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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Author: Duke Anderson
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The writer presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this book are precise.

When compared to other ebooks and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.

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Dealing with Very High Blood Glucose Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a severe diabetic complication that has to be managed in a hospital. It's characterized by high blood glucose (though it need not be very high) associated with an acid condition of the blood due to the production of ketones, which are the products of fat breakdown. The root of the illness is a lack of insulin. Without enough insulin, glucose can't get into insulin-dependent cells like muscle and the liver, so glucose accumulates in the blood, and the body turns to fat for energy.

Impaired Glucose Tolerance IGT and Impaired Fasting Glycemia IFG Nondiabetic Fasting Hyperglycemia

Impaired glucose tolerance (IGT) was considered a class in the previous WHO classification but is now categorized as a stage in the natural history of disordered carbohydrate metabolism. A stage called 'impaired fasting hyperglycemia' or impaired fasting glycemia (IFG) or 'non-diabetic fasting hyperglycemia' is now recognized as these people also appear to be at greater risk for progression to diabetes and macrovascular disease, although prospective data are sparse and early data suggest a lower risk of progression than IGT (21). IFG refers to fasting glucose concentrations which are lower than those required to diagnose diabetes mellitus but higher than the 'normal' reference range.

Fetal Complications Secondary to Maternal Hyperglycemia

If the mother has hyperglycemia, the fetus will be exposed to either sustained hyperglycemia or intermittent periods of hyperglycemia. Both situations prematurely stimulate fetal insulin secretion. The Pedersen hypothesis links maternal hyperglycemia-induced fetal hyperinsulinemia to morbidity of the infant (2). Fetal hyperinsulinemia may cause increased fetal body fat (macrosomia) and, therefore, a difficult delivery, or cause inhibition of pulmonary maturation of surfactant and, therefore, respiratory distress of the neonate. The fetus may also have decreased serum potassium levels caused by the elevated insulin and glucose levels and may, therefore, have cardiac arrhythmias. Neonatal hypoglycemia may cause permanent neurological damage. The maternal postprandial glucose level has been shown to be the most important variable to impact the subsequent risk of neonatal macrosomia (5). When the postprandial glucose levels are maintained below 120 mg dL 1 h after beginning the meal, the...

Requirement for Intracellular Hyperglycemia

Clinical and animal model data indicate that chronic hyperglycemia is the central initiating factor for all types of diabetic microvascular disease. Duration and magnitude of hyperglycemia are both strongly correlated with the extent and rate of progression of diabetic microvascular disease. In the Diabetes Control and Complications Trial (DCCT), for example, type 1 diabetic patients whose intensive insulin therapy resulted in HbA1c levels 2 lower than those receiving conventional insulin therapy had a 76 lower incidence of retinopathy, a 54 lower incidence of nephropathy, and a 60 reduction in neuropathy (3). Similarly, several studies have shown that glycohemoglobin A1 is an independent risk factor for cardiovascular disease (6,7) in type 1 diabetes. Intimal-medial thickness (IMT) of the carotid artery, which is strongly correlated with coronary heart disease (CHD), was demonstrated to be increased in type 1 diabetes (8,9). Although all cells in a person with diabetes are exposed to...

Hyperglycemia in Acute Stroke

Background Stroke Stroke and Hyperglycemia Hyperglycemia After Stroke Etiology of Hyperglycemia in Acute (Ischemic) Stroke Admission Hyperglycemia and Clinical Outcome After Stroke Glucose Levels and Lesion Volume How Does Hyperglycemia Affect the Ischemic Brain Treatment of Hyperglycemia Conclusions Recommendations References Hyperglycemia is frequently found (40-60 ) after all kinds of stroke and it has been related to increased lesion size and poor clinical outcome. In this chapter, we will primarily focus on ischemic stroke we will outline the incidence and natural course of post-stroke hyperglycemia and discuss the possible etiologies of post-stroke hyperglycemia. Subsequently, we will present an overview of various mechanisms that could explain how hyperglycemia is detrimental after ischemic stroke. Finally, we will address the question whether inhospital hyperglycemia should be treated in stroke patients, and if so decided, the glucose levels that should be targeted and the...

Hyperglycemia And Proteinuria

The onset of microalbuminuria in patients with type 2 diabetes may be transient and related to increases in glomerular filtration rate in association with hyperglycemia. Albuminuria has been shown to decrease with decreases in glucose levels in patients with newly diagnosed type 1 or type 2 diabetes 4547 . However, other researchers reported no decline in albumin excretion with control of hyperglycemia in patients with newly diagnosed type 2 diabetes 48 . The United Kingdom Prospective Diabetes Study showed that the risk for microalbuminuria was proportional to the level and duration of glucose elevation 49 . Furthermore, in type 1 diabetes the level of glycosylated

Cgm Trend Data Used To Minimize Postprandial Hyperglycemia And Avoid Hypoglycemia

Insulin Pump Catheter

However, patients given real-time access to CGM glucose sensor information have quickly learned to utilize the trend data to minimize postprandial hyperglycemia and avoid hypoglycemia. Most patients have not required extensive education to utilize the real-time BG data safely and effectively (22-24). In a randomized, prospective clinical trial using the Algorithms currently being tested in the research setting, utilize glucose trend data and insulin delivery data to minimize hyperglycemia following consumption of a meal. The CGM system algorithms often consider time since last meal, onset time of current meal, meal size, meal composition, estimated time of gastric emptying intestinal absorption, time dose of previously delivered insulin, time intensity of previous exercise and an estimate of insulin sensitivity (19,20,28-30). Postprandial hyperglycemia can be minimized by injecting rapid-acting insulin into the subcutaneous (sc) tissue 0 to 20 min before a meal. Moderate hyperglycemia...

Riddle Mc Hart J. Hyperglycemia Recognised And Unrecognised As A Risk Factor For Stroke And Transient Ischemic Attacks.

Allport L, Butcher K, Baird T etal. (2004). Insular cortical ischemia is independently associated with acute stress hyperglycemia. Stroke 35 1886-91. Baird TA, Parsons MW, Phanh T etal. (2003). Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke 34 2208-14. Gray CS, Hildreth AJ, Alberti KGMM, O'Connell JE on behalf of the GIST Collaboration (2004b). Post stroke hyperglycemia natural history and immediate management. Stroke 35 122-6. Riddle MC, Hart J (1982). Hyperglycemia, recognised and unrecognised, as a risk factor for stroke and transient ischemic attacks. Stroke 13 356-9. Song EC, Chu K, Jeong SW et al. (2003). Hyperglycemia exacerbates brain edema and perihematomal cell death after intracerebral hemorrhage. Stroke 34 2215-20. Woo E, Ma JTC, Robinson JD, Yu YL (1988). Hyperglycemia is a stress response in acute stroke. Stroke 19 1359-64.

