Home Remedies for Hyperglycemia

Blood Sugar Miracle

If you are one of the many people suffering from high blood sugar or diabetes, this is the solution that you have been looking for. This ebook from Duke Anderson can teach you how to reverse the symptoms that you are facing in less than 3 weeks from your OWN home! It doesn't have to be hard to help your blood sugar get to where it needs to be Don't make it any harder! This is the solution that you need to get your blood sugar under control. You don't have to undergo dangerous, expensive surgery, leave scars from needles, or spend huge amounts of money on pharm drugs that end up doing nothing for you. The blood sugar problems that you have are reversible and curable, if you know the methods to use! And you can learn those methods inside this book. This book will mean a lifestyle change for you!

Blood Sugar Miracle Summary


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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...

Intracellular calcium levels Decrease myocardial apoptosis post reperfusion

Therapy and control of hyperglycemia also improves outcomes in critically-ill patients in whom withdrawal of sulfonylureas was not a significant factor 42 . Continuous infusion of intravenous insulin to maintain a blood glucose level that was at or less than 110 mg dL reduced death, septicemia, and renal failure in a predominantly non-diabetic Belgian population of surgical patients who were mechanically-ventilated and critically ill. Aggressive glucose control also reduced complications in diabetic patients who were undergoing cardiac bypass surgery 43-44 and reduced target vessel revascularization in diabetics who were undergoing percutaneous revascularization 45 . Glycemic control also is associated with a decreased risk for congestive heart failure in DM 46 .

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

At least two underlying defects have been postulated in the pathogenesis of this condition. First, b-cell dysfunction and failure that lead to elevated glucose levels result in oxidative stress that causes increased cardiovascular morbidity. Second, insulin resistance, which is associated with endothelial dysfunction, inflammation, and abnormal fibrinolysis contributes to cardiovascular disease 6,7 . Most patients have both defects and the defects frequently are interrelated, in that hyperglycemia itself can lead to insulin resistance and insulin resistance can cause b-cell dysfunction. Fig. 1 illustrates these interactions and outlines a pathway between these defects and cardiovascular disease.

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 Many of the features of insulin resistance that are present before the onset of hyperglycemia remain operative during the natural history of the diabetes mellitus and contribute greatly to atherosclerosis and associated comorbidities 13,14 . Insulin resistance contributes to the development of atherosclerosis through...

DEXA dualenergy Xray absorptiometry

Diabetes mellitus An illness caused by decreased production of insulin or by decreased responsiveness of tissues to it. Insulin, produced by the pancreas, lowers blood glucose levels, and diabetes is characterized by high blood sugar levels. Type I diabetes, also called insulin-dependent diabetes or juvenile-onset diabetes, affects younger people who need insulin injections to control it. Type II diabetes, also called noninsulin-dependent diabetes or maturity-onset diabetes, usually affects middle-aged, overweight people and can often be controlled by a special diet and tablets to lower the blood sugar. Well-known complications of diabetes include blindness caused by damage to blood vessels of the retina, kidney failure caused by damage to the glomeruli that filter urine, and an increased chance of developing infections. Diabetes is also associated with less well-known complications that can affect muscles, joints, and soft tissues.

Circulating Cells With Angiogenic Potential As Effectors And Biosensors Of Pathological Changes In Dm

Most of the current explanations for impaired new blood vessel growth in DM focused on alterations in the function of mature ECs 64 . A growing body of evidence indicates that neovascularization in adults does not exclusively depend on resident vascular cells, but also involves bone marrow-derived circulating cells and CPC 65, 66 . Hyperglycemia and DM are associated with EC dysfunction 67 Another important cell type that recently has attracted a lot of attention is the circulating monocyte. Monocyte function is severely affected in DM. An important physiologic function of monocytes is their ability to migrate towards gradients of growth factors or cytokines, also defined as chemotaxis. The chemotactic response of monocytes to VEGF-A was completely blunted in monocytes freshly isolated from diabetic individuals, but remained intact towards the (strong) inflammatory mediator and tripeptide fMLP 30 . This functional defect in diabetic monocytes was independent of VEGFR-1, which...

