controls) in response to oral glucose stimulation. Because of the clinical course, metabolic studies and the uniform absence of glutamic acid decarboxylase antibodies these subjects are considered to be Type 2 diabetes. Interestingly, these subjects had an increase in either HLA DR 3 or DR4. Morrison (103) has reported similar cases in Jamaican blacks, who present with DKA or severe hyperglycemia who are ultimately not insulin-dependent. Umpierrez (105) also...

Atypical Diabetes of Childhood

Not all diabetes in childhood represents autoimmune Type 1 diabetes and a distinct minority has an atypical version. Winter (107) described African American youths who presented with severe hyperglycemia, varying degrees of obesity, with and without ketoacidosis, who subsequently did not have an obligate requirement for insulin. There was no evidence of autoimmune markers nor an increase in frequency of HLA DR3 and HLA DR4. They represented 9 of their clinic population. In a community incidence study, Lipton found that 7 of African American boys and 16 of African American girls were obese and many had positive family histories of diabetes suggesting atypical diabetes (108). Another clinic-based study notes that 50 of African American children and adolescents with Type 2 diabetes had presented with diabetic ketoacidosis and were obese. Type 2 diabetes was diagnosed by virtue of the lack of insulin dependence for short-term survival and lack of autoimmune markers. They did not identify...

Mortality of Diabetes

22-year mortality data from the NHANES I study showed the age-adjusted mortality rate for non-Hispanic blacks with Type 2 diabetes was 23 higher than for non-Hispanic whites (179). The mortality for African American women and men with diabetes was significantly higher than for those without diabetes (40 and 50 respectively) (179, 180). Diabetes was listed as an underlying cause of death in only 7.7 of diabetic men and 13.4 of diabetic women. This confirms that mortality data among African Americans (and others) with diabetes suffers from severe underreporting the data are derived from hospital death certificates which list proximal cause but not underlying illness (1). Mortality rates for African American and whites are similar at age < 15 years for Type 1 diabetes (0.1 per 100 000 population) (181-184).

Certified Diabetes Educator

The certified diabetes educator (CDE) will educate you about the kind of diabetes you have and your medication options. She will educate you about the importance of controlling glucose, lipids, and blood pressure to prevent complications and about the effects of exercise and emotions on glucose control. She will also show you how to use glucose monitors, how to treat high and low glucose levels, and how to exercise safely. If you are on insulin, she will teach you how to inject insulin and how to use your insulin pens or pumps.

Diabetes Medicine Combinations

Many people with diabetes are on more than one medicine to control glucose levels, and pharmaceutical companies make combination pills that is, a pill containing two different diabetes medicines. Since many insurance companies make their customers pay a part of the cost of each prescription (a copayment), the combination pill has the benefit of eliminating one of the copayments. However, the disadvantage of these combinations is that you lose some of the flexibility of adjusting the individual doses of the medicines. Also, if you need to discontinue one of the two medications, you may have to go back to the doctor and get a prescription for the single medicine that you are continuing. The combination pill usually has a different name, and often patients (and physicians) forget that the pill contains two different medicines. If you are prescribed a combination pill, make sure that you are not taking both a combination pill and one of the components of the combination pill as a separate...

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