Hyperglycemia Causing Cardiac Conduction Defect

Hypoglycemia Schematic Diagram

Chronic exposure to hyperglycemia has long been recognized to be the major cause of vascular disease in diabetes and the severity of microangio-pathic complications is directly related to the quality of glycemic control (14). Conversely, recurrent exposure to hypoglycemia of any severity causes syndromes that are both hypoglycemia-related and impair the capacity of the individual to respond to this metabolic stress, further increasing the risk of severe hypoglycemia and effectively creating a vicious circle that is difficult to break. These syndromes of counterregulatory hormonal deficiencies and impaired awareness of hypoglycemia (IAH) develop over a period of years and ultimately affect a substantial proportion of people with type 1 diabetes and a lesser number with insulin-treated type 2 diabetes. They are considered to be components of hypoglycemia-associated autonomic failure (HAAF), through down-regulation of the central mechanisms within the brain that would normally activate...

Approach To The Surgical Patient With Hyperglycemia

Diabetic and non-diabetic patients develop hyperglycemia during surgery and medical illness due to enhanced hepatic gluconeogenesis, relative insulin deficiency, and decreased sensitivity of the liver, skeletal muscle, and adipose tissue to the actions of insulin (1-3). While clinical evidence suggests a direct association between hyperglycemia and adverse outcome in patients undergoing vascular and cardiac surgery, there is little prospective data available to indicate that glucose control improves outcome in the average hyperglycemic patient undergoing other types of surgical procedures (4-13). The adverse effects of hyperglycemia are mediated in large part by enhanced oxidative stress, which is not counter-balanced by endogenous antioxidants. The optimal range of blood glucose (BG) control in a specific patient population remains controversial. The fear of hypoglycemia (change in mental status, seizure, coma, myocardial ischemia, arrhythmia, and death) dictates the psychology of...

Hyperglycemia Introduction

The current classification of diabetes in different subtypes is based on the defect(s) that causes hyperglycemia, namely, aberrant or deficient insulin secretion or insufficient insulin action (1). Type 1 diabetes (T1D) originates from autoimmune-mediated destruction of the pancreatic P-cells that normally produce insulin, thus resulting in absolute insulin deficiency. Other types of pancreatic disease involving destruction of the P-cells, such as alcoholic pancreatitis, are classified otherwise. Previously, T1D was also known as juvenile-onset diabetes or insulin-dependent diabetes mellitus (IDDM). However, these expressions may result in misclassification and indistinct prognosis and therapeutic options. Criteria to diagnose T1D are shown in Table 1 (1). Note that diagnostic criteria do not include HbA1c levels, which are exclusively used to follow glycemic control, but not diagnosis.

How Does Hyperglycemia Affect The Ischemic Brain

Although an accumulating number of studies have convincingly demonstrated an association between hyperglycemia and poor outcome after stroke, it remains controversial whether this association is causal, i.e., hyper-glycemia is actually causing poor outcome. Hyperglycemia could also be epiphenomenal to a more pronounced stress reaction with higher levels of blood glucose in more severe stroke. Indeed, higher levels of glucose have been associated with more severe stroke (7, 7375). On the other hand, most but not all (30, 76, 77) studies showed that the deleterious effect of hyperglycemia is independent of clinical severity (7, 13, 53, 75, 76). Several (mainly experimental) studies and observations from imaging studies have provided clues as to how impaired glucose metabolism resulting in hyperglycemia and insulin resistance could be detrimental to the ischemic brain. In this context, it is important to realize that the sequence of reactions that occur after arterial occlusion, leading...

Hyperglycemia the Common Factor

The epidemiological attempt to study the natural history and pathogenesis of diabetes as a whole can only rely on one common and stable factor, high blood glucose, despite the wide variation in clinical manifestations and various contributing factors. However, high blood glucose alone does not answer all the questions. Over the past 30 years, evidence has accumulated that numerous and etiologically different mechanisms (genetic, environmental or immunologic processes) may play an important role in the pathogenesis, the clinical course and the emergence of complications of the 'diabetic state' (9,14). Does correction of hyperglycemia prevent all of the various pathologic changes observed with diabetes There is some evidence that people with diabetes who are not treated develop more complications than well-controlled patients (9,15,16). However, there are few instances in which characteristic complications of diabetes have been described before hyper-glycemia was observed. This...

Preliminary findings from the largestever study of treatments for diabetes provide no evidence that intensive treatment

Interim results from the ADVANCE Study, involving 11,140 high-risk patients with type 2 diabetes, provide no evidence of an increased risk of death among those patients receiving intensive treatment to lower blood glucose (sugar). ADVANCE was designed to answer two questions in patients with type 2 diabetes first, does intensive treatment to lower blood pressure improve outcome and second, does intensive treatment to reduce blood glucose improve outcome. In September 2007, the ADVANCE Collaborative Group published evidence in The Lancet showing that the blood pressure lowering treatment had reduced the death rate among participants. In January 2008, the part of the study designed to assess the effects of the intensive treatment to reduce blood glucose was completed. As in ACCORD, this intensive treatment program was designed to lower blood glucose to levels below those usually recommended by clinical guidelines.

Control of Hyperglycemia

Several studies demonstrate the importance of intensive glycemic control in preventing or reducing microvascular complications of DM. The effect of intensive glycemic control on macrovascular complications in type 1 and type 2 DM is not as convincing. The Diabetes Control and Complications Trial (DCCT) demonstrated compelling evidence in support of a major reduction in chronic micro-vascular complications among type 1 diabetics under tight glycemic control. In the same study, tight glycemic control was associated with a reduction in major macrovascular events by approximately 50 compared with that in those in whom glycemic control was conventional or less stringent. This difference did not achieve statistical significance. Similarly, the United Kingdom Prospective Diabetes Study (UKPDS) has shown that during 10 years of follow-up intensive glycemic control with either insulin or sulfonylureas decreased the risk of micro-vascular complications by 25 in non-insulin-requiring diabetics....