Biochemical Mechanisms Of Cellular Dysfunction During Angiogenesis In Dm

DM is a complex metabolic state with hyperglycemia considered to be a key causal factor in the development of diabetic vascular complications by causing divergent cellular dysfunction 67 . Hyperglycemia occurs as a result of an impaired glucose utilization by tissues due to either whole-body insulin resistance in DM type 2 or lack of sufficient availability of insulin in DM type 1 146 . Generally, lack of physiological effects of insulin on the cells and related hyperglycemia-induced cellular biochemical alterations are two major factors resulting in cellular dysfunction in DM. In the following, we are discussing major biochemical pathways through which elevated glucose levels can lead to cellular dysfunction increased polyol pathway flux increased advanced glycation end-product (AGE) formation activation of protein kinase C (PKC) isoforms and increased hexosamine pathway flux increased formation of reactive oxygen species (ROS) and other products of abundant oxidative stress, e.g....

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...

Definition of the Disease

Diabetes mellitus is a group of metabolic disorders of carbohydrate metabolism that result in hyperglycemia. The disease is classified into several categories.4 Type 1 diabetes formerly known as insulin-dependent diabetes mellitus (IDDM) usually has onset in childhood, frequently presents with an acute episode of severe hyperglycemia often progressing to ketoacidosis, and produces sudden weight loss. Type 2 diabetes formerly known as non-insulin-dependent diabetes mellitus (NIDDM) is commonly associated with obesity, and hyperglycemic episodes usually occur without ketoacidosis. Although onset is more common in adulthood, the frequency of type 2 diabetes in children is increasing as a result of the rising prevalence of childhood obesity.2 Other forms of diabetes are rare. These include endocrinopathies such as Cushing's syndrome, reactive diabetes due to pancreatic insult by drugs or infection, and rare genetic congenital causes, including maturity-onset diabetes of the young (MODY)....

Differential Diagnosis

The diagnosis of diabetes is based solely on documenting an increased concentration of glucose in the blood. There are three ways to diagnose diabetes in a nonpregnant individual, and each must be confirmed on a subsequent day (unless there are unequivocal symptoms of hyperglycemia). The diagnostic criteria of the American Diabetes Association (ADA) are (1) symptoms of diabetes and a casual* plasma glucose concentration > 200 mg dL (11.1 mmol L), (2) fasting* plasma glucose (FPG) > 126 mg dL (7.0 mmol L), or (3) plasma glucose > 200 mg dL (11.1 mmol L) 2 hours after a 75-g oral glucose load.2 FPG is the recommended diagnostic test because of simplicity, acceptability to patients, and low cost. OGTT is more sensitive than FPG, but suffers from a lack of reproducibility. In addition to measurement of FPG, initial laboratory evaluation should include a fasting lipid profile to monitor for dyslipidemia and urine analysis for ketones and protein.2,5 Adults should furthermore have...

Foundations for practical nutritional information

Table 7.2 Developing nutritional data sets related to health end-points associated with elevated blood glucose A food company that had not kept abreast of nutritional knowledge recently formulated a new 'diabetic muesli bar', replacing all sucrose sources with dextrins, in the belief that 'sugar' replacement would improve blood glucose control. However, such wisdom was obsolete, because sucrose, being half fructose, induces a much lower blood glucose response than dextrins, which are rapidly digested glucose polymers. The new 'diabetic' bar had a greater glycaemic impact than the unmodified version.

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.

Case Study 2 The Dangers of Special Nutrients

Sodium in the metallic form is too reactive to be present. As a cation it is very nontoxic and is, of course, widespread in commercial products. Lead and mercury are well-known to be very toxic and their inclusion in medicinal products is rare and, on those occasions when they are present, it is in very low amounts. One cannot, of course, absolutely rule out the accidental inclusion of lead or mercury in a specific batch or bottle of a medicinal. Chromium is an essential element. It is also a popular nutritional supplement particularly in the form of chromium picolinate. In this form it is represented as contributing to effective weight loss, lower blood sugar, and improved cholesterol profile. The recommended daily allowance is 50 to 200 g. This lady was using 1200 to 2400 g per day of chromium picolinate for at least the previous 4 months. Normal chromium plasma concentrations equal 0.1 to 2.1 g mL (Chromium VI) and her plasma concentration was 4.6 g mL 24 hours after admission. Her...

