Foods to eat with Diabetes

Reverse Diabetes Now

Reverse Your Diabetes Today by Matt Traverso can be described as comprehensive eBook that reveals what can you do to reverse diabetes, what can you eat to reverse diabetes and what can reverse type 2 diabetes and part 1 diabetes conditions by natural means with 3 short weeks or fewer. Reverse Your Diabetes today is presented especially for those who are experiencing difficulty with their blood sugar levels. This diabetes healing program provides users with natural remedies for diabetes that are proven totally safe to apply. In fact, the author has research thousands of websites; read dozens of magazines, books, diet plans, and brochures out there to find out how to reverse diabetes for good. This treatment offers the tools that are proven effective by many people in many areas all over the world. Reverse Diabetes Today PDF is an extremely comprehensive treatment that encourages people to make positive changes in daily habits, more concretely, dieting, regularly exercising, and weight managing routines to reverse diabetics. Read more...

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Prevention of Cardiovascular Disease in Patients who have Diabetes119

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 Patients185

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.

Therapeutic Strategies in Diabetes and Cardiovascular Disease

Diabetes is now considered the equivalent of having 2 or 3 major risk factors for coronary atherosclerosis. Also, the presence of diabetes increases the risk of any procedure and is associated with a poorer prognosis compared with individuals without diabetes. Also, diabetes dictates certain clinical approaches to disease. Thus today's clinician needs a full understanding of this disease and its effect on management decisions. I was delighted that Dr. Prakash Deedwania, who has had a long and productive interest in diabetes and cardiovascular disease, was willing to organize and contribute to articles on this topic. This broad topic has been divided between two issues of the Cardiology Clinics. The first issue (November 2004) dealt with pathophysiology, clinical epidemiology, and the relationship between diabetes and other diseases such as heart failure and hypertension. The second issue deals with management strategies for preventing and treating the cardiovascular complications of...

Evolution In Diagnostic Criteria For Diabetes

The question of diagnostic criteria for type 1 diabetes does not usually give risk to much debate because of its clear acute-onset phenotype, and the logical link between aetiology (lack of insulin) and treatment modality. However, the recognition of a non-insulin-dependent form of diabetes, in which there was a much less clear distinction between normality and disease, created a need for diagnostic criteria. Classification with only the help of symptoms and clinical signs was soon regarded as unsatisfactory. Another major impetus for the development of diagnostic criteria was the recognition that the absence of standardisation was an obstacle to epidemiological and clinical research. In 1964, the World Health Organisation (WHO) convened an Expert Committee on Diabetes Mellitus which attempted to provide a universal classification of the diabetes syndrome. But it was not until 1980 that an international accepted classification was established. Two international work groups, the...

Human insulins and analogs

Over 100 million patients currently require insulin, with a worldwide market of about U.S. 6 billion. Human insulin (Humulin , Eli Lilly) was the first therapeutic recombinant polypeptide to be approved by the FDA in October 1982. Recombinant human insulin is synthesized in E. coli bacteria and is chemically and physically equivalent to pancreatic human insulin and biologically equivalent to human and pork insulin.60,61 The advantage of human insulin lies in its lower antigenicity relative to animal-derived insulins.62 Human insulin has now largely replaced the animal-derived insulins. Before 1986, human insulin was prepared by the production of genetically engineered A and B chains in separate fermentations. These two chains were then isolated, purified, and joined chemically. Recombinant insulin is currently produced by production of proinsulin, followed by the enzymatic cleavage of the C-peptide to produce human insulin. Humulin produced by these two...

Impaired insulin secretion and insulinstimulated glucose uptake

Glucose oxidation requires less oxygen than FFA oxidation to maintain ATP production. Thus, myocardial energy use is more efficient during the increased dependence on glucose oxidation with ischemia (approximately 11 more ATP is generated from glucose oxidation as compared with FFA oxidation). In the setting of relative insulinopenia (insulin resistance or frank DM) that is exacerbated by the stress of AMI, the ischemic myocardium is forced to use FFAs more than glucose for an energy source because myo-cardial glucose uptake is impaired acutely. Thus, despite acute hyperglycemia, a metabolic crisis may ensue as the hypoxic myocardium becomes less energy efficient in the setting of frank DM or insulin resistance. Insulin augments the translocation of GLUT-1 and GLUT-4 receptors to the sarcolemma and can diminish FFA release from myocytes and adipocytes 27 . Thus, the extent to which the myocardium expresses an intact response to insulin, therapeutic augmentation of oxidative glucose...

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...

Role of Insulin Secretagogues and Insulin Sensitizing Agents in the Prevention of Cardiovascular Disease in Patients

Cardiovascular disease is the leading cause of death among patients who have diabetes mellitus. Patients who have diabetes mellitus have a greatly increased relative risk of cardiovascular disease when compared with patients who do not have diabetes mellitus 1 . Furthermore, in patients who have established cardiovascular disease, the rate of subsequent cardiovascular events is significantly higher than in individuals who do not have diabetes mellitus 2 and is associated with greatly increased morbidity and mortality. Epidemiologic studies showed that diabetic patients are more prone to develop complications following cardiovascular events 3 . Moreover, diabetic patients who have ischemic heart disease have a substantially worse outcome after coronary interventional procedures compared with nondiabetic patients 4 . The basis for these differences in outcome remained unclear. In most animal studies, diabetic myocardium demonstrates an enhanced sensitivity to the detrimental effect of...

Potential beneficial effects of insulinsensitizing agents on cardiovascular risk factors

Several epidemiologic studies showed that hyperinsulinemia is an independent risk factor for cardiovascular disease 18 . Correction of insulin resistance clearly is important in the management of type 2 diabetes mellitus and may decrease the risk for cardiovascular disease. In the UKPDS, patients who had type 2 diabetes melli-tus and were treated with metformin, which decreases hyperinsulinemia and insulin resistance, had a 30 reduction in cardiovascular disease events and mortality compared with those who received conventional treatment 11 . The thiazo-lidinediones also improve insulin sensitivity and may exert numerous nonglycemic effects in patients who have type 2 diabetes mellitus 19,20 . Additional clinical trials are being conducted to evaluate whether treatment of diabetes mellitus with agents that reduce insulin resistance, such as the thiazolidinediones, is superior to treatment with agents that stimulate insulin secretion, such as the sulfonylureas.

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...

Insulin Resistance Related Aberrations in Cellular Function

Insulin resistance in DM is featured by the lack of both metabolic and vascular actions of insulin. The former results primarily in hyperglycemia whereas the latter renders the cells lacking important biochemical effects of insulin. The important action of insulin on the vasculature is related to its ability to promote vasodilatation, which is endothelium-dependent 147, 148 . Insulin triggers NO release enrolling PI3K Akt eNOS pathway 149, 150 and upregulates eNOS expression 151 . Insulin-resistance is characterized by impaired vasodilatory responses to insulin 152 and cholinergic stimuli 153, 154 . Furthermore, both metabolic and vascular effects of insulin share the same signaling pathways such as PI3K Akt pathway 155 . Both insulin resistance and the down-regulation of the PI3K Akt pathway in type 2 DM has been described in animals and in humans 87, 156, 157 . Insulin action in vascular cells also involves activation of mitogen-activated protein kinase (MAPK) signaling pathways 158...

Selection of antihypertensive drug in diabetes mellitus

ACE inhibitors, nondihydropyridine CCBs, TDs, and bBs reduced CV complications in patients who had diabetes and hypertension in several long-term, large, RCTs (Tables 3 and 4). Limited data is available with direct comparisons of various drugs in diabetic, hypertensive patients (Table 5). INSIGHT 70 ) that newer agents, such as ACE inhibitors and CCBs, are better than diuretics and bBs in reducing CV events in treating hypertension in the general population. Because diabetes is an important and independent risk factor for CV morbidity and mortality and because most diabetics die of CV complications 1 , subgroup analysis of diabetic, hypertensive patients in these trials revealed that most required multiple drugs for adequate control of their BP. In the CAPPP trial, diabetic patients who were on captopril had less cardiac mortality and all-cause mortality than did those who were on bBs or TDs 26 . The report did not further divide the impact of captopril over bBs or TDs. However, the...

Studies In Newly Diagnosed Diabetes

Several interventions have been evaluated in individuals with newly diagnosed type 1 diabetes, in an attempt to interdict the disease process and preserve B-cell function. Interpretation of these has been complicated by a number of factors. Early studies often used 'remission' as an outcome, based on cessation of insulin therapy or very low doses of insulin. In fact, there was even a recommended definition of remission promulgated52. Yet, most recent investigations have focused more on preservation of C-peptide as a biochemical marker of B-cell function2. Moreover, it has come to be appreciated that more intensive insulin therapy and or better maintenance of glycaemic control results in better preservation of B-cell function53-56. Of these, probably the best data come from the Diabetes Control and Complications Trial (DCCT)56. Individuals who entered the DCCT with high residual B-cell function (stimulated C-peptide levels of 0.2-0.5 pmol ml) (n 303) and who were randomized to...

Diabetes as a coronary heart disease riskequivalent

Based on the observations from several epidemiologic studies, diabetes is designated a coronary heart disease (CHD)-risk equivalent by the National Cholesterol Education Program's Adult Treatment Panel III (ATPIII) 1 . The 10-year risk of major CHD events in patients who have diabetes is greater than 20 this is comparable to the rates that are observed in nondiabetic patients who have established CHD. This inference has been borne out, particularly by data from a population study in Finland 2 and a multi-national study, the Organization to Assess Strategies for Ischemic Syndromes 3 , of patients who had type 2 diabetes who frequently had multiple, coexisting risk factors for cardiovascular disease (CVD). The increased risk for CHD may precede the clinical diagnosis of diabetes by many years. This was documented best in the long-term study of more than 117,000 women in the Nurses' Health Study nearly 6000 women developed diabetes during 20 years of follow-up. There was an approximately...