Hyperglycemia and Adverse Pregnancy Outcome HAPO Study

Existed, making the decision regarding cutoffs difficult. The risk of macrosomia increased approximately fivefold as fasting glucose increased above 75 mg dl, 1-h glucose increased above 105 mg dl, or 2-h glucose increased above 90 mg dl. In other words, a fasting glucose greater than or equal to 100 mg dl was associated with a risk of macrosomia five times that of a fasting glucose less than 75 mg dl, with absolute macrosomia rates of 25 vs. 5 . Correlation with other outcomes was less marked, although still significant. HAPO excluded women with severe hyperglycemia from the analysis (fasting glucose greater than 105 mg dl or 2-h glucose greater than 200 mg dl), so the association actually underestimated the strength of the correlation by excluding women with extremely elevated glucose. An initial recommendation for screening cutoffs incorporating the HAPO results is expected later in 2009. Following the publication of the consensus opinion, it is likely that medical organizations...

The Effect of PPARy Ligands on the Enhancement of Insulin Sensitizing Action Via Improving Hyperglycemia

The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study reported that the strict maintenance of euglycemia by intensive insulin treatment can delay the onset and slow the progression of DN in patients with type 1 and type 2 diabetes mellitus (57,58). These studies suggested that the adverse effects of hyperglycemia are the main cause for the development of long-term complications in diabetes such as kidney disease. TZDs as PPAR-y ligands are a new class of oral antidiabetic agents that are used widely and improve insulin resistance, hyperinsulinemia, and hyperglycemia in patients with type 2 diabetes (59-62). Because amelioration of hyperglycemia can prevent the development and progression of DN, TZDs could be renoprotective in patients with type 2 diabetes and in the corresponding animal models of the disease by their insulin sensitizing ability (63). In fa fa rats, one of type 2 diabetic models, treatment with TZDs reduced albuminuria, improved...

Can hypoglycaemia be avoided by constant high blood glucose levels

Having persistently high blood glucose levels will avoid hypoglycaemia, but unfortunately it dramatically increases the risk ofdeveloping the long-term complications of diabetes. Maintaining the balance between risky hyperglycaemia and troublesome hypoglycaemia can be very difficult for patients on insulin, but is much easier these days with the different preparations and injection devices available. If you are having troublesome hypo attacks, followed by high blood glucose levels, please

Strokeand Hyperglycemia

Hyperglycemia is a frequent finding in various medical emergencies, and it has clearly been associated with poor outcome. Hyperglycemia is potentially modifiable, and in the past decade a number of trials have been Also after stroke, hyperglycemia is frequent and is independently associated with poor outcome. Although this is already known for a few decades, the 1994 guidelines for the treatment of ischemic stroke from the American Heart Association (AHA) did not make any recommendation for the treatment of hyperglycemia in these patients. More recent (2007) consensus papers recommended treating glucose levels more strictly, despite the lack of apparent evidence of a clinical benefit (4-6). In this chapter, focusing on ischemic stroke, we will first outline the incidence and the natural course of post-stroke hyperglycemia, next we will discuss the etiology of post-stroke hyperglycemia and the various mechanisms that could explain how acute hyperglycemia can be detrimental after...

Pathways Of Hyperglycemiainduced Damage

As glucose is metabolized, both intra- and extracellular environments are affected by hyperglycemia and endothelial damage can occur. There is a debate (4,6,44) over the pathways through which these hyperglycemia-induced changes in cellular conditions lead to complications. We focus on four major pathways that have been implicated in the process leading to microvascular complications (i) increased polyol pathway flux, (ii) increased advanced glycation end product (AGE) formation, (iii) activation of protein kinase C (PKC) isoforms, and (iv) increased hexosamine pathway flux. While we will focus on these pathways and their association with microvascular complications, these pathways may be implicated in macrovascular complications as well. Further, these pathways are not mutually exclusive. One or more of the pathways may be operating at a given time, and the progression toward complications may require an interaction among them. (ii) AGEs cause tissue damage and have been used to...

Treating Hyperglycemia

The other diabetic emergency is hyperglycemia, or too much blood sugar. It is unpredictable, possibly deadly, and happens from time to time to all people with diabetes. This is more rare than hypoglycemia but still very dangerous. People with types 1 and 2 can suffer from it but react differently. Someone who is hyperglycemic must have an injection of quick-acting insulin and drink lots of sugar-free liquids. If the condition does not improve rapidly, the person must seek emergency medical help. Sometimes, people who do not yet know they have type 2 diabetes can develop hyperglycemia. They and people already diagnosed with type 2 who experience this condition can have it for a long time without realizing it. Their glucose level can zoom to extremely high levels, which can lead to coma and death. Hyperglycemia leads to a condition called HHS. It can happen to people who do not use insulin but take oral medicines. HHS symptoms are sleepiness or mental confusion, extreme thirst, no...

Hyperglycemia Induced Tissue Damage Pathways and Causes

Since the initial findings from the Diabetes Control and Complications Trial (DCCT) were published in 1993 (1), the intensification of diabetes management to prevent or slow the onset of the complications associated with type 1 diabetes (T1D) has been a hallmark of diabetes treatment. The DCCT findings confirmed the strong link between hyperglycemia and the complications and put to rest a debate about the necessity of tight glycemic control see (2) and (3) for the history of this debate . During the past two decades, much attention has been paid to the mechanisms that promote hyperglycemia-induced tissue damage and to the potential ways to modify this process (4-6). The targeted population for intensified diabetes management may well be 2 million adults with T1D in the United States based on the estimate of 10 of the 20.6 million diabetes patients (7). Further, the incidence of T1D appears to be increasing with a tendency toward younger age at onset (8-10). Taken together, there is a...

Pathogenesis of hyperglycemia in type diabetes

Type 2 diabetes is a heterogeneous disease manifested by hyperglycemia that results from multiple dysregulated biologic pathways. Each of these pathways represents a potential target for therapy (see Figure 3.2). The two major metabolic abnormalities are 1) insulin resistance in skeletal muscle, liver, and adipocytes, and 2) a progressive decline in insulin production by pancreatic p-cells 6 . Insulin resistance results from both environmental factors (predominantly obesity and physical inactivity) and genetic factors that have yet to be fully identified. Early in the natural history of type 2 diabetes, insulin-resistant individuals who are prediabetic compensate by secreting increased amounts of insulin. Hyperglycemia results as the capacity of the pancreas to secrete insulin deteriorates and endogenous insulin production is insufficient to overcome insulin resistance. Because p-cell failure is progressive, treatment interventions must be continuously monitored and advanced. The...