Answers and Discussion

Q1. (Answer a) Chromium can have many different oxidation states from -2 up to +6. Its specific oxidation state is very important. Hexavalent chromium is considered to be 100 times more toxic than trivalent chromium. It causes many industrial problems in addition to cancer. Trivalent chromium has very low solubility although present in yeast, meat, and whole grains, it is absorbed only to the extent of 1 . It is believed to be essential for normal glucose metabolism because patients on long-term parenteral nutrition who were chromium deficient had insulin resistance, hyperglycemia, and glycosuria.

Other systemic fungal infections

Many other fungal species can cause invasive infection besides the more common systemic fungal infections listed above. In Southeast Asia, Penicillium marneffei is a major cause of invasive fungal infection in patients with advanced HIV infection. Paraco-ccidioides brasiliensis is a major fungal pathogen in some areas of South America. P. brasiliensis causes asymptomatic infection in normal individuals that can remain latent and disseminate if the immune system subsequently becomes impaired. Recently, there have been several reports of systemic fungal infection with the Saccharomyces cerevisiae, which is commonly known as brewer's or baker's yeast. Although rare, these cases illustrate how a usually nonpathogenic organism can cause serious infection if it colonizes a susceptible host. Pseudallescheria boydii is a mold that causes severe infections in patients with prolonged neutropenia or who are receiving high-dose corticos-teroid therapy. P. boydii infections are similar to those...

Diagnostic Efforts in Detection and Limitation of the Primaries

Hyperglycemia is common in patients with chronic pancreatitis, resulting in a markedly decreased sensitivity of FDG-PET for detecting malignant tumors, owing to a competitive interaction between FDG and glucose for uptake by the tumor. In a recently published study, the sensitivity in detecting pancreatic cancer decreased to 42 when the blood glucose level was higher than 130 mg 100 ml (Diederichs et al. 1998). Furthermore, foci of acute inflammation within pancreatic masses may cause false-positive results. These inflammatory reactions may not be detectable by routine clinical parameters (Shreve 1998). In 42 patients Sendler et al. (2000) compared the results of PET and of spiral CT and conventional ultrasonography (US) completed in the course of the routine diagnostic procedures prior to pancreatic surgery. When only the results with scores of IV and V were regarded as positive in the sense of representing definite malignancy, FDG-PET gave a sensitivity of 71 and a...

Neurological disease 333

As all protease inhibitors, it seems to create metabolic toxicity to a certain degree. Researchers have yet to determine which drug or drugs or whether HIV itself is the root of these problems. It is also available in a children's formula. There has been a government warning about protease inhibitors' causing high blood sugar level and diabetes. Symptoms to watch for include increased thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin. (Trade name is Viracept.)

Sitespecific drug delivery

Delivery of insulin and an absorption promoter to the colon has also been attempted using a soft gelatin capsule coated with a polyacrylic polymer (Eudragit) having pH-dependent properties.47 Delivery of insulin-like growth factor I (IGF-I) to rat and minipig colonic mucosae under in vitro conditions has been investigated. IGF-I is a 7649-Da protein of 70 amino acids that exerts its biological actions through specific IGF-I receptors. It has been found useful to lower blood glucose levels in insulin-resistant diabetic patients in clinical studies. IGF-I was absorbed intact across rat colonic mucosa as determined by reverse-phase high-performance liquid chromatography (RP-HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and Western blotting.48

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

Sensitivity to insulin is variable in the population at large. Cellular insulin resistance develops as the result of a complex interplay of genetic and environmental factors. Hyperinsulinemia occurs as an adaptive response to the increasing insulin resistance. Type 2 diabetes develops when insulin-resistant individuals cannot maintain the degree of excess insulin secretion needed to overcome insulin resistance. There are two aspects to the type 2 diabetic state hyperglycemia and hyper-insulinemia. Insulin resistance and hyperglycemia seem to set the stage for the development of the metabolic syndrome, characterized by dyslipide-mia, hypercoagulability, hypertension, and trun-cal obesity (Table 1). Several of the metabolic derangements seen with the metabolic syndrome are well-established risk factors for CV disease