Rationale For The Prevention Of Type 2 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...

The Insulinlike Growth Factor And Its Receptor In Pancreatic Diseases

Insulin-like growth factors (IGFs) have been implicated as regulators of cell differentiation and cell proliferation in a number of cell systems and have been reported to play an important role in growth regulation of human tumors.43,44 The IGF family includes IGFs Type I and Type II (IGF-I and IGF-II), which are structurally related to proinsulin. IGF-I is a mitogenic factor that has the ability to bind and activate the insulin receptor as well as the IGF-I receptor.45-48 The IGF-I receptor binds IGF-I with higher affinity than insulin, and in general the mitogenic effects of both factors are mediated by the IGF-I receptor. Ligand binding to the IGF-I receptor results in activation of the intracellular receptor kinase domains and transphosphorylation.45-48 Following receptor phosphory-lation, adapter molecules (IRS-1 and IRS-2) associate with the receptor and are phosphorylated. The presence of a variety of phosphorylation motifs on each of the two IRS proteins enables them to...

The Collaborative Atorvastatin Diabetes Study

A Primary Prevention Trial, Collaborative Atorvastatin Diabetes Study (CARDS), exclusively in patients with type 2 diabetes who had one additional risk factor was recently published 28 . A total of 2838 patients, age range 40-75 years, were randomized to 10 mg atorvastatin versus placebo and followed over a mean period of 3.9 years. In this trial, the mean LDL-cholesterol level was 118 mg dL, which was reduced by 40 in the drug treated group. The combined primary end-points of acute CHD events, coronary re-vascularization or stroke were reduced by 37 (P 0.001), whereas stroke events were reduced by 48 , and total mortality by 27 (P 0.059). The risk reductions were independent of baseline lipid levels and in post-hoc analyses 743 patients with baseline LDL < 100 mg dL had a 26 reduction in major cardiovascular events, which is consistent with the results in the HPS 25 . Fig. 1. Effects of simvastatin on first major vascular event in patients who do or do not have diabetes according...

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...

Definition Of Type 2 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 2 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...

Step 2 Determining if You Have Heart Disease or Diabetes

We now know that diabetes carries similar risks for heart health. So if you have any of the previously mentioned heart conditions, especially in combination with diabetes, you'll probably be in the most aggressive treatment group (very high risk), so you can skip over the next few steps that help determine that category and go to Step 6. If you have diabetes but are very young and free from heart disease or other risk factors, you might not need such aggressive treatment. If you fall into that category, you will most likely be in the high-risk category skip to Step 6. If you don't have a heart problem or diabetes, go to Step 3.

Role of combination therapy in diabetes and dyslipidemia

Despite the known pharmacologic effects of fibrates and nicotinic acid in ameliorating the underlying defects of diabetic dyslipidemia (increased triglyceride-rich lipoproteins low HDL cholesterol small, dense LDL particles), the role of combining these agents with statins remains uncertain and further clinical trials are needed. Trials like the VA-HIT and DAIS are supportive of the potential of adding fibrates to statins because combined lipid disorders are common in patients who have insulin resistance and type 2 diabetes. In short-term studies, statins and fibrates were more effective in normalizing all lipid abnormalities than either agent alone without significant risk for adverse events, including myositis 51,52 . Caution should be exercised in patients who have potential drug interactions (eg, cyclo-sporin, antifungal agents, protease inhibitors, erythromycin) or renal disease. Long-term trials of combination therapy with statins and fenofi-brate are in progress (Table 5)....

Prevention Of Type 2 Diabetes

Interventions have been targeted at altering a number of behavioral factors including obesity, dietary intake and physical activity. Obesity, of course, should be considered the result of behavioral, genetic and physiological factors and not simply behavioral. Pharmacological interventions have primarily used hypoglycemic or anti-hyperglycemic medication to reverse insulin resistance (biguanides, thiazolidenediones), failure of insulin secretion (sulfonylureas), or glycemic excursions (alpha-glucosidase inhibitors). Trials have attempted to alter glucose metabolism using metal supplementation (magnesium, chromium) or antioxidants (beta-carotene, vitamin E). Trials that have used Table 6.2. Summary of established and possible* individual level risk factors for type 2 diabetes mellitus Family history of diabetes Maternal history of diabetes post-challenge) Low insulin secretion Insulin resistance syndrome (low HDL-C, high triglycerides, hypertension, fibrinolytic defects, glucose...

Insulin Receptor Number

Insulin receptor number has often been claimed as a potential indicator of Cr deficiency in humans (e.g., 81 ). Despite the number of times this claim has been made, this claim is based on only a single study using only seven hypoglycemic subjects IR number per cell (red blood cell) was increased significantly after 6 weeks but not 12 weeks of Cr treatment 82 . Other studies, including rat studies, have failed to observe any effects on IR number (e.g., 83 but see 84 on statistical analysis of the data).

The burden of diabetes

Type 2 diabetes is a complex chronic disease with increasing microvascular and macrovascular complications imposing a significant public health and economic burden 1 . Even though a number of efficacious treatments are available, suboptimal applications of these in clinical practice has led to gaps in diabetes prevention and management. Barriers for providers include time constraints, forgetfulness, a perception of patients as noncom-pliant, and inadequate knowledge of outcomes from clinical trials. Barriers for patients include inadequate comprehension of the gravity of the disease, little motivation toward prevention of diabetes and its complications, insufficient time, and lack of socioeconomic resources and support 2-4 . The prevalence of diabetes has increased by 61 from 1990 to 2001 with type 2 diabetes accounting for 95 of this increase 5 . The annual cost of the disease is estimated at 132 billion accounting for more than 10 of the United States healthcare expenditure....

Risk factors for diabetes

The increase in prevalence of type 2 diabetes is paralleled by the rising rate of obesity and metabolic syndrome. As body mass index (BMI) increases, the risk of developing type 2 diabetes increases correspondingly. The prevalence of type 2 diabetes is three to seven times higher in obese patients and is 20 times higher in those with a BMI greater 35 kg m2 than in those with a BMI between 18.5 and 24.9 kg m2 7-8 . This increased prevalence, however, may vary among ethnic groups. Obesity is a component of metabolic syndrome. The National Cholesterol Education Program Adult Treatment Panel (NECP-ATP III) defines metabolic syndrome using the objective clinical criteria given in Table 1 9 . Metabolic syndrome is defined as the presence of any three of the risk factors. The clustering of risk factors associated with this syndrome predicts development of manifest diabetes and cardiovascular disease. Hence, prevention of type 2 diabetes should aim to treat and prevent components of Fasting...

Interaction between angiotensin endothelium and insulin resistance

Insulin resistance is associated with metabolic syndrome, which increases the risk of adverse cardiovascular outcomes. There is definitive evidence that insulin resistance and endothelial dysfunction progress in parallel. As insulin resistance progresses to clinical metabolic syndrome, impaired glucose tolerance, and development of diabetes, there is a parallel track that leads from endothelial dysfunction to inflammation, with increased oxi-dative stress leading to overt atherosclerotic disease. Insulin resistance has been shown to interact with this parallel track of endothelial dysfunction through the accumulation of free fatty acids, proinflammatory adipokines, and TNF alpha 59 . In addition, increased oxidative stress, oxidation of LDL, the reduction of HDL, and the development of hypertension, hyperuricemia, and hy-perglycemia contribute to the mechanisms of underlying endothelial dysfunction in insulin resistance 51 . Because angiotensin II plays a significant role in...

Obesity and type 2 diabetes mellitus

The incidence and prevalence of overweight and obesity have increased dramatically in the United States during the last generation (4). Figure 1 shows the prevalence of obesity among US adult men and women, based on representative samples of the population, from 1960 to 2000. The prevalence of obesity doubled during this time, although the figure makes it clear that the increases have been mainly attributable to the period since 1980. In 2000, it was estimated that approximately 65 of the US population could be classified as overweight (BMI 25.0-29.9kg m2) or obese (BMI > 30kg m2). Obesity is the strongest risk factor for the development of type 2 diabetes mellitus, with the top decile of BMI in the population showing a 40-fold to 50fold increased risk compared with the lowest decile (4). Therefore, it is not surprising that the incidence of type 2 diabetes mellitus has been rising in concert with that of obesity. Data released by the National Institute of Diabetes and Digestive and...

Clinical studies of renin angiotensin aldosterone system inhibition and outcomes of insulin resistance

ACE inhibition with captopril improves insulin sensitivity 107 , in some cases allowing withdrawal of sulfonylurea and reduction of the insulin dose 108,109 . Hence, a few randomized trials have attempted to assess changes in insulin sensitivity comparing ACE inhibitor and placebo (Table 8) 110-117 . The results were heterogeneous, but the use of ARBs to assess insulin sensitivity seemed to show some promise, and these results were not quite as heterogeneous as those seen with ACE inhibitors. Of the seven studies shown in Table 9, five showed success in Prevention of type 2 diabetes mellitus by renal angiotensin aldosterone inhibition Prevention of type 2 diabetes mellitus by renal angiotensin aldosterone inhibition type 2 diabetes diabetes mellitus on insulin sensitivity in patients or type 2 diabetes Insulin insulin and type 2 diabetics 2 diabetics diabetics type 2 diabetics type 2 diabetics or persons with impaired glucose tolerance Definitions IVGTT, intravenous glucose tolerance...