Hyperglycemiainduced Process

Effect of agents that alter mitochondrial metabolism on hyperglycemia-induced ROS formation in bovine aortic endothelial cells. Cells were incubated in 5 mM glucose, 30 mM glucose alone, and 30 mM glucose plus either rotenone, thenoyltrifluoroacetone (TTFA), carbonyl cyanide m-chlorophenylhydrazone (CCCP), antisense, uncoupling protein-1 (UCP-1), or manganese superoxide dismutase (Mn-SOD) hemagglutinating virus of Japan (HVJ)-liposomes, and ROS were quantitated. (Reproduced with permission from ref. 111.) Fig. 6. Effect of agents that alter mitochondrial metabolism on hyperglycemia-induced ROS formation in bovine aortic endothelial cells. Cells were incubated in 5 mM glucose, 30 mM glucose alone, and 30 mM glucose plus either rotenone, thenoyltrifluoroacetone (TTFA), carbonyl cyanide m-chlorophenylhydrazone (CCCP), antisense, uncoupling protein-1 (UCP-1), or manganese superoxide dismutase (Mn-SOD) hemagglutinating virus of Japan (HVJ)-liposomes, and ROS were quantitated....

Models For Hyperglycemia And Stroke

Clinical studies clearly show that admission hyperglycemia is related to the outcome after stroke (Chapter 9). It is less clear, however, if this relation is causal, i.e., high admission glucose causes poor outcome. Issues that need to be resolved are as follows (i) whether stroke-related hyperglycemia reflects pre-existent metabolic abnormalities, such as impaired glucose tolerance, (ii) whether such pre-existent metabolic abnormalities already compromise the brain, which might explain the relatively poorer functional outcome in relation to hyperglycemia, (iii) if hyperglycemia in the days after the initial event is still harmful to the brain or may even represent a compensatory event for reductions in energy supply to the ischemic area, and (iv) if correction of hyperglycemia improves outcome. Studies in animal models can help to clarify these issues. The timing and severity of hyperglycemia in relation to stroke can be readily manipulated in rodent models. A range of rodent models...

What you need to know about high blood glucose

If your blood glucose stays over 180, it may be too high. (See the chart on page 11.) It means you don't have enough insulin in your body. High blood glucose can happen if you miss taking your diabetes medicine, eat too much, or don't get enough exercise. Sometimes, the medicines you take for other problems cause high blood glucose. Be sure to tell your doctor about other medicines you take. If you're very thirsty and tired, have blurry vision, and have to go to the bathroom often, your blood glucose may be too high. Very high blood glucose may also make you feel sick to your stomach. If your blood glucose is high much of the time or if you have symptoms of high blood glucose, call your doctor.

Adjusting for Hyperglycemia

Insulin doses will be adjusted upward when a pattern demonstrating hyperglycemia at a given time of day is present for 2 to 3 days in a row at the same time of day and the hyperglycemia is unexplained by increased food intake, inactivity, or the somogyi phenomenon (rebound hyperglycemia). If the hyperglycemia is explained by an increased food intake or a decline in physical activity, it is preferable to correct the underlying lifestyle indiscretion rather than to raise the insulin dose(s). If fasting hyperglycemia is present, and particularly if fasting hyperglycemia is seen in association with wide variation in BG values, including the presence of normal and or lower values, one must exclude the possibility that the highs represent rebound in response to nocturnal hypoglycemia. This distinction is accomplished by asking the patient to check a BG reading between 2 and 3 AM to see if it is normal. If the overnight BG is high, then it is appropriate to adjust the basal insulin dose...

Treatment Of Hyperglycemia

Although the association between hyperglycemia and poor outcome is well established in stroke patients, it remains unclear if patients benefit from tight glycemic control. In experimental stroke reduction in blood, glucose with insulin to the lower physiological range (3-4 mmol L) reduced infarction size (118, 119). In human studies, treatment of hyperglycemia in patients with stroke remains the subject of debate. (possibly 7.8-10.3 mmol L) should probably trigger the administration of insulin. This recommendation is based on two observations first, the increased risk of poor outcome associated with hyperglycemia second, the accumulating evidence from trials in other medical emergencies than stroke which demonstrates that tight glycemic control improves outcome such as in patients admitted to the ICU (3,120), patients with myocardial infarction (2, 121), or patients undergoing coronary artery bypass grafting (CABG) (122, 123). These results, however, cannot directly be extrapolated to...


Having high levels of glucose in your blood over time may lead to the complications of diabetes. But blood glucose levels can also become dangerously high in the short term and cause a life-threatening situation that could result in coma or death. It is important to know what the warning signs are and how to treat hyperglycemia. Type 1 Diabetes. Having too little insulin in your body leads to too much glucose. A rare and serious, but often preventable, emergency can arise from high blood glucose levels. Diabetic ketoacidosis (DKA) occurs when you don't get enough insulin, and is mostly a problem for people with type 1 diabetes. Any time your body doesn't have enough insulin, muscles can't take in the glucose that they need. They feel starved, so your body breaks down fat for energy. Ketones are the by-products of this breakdown. If ketones form faster than your body can get rid of them in the urine, they build up in the blood. These acidic products poison the blood. At the same time,...

Determinants And Mechanisms

Possible risk factors for changes in cognitive functioning and brain structure in patients with type 2 diabetes include diabetes-specific factors (e.g., hyperglycemia, glucose-lowering therapy, microvascular complications), factors that are linked to diabetes but are not specific to the disease (e.g., hypertension, stroke, depression), genetic factors and demographic, socio-economic, and lifestyle factors (Fig. 2). All of these risk factors may affect cognitive functioning at different times during life span, but there are still relatively few studies that have specifically addressed these risk factors in relation to cognition in patients with type 2 diabetes. Fig. 2. Relation between type 2 diabetes, related risk factors and cognitive decline. It shows a putative course of development for cognitive dysfunction in type 2 diabetes. In our view, impaired cognitive functioning in patients with type 2 diabetes develops against a background of genetic predisposition and socio-economic and...