Endogenous Substances Toxic To Pancreatic Pcells

Animal models studies197,198 and human autopsy series199-202 have provided evidence that, in addition to p-cell dysfunction, the reduction in the p-cell mass is involved in the pathogenesis of p-cell failure in Type 2 diabetes mellitus. Notably, in one of these reported autopsy series,199 the islet p-cell mass was shown to be reduced in Type 2 diabetic subjects and was associated with increased rate of apoptosis. Accordingly, it appears that p-cell mass defects also exist in Type 2 diabetes they do in Type 1 diabetes. Studies from animals and man have suggested that long-term exposure to hyperglycemia and hyperlipidemia in diabetic conditions contribute to the deterioration of p-cell function, causes impaired insulin secretion, and even p-cell death.203-206 (See also Chapter 9 and Chapter 28.) of insulin gene expression caused by chronic hyperglycemia and the resultant glucose toxicity in Zucker diabetic fatty rat was, in part, explained by chronic oxidative stress. Studies have shown...

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

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.

Biguanides including combinations

The DPP is the first large, carefully randomized study to show that met-formin will delay or prevent diabetes in high-risk IGT subjects. The effect was smaller than that seen in the study in China by Li et al.212 Interestingly, in the DPP, fasting plasma glucose levels were reduced similarly in the metformin and lifestyle groups, though two-hour glucose levels were reduced much more by lifestyle intervention, consistent with metformin's action on hepatic glucose production. It is not known whether the reduction in incidence is due to an acute metabolic effect of treatment of hyperglycemia, or a more fundamental change in glucose homeostasis. A washout study is underway to explore this question. The long-term duration of the metformin effect is also not known.

Trials examining glycemic management techniques

The ORIGIN trial (Outcome Reduction with Initial Glargine Intervention) is a multicenter international study that will randomize in a 2 x 2 factorial design 10,000 people 50 years of age or older at high risk for CVD who have early type 2 diabetes mellitus as defined by an HbAlc level less than 9 if drug nai've or a lower Alc if treated with one oral antidiabetic agent. Persons who have prediabetes with either impaired fasting glucose (IFG) or with impaired glucose tolerance (IGT) will also be included. For the first randomization, patients will be assigned to treatment with insulin glargine titrated to normalize fasting glucose to < 95 mg dL versus standard care, which generally will involve metformin or sulfonylurea therapy, at least in patients who have fasting hyperglycemia with sequential conventional tactics aiming at achieving Alc < 7 . Patients also will be randomized to a supplement of omega-3 polyunsatu-rated fatty acids versus placebo. The primary endpoint is combined...

Beneficial Effects Of CrIii And Questions Concerned

A large body of literature has implicated Cr(III) as an essential element involved in the action of insulin as demonstrated in the studies of Cr deficiency in both experimental animals and humans. The role of Cr(III) in animals was reported about four decades ago in 1959 17 . The study reported that Cr was required for maintaining normal glucose tolerance in rats 17 . Its essentiality in humans was reported later in 1977 18 . A 40-year-old female patient who had received total parenteral nutrition (TPN) for more than 5 years developed severe diabetes. The signs included weight loss and hyperglycemia that was refractory to increased insulin dosing. These symptoms were ameliorated substantially following supplementing Cr to the patient for 2 weeks. In addition, other studies also showed that Cr was required for maintenance of normal glucose tolerance in humans 19-21 . In one case, a patient developed severe glucose intolerance, weight loss, and a metabolic encephalopathy-like...

Glucose6phosphate dehydrogenase G6PD deficiency 201

Glucose Also sometimes called blood sugar. A form of sugar that is the body's primary fuel. Glucose broken down from food can be converted into energy or stored. Abnormally low (hypoglycemia) or high (hyperglycemia) levels of glucose in the blood often indicate metabolic problems such as diabetes mellitus. Diabetes mellitus occurs when the body cannot use glucose for fuel either because the pancreas is not able to make enough insulin or because the insulin that is available is not effective. As a result, glucose accumulates in the blood instead of entering body cells.