Excessive production of very lowdensity lipoproteins vldls the primary lipid abnormality in the insulinresistant state

The primary metabolic abnormality associated with insulin-resistant states is overproduction of VLDLs. Because newly secreted VLDL particles are TG rich, the result is mild-to-moderate hypertriglyceridemia. If the overproduction of VLDLs is accompanied by other defects, such as Apo C-II deficiency (which reduces lipoprotein lipase activation), or a defect in the hepatic clearance of TG-rich Apo B-containing lipopro-teins, the result can be more severe hypertriglyceridemia (Fredrickson Types IV and V) and or mixed dyslipidemia, involving elevations in TG and LDL-C (Types IIB and III). Two features of the insulin-resistant state are centrally involved in the pathogenesis of VLDL overproduction elevated circulating levels of FFAs and hyperinsulinemia. It appears that both must be present to generate overproduction of VLDLs. For example, in subjects with normal insulin sensitivity, a glucose infusion will not only increase the plasma insulin concentration but also lower levels of FFAs and...

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).

Comprehensive cardiovascular risk reduction in diabetes mellitus

Although in the past the treatment of diabetes has focused on glycemic control, there is emerging evidence that therapy addressing the concurrent CV risk factors that frequently coexist in the diabetic patient is essential to provide comprehensive CV risk reduction. This approach has been strengthened by results from a number of randomized, controlled trials of intensive glycemic control that have failed to show a definite independent link between glycemic control and CV risk reduction. Because the risk of CV events is additive for various risk factors that are frequently present in diabetic patients (Fig. 6), treatment should address all of the CV risk factors in diabetic patients and should not be confined to glycemic control. Interventions addressing individual CV risk factors in diabetic patients can result in a 15 Goals for risk factor management in diabetes Goals for risk factor management in diabetes The Steno-2 Trial prospectively examined the benefits of multifactorial...

Prevention of Cardiovascular Outcomes in Type 2 Diabetes Mellitus Trials on the Horizon

ADivisions of Endocrinology and General Medicine and Clinical Epidemiology, Diabetes Care Center, University of North Carolina School of Medicine, CB 7110, 5039 Old Clinic Building, Chapel Hill, NC 27599-7110, USA bDalla,s Diabetes and Endocrine Center, 7777 Forest Lane, C-618, Dallas, TX 75230, USA cUniversity of Texas Southwestern Medical School, Dallas, TX, USA Type 2 diabetes mellitus is a clinical syndrome characterized by hyperglycemia in which early cardiovascular (CV) death is the predominant clinical outcome. In the last 20 years several clinical trials have demonstrated unequivocally techniques that reduce the risk for CV events in patients who have diabetes mellitus these studies form the basis for current guidelines regarding management of patients who have diabetes mellitus, specifically in the areas of lipid modification, blood pressure reduction, modulation of the renin-angiotensin system, antiplatelet therapy, and invasive revascu-larization procedures. Despite the...

Diabetes Mellitus And Arterial Hypertension Differentially Affect Macrophage Recruitment And Collateral Growth

Further indication of the restriction of macrophage involvement to the early prolif-erative phase of collateral development and the physiological importance of the late remodeling phase came from experiments investigating the influence of different risk factors, namely the metabolic syndrom and arterial hypertension on collateral growth 64 . We investigated at which level two prominent risk factors, diabetes mellitus type II and arterial hypertension, impair collateral formation and assessed proliferative index (PI BrdU infusion), macrophage accumulation (M0 ED 2 staining), collateral score (post-mortem angiography), collateral conductance (CC collateral flow pressure gradient under maximal vasodilatation) and effect of MCP-1 treatment one week after femoral artery occlusion in normotensive Zucker Fatty Diabetic (ZDF) rats and control animals (ZDL rats). Results were compared with those of ZDF and ZDL rats rendered hypertensive via the Goldblatt method. While diabetic animals showed...

Clinical studies on renin angiotensin aldosterone system inhibition and outcomes of new onset diabetes

ACE inhibitors and ARBs have been studied extensively in hypertension, congestive heart failure, coronary artery disease, and renal disease (Table 6). Both drugs consistently reduce risk of coronary events (particularly ACE inhibitors), stroke, and diabetic complications of microvascu-lar disease. In addition, secondary endpoints of some of these studies have suggested reduced incidence of new-onset diabetes. In the Heart Outcomes Prevention Evaluation (HOPE), the incidence of diabetes was 34 lower in the ramipril-treated group than in the group receiving placebo 29,96 . In the LIFE study comparing losartan with atenolol for treating hypertension with left ventricular hypertrophy, losartan was associated with a 25 reduction in new-onset diabetes compared with atenolol 33,98 . Even in the more recent Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, the incidence of new-onset diabetes was significantly lower in the lisinopril arm than in the chlorthalidone...

Aggregation behavior of insulin

Insulin is an example of a protein that has a quaternary structure (i.e., it normally exists in a self-associated form rather than as a monomer). Insulin exists as a monomer only at a very low concentration (< 0.1 M, 0.6 mg ml). At higher concentrations, insulin exists as a dimer. The dimers are believed to result from the hydrophobic association of the B23 to B28 regions on insulin monomers. In the presence of zinc ions and in the pH range 4.0 to 8.0, three dimers come together to form a hexamer. At concentrations of 2 mM and above, the hexamer is formed at neutral pH without the assistance of zinc ions. The insulin formulations on the market predominantly are either neutral solutions or suspensions of zinc insulin and exist primarily in hex-americ form104 insulin concentrations in blood are sufficiently low so that insulin circulates and brings about its biological effects as a monomer.105 However, there is no anomaly here because at low concentrations, insulin dissociates into...

Adultonset diabetes and chromium

The potential relationship between chromium excretion and insulin signaling raises questions about potential associations between chromium action and diabetes. Over 120 million people across the planet have been estimated to have diabetes mellitus, with approximately 16 million of these in the United States. Between 90 and 95 of the US cases are of type 2 diabetes (also called adult-onset or non-insulin dependent diabetes). Type 2 diabetes is the form responsible for the rapid increase in diabetes cases over the last few decades, and the number of cases are increasing rapidly, especially in third-world countries. Obesity is a risk factor for adult-onset diabetes, and the occurrence of the syndrome increases with age both the average age and rate of obesity are increasing in the United States. African Americans, American Indians, Hispanics, and Pacific Islanders are especially susceptible to the disease. Unlike juvenile diabetes, which is an autoimmune disorder, type 2 diabetes results...

Chromiumiii Diabetes And Insulin Response

Dietary trivalent chromium has been shown to play an important role in type 2 diabetes mellitus, gestational diabetes, steroid-induced diabetes, and glucose tolerance by providing significant beneficial effects on the insulin system, often enhancing insulin sensitivity and overcoming glucose intolerance. The relationship between Cr(III) and its effect on diabetes was determined by Davis and Vincent in 1997 in which chromium has been shown to bind to insulin receptor, thus resulting in the increase of tyrosine protein kinase activity 22 . Numerous clinical researches using dietary Cr(III) demonstrated significant beneficial effects on the insulin system. Anderson et al. in 1997 noted that chromium supplementation may prove to be a useful means to prevent or treat type 2 diabetes mellitus 23 . Several studies demonstrated that animals fed a chromium-deficient diet developed the earliest stage of diabetes, high blood insulin levels, which was reversed by adding chromium-rich foods 15, 24...

On Collateral Development In Diabetes Mellitus Dm Angiogenesis And Collateral Growth

By activating liberating growth factors (GFs) such as basic fibroblast GF (bFGF), vascular endothelial GF (VEGF) and insulin-like GF-1 (IGF-1), sequestered within ECM 4 . 1.1. Diabetes Mellitus and Vascular Pathology Diabetes mellitus (DM) is associated with an increased incidence of morbidity and mortality from atherosclerotic disease including CAD and PAD 9, 10 . The pathogenic influence of DM on the development and prognosis of CAD is well established. The risk of myocardial infarction (MI) increases and appears to be associated with hyperglycemia 11, 12 . The risk for the development of microvascular disease, however, was thought to occur only with more extreme hyperglycemia 13 . Furthermore, increased mortality following MI and stroke is associated with hyperglycemia and increased levels of glycosylated HbA1c correlated with higher incidence of another fatal MI and stroke 14 . Importantly, no clear threshold can be provided for the risk of developing macrovascular complications...

Evolution Of The Classification Of Diabetes

Over 2000 years ago two Indian physicians, Charaka and Sushruta1 were the first to recognise that diabetes is not a single disorder. Throughout history renowned scientists and physicians such as Galen, Avicenna, Paracelcus and Maimonides have made reference to diabetes2. During the eighteenth and nineteenth centuries a less clinically symptomatic variety of the disorder was again noted. It was identified by heavy glycosuria, often detected in later life and commonly associated with overweight rather than wasting. Under the present classification this would be regarded as type 2 diabetes. A huge step forward in understanding the aetiology of diabetes was achieved through the experiments by Josef von Mering and Oskar Minkowski which led to the theory of pancreatic diabetes and were published as 'Diabetes Mellitus After Extirpation of the Pancreas' in 1889. The discovery was made after removing the pancreas from a dog which, although it survived the experiment, began urinating on the...