Hyperglycemic Hyperosmolar State Definition and Epidemiology

The hyperosmolar hyperglycemic state (HHS) is also an acute complication that may occur in patients with diabetes mellitus. It is seen primarily in patients with T2DM and has previously been referred to as hyperglycemic hyperosmolar non-ketotic coma or hyperglycemic hyperosmolar non-ketotic state (13). HHS is marked by profound dehydration and hyper-glycemia and often by some degree of neurological impairment.

Abduljalil Et Al. 2008 Eur J Pharmacol

Effects of prior hypoglycemia and hyperglycemia on cognition in children with type 1 diabetes mellitus. Pediatric Diabetes 2008 9 87-95. 75. Perantie DC, Wu J, Koller JM, et al. Regional brain volume differences associated with hyperglycemia and severe hypoglycemia in youth with type 1 diabetes. Diabetes Care 2007 30 2331-2337. 115. Malone JI, Hanna S, Saporta S, et al. Hyperglycemia NOT hypoglycemia alters neuronal dendrites and impairs spatial memory. Pediatric Diabetes 2008 9 531-539.

Neurological Complications In

Been at least 12 cases of homonymous hemianopsia reported in patients with hyperosmolar hyperglycemia (64, 71-75). In addition to hemianop-sia, these patients have noted other visual disturbances including blurred or fragmented vision, visual-field hallucinations, and flashing lights (64, 74). MRI findings such as decreased T2 signal of the white matter, subtle gyral swelling, and enhancement of the overlying meninges have been observed in these patients (64). Other studies have reported transient hemianopsia without MRI changes (74). Case reports range from mild improvement to total resolution in visual disturbances after treatment of the underlying hyper-glycemic state (64, 74). In cases of hemianopsia, it is important to consider HHS as the cause when no lesion is detected on MRI. Other visual phenomena reported in patients with HHS include polyopia, flashing and flickering lights, hallucinations, and a persistence and transposition of objects in the visual fields (74).

Esther van den Berg Yael D Reijmer and Geert Jan Biessels

This chapter addresses the effects of type 2 diabetes mellitus on cognitive functioning. It covers the nature and severity of cognitive decrements in relation to diabetes and pre-diabetic stages. Possible risk factors and pathophysiological mechanisms, such as vascular risk factors, hypoglycemia and hyperglycemia, microvascular and macrovascular complications, depression, genetic factors, and lifestyle, will be examined. Moreover, the chapter provides a description of structural changes in the brain, such as infarcts, white-matter hyperintensities, and brain atrophy in relation to diabetes and cognitive

Need For Improving Diabetes Care References

Type 2 diabetes (T2D) is the most common form of diabetes, a metabolic disorder characterized by hyperglycemia resulting from defects in insulin action, insulin secretion, or both. Early diagnosis of T2D and the high-risk category of pre-diabetes may help reduce the associated public health and clinical burden. Available diagnostic strategies include fasting plasma glucose, oral glucose tolerance test, and casual plasma glucose in the presence of symptoms of hyper-glycemia. Potential use of hemoglobin A1c as part of the strategy for screening and diagnosis has been recently proposed. Those with risk factors for T2D should be targeted including patients with overweight obesity, those with family history of T2D, those aged 45 years and older, race ethnic minorities (such as Native Americans, African Americans, Latinos, and Asian Americans), women with history of gestational diabetes, and those with metabolic syndrome abnormalities (high blood pressure, low HDL cholesterol, and high...

Cerebral Edema In Dka Risk Factors

Hyponatremia, hyperkalemia, and uremia have also been associated with cerebral edema in DKA (37). Uremia and hyperkalemia may be reflective of longer illness duration, severity of insulin deficiency, and pre-renal failure states. Glaser et al. found an association with higher initial serum urea nitrogen levels (for each increase of 9 mg dl, RR 1.7, 95 CI 1.2-2.5) and cerebral edema (28). There was no association with the degree of hyperglycemia. Mahoney et al. and Edge et al. also found no association with degree of hyperglycemia (36, 37). In a recently published study, MR diffusion-weight imaging was used to quantify cerebral edema (38). The apparent diffusion coefficients (ADCs) of brain water during and after DKA treatment were compared in 26 children and correlated with clinical and biochemical variables. Serum urea nitrogen levels and initial respiratory rates were elevated. ADC was not correlated with initial serum glucose or sodium abnormalities. Although initial reports...

Biomedical Risk Factors

Three types of diabetes-related biomedical variables have been linked to the appearance of neurocognitive anomalies in children with diabetes moderately severe episodes of hypoglycemia, ketoacidosis, and chronic hyperglycemia. our understanding of these associations remains imperfect, unfortunately, because so few studies have adequately ascertained those biomedical variables in pediatric samples. Rather than capturing most, or even a representative number, of those events over the course of the diabetic child's disease, the best investigators have been able to do is to estimate metabolic control from one or a handful of glycosylated hemoglobin values, count severe hypoglycemic episodes retrospectively (missing virtually all episodes of nocturnal hypoglycemia), and rely on often incomplete medical records or parents' delayed recall to quantify the number, duration, and severity of episodes of ketoacidosis. Diabetic ketoacidosis (DKA) results from an absolute or relative deficiency in...

Glucose Levels And Lesion Volume

Stroke Hyperglycemia

If hyperglycemia is indeed casually related to poor outcome after stroke, one would expect a relation between higher levels of blood glucose and an increased lesion volume. In hemorrhagic stroke, only little is known about the association between glucose levels and the size of the hemorrhage or its evolution during the clinical course. The evidence is limited to experimental settings where it has been shown that hyperglycemia exacerbates brain edema and peri-hematomal cell death after hemorrhagic stroke (56). In patients with ischemic stroke treated with rt-PA, hyperglycemia has been associated with an increased risk of hemorrhagic complications (57-59). In contrast to hemorrhagic stroke, research concerning hyperglycemia and lesion volume after ischemic stroke is much more extensive. Central in the pathophysiology of ischemic stroke is the concept of the ischemic penumbra (Fig. 1C). The penumbra is a rim of tissue surrounding the infarct core that consists of potentially salvageable...