Differential Diagnosis of Hyponatremia

Solutes in the ECF that causes an extracellular shift of water or an intracellular shift of Na+ to maintain osmotic balance between the extra- and intracellular. The most common cause of this type of hyponatremia is severe hyperglycemia. In fact, true plasma Na+ in the setting of hyperglycemia can be calculated by adding 1.6 mmol L of Na+ for every 100 mg dL increase of glucose above 100 mg dL.

No of antihypertensive agents Trial Target BP mm Hg 1234

Hyperglycemia A causal relationship between hyperglycemia and microvascular disease is well established. Studies have also documented that glycemic control delays or prevents the manifestations of microvascular disease. The relationship between hyperglycemia and macrovascular disease has been a subject of constant debate, however. The largest study addressing this issue, the UKPDS, was designed to show whether intensive control of glucose lowers the risk of complications compared with conventional treatment in newly diagnosed type 2 diabetics 33,34 . Approximately 2500 patients were enrolled in each group. During a mean follow-up of 10 years, with intensive therapy there was a 12 reduction in any diabetes-related endpoint and a significant reduction in the microvascular endpoints (25 reduction P 0.0099). A 16 reduction in myocardial infarction (P 0.052) and nonsignificant reductions in diabetes-related and all-cause mortality were noted in the intensively treated group. Thus, although...

Regulation Of Pancreatic Secretion

The enteroinsular axis has also been characterized. GIP is also called glucose-dependent insulinotropic polypeptide. On absorption of glucose, galactose, sucrose, or fat (corn oil), the duodenum secretes GIP.29-32b GIP has been identified as a possible incretin, which is an endocrine factor from the gut with insulinotropic activity. The direct metabolic effects of GIP include antagonizing the lipolytic action of glucagon in fat cells, reducing glucagon-induced increase of cyclic adenosine monophosphate, and reducing hepatic glucose output without a concomitant rise in plasma insulin.33 Incretins are released by nutrients and stimulate insulin secretion in the presence of elevated blood glucose levels. The connection between the gut and the pancreatic islets has been coined the enteroinsular axis. Because the enteroinsular axis acts as a feedback loop for suppression of pancreatic secretion, Isaksson and Ihse34 have proposed its use in the treatment of pain induced by pancreatic...

On Collateral Development In Diabetes Mellitus Dm Angiogenesis And Collateral Growth

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 in DM 15 . The same study, the United Kingdom prospective diabetes study (UKPDS) has clearly shown that the incidence of cardiac and peripheral macrovas-cular complications of DM tremendously increases with increasing...

Relative glycaemic potency and glycaemicglucose equivalents

Health consequences of hyperglycaemia are multiple and most evident in the diabetes mellitus syndrome.28,49,50 Persistently raised blood glucose causes protein glycation throughout the body, leading to cumulative, diffuse damage, emerging as pathology in a number of organ systems. Basal membrane damage is commonly an underlying factor in changes to micro-vessels involving the eyes, kidneys and nerves.51 Intense insulin production in response to diabetic hyper-glycaemia, or to repeated acute glucose loading from large intakes of highly digestible carbohydrate, is thought to contribute to the progression of glucose intolerance, through b-cell toxicity, leading to loss of the capacity of the pancreas to produce insulin.52 Hyperinsulinaemia as a response to elevated blood glucose Post-prandial glycaemia may also lead to a number of acute and sometimes serious disorders, as the body attempts to counter the osmotic effects of high blood sugar levels. The excretion of sugar by the kidneys...