Insulin In Pancreatic Diseases

Insulin is an anabolic hormone with powerful metabolic effects. It is synthesized by the beta cells of the islets of Langerhans as a single chain precursor called proinsulin. Insulin consists of 2 dissimilar polypeptide chains, an A chain with 21 amino acids and a B chain with 30 amino acids, which are linked by 2 disulfide bonds. Chain A and Chain B are derived from a 1-chain precursor, proinsulin. Proinsulin is converted to insulin by the enzymatic removal of a segment that connects the amino end of the A chain to the carboxyl end of the B chain. This segment is called the connecting C peptide.16-18 Like other growth factors, insulin uses phosphorylation and the resultant protein-protein interactions as essential tools to transmit and compartmentalize its signal. Insulin initiates its wide variety of growth and metabolic effects by binding to the insulin receptor. The insulin receptor belongs to the large family of growth factor receptors with intrinsic tyrosine kinase activity.18...

Evidence from lipid lowering trials in diabetes

Given the heterogeneity of lipoprotein and the complexity of lipoprotein metabolism in patients who have diabetes, the optimal approach for lipid management remains to be determined. Over the past 10 years, a variety of randomized, controlled trials with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) established the efficacy of these LDL-lowering agents in reducing cardiovascular outcomes. In four of these large trials (Scandinavian Simvastatin Survival Study 4S , Cholesterol and Recurrent Events CARE , Long-term Intervention with Pravastatin in Ischemic Disease LIPID , and Air Force Texas Coronary Atherosclerosis Prevention Study AF-CAPS TexCAPS ), subgroup analyses revealed similar coronary artery disease risk reductions in smaller numbers of diabetic patients compared with the general population. (Table 1) 15-21 . The most recent and largest trial (more than 20,000 subjects) was the Heart Protection Study (HPS) which randomized 5963 patients who had diabetes 22,23...

Is lifestyle modification adequate to prevent onset of diabetes

Metabolic syndrome carries with it the underlying pathophysiologic feature of insulin resistance with tissue resistance to insulin action, compensatory hyperinsulinemia, and excessive circulating free fatty acids 78,79 . In addition, cardiovascular risk factors of low HDL and high triglyceride levels, hypertension, and lack of physical activity have all been shown to be predictors of non-insulin-dependent diabetes 80 . The relationships between metabolic syndrome and cardiovascular mortality as well as chronic complications of type 2 diabetes have been well described 81,82 . Several studies have shown impaired glucose tolerance to be a predictor of progression to type 2 diabetes 8385 . In addition, in one study, adiponectin was an independent predictor of type 2 diabetes 86 . It follows, then, that aggressive intervention in patients with impaired glucose tolerance or metabolic syndrome would translate to diabetes prevention. In addition to the Da Qing study, the Finnish diabetes...

New Doctor for a Man with Diabetes and Hypertension

A recently retired 65-year-old African-American man with a 10-year history of type 2 diabetes mellitus (DM) moved to a new city to be near his grandchildren. He presented to his new primary care physician's office for routine evaluation. Over the preceding 12 months he had been making efforts to increase his physical activity with a daily 30-minute brisk walk. He had received extensive instruction regarding an optimal diet for diabetes, but he admitted to frequent indiscretions. He produced a diary of his self-monitored whole-blood glucose values that was incomplete, and indicated sporadically inadequate control, with most fasting values in the 100-125 mg dL range, but some above 160mg dL. His prior medical records indicated a history of microalbuminuria of 100mg day on several occasions. In addition to diabetes, other medical issues included chronic hypertension and gastroesophageal reflux disease. His daily medications were insulin, hydrochlorothiazide, enalapril, aspirin, and...

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...

Diabetes Mellitus

According to the 1988-1994 National Health and Nutrition Examination Survey III (NHANES III), the prevalence of diabetes is 1.8 times higher in Mexican Americans than in whites (20.3 vs. 11.2 ) (Harris et al. 1998a). The influence of indigenous and African admixture has been hypothesized as accounting for the disproportionate rate of diabetes among Latinos. Rates of diabetes in Mexican Americans have increased 17 since the 1982-1984 Hispanic Health and Nutrition Examination Survey (HHANES) (Harris et al. 1998a). These findings are consistent with data from the Behavioral Risk Factor Surveillance System (BRFSS) for 1990-1998, which reflect a 38 increase in the prevalence of diabetes among Latinos (Mokdad et al. 2000). The age-and sex-standardized prevalence of undiagnosed diabetes also was higher in Mexican Americans than in whites (4.2 vs. 2.5 ) (Harris et al. 1998a). A major problem that contributes to excess morbidity and secondary complications due to diabetes in Latinos is their...

Insulin

Local insulin in the pancreas appears to be important for hormonal actions of secretin and CCK. It has been shown in rats that upon immunoneu-tralization of endogenous insulin, postprandial PES is impeded and the physiological doses of secretin and CCK are unable to stimulate PES.16 Similar effects of immunoneutralization of insulin have been observed in isolated and perfused rat and dog pancreata suggesting that insulin plays a local regulatory role. It is likely that endogenous insulin plays a permissive role for the actions of secretin and CCK (Section 6.17). For additional information, see Chapter 13 and Chapter 14.

Type 2 Diabetes

Representing as it does the majority of people with diabetes worldwide, type 2 diabetes is unfortunately the least satisfactory of the classifications. This reflects the fact that there are likely to be many aetiological and patho-physiological routes to developing a condition of sustained, survivable hyperglycaemia. How are we likely to make progress in further dissecting this large group into clinically relevant aetiological subgroups 1. Further definition of specific types. It is possible that, lurking among the type 2 diabetic population, are a number of as yet unrecognised single-gene syndromes. As the genetic effort to identify such monogenic diseases intensifies, some such conditions will emerge9. While they may be important, they are unlikely to represent a large proportion of people with what we currently call type 2 diabetes. 2. Classification on pathophysiology. As we gain more insight into the pathophysiological features of type 2 diabetes, we may achieve a meaningful...

Type 1 Diabetes

The relevance of further sub-classifying type 1 diabetes may appear less immediately apparent than for type 2. After all, once total beta-cell destruction has occurred then insulin replacement therapy will have to be used irrespective of the cause. However, certain genetic sub-types may be at much higher risk of other autoimmune diseases or complications, for example, and the identification of these at an early stage would be highly relevant. The real importance of sub-phenotyping in type 1 diabetes will be in the research effort to identify at risk and presymptomatic individuals and to intervene in their autoimmune

Insulin sensitizers

Although available internationally for decades, metformin, a biguanide, was not released in the United States until 1995 73 . An earlier bigua-nide, phenformin, was removed from the market in the 1970s because of an association with lactic acidosis 74 . In contrast to the sulfonylureas, metformin does not stimulate insulin secretion 75,76 . Metformin is the only biguanide that is available for clinical use (Box 2). Its efficacy as monotherapy and in combination with other agents is well-established 73 . Metformin is the only drug that has been shown to decrease cardiovascular events in patients who have type 2 diabetes mellitus independent of glycemic control 11 . Although metformin has a small effect as a peripheral insulin sensitizer, its main mechanism is inhibiting hepatic gluconeogenesis. Nevertheless, metformin treatment decreases plasma

Diabetes

Diabetes has long been recognized as a major risk factor for heart disease, but we now have evidence that an otherwise-healthy middle-aged individual with diabetes is just as likely to have a first heart attack as a nondiabetic person who has already suffered a heart attack is to have a second coronary event. Because we have always treated individuals who have had a previous heart attack very aggressively because this is one of the biggest predictors of future coronary events we have begun to do the same thing in our diabetic patients. To put some specific numbers to the magnitude of this risk, research has shown that people with diabetes have a 15 percent to 25 percent chance of developing serious heart problems over a ten-year period. Even more sobering, a person with diabetes who has a heart attack is twice as likely to die from it as a person without diabetes would be. Two-thirds of people with diabetes die of some form of heart or blood vessel disease. Although there's a genetic...

Insulin Signaling

From the appearance of insulin in the bloodstream, the insulin signaling pathway begins with the binding of insulin to the extracellular a-subunits of the transmembrane protein insulin receptor (Fig. 1). Insulin receptor consists of two extracellular a-subunits and two transmembrane j8-subunits. This binding of insulin turns the receptor into an Fig. 1. Insulin signaling pathway. autokinase, phosphorylating itself at three tyrosine residues (1158, 1162, and 1663 following the human sequence) of the j8-subunit. This conversion turns the receptor into an active kinase catalytically phosphorylating tyrosine residues of several substrate proteins. Known substrates include the insulin receptor substrate proteins (IRS), Shc, Gab-1, and others. These proteins in turn recruit other proteins inside the cell, which possess phosphotyrosine-binding domains (SH2 and PTB domains), forming signaling centers. These adapter molecules include PI3K (phosphatidylinositol 3-kinase) and Grb2. Association...

Functions of insulin

Prior to summarizing the influence of IR on lipid metabolism, it is instructive to briefly review some of the functions insulin plays in its role as the master metabolic hormone. Insulin has a number of actions beyond the promotion of cellular uptake of glucose. It suppresses hepatic gluconeogenesis and shifts the metabolic state of tissues (particularly skeletal muscle) toward the oxidation and storage (as glycogen) of energy from carbohydrate. At the same time, insulin suppresses the activity of hormone-sensitive lipase. This, in turn, reduces the release of free fatty acids (FFAs) from adipose tissues into the circulation and thereby lowers the availability of FFAs as a substrate for oxidation. Insulin also stimulates lipoprotein and hepatic lipases, enhancing the hydrolysis of TGs in circulating lipoproteins and allowing their FFAs to move into cells. In the liver, insulin stimulates the breakdown of apolipoprotein (Apo) B. Not all of the actions of insulin may be impaired to the...