Etiology And Precipitating Factors

Glucose levels rise in the setting of relative insulin deficiency. The low levels of circulating insulin prevent lipolysis, ketogenesis, and ketoacidosis (62) but are unable to suppress hyperglycemia, glucosuria, and water losses. Levels of counter-regulatory hormones such as glucagon, catecholamines, cortisol, and growth hormone are elevated, increasing gluconeogenic substrates, gluconeogenesis, and glycogenolysis. Meanwhile, glucose utilization is decreased. Glucose levels rise, leading to glucosuria, osmotic diuresis, and dehydration (14). Those patients who are unable to maintain an adequate fluid intake to compensate for the urinary losses, for example, elderly patients, will develop marked hyperglycemia and a hyperosmolar state. Mental status changes are more common in HHS than in DKA because of the greater degrees of hyperosmolarity in HHS (63). HHS typically presents with one or more precipitating factors, similar to DKA. Precipitating factors may include infection,...

Prediabetes And Cognition Prediabetic Stages

Global Atrophy The Brain

Acute rises of peripheral blood glucose and insulin, after, for example, glucose ingestion, may directly influence cognitive performance (see Chapter 18). Indeed, acute improvement of cognitive performance has been reported after ingestion of glucose (39). However, these changes are temporary. The consequences of long-term exposure to elevated blood glucose or insulin levels, which are considered in this chapter, may be quite different.

Medical Complications

Hyperglycemia In the first 12 h after stroke onset, plasma glucose concentrations are elevated in up to 68 of patients, of whom more than half are not known to have diabetes mellitus (53). An initially high blood glucose concentration in patients with acute stroke is a predictor of poor outcome (53, 54). Lowering blood glucose in the acute stage of ischemic stroke has been in only one phase III clinical trial that was terminated prematurely. This trial did not show a benefit on long-term functional outcome of early administration of insulin, but the reduction in serum glucose achieved was only small (55). For more information on hyperglycemia in the acute phase of stroke, the reader is referred to Treatment of Hyperglycemia, Chapter 9.

Depression Treatment Considerations For Diabetic Patients

These agents act by increasing serotonergic functioning, which in turn increases insulin sensitivity and reduces plasma glucose. Most studies have investigated fluoxetine (doses up to 60mg day) and sertraline. Patients' depressive symptoms responded, and they experienced weight loss, decreased fasting plasma glucose, and lowered HgbA1c levels. Cat-echolamines, on the other hand, are associated with insulin resistance and hyperglycemia. Depressed diabetic patients who were administered nor-triptyline, a norepinephrine-reuptake inhibitor, had poorer glycemic control. Other tricyclic antidepressants can increase food cravings, increase weight, and raise serum glucose levels. Because both catecholamines and serotonin have been implicated in diabetic neuropathy, dual-action antidepressants may be the preferred agents, particularly in non-depressed subjects.

Risk Factors For Stroke In Diabetic Subjects

Traditional risk factors for stroke such as arterial hypertension, dyslipi-demia, atrial fibrillation, heart failure, and previous myocardial infarction are more common in people with DM (3, 36). However, the impact of DM on stroke is not just due to the higher prevalence of these risk factors, as the risk of mortality and morbidity remains over twofold increased after correcting for these factors (4, 37). Risk factors for stroke in diabetic patients identified in previous studies are summarized in Table 2. It is informative to distinguish between factors that are non-specific and specific to DM. DM-specific factors, including chronic hyperglycemia, DM duration, DM type and complications, and insulin resistance, may contribute to an elevated stroke risk either by amplification of the harmful effect of other classical non-specific risk factors, such as hypertension, or by acting independently. Age, male sex, arterial hypertension, atrial fibrillation Prior cerebrovascular disorders,...

Pathophysiological Models Are We There

Based on this critical review of the pediatric literature, it should be obvious that we are not yet in a position to make strong statements about the etiology of neurocognitive dysfunction in the child with diabetes. Indeed, only one attempt has been made to address some of those findings, with the diathesis or vulnerability model (50) offering an explanation for why it is that children with an early onset of diabetes seem to be especially likely to manifest significant brain abnormalities. According to this model, in the very young child diagnosed with diabetes, chronically elevated blood glucose levels interfere with normal brain maturation at a time when those neurodevelopmental processes are particularly labile, as they are during the first 5-7 years of life (128-131). The resulting alterations in brain organization that occur during this sensitive period will not only lead to delayed cognitive development and lasting cognitive dysfunction, but may also induce a predisposition or...

Methodological Considerations

When studying children with any type of chronic disorder, it is critically important to be able to identify and document, for each child, the nature and extent of their disease process from both a biomedical and a psychosocial perspective. For the diabetic child, we ought to - but hardly ever - have medical, metabolic, and psychosocial data from diagnosis onward. Did the child experience ketoacidosis and or cerebral edema around the time of diagnosis or anytime thereafter Since diagnosis, how often and for what duration did the child experience excessively low - and excessively high - glucose values, and how were these episodes of hypoglycemia and hyperglycemia operationalized When did the child begin to show evidence of microvascular complications and other comorbid conditions like blood pressure elevations, and how did these progress over time How did the child cope psychologically with the diagnosis of diabetes and with diabetes-related events, like the occurrence of a hypoglycemic...

Blood pressure results

High blood glucose can make the blood vessels in the eyes bleed. This bleeding can lead to blindness. You can help prevent eye damage by keeping your blood glucose as close to normal as possible. If your eyes are already damaged, an eye doctor may be able to save your sight with laser treatments or surgery. Too much glucose in your blood is very hard on your kidneys. After a number of years, high blood glucose can cause the kidneys to stop working. This condition is called kidney failure. If your kidneys stop working, you'll need dialysis (using a machine or special fluids to clean your blood) or a kidney transplant.

Prevention Or Delay Of Type Diabetes

Three recent trials in older adults with T2D have assessed the effect of lowering blood glucose to near-normal levels on cardiovascular risk. First, patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (n 10,251) had a mean age of 62.2 years at entry and 10 years of diabetes duration. Sixty-two percent were men, and 30 had prior macrovascular disease and a baseline median HbA1c level of 8.1 (48). Study patients were assigned to receive intensive therapy (median HbA1c level achieved of 6.4 ) or standard therapy (median HbA1c level achieved of 7.5 ). After a median follow-up of 3.4 years, compared to the standard-therapy group, those in the intensive-therapy group had higher overall mortality (4 vs. 5 ) and cardiovascular mortality (1.8 vs. 2.6 ) and greater-number of hypoglycemic events (1 vs. 3.1 ). Second, patients in the Action in Diabetes and Vascular Disease Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Study (n 11,140) had a...