Recent Weight Loss and Polyuria in a 52Year Old

The markedly increased random serum glucose concentration suggested diabetes mel-litus, and after considering the history and presentation, the physician thought that it was most likely type 2 diabetes. The increased HbA1c concentration indicated that the hyperglycemia had been present for some time.1 Measurement of plasma glucose on a subsequent day gave a value of 300mg dL (16.7 mmol L), establishing the diagnosis of diabetes mellitus.2 The patient was counseled regarding changes in diet and exercise, and was started on 850 mg oral metformin twice daily (bid). On a follow-up visit one week later his casual (nonfasting) capillary blood glucose concentration obtained by finger stick was 230mg dL (12.8 mmol L). The physician prescribed self-monitoring of blood glucose (SMBG) twice a day. Within a few months the patient gained 6 lb and his HbA1c had dropped to 6.1 . He returned to the clinic after 6 months for a follow-up visit to monitor his glycemic control. He admitted to having...

Neuronal Energy Deprivation

Brain Reperfusion Images

20 mM, significantly prolongs the hypoxic period from which hippocampal neuronal function could recover (Fig. 5). Thus, the higher the concentration of glucose during O2 deprivation in vitro, the better the recovery of neuronal function posthypoxia. This relationship is in disagreement with in vivo findings, in which hyperglycemia has been shown to aggravate neuronal ischemic damage, a phenomenon known as the glucose paradox (79,80). These findings led to the formulation of the lactic acidosis hypothesis of cerebral ischemic damage (50,81). The glucose paradox, and other apparent contradictions between results obtained in vitro and in vivo, mostly in the early and mid-1980s, impeded the acceptance of the hippocampal slice preparation as a valuable tool in the study of brain energy metabolism and brain encephalopathies. Although these in vitro results befit the general understanding of both the aerobic and anaerobic energy metabolism pathways and their consequences (including the more...

Chemical modification

Nobex Corporation (North Carolina) has used an approach to attach low molecular weight polymers at specific sites on proteins to create a conjugated molecule with improved oral absorption. The carrier molecules used revers-ibly destabilize the native protein, favoring a partially unfolded conformation. This noncovalent interaction between the carrier and partially unfolded protein conformation increases solvent exposure of hydrophobic side chains, thereby increasing lipid solubility and oral absorption of the protein by a passive and transcellular route.52 Nobex has developed a hexyl insulin mono-conjugate 2 (HIM2) in which a single amphiphilic oligomer is covalently linked to the free amino group on the Lys-B29 residue of insulin via an amide bond. Lysine residue was an important site for enzymatic attack, so the conjugate has improved stability, the conjugate is more soluble in water, and about 30 to 35 of the insulin surface is covered by the polymer.13,53 The company currently has...

Approaches to enhance transdermal peptide delivery 831 Skin microporation

The first microneedles used were etched into a silicon wafer using lithography and reactive ion etching to form a 20-by-20 array in which each needle measured 80 m at the base and tapered to a height of 150 m with a radius of curvature at the tip of about 1 m. Solid metal microneedles have been reported to enable insulin delivery and lower blood glucose levels by as much as 80 in diabetic hairless rats in vivo.30 However, hollow microneedles can also be used, although they are more difficult to make and use.25

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...

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...

Institutional review board

Insulin Insulin is a hormone that is secreted by the pancreas in response to high blood sugar levels. Insulin allows the body to metabolize and make use of glucose. The inability of the body to secrete the right amount of insulin or resistance of the body to insulin is the cause of diabetes. Insulin is found in humans and in other vertebrates. Animal insulin has for many years served as the treat

Renal disease microalbuminuria proteinuria and nephropathy Reduced development of coronary collateral vessels

Recent data shown that the prevalence of DM or impaired glucose tolerance (IGT) may be as high as 70 in patients who have AMI 19 . In 181 consecutive nondiabetics who had AMI, more than two thirds of patients were diagnosed with DM or IGT by oral glucose tolerance testing. Previously undiagnosed DM accounted for one half of all patients who had AMI and an abnormal glucose metabolism. Only one third of subjects met criteria for DM based on fasting blood glucose criteria. Although a random blood glucose at the time of admission for AMI may not be reliable in making the diagnosis of DM, concern that the diagnosis of IGT or DM is erroneous in the acute setting because of stress hyperglycemia may be unwarranted the results of glucose tolerance testing that was performed at the time of AMI were similar to those performed 3 months later. Two recent studies in patients who presented for coronary angiography similarly showed that previously undiagnosed DM or IGT was present in up to two thirds...