If You Have Diabetes

The fight for a healthy heart is even more important for people with diabetes than it is for people without. According to the American Diabetes Association, over a ten-year period, people with diabetes have a 15 percent to 25 percent chance of developing heart problems, and more than 65 percent of people with diabetes die from heart disease or stroke. Experts don't fully understand why diabetes causes cardiovascular disease, but it's clear that people with diabetes especially type 2 diabetes often have various heart disease risk factors, such as high cholesterol, high blood pressure, high triglycerides, and obesity. Diabetes also tips the balance of good and bad cholesterols in an unhealthy direction. Most diabetics have low HDL and high triglyceride levels and many have LDL levels above the current 100 mg dL target goal. The high blood sugar associated with diabetes may have another negative affect on cholesterol it may be responsible for accelerating the chemical change known as...

Diabetes Issues

American Diabetes Association (ADA) (800) DIABETES (342-2383) diabetes.org The American Diabetes Association is a nonprofit health organization providing diabetes research, information, and advocacy. It conducts programs in all fifty states and the District of Columbia. The ADA's mission is to prevent and cure diabetes and to help improve the lives of those affected by the disease.

Insulin Factories

Insulin, the diabetes-treating hormone, is now mass-manufactured from transgenic bacteria that have been engineered to carry and express the human insulin gene. The human insulin saga is of historical interest because it provides one of the first success stories in genetic engineering and also illustrates the broader trials and tribulations of the neophyte GM enterprise. In the spring of 1976, in Indianapolis, the pharmaceutical giant Eli Lilly convened a national scientific symposium about insulin. For decades, Lilly had purified this pancreatic protein, for human therapeutic purposes, from slaughtered cattle and pigs. When administered by injection, animal insulin enables diabetics to metabolize sugars that otherwise accumulate in their bodies at debilitating and sometimes fatal levels. Lilly had done well in the insulin trade, tallying about 160 million in annual sales to a market of more than 1 million insulin-dependent diabetic sufferers in the United States alone. But Lilly's...

Strategy and Selection of Drug Therapy139

The coexistence of hypertension and diabetes dramatically and synergistically increases the risk of microvascular and macrovascular complications. Overwhelming evidence supports aggressive treatment of hypertension in diabetic patients. Tight blood pressure control is cost-effective and is more rewarding than glycemic control. The optimal goal of blood pressure control in diabetics should be 130 80 mm Hg. In subjects who have diabetes and renal insufficiency, the blood pressure should be lowered to 125 75 mm Hg to delay the progression of renal failure. The choice of an antihypertensive agent should be based on proven effects on morbidity and mortality rather than on surrogate parameters, such as lipid or glucose. Limited data suggest that an angiotensin-converting enzyme (ACE) inhibitor is the agent of choice, especially in those who have proteinuria or renal insufficiency. b-Blockers can be the first-line agent in diabetics who have coronary heart disease. Thiazide diuretics and...

The Role of Intensive Glycemic Control in the Management of Patients who have Acute Myocardial Infarction

Individuals who have diabetes mellitus (DM) have a twofold to fourfold increased risk of cardiovascular disease and nearly twice the early mortality from acute myocardial infarction (AMI) compared with nondiabetic subjects 1-5 . Furthermore, the mortality difference between diabetics and nondiabetics continues to increase throughout the first year 4 . For more than 70 years it has been recognized that glucosuria is present frequently in nondiabetic patients who have AMI 6 . Acute hyperglycemia is documented in up to half of all patients who have AMI, whereas previously diagnosed DM is present in only 20 to 25 of these patients 7,8 . Elevated plasma glucose and glycated hemoglobin levels at admission are recognized as independent prognosticators of in-hospital and long-term cardiovascular events in diabetics and nondiabetics who have AMI 8-12 . Acute hyperglycemia is associated with an approximate fourfold risk of death with AMI in nondiabetics compared with a nearly twofold increased...

Bimodal Glucose Distribution As A Determinant Of Diagnostic Threshold

The 2 h cut-point originates from the shape of the distribution of 2 h glucose in various populations and the shape of the risk curve relating 2 h glucose to the microvascular complications of diabetes. In certain high risk populations, 11.1 mmol l was found to the point separating two components of the bimodal population distribution of 2 h PG values16,17,18. In addition, in several studies, the prevalence of diabetes-related microvascular disease was found to sharply increase above 2 h PG levels of around 11.1 mmol l and similarly at fasting plasma glucose levels of 7.8 mmol l19. Based on the chosen 2 h PG thresholds of 11.1 mmol l and 7.8 mmol l FPG, an enormous body of clinical and epidemiological data was then collected. Newer data in lower risk populations did not demonstrate bimodality. In these populations, glucose values were more normally distributed, making it difficult to identify a threshold separating those individuals who are at substantially increased risk for some...

Intracellular calcium levels Decrease myocardial apoptosis post reperfusion

Experimental data also support a direct cardioprotective effect of insulin 35-36 . Experimental GIK infusion was equally effective in reducing infarct size when given throughout the entire ischemia reperfusion cycle or only during reperfusion 37 . Subsequently, insulin attenuated myo-cardial apoptosis that was associated with reperfusion 38 . Additionally, some of the benefit that was seen in recent trials of insulin therapy in AMI in diabetic subjects may have been due to the withdrawal of sulfonylurea therapy. Although controversial, sulfonylureas block ATP-sensitive potassium channels and may impair ischemic preconditioning and coronary vasodilation and increase mortality in AMI 39-40 . Analogous to the setting of AMI, hyperglyce-mia in critically-ill subjects is associated with increased complications 41 . Aggressive insulin therapy and control of hyperglycemia also improves outcomes in critically-ill patients in whom withdrawal of sulfonylureas was not a significant factor 42 ....

Urine Glucose Measurement

Perhaps the first diagnostic test for diabetes was described in ancient China with the observation that ants were attracted to the urine of persons with diabetes. The London physician Thomas Willis (1621-1675) noted that diabetic urine tasted 'wondrous sweet' and in 1766 another Englishman, Matthew Dobson, demonstrated the chemical presence of sugar in diabetic urine and observed that serum from diabetics was sweet-tasting. By the 1840s, such chemical tests as Fehling's were developed for sugar in urine. Benedict's urine test was described in 1911 and for many decades remained the mainstay for assessing control of diabetes. Few studies have examined the properties of random blood glucose (measured by reflectance meter in both studies) in relation to other means of diabetes testing (Table 2.4). In these two studies an OGTT was performed in the whole population irrespective of the random glucose value obtained. In order to achieve a sensitivity of 80-90 , the specificity of a random...

Oral Glucose Tolerance Test

The oral glucose tolerance test (OGTT) has for many years been the accepted standard for the diagnosis of diabetes. It is, however, time consuming and inconvenient requiring considerable preparation. Many would therefore regard it as unsuitable for widespread use among people with risk factors for diabetes. Unless conducted in the inpatient setting, the recent dietary intake and duration of the pre-test fast cannot be standardised in the way the protocol demands, and these factors can affect the results54,55. Paired OGTTs performed two to six weeks apart have shown that among people who are diagnosed as having diabetes in an initial OGTT, 95 of values in the second OGTT lie within 20 of the initial fasting glucose and 36 of the initial 2 h glucose56. A new intermediate group of individuals whose glucose levels, although not meeting criteria for diabetes, are too high to be considered normal was established based on fasting blood glucose measurement and called impaired fasting glucose....

Effect of glycemic control on cardiovascular disease

Improved blood glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unclear. This is particularly true when older medications are used to treat hyperglycemia. Previously, there was concern that sulfonylureas may increase cardiovascular mortality in patients who have type 2 diabetes mellitus and that high insulin concentrations may enhance atheroma formation. In the UKPDS trial, however, the effects of intensive blood glucose control, with either sulfo-nylurea or insulin and conventional treatment, on the risk of microvascular and macrovascular complications in patients who had type 2 diabetes A previous study that was performed in the 1970s, the University Group Diabetes Program (UGDP), concluded that tolbutamide treatment may increase cardiovascular mortality. Criticism of the methodology that was used in the study and the poor overall glycemic control that was achieved reduced the impact of the study. The large...

Hypoglycemia that is most likely to affect the elderly those who have worsening renal function and those who have

An early trial by the UGDP 23 , which explored the effectiveness of oral agents versus insulin, found increased cardiovascular mortality in the cohort of patients that was randomized to sulfonylureas. Widespread criticism of the project's methodology placed the validity of its findings in doubt 24 . Nevertheless, concern about cardiovascular risk remains and the package insert for sulfonylureas that is mandated by the US Food and Drug Administration includes a warning about possible cardiovascular risks. In addition, a retrospective analysis of patients who had diabetes mellitus and underwent balloon angioplasty after myocardial infarction reported increased early mortality (odds ratio 2.7 after adjustment for several covariates) in 67 persons who took sulfonylureas and in 118 who used insulin or lifestyle therapy alone 31 . This phenomenon was shown experimentally to limit anginal pain, minimize irreversible tissue injury, and protect myocardial function. KATP channels in myocardial...

Sometimes requires discontinuation Contraindicated in active hepatic renal and coronary artery disease

Insulin levels and corrects many of the nontradi-tional risk factors that are associated with the insulin resistance syndrome 77 . In the UKPDS, treatment with metformin (another drug that decreases hyperinsulinemia and insulin resistance) produced greater reduction in cardiovascular disease events and mortality than sulfonylureas and insulin 8 . The latter drugs decreased blood glucose level to a similar degree as metformin but did not decrease plasma insulin concentrations. This effect may have been mediated through a decrease in insulin resistance, although other effects of metformin, such as improvement in lipid profile, improved fibrinoly-sis, and prevention of weight gain, may be important 8 . Metformin has a favorable, albeit modest, effect on plasma lipids, particularly in decreasing triglycerides and low-density lipopro-tein (LDL) cholesterol however, it had little, if any, effect on HDL cholesterol levels 78 . Met-formin use was associated with decreased plas-minogen...