Relationship Between Depression And Vascular Disease

Chronic pro-inflammatory cytokine activation is also associated with coronary artery syndromes and thought to mediate the relationship between depression and cardiovascular disease, as well as that between cardiovascular disease and diabetes (70, 71). Specifically, interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) increase hyperglycemia and interfere with lipid metabolism. They are important in the pathogenesis of atherosclerosis. As symptoms of stress increase, so does systemic inflammation, increasing cardiovascular risk (72).

Take other tests for your diabetes Urine tests

You may need to check your urine if you're sick or if your blood glucose is over 240. A urine test will tell you if you have ketones in your urine. Your body makes ketones when there isn't enough insulin in your blood. Ketones can make you very sick. Call your doctor right away if you find moderate or large amounts of ketones, along with high blood glucose levels, when you do a urine test. You may have a serious condition called ketoacidosis. If it isn't treated, it can cause death. Signs of ketoacidosis are vomiting, weakness, fast breathing, and a sweet smell on the breath. Ketoacidosis is more likely to develop in people with type 1 diabetes.

Identifying Neurocognitive Phenotypes

A very large neuroimaging literature indicates that adults with either type 1 or type 2 diabetes manifest structural changes in a number of brain regions for comprehensive critical reviews see (73, 74) , but until very recently, there had been little pediatric research on this topic. In what may be the largest study to date, MRI scans were acquired from 108 diabetic and 51 age-matched nondiabetic children, 7-17 years of age, and voxel-based mor-phometry techniques were used to quantify between-group differences in gray- and white-matter volumes, and to correlate those values with measures of recurrent severe hypoglycemia and chronic hyperglycemia (75). Although brain volumes were found to be comparable in the two groups, analyses restricted to the diabetic sample showed statistically reliable relationships between metabolic variables and specific brain regions. Compared to those children with no past history of severe hypoglycemia, those who experienced 1 or more episodes of severe...

Complications Cerebral Dysfunction In

Cerebral abnormalities may occur in the setting of hyperglycemia and ketoacidosis. When compared to those with T1DM and normoglycemia, patients with diabetic ketoacidosis demonstrate increased levels of tryptophan and 5-hydroxyindoleacetic acid in the cerebrospinal fluid (CSF) (21). Plasma tyrosine and CSF tyrosine and homovanillic acid concentrations are typically normal. Similar findings are demonstrated in those with uremia and hepatic encephalopathy, as well as in rodents with diabetes and DKA secondary to streptozotocin administration. Magnetic resonance (MR) spec-troscopy studies in children with DKA have demonstrated possible neuronal injury and or dysfunction. In one study, 29 children underwent MR spectroscopy and were evaluated with brain ratios of N-acetylaspartate (NAA) to creatinine (Cr) during therapy and after recovery from DKA (22). NAA Cr levels were significantly lower during DKA therapy in the basal ganglia suggesting compromised neuronal function.

Diabetes And Dementia

Impairment and Alzheimer's disease (15). Autopsy studies have not confirmed this relationship between Alzheimer's disease and T2DM (23). Therefore, diabetes may increase the risk for serious memory loss, presenting very much like Alzheimer's disease with a different pathophysi-ology than typical Alzheimer's disease. Convergent evidence supports the notion that insulin plays a role in both the beneficial effects of acute hyper-glycemia and the detrimental effects of chronic hyperglycemia on cognition. As we previously noted, an acute rise in plasma glucose is rapidly followed by a rise in plasma insulin. Therefore, the beneficial effects attributed to increased plasma glucose levels may, in part, reflect effects of increased plasma insulin levels. (We will present evidence supporting this possibility in the following section.) However, detrimental effects may follow chronic glucose and insulin elevations. In T2DM, hyperglycemia is produced by two deficits insulin resistance and...

Longterm Complications

The pathogenesis of diabetic complications is multifactorial, complicated, and not yet fully elucidated. In brief, focusing on the role of hyperglycemia, so-called advanced glycation end products (AGEs) and sorbitol are considered to contribute to tissue damage. In addition there may be more tissue-specific factors that contribute to tissue damage, like protein kinase C in the kidney. An overview of current insights into the pathogenesis of long-term diabetic complications is supplied by Michael Brownlee (23).

Prevention Of Stroke In Patients With Dm

Regarding prevention of stroke in patients with DM, it may be less relevant than in non-DM subjects to distinguish between primary and secondary prevention as all patients with DM are considered to be high-risk subjects regardless of the history of cerebrovascular accidents or the presence of clinical and subclinical vascular lesions. However, the aggressiveness of the preventive measures should be most pronounced in those who have DM and history of stroke or TIA. Obvious targets for the prevention of stroke in patients with DM are the correction of DM-specific risk factors, mainly hyperglycemia, and other diabetes non-specific factors, such as arterial hypertension or dyslipidemia. While in most trials addressing the correction of these latter factors the relative risk reduction was similar between patients with or without DM, the absolute risk reduction of stroke was usually higher in those with DM due to significantly higher risk in this subgroup of subjects.

After Stroke

A retrospective study by Melamed (7, 15) showed in 1976 that hyper-glycemia after stroke is frequent and relates to the severity of the stroke and in-hospital mortality. Since then many studies have reported similar associations and showed that this association is more pronounced if hyperglycemia persists during the first 24 h (18) or week (50, 51). Fig. 2. Unadjusted relative risk (RR) of in-hospital or 30-day mortality after stroke in patients with stress hyperglycemia compared with those without stress hyperglycemia. In patients without known diabetes the pooled relative risk for ischemic stroke is 3.3 (95 confidence intervals (CI) 2.3-4.6) for hemorrhagic stroke 2.4 (95 CI 0.7-8.73). (From Capes et al. (8). Reprinted with permission from Lippincott Williams & Wilkins.) Fig. 2. Unadjusted relative risk (RR) of in-hospital or 30-day mortality after stroke in patients with stress hyperglycemia compared with those without stress hyperglycemia. In patients without known diabetes the...

Choreiform Movements

Chorea or ballismus has been observed in the hyperosmolar hyperglycemic state (76). In a report of HHS patients presenting with chorea, the mean age was 71.1 years and had a 2 1 ratio of women to men (76). In patients with HHS, choreiform movements are often but not always unilateral and occur concurrent with or shortly after the episode of hyperglycemia (77). Diabetes is usually newly diagnosed in these patients and develops subacutely over days to months (77). In states of hyperglycemia, potential pathological causes of choreiform movements include decreased GABA-enkephalin inhibitory neurons, intracellular acidosis, accumulation of extracellular glutamate, brain edema formation, disruption of the blood-brain barrier, and global decrease in cerebral blood flow (78, 79). Resolution of hyperglycemia and increases in GAB A levels do not always reverse chorea (77, 78). Chronic arteriolar disease and lacunar infarctions have been proposed as a mechanism, but subacute development of...