Impaired Angiogenic Signaling in Models of Regional Ischemia

Following hyperglycemia, glycation of bFGF with intracellular sugars reduces its high-affinity heparin-binding capacity and its mitogenic activity 82 . Similarly, glycation of bFGF lowered its chemotactic potential towards EC, and when injected into normoglycemic mice, bFGF displayed a weaker angiogenic effect compared to non-glycated bFGF 92 . These results suggest that reduced new vessel growth observed in DM may be a consequence of growth factor glycation. In addition to glycation of growth factors, glycation of ECM proteins has been shown to reduce their proteolysis and, therefore, affect angiogenic processes 80 .


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.

Choosing treatment

A new study, the BARI 2 Diabetes (BARI 2D), is being performed in patients who have type 2 diabetes mellitus and documented CAD 175 . The aim of this study is to compare treatment efficacy between initial elective revascularization, either surgical or catheter-based, combined with aggressive medical therapy and aggressive medical therapy alone. Also, this trial compares 5-year mortality in a strategy of hyperglycemia management with insulin sensitizers versus insulin secre-tagogues. The prevalence of diabetes mellitus in the United States is enormous and is increasing rapidly. Patients who have diabetes mellitus respond less favorably to percutaneous coronary interventions and surgery compared with non-diabetic patients. These considerations led to the initiation of the BARI 2D trial. It is designed to determine whether treatment that is targeted to attenuate insulin resistance can arrest or retard progression of CAD compared with treatment that is targeted to the same level of...

Jay S Skyler

Although studies in animal models have used degree of insulitis as a histo-pathological indicator of the type 1 diabetes disease process, histological studies in human beings are very limited20. Thus, B-cell function (insulin secretion), measured by assessing C-peptide response (either basal or more likely, in response to a provocative challenge) has been used to evaluate interventions in new-onset type 1 diabetes21, while the evolution from prediabetes to overt hyperglycemia has been used in trials prior to disease onset.

Endocrine Pancreas

The effect of nutritional factors on the islet cells is less clear than are the nutritional relationships in the exocrine pancreas. The responsiveness of the p-cells to blood glucose levels is well established. It has been postulated that persistent hyperglycemia in the mild-moderate Type 2 diabetic stresses the p-cells and leads to a progressive decline in the functional capacity to secrete insulin. This somewhat mystical pathoge-netic scheme seems to neglect the more important consideration of the underlying cause of the islet dysfunction (see Chapter 9, Chapter 27, and Chapter 28).

Animal studies

Animal studies are mentioned briefly since two models of type 2 diabetes are relevant to the human condition and have allowed calorific restriction over much of the lifespan, which is difficult to achieve in humans. In the first model, using Israeli sand rats (Psammomys obesus), Walder and colleagues showed that restriction of food intake to 75 of ad libitum levels post-weaning led to complete restriction of the hyperglycemia that develops in this animal in laboratory settings165. Hyperinsulinemia was not completely prevented, however, and this led the authors to conclude that a genetic component may also exist to raise insulin levels. followed by elevations in fasting insulin and decreases in insulin stimulated glucose disposal. Acute insulin secretion then rose to compensate, and later declined as hyperglycemia developed168.

Rectal delivery

The protein with rectal delivery that has been most widely investigated is insulin. The use of penetration enhancers is required for rectal delivery of insulin, and several such compounds have been investigated. Compounds that have been reported to enhance the rectal absorption of insulin in various animal species include sodium salicylate and 5-methoxysalicylate in dogs,146 enamine derivatives in dogs147 and rabbits,148 and glyceryl esters of acetoace-tic acid in rabbits.149 A preparation of a solid dispersion of insulin and a triglyceride base containing lecithin has also been reported to be an effective suppository for lowering blood glucose levels in dogs.150 Effective rectal absorption of insulin in humans has also been reported when administered in combination with sodium cholate.151