What is the optimal target blood pressure

JNC VII 19 recommends the target BP to be less than 130 85 mm Hg in diabetics who have hypertension. The ADA 22 and the CMA 23 have pushed the target even lower, with a goal for diastolic BP of less than 80 mm Hg. What is the evidence for these recommendations Three, randomized, actively-controlled trials provided some direct evidence regarding the need for aggressive BP control (see Table 4) 3,52,75 . The intensive BP control in UKPDS 38 3 trial was achieved at a target of 144 82 mm Hg. Compared with conventional control (BP 154 87 mm Hg), there was a 32 , 44 , and 37 reduction of diabetes-related death, stroke, and microvascular complications, respectively. For a 10 mm Hg greater reduction in systolic BP, there was a significantly greater reduction in the risk of CV end points, including MI and heart failure. In the ABCD trial 75 , 470 patients who had type 2 diabetes with a baseline BP of approximately 155 98 mm Hg were assigned randomly to intensive BP control (achieved 132 78 mm...

Is Disease Prevention Possible

Although p-cell function can be preserved and extended beyond the time of diagnosis, there is little realistic hope of restoring normal metabolic function at this stage of the disease. it is therefore logical to attempt p-cell rescue at an earlier stage when the p-cell mass is largely intact. Work done over the past 25 years has transformed our understanding of the sequence of events culminating in immune-mediated p-cell failure, but the average diabetes specialist is still in the position of a nephrologist unable to identify renal dysfunction until his patients present for dialysis. Some 90-95 of children with type 1 diabetes have (HLA) human leukocyte antigen genotypes conferring susceptibility to the disease, but only around 5 of those with the highest risk combination will develop diabetes in childhood. Prospective studies have shown that islet autoantibodies typically appear within the first three years of life3, although this should not be taken as dogma, and the influence of...

Requirements To Prevent A Chronic Disease

As is further developed in Chapter 8 in relation to screening, several pieces of knowledge must be available in order to know if it is possible to prevent any chronic disorder, including diabetes. These include a knowledge of the natural history of diabetes (with a reasonably long pre-clinical phase of the natural history), an effective and simple screening test or tests for a high-risk state, and effective interventions that, if applied earlier in the pre-clinical phase, would prevent or delay the onset of the disease. The pre-clinical stages of the development of type 2 diabetes are well known. For many years it has been shown that glucose levels become elevated prior to the development of diabetes. This stage of the natural history has been called 'chemical diabetes', IGT24,25, or most recently IFG26. However, when fasting glucose begins to rise, this may be a pathophysiologically later stage than is IGT, which usually has elevations of post-challenge glucose as the first...

Selection Criteria For Studies

Studies are included if they were either randomized controlled trials (RCTs) or community-based trials, or if they were large, prospective epidemiological studies of sufficient rigor and generalizability to be useful. Some of the historically important studies in diabetes prevention do not meet these criteria for quality but they are mentioned for completeness, with comments about their design or conduct. The numerous clinical, ecological, cross-sectional and retrospective studies that have been conducted have been largely omitted, unless they provide the only evidence bearing on an issue.

Triglyceride and highdensity lipoprotein intervention

Unlike the plethora of trial evidence of CHD risk reduction with statins, the evidence from drugs to decrease triglycerides or increase HDL cholesterol is sparse. A meta-analysis of 17 observational studies suggested a significant relationship of triglycerides with CHD, even after adjustment for HDL cholesterol, especially in women 33 . In the 4S trial, in post hoc analyses, patients who had the lipid triad (elevated LDL, elevated triglyceride, decreased HDL cholesterol) had the highest event rates in the placebo arm and the greatest risk reduction with simvastatin 34 . Despite a mechanistic plausibility of increased risk with these lipid abnormalities in patients who had metabolic syndrome and diabetes, few long-term randomized trials have been completed (Table 2). In the Helsinki Heart Study, a primary prevention trial, a small subgroup of 135 patients who had diabetes achieved a 68 , but nonsignificant, decrease in CHD events with gemfibrozil over 5 years 35 . In the St. Mary's...

Lifestyle modifications and its effects on prevention

Multiple clinical trials have tested lifestyle modification to prevent type 2 diabetes. The inclusion criteria for all trials were impaired glucose tolerance based on two blood glucose measurements a fasting value of less than 126 mg dL, and a glucose value of 140 to 200 mg dL 2 hours after consumption of 75 g of glucose. In the United Kingdom, Jarrett et al in the Borderline Diabetes Study and Keen et al in the Bedford Survey found no effect of dietary modification on preventing diabetes 12 . A Swedish study, however, found that diabetes counseling and tolbutamide reduced the incidence of diabetes, although intention-to-treat analysis was not performed 13 . More recently, the three studies of primary prevention that used lifestyle intervention have shown significant results. The Finnish Diabetes Prevention Study, the Da Qing Imaired Glucose Tolerance and Diabetes Study, and the Diabetes Prevention Program revealed that aggressive dietary intervention and an exercise program reduced...

The renin angiotensin aldosterone system as a therapeutic target

Studies on prevention of type 2 diabetes with life style modifications Finnish Diabetes Prevention Study 15 Da Qing Impaired Glucose Tolerance and Diabetes Study 14 Diabetes Prevention Program 16 Adjusted reduction in incidence of type 2 diabetes ( ) blocking the conversion of angiotensin I to angiotensin II and by catalyzing the breakdown of bradykinin, exert numerous beneficial effects that maintain blood pressure and salt and water homeostasis. In addition, the vasodilating, antiinflammatory, plaque-stabilizing, antithrombotic, and antiproliferative properties of ACE inhibitors produce salutary effects. Numerous studies have demonstrated a significant benefit with use of ACE inhibition. The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), the Studies on Left Ventricular Dysfunction (SOLVD) treatment and prevention study, and the Vasodilator-Heart Failure Trial II (V-HeFT II) demonstrated significant overall mortality reduction in patients with congestive heart...

Role of renin angiotensin aldosterone system activation

CHF, congestive heart failure CV, cardiovascular LVH, left ventricular hypertension IDNT, Irbesartan Diabetic Nephropathy Trial MI, myocardial CHF, congestive heart failure CV, cardiovascular LVH, left ventricular hypertension IDNT, Irbesartan Diabetic Nephropathy Trial MI, myocardial less well studied but seems to mediate beneficial effects that include vasodilation, inhibition of cell growth, and proliferation as well as cell differentiation 48,49 . The differential effects are shown in Fig. 1. The sequential progression of cardiovascular disease begins with the risk factors of hypertension, diabetes, smoking, metabolic syndrome, and dyslipidemia. These risk factors are independently associated with levels of angioten-sin II that in turn trigger the cascade of events. Progression to atherosclerotic disease and left ventricular hypertrophy leads to plaque destabili-zation in the face of uncontrolled risk factors, with acute coronary syndrome and myocardial infarction as the sequelae...

Role of the renin angiotensin aldosterone system in vascular endothelial function

Angiotensin II and the sequential progression of cardiovascular disease. CAD, coronary artery disease DM, diabetes mellitus HTN, hypertension LVH, left ventricular hypertrophy. Fig. 2. Angiotensin II and the sequential progression of cardiovascular disease. CAD, coronary artery disease DM, diabetes mellitus HTN, hypertension LVH, left ventricular hypertrophy.

Improvement of endothelial function

Endothelial dysfunction leads to defects in insulin-mediated glucose uptake. Blockade of vascular nitric oxide synthesis with L-arginine analogue also impairs endothelial dependent va-sodilation. Endothelial function improves with exercise, a low-fat, low-carbohydrate diet, and with use of statins and ACE inhibitors (Table 5) 29,59,67 . Angiotensin I blockade has not shown any improvement of endothelial dysfunction, but benefit has been noted with peroxisome pro-liferator activated receptor gamma (PPAR-y) stimulator, antioxidants, hormone replacement therapy, and L-arginine 66,68,69 . In addition, the ACE inhibitor quinapril significantly improved endothelial function in multiple studies, both in normotensive volunteers and in subjects with coronary artery disease 70-77 .

Clinical studies nonrandomized

Odea conducted a pre-post evaluation of 14 Australian Aborigines (10 with diabetes, four normal) who lived in an urban environment and were willing to return to a hunter-gatherer lifestyle in their ancestral homelands for seven weeks73. After metabolic evaluation, the subjects and study team travelled into remote northwestern Australia and ate nothing that they did not hunt or gather directly for most of the period. Two environments (one inland and one coastal) provided some variation in intake. On average, 64 of energy intake was from animal sources. It was very low in fat (13 ), with approximately 33 carbohydrate and 54 protein. This represented a marked change from the pre-test urban diets, which averaged 50 carbohydrate, 40 fat and 10 protein. Once in the bush, only about 1200 Kcal person day was ingested, resulting in an average loss of 1.2 kg week (total -8.1 kg) in subjects with diabetes. Upon return to an urban setting, metabolic measurements were repeated. Marked improvements...

Communitybased studies of lifestyle change

A different approach to diabetes prevention has been attempted in small numbers of studies in adults and children. These studies have focused on community-, church- or school-based interventions aimed at improving cardiovascular (CV) and diabetes risk factors. Such studies are difficult to evaluate using the usual RCT paradigm since randomization is often not feasible or is not at the individual level (e.g. schools or classrooms may be the unit of Ramaiya et al. reported a six-year follow-up of a community health education program among a Hindu Indian subcommunity from Dar Es Salaam, Tan-zania81. Using a pre-post design, this program resulted in a decrease in diabetes prevalence from 11.8 to 8.2 , and IGT prevalence was said to decrease from 26.5 to 10 . Small significant reductions in fasting and 2 h glucose levels, lipids, BP and weight were noted, along with an increase in physical activity. The senior author has indicated that only the abstract has been published and no follow-up...

Prospective observational epidemiological studies

Table 6.4 summarizes the published prospective epidemiological studies of physical activity and development of type 2 diabetes. In each case, the adjustment variables are noted, but less detail is given about individual studies than in Table 6.3 since they provide somewhat weaker evidence for prevention than RCTs. This is primarily true because any one factor cannot be varied independently of others which may also be associated with altered risk. ciations between physical activity and glucose levels, with one showing a strong genetic effect101, while the other did not102. Regardless of this concern, prospective studies still provide some of the strongest data suggesting that higher levels of physical activity may protect against type 2 diabetes. One of the earliest studies to explore the role of physical activity was published by Medalie and colleagues from the Israeli Ischemic Heart Disease Project103. They did not show detailed results, but noted no association of five-year clinical...

Percutaneous coronary intervention versus bypass surgery as revascularization modality

The Bypass Angioplasty Revascularization Investigation (BARI), reported that in diabetic patients who had symptomatic multi-vessel disease, CABG resulted in a significantly better outcome compared with PCI at 5 years 5 and at 7 years 6 . Among treated diabetic patients, 5-year survival was 80.6 for the CABG group and 65.5 for the percutaneous transluminal coronary angioplasty (PTCA) group (P 0.003). The benefit was confined largely to patients who had more severe multi-vessel disease and those who received left internal mammary artery (LIMA) bypass grafts no benefit was seen in patients who received only saphenous vein grafts. In the BARI registry, with revascularization modality primarily based on physician judgement, the all-cause mortality was 14.4 for PTCA versus 14.9 for CABG (P 0.86 relative risk RR 1.10), with corresponding cardiac mortality rates of 7.5 and 6.0 , respectively (P 0.73 RR 1.07) 7 . The higher mortality with PCI in diabetics was confirmed in the 8-year follow-up...

Comprehensive Risk Reduction of Cardiovascular Risk Factors in the Diabetic Patient An Integrated Approach

The Egyptians recognized diabetes as a pathologic entity nearly 3500 years ago. It was noted to be a rare condition but was known to reduce longevity. The condition now defined as type 2 diabetes is seen worldwide and has reached epidemic proportions. By the year 2025, the number of individuals with diabetes mellitus in the world is expected to exceed 300 million with a prevalence of 5.4 1 . Diabetes continues to affect a substantial proportion of adults in the United States. Data from the National Health and Nutrition Enhancement Survey 1999-2000 indicate that 8.3 of persons over the age of 20 years have either diagnosed or undiagnosed diabetes, and this percentage increases to 19.2 for persons aged more than 60 years in the United States. Men and women are affected similarly by diabetes 2 . In 1999-2000, an additional 6.1 of adults had impaired fasting glucose tolerance, increasing to 14.4 for persons aged more than 60 years and with a greater incidence in men than in women 3 ....

Pharmacological studies

Pharmacological interventions to prevent diabetes or its complications early in the natural history have been published since the 1960s180. The rationale for Reviews of the use of such agents have been published10,180-182. Early trials were often aimed at subjects with 'chemical diabetes', considered to be 'early diabetes' by older criteria. Such studies often included a majority of people with what would now be considered IGT, and thus are reasonably relevant to a review of primary prevention. Agents available in the 1960s included firstgeneration sulfonylureas and biguanides. Similar to lifestyle studies, criteria for outcomes varied and were a mixture of glucose tolerance, fasting glucose and other end-points. Table 6.7 summarizes the RCTs that have been published.

Altered calcium and magnesium homeostasis

The details of these various coagulation pathway abnormalities have been extensively covered in a recent paper by Sobel 54 . The authors of this article believe it is important to emphasize the role of platelet dysfunction in the setting of diabetes mellitus with a view toward practical implications of antiplatelet therapy. Multiple biochemical and functional abnormalities in the platelet function have been documented in type 1 and type 2 diabetes and are noted in Box 1. Together these abnormalities lead to increased platelet aggregability and adhesiveness. The correction of this increased platelet aggregability and adhesiveness with antiplatelet agents such as aspirin should logically reduce CV events in diabetics. Although there are no prospective studies designed for investigating the therapeutic role of aspirin in the diabetic cohort, several lines of evidence support its use in reducing CV risk in diabetic patients. In the recently completed Primary Prevention Project study,...

Current state of affairs and future directions

Although the wisdom of addressing multiple risk factors seems to be intuitively obvious, this approach is not what transpires in practice. Data from National Health and Nutrition Enhancement Survey 1999-2000 reveal that only 37 of adults with diagnosed diabetes in the United States are achieving the ADA goal of glycosylated hemoglobin levels less than 7 44 . In addition, 37 of adults with diagnosed diabetes have glycosylated hemoglobin levels greater than 8 . Only 36 of individuals with diabetes have achieved the current goals for blood pressure set in the JNC 7. More than half the individuals with diagnosed diabetes have cholesterol levels above 200 mg dL. Thus, there is great room for improvement in the provision of diabetes care and education to capitalize on knowledge currently available. A systematic approach to the treatment of diabetes that addresses multiple risk factors is needed. The increased awareness of the importance of controlling risk factors for vascular disease among...

Biguanides including combinations

Papoz and colleagues at the Hotel Dieu, Paris conducted a randomized, doubleblind trial of a sulfonylurea (S) (glibenclamide, 2 mg twice daily), biguanide (B) (dimethylbiguanide, 0.85 g twice daily), alone and in combination (S+B) in a 2 X 2 factorial design with placebo202. Men aged 25-55 years (x 45 yrs) who had borderline glucose tolerance (most would have IGT by current criteria) were randomized from 1969 to 1971 and tested for glucose and insulin levels every six months for two years. There were 28 drop-outs, with similar levels across treatment groups. At two years, there were no significant differences in glucose or insulin levels in any group, though B, S+B and placebo groups all lost about 4 kg of weight, more than the 2 kg in the S group. Worsening to diabetes was not reported. The trial could have detected as significant drop of 21 mg dl (1.2 mmol L) in 2 h glucose with 95 power, though actual differences were very small (0-2 mg dl, 0-0.1 mmol L) between groups. This study...

Trials examining glycemic management techniques

The second fundamental question in diabetes management is whether particular glucose-lowering approaches, and more specifically insulin sensitizers, provide benefits beyond glucose lowering in managing CV risk. The possibility first was suggested based on the notion that insulin resistance is linked epidemiologically with components of the metabolic syndrome including dyslipidemia, dysglycemia, hypertension, a procoagulant state, vascular inflammation, endothe-lial dysfunction, and premature vascular disease 13,14 . Several small and medium-sized studies have supported the idea that insulin-sensitizing approaches could be superior to approaches that supplement deficient insulin secretion, suggesting improvements in markers of CV risk during treatment with metformin and thiazolidinediones when compared with other therapies. Furthermore, in the UKPDS, among overweight subjects, those randomly assigned to initial therapy with metformin (but not to insulin or sulfonylurea) demonstrated a...

Studies examining nonglycemic therapies

This leaves questions regarding the appropriate management of the patient who has diabetes mellitus and flow-limiting coronary disease. Two trials will explore these issues robustly. The BARI 2D trial will explore whether intensive medical management or intensive medical management plus bypass surgery or PCI improves survival in patients who have type 2 diabetes mellitus 15,16 . The FREEDOM trial (Future Revascularization Evaluation in Patients with Diabetes Mellitus Optimal Management of Multivessel Disease) will compare CABG to PCI using the drug-eluting stents in diabetic patients who have multivessel disease, following the patients for 5 years to examine mortality as the primary endpoint. Investigators at 100 sites will recruit 2300 patients who have diabetes mellitus and at least two stenotic lesions in at least two major epicardial coronary arteries amenable to either PCI or surgical revascularization over 18 months. Intermediate endpoints, quality of life, neurocogni-tive...

Pharmacological trials

A three-year primary prevention study is underway in Hoorn, the Netherlands, also using acarbose among 150 subjects with IGT. After screening of potentially eligible subjects, those who have a mean of two fasting plasma glucose levels < 7.8 mmol l (140 mg dl) and the mean of two 2 h post-load glucoses > 8.6 - < 11.1 mmol l (> 155.0 - < 200 mg dl) have been randomized to either 50 mg of acarbose three times a day or placebo. Subjects will have three-monthly fasting glucose levels, and an OGTT at 1.5 and three years for the primary endpoint of type 2 diabetes. A useful addition to this small trial is the performance of a hyperglycemic clamp at randomization and at three years to assess insulin resistance. Completion is expected in 2002. Table 6.8. Primary prevention trials for type 2 diabetes mellitus underway as of 2002.