Islet Maintenance

Adult islet neogenesis leading to p-cell mass expansion can be induced by partial pancreatic duct obstruction initiated through cellophane wrapping of the hamster108,109 or monkey110 pancreas. The new p-cell mass displays normal glucose-responsiveness with a normal counter-regulatory mechanism.111 Moreover, the cellophane wrapping-induced neogenic islets are able to reverse hyperglycemia in streptozotocin (STZ)-treated hamsters.112,113 p-cell mass expansion in this model is mediated by islet neogenesis associated protein (INGAP), an acinar cell protein.113 It is noteworthy that some beneficial effects were observed using partial pancreatic ligation in children with type 1 diabetes over 70 years ago.114-117 It is significant that in vivo studies have not produced any evidence of hyperfunctioning (e.g., hypoglycemia) or unchecked cell growth (e.g., tumor formation), suggesting that the induction of p-cell mass expansion in the normal adult pancreas may be regulated by inherent...


Essential for neuronal function and, if levels fall too low, hypogly-caemia causes neuroglycopenia, which can cause coma and death. On the other hand, sustained high blood glucose levels cause widespread damage to the body, particularly to blood vessels, as in diabetes mellitus. The liver plays a critical role in maintaining normal blood glucose levels. It is a major store of glucose, in the form of glycogen, which is synthesized when there is excess substrate. The liver can store enough glycogen to be broken down by glycogenolysis, to maintain normogly-caemia for about 18 h. Athletes sometimes maximize liver glycogen


Glycogen Streptozotocin

STZ, derived from the soil microorganism Streptomycetes achromogenes in 1960, has been found to have a significant antimicrobial action for a wide spectrum of organisms.2,3 However, during the preclinical toxicology studies, it was found that this compound causes hyperglycemia when given by intravenous administration in rats and dogs within a few hours.4,5 Therefore, its use as an antimicrobial agent was abandoned. At the same time, its antitumor activity was demonstrated.6 Characteristically, STZ primarily damages p-cells, leading to alterations in blood glucose and insulin levels. Hyperglycemia is observed as early as 2 hours after STZ administration with a concomitant drop in blood insulin levels. However, about 6 hours later, the opposite situation occurs blood glucose levels drop while insulin levels begin to increase. Eventually, blood insulin levels decrease and hyperglycemia occurs. The responsiveness of p-cells to glucose, which temporarily returns to normal after an initial...

Hand Transplants

The most commonly reported complications are transient hyperglycemia, which was treated with insulin viral and fungal infections, treated with antiviral and antifungal agents and Cushing syndrome. High serum creatinine, anemia, and transient hypertension and avascular bone necrosis were among other side effects of immunosuppressive agents. These complications were treated by reducing the dosage of immunosuppressive drugs.4,6


A single injection of alloxan caused a prompt onset of hyperglycemia and glycosuria within 24 to 48 hours in dogs. Alloxan causes characteristic changes in blood sugar and insulin levels similar to the effect of STZ. After alloxan treatment, a typical three-phase blood sugar curve develops initial hyperglycemia, followed by hypogly-cemia, and permanent hyperglycemia.137 A high functional activity on pancreatic p-cells, along with inhibitory effects after alloxan administration, has also been observed in duct-ligated rats.139 It was proposed that alloxan may have stimulatory effects on the pancreatic islets during the first hours of exposure. A short-term rapid increase in insulin release and subsequent complete suppression of the islet response to glucose, even though in high concentrations, was also demonstrated in vitro140 and in vivo.132 House et al.141 found similar results in alloxan treated hamsters. An initial p-cell stimulatory effect of alloxan was found in the early phase...


People with ischemic heart disease than in the general population. These may be divided into those that are not reversible, aging, male sex, and genetic factors those that are reversible, use of tobacco, hypertension, obesity, sedentary lifestyle, and stress and others that may not be reversible hyperlipidemia, hyperglycemia, diabetes mellitus, decreased levels of high-density lipoproteins, and behavior patterns. In the late 1990s, reports noting an increase in the incidence of heart attacks, angina, or other cardiovascular symptoms in people with HIV began to surface. Associations with protease inhibitors were made, and concerns were expressed about the long-term effects of the high blood lipid levels also observed in those on protease inhibitors.