Prevention Strategies

Type 2 diabetes has multiple risk factors and, at the current state of knowledge, is regarded as a heterogeneous disorder. Given these facts, interventions can be targeted at the multiple risk factors, either in the entire population or in high-risk subjects, perhaps using both approaches. Tuomilehto and colleagues have succinctly summarized these approaches6. Given the widespread and increasing prevalence of obesity in the USA and other countries274,275, a population-based strategy to reduce obesity is likely to lead to widespread benefits for diabetes and related disorders. A high-risk strategy involves identification of persons with levels of pre-diabetic risk factors that place them at high risk to develop diabetes in the near future6. This is the approach that was taken in all of the larger clinical trials recently completed. These studies have identified persons with IFG or postchallenge glucose levels characteristic of IGT, obesity, family history of diabetes, history of...

Prevention Of Obesity

Studies that aim to reduce obesity or prevent it from developing are relevant to the prevention of type 2 diabetes, since obesity is one of the major modifiable risk factors. Like diabetes, overweight and obesity have been the outcomes for a large number of clinical trials and observational studies exploring risk factors for their development and reduction. Comprehensive reviews of is not possible to review them here. The interventions studied have been similar to those for type 2 diabetes, and have focused on lifestyle modification as well the use of selected pharmacological agents that may reduce weight. No large RCTs have investigated the prevention of obesity (in contrast to obesity reduction) as it relates to type 2 diabetes. Several community-based cardiovascular prevention studies have included obesity as one of several outcomes, often with limited success265-267. However, hypertension prevention trials with individual, rather community interventions, have often used weight...

No of antihypertensive agents Trial Target BP mm Hg 1234

Multiple antihypertensive agents are needed to achieve target blood pressure. BP, blood pressure DBP, diastolic blood pressure MAP, mean arterial pressure SBP, systolic blood pressure. (Adapted from Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes a consensus approach. Am J Kidney Dis 2000 36(3) 646-61 with permission.) Fig. 4. Multiple antihypertensive agents are needed to achieve target blood pressure. BP, blood pressure DBP, diastolic blood pressure MAP, mean arterial pressure SBP, systolic blood pressure. (Adapted from Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes a consensus approach. Am J Kidney Dis 2000 36(3) 646-61 with permission.) improves renal outcomes in patients with type 2 diabetes and nephropathy over and above the improvement attributable to blood pressure control alone. The renoprotective effect of losartan corresponded to an average delay...

Individual drug review

Angiotensin-converting-enzyme (ACE) inhibitors are the initial drug choice for patients who have diabetes and hypertension, especially those who have albuminuria. Although initially recommended based on a small set of data, several recent RCTs clearly support the use of ACE inhibitors based on their favorable impact on CV and renal outcomes. inhibitors also reduce insulin resistance. ACE inhibitors decreased the incidence of new-onset diabetes mellitus in the Captopril Prevention Project (CAPPP) 26 and the Heart Outcomes Prevention Evaluation (HOPE) 27 studies. This is believed to occur secondary to improved insulin sensitivity, which also might result in better glycemic control in diabetic patients 28,29 . No large, randomized, placebo-controlled trial involved only diabetic patients with ACE inhibitors. Nevertheless, the benefit of ACE inhibitors in diabetic patients who had hypertension was well-illustrated in the HOPE trial. In the HOPE 27,30 study, 56 of the subjects were...

Clinical nonrandomized studies

At 1 and 2 years, no weight loss occurred in either group. In the analysis, they stratified subjects by level of insulin response to an IVGTT. However, no real differences were seen across these groups. There was a small improvement in glucose tolerance in the low insulin responders, but no changes in fasting or 2 h glucose levels at two years. This study did not find a beneficial effect of sulfonylurea on insulin secretion or glucose tolerance, though the study groups were small. Without randomization or adjustment for baseline differences between groups, it appears that this study, like others conducted in the same period187,195,202, provides limited evidence of benefit for sulfonylureas in prevention or improvement of glucose tolerance. One study which used chlorpropamide did not use controls203 and is not included. consistent with the prior studies, given their wide confidence intervals. The six-year follow-up of the FHS-II200 does not support an effect on diabetes incidence using...

Trials examining glycemic targets

The most hotly debated clinical questions in diabetes mellitus are whether glycemic control is associated with a reduction in CVD outcomes and how low a glycemic target should be pursued. Because the risk for severe hypoglycemia increases as lower targets are achieved, there is a floor below which benefits will be counterbalanced by risk. Guidelines suggest that hemoglobin A1c (HbAlc) targets of less than 7 3 , 6.5 4 , or 6.1 5 are appropriate. These goals have been imputed by examining epidemiologic studies because there are no CVD outcomes studies in diabetes mellitus that have provided clear-cut, statistically significant reductions in endpoints. Indeed, no reported interventional outcome study has yet achieved the above recommended A1c targets. The clinical trial that comes closest to meeting such criteria is the United Kingdom Prospective Diabetes Study (UKPDS) 6 , which suggests that the method of glucose lowering may be more important than the target or the average level of...

Evidence For Matching The Fpg Threshold With The 2 H Pg Threshold

The 1985 WHO criteria selected the fasting and 2 h cut-offs on estimates of the thresholds for microvascular disease. After reviewing the statistical relation between the FPG distribution and 2 h PG distribution, it became evident that these criteria effectively defined diabetes by the 2 h PG alone because the fasting and 2 h cut-point values were not equivalent at those levels. Almost all individuals with FPG greater than or equal to 7.8 mmol l have 2 h PG levels of 11.1 mmol l or above when given an OGTT. On the other hand, only about one-quarter of those with 2 h PG exceeding 11.1 mmol l (and without previously known diabetes) have FPG greater than 7.8 mmol l36. Thus, the cut-point of FPG 7.8 mmol l defined a greater degree of hyperglycaemia in comparison to the cut-point of 2 h PG 11.1 mmol l. Understandingly, this discrepancy is undesirable, and therefore the ADA Expert Committee investigated cut-point values for both tests which reflect a similar degree of hyperglycaemia and...

Significance and treatment of individual risk factors

The mechanism of the hypertriglyceridemia is understood to result from varying sensitivities to insulin in the tissues in the individual's body. Defects in the ability of insulin to mediate muscle use of glucose and to inhibit lipolysis in adipose tissues seem to be the primary abnormalities causing the insulin-resistant state 10 . The resistance at the level of the muscle and adipose tissue leads to persistently higher ambient levels of insulin and free fatty acids. In response to the higher levels of free fatty acid, the hepatic tissue increases the rate of conversion of free fatty acids to triglycerides. This increased conversion is accentuated by the normal insulin sensitivity of the hepatic tissues in the face of compensatory hyperinsulinemia. The appreciation of the differences in the insulin sensitivity of the various tissues has led to better understanding of the abnormalities caused by insulin resistance. Although the classical diabetic dyslipidemia...

Gayle Reiber

Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland, UK Division of Diabetes Translation, Mailstop K-10, 477 Buford Highway NE, Atlanta, GA 30341-3724, USA Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Diabetes and Lipid Research, 3512 Fifth Avenue, Pittsburgh, PA 15213, USA Division of Endocrinology, Diabetes and Metabolism, University of Miami, Chairman, NIDDK Type 1 Diabetes TrialNet, 1450 NW 10th Avenue - Suite 3061, Miami, Florida 33136, USA Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Department of Public Health, University of Helsinki, Mannerheimintie 166, 00300 Helsinki, Finland The Evidence Base for Diabetes Care. Edited by R. Williams, W. Herman, A.-L. Kinmonth and N. J. Wareham Copyright 2002 John Wiley & Sons, Ltd.

Disease

Cardiovascular (CV) complications are the leading cause of death and disability in patients with type II diabetes mellitus. As described in the November 2004 issue of the Cariology Clinics, it is important to recognize that vascular abnormalities and dysfunction begin in the prediabetic phase, which often precedes development of clinical signs and symptoms of diabetes by an average of 5 to 6 years. Although due emphasis has been placed on tight control ofblood glucose in diabetic patients during the past two decades, the management of other frequently associated coronary risk factors has not received as much attention. A large number of randomized clinical trials have now shown that aggressive management of most associated risk factors in particular hypertension and hyperlip-idemia in diabetic patients is associated with significant reduction of the risk of future CV events. As a matter of fact, beginning with the findings from the United Kingdom Prospective Diabetes studies, many of...

Mellitus

Diabetes has been linked to a number of other conditions including hypertension, obesity, dislipidaemia and coronary heart disease, and also to environmental factors such as physical activity and nutrition. To complicate the picture further, several genetic factors are thought to play a significant role in the predisposition to diabetes and its complications. With so many factors involved in the aetiology of this disease or disease group, it is not surprising that a single biomedical test, such as blood glucose, has not produced a definitive and precise threshold for diagnosis or prediction of the disease and its complications. As discussed above, throughout the history of diabetes classification various methods and cut-off values were employed as diagnostic of diabetes until the desire to conduct international comparisons encouraged the development of standardised diagnostic criteria. Such an approach has obvious merits for epidemiological studies, but can present the clinician with...

Summary

Hyperglycemia is associated with excess mortality in AMI and should be treated aggressively in the intensive care setting. The exact goal of therapy is unclear because different blood glucose targets were used in earlier studies (eg, 215 mg dL in DIGAMI versus 110 mg dL in the Belgian study of critically-ill patients). In the setting of AMI, it is prudent to avoid excessive hypoglyce-mia and, thus, more modest goals for blood glucose may be considered until more definitive data are present. Aggressive therapy with continuous infusion of insulin seems to improve a host of metabolic and physiologic effects that are associated with acute hyperglycemia and improves mortality in the acute setting. Aggressive glycemic control should be coupled with appropriate use of reperfusion therapies, glycoprotein IIb IIIa inhibitors, aspirin, b-blockers, ACE inhibitors, and antithrombotic agents. were not well-powered did not achieve aggressive, durable glycemic control and did not use...

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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