Ominous Octet Diabetes

When inadequate insulin secretion from pancreatic -cell dysfunction is also present, hyperglycemia develops, heralding the onset of T2D (14-17). In the natural history of progression to diabetes, -cells initially increase insulin secretion in response to insulin resistance and, for a period of time, are able to effectively maintain glucose levels below the diabetic range. However, when -cell function begins to decline, insulin production is inadequate to overcome the insulin resistance, and blood glucose levels rise. Insulin resistance, once established, remains relatively stable over time. Therefore, progression of T2D is a result of worsening -cell function with pre-existing insulin resistance. Fig. 1. Defects in the pancreas and in target tissues for insulin action in type 2 diabetes. In the non-diabetic individual, insulin suppresses hepatic glucose output, stimulates glucose uptake and utilization in muscle and adipose tissue, and suppresses lipolysis in adipose tissue. When...

Inder Nagra 4 Chorea

Cerebral edema in diabetic comas. II. Effects of hyperosmolal-ity, hyperglycemia and insulin in diabetic rabbits. J Clin Endocrinol Metabol 1974 38(6) 1057-1067. 64. Lavin PJ. Hyperglycemic hemianopia a reversible complication of non-ketotic hyper-glycemia. Neurol 2005 65(4) 616-619. 70. Maccario M. Neurological dysfunction associated with nonketotic hyperglycemia. Arch Neu-rol 1968 19(5) 525-534. 71. Harden CL, Rosenbaum DH, Daras M. Hyperglycemia presenting with occipital seizures. Epilepsia 1991 32(2) 215-220. 72. Duncan MB, Jabbari B, Rosenberg ML. Gaze-evoked visual seizures in nonketotic hyper-glycemia. Epilepsia 1991 32(2) 221-224. 75. Seo DW, Na DG, Na DL, Moon SY, Hong SB. Subcortical hypointensity in partial status epilepticus associated with nonketotic hyperglycemia. J Neuroimaging 2003 13(3) 259-263. 76. Oh SH, Lee KY, Im JH, Lee MS. Chorea associated with non-ketotic hyperglycemia and hyperintensity basal ganglia lesion on T1-weighted brain MRI...

Type l Diabetes

Type 1 diabetes is a life long metabolic disorder that is characterized by absolute insulin deficiency resulting in hyperglycemia and lipolysis. Type 1 diabetes accounts for 5-10 of the total diabetes population, the majority of the other patients has type 2 diabetes. Insulin deficiency originates with autoimmune mediated P-cell destruction. Without insulin treatment, type 1 diabetes leads to dehydration and ketoacidosis and can ultimately be fatal. Prolonged exposure to hyperglycemia is responsible for microvascular damage in the eye, kidneys and nervous system and contributes to macrovascular disease of the coronary, cerebral and peripheral arteries. Limited joint mobility and the diabetic foot are other complications related to chronic hyperglycemia. currently, the corner stone of the treatment of type 1 diabetes is exogenous insulin substitution aiming to restore near-normal glycemia in order to prevent or delay long-term complications. Recurrent hypoglycemia is a frequent...


Inhibiting the enzymes that catalyze this process, thereby delaying carbohydrate absorption. Sitagliptin, a dipeptidyl-peptidase (DPP)-IV inhibitor, is an agent that reduces blood glucose with less risk of hypoglycemia. Met-formin is recommended as first choice for pharmacologic treatment and has good efficacy to lower HbA1c by approximately 1-1.5 as monotherapy (57). However, most patients will eventually require treatment with combinations of oral medications with different mechanisms of action simultaneously in order to attain adequate glycemic control. Table 3 lists the available classes of oral antidiabetic medications, their mechanisms of action, and side effects. In addition to hyperglycemia, individuals with T2D often have a constellation of other metabolic abnormalities which increase their CVD risk (60-64). Risk determinants of CVD include the presence or absence of coronary heart disease (CHD), other clinical forms of atherosclerotic disease, and the major risk factors high...

And Depression

One view is that depressive symptoms are triggered by the existence of diabetes. Depressive symptoms are associated with biochemical changes related to the diabetes (i.e., hyperglycemia, inflammation, activation of the hypothalamic-pituitary-adrenal axis, stress) and may be important factors in disrupting overall metabolic control (7, 32, 33). Further, the presence of depression and depressive symptoms may present as a result of lifestyle choices (i.e., poor diet, no physical activity) and psychological stress associated with managing the illness that are frequently associated with the presence of diabetes. Treated type II diabetes has been associated with a significantly higher chance of developing depressive symptoms, even after controlling for BMI and co-morbidities (30), and well-functioning older adults with diabetes are at nearly twice the risk of developing depressive symptoms than those without diabetes (34). depression can cause abnormalities in the...

Type Diabetes

The two rodent models most commonly used for this kind of study include streptozotocin-induced diabetes in rodents and the spontaneously diabetic BB Wor-rat. The first model develops incomplete insulin deficiency and severe hyperglycemia and is sustained without insulin supplementation. The second model develops acutely an immune-mediated -cell destruction with complete insulin (and C-peptide) deficiency and requires daily insulin supplementation for its survival (see Chapter 16) (36). Hence, the overriding metabolic abnormalities in these type 1 diabetic models are hyperglycemia and insulin deficiency.

Background Stroke

Therefore, it remains of major importance to improve the treatment options for patients suffering from a stroke. Modifiable factors, associated with poor outcome after stroke, such as hyperglycemia, have the potential for being new treatment targets. One of the drawbacks when reviewing the literature on hyperglycemia in acute stroke is that the distinction between stroke subtypes is not always clearly defined. Moreover, the definition of hyperglycemia varies substantially from study to study. In this chapter we will mainly focus on hyper-glycemia after ischemic stroke and just briefly discuss about other stroke subtypes. Concerning the definition of hyperglycemia, we adopted the definition used in each separate study.

If you smoke quit

Over time, high blood glucose can harm the nerves in your body. Nerve damage can cause you to lose the feeling in your feet or to have painful, burning feet. It can also cause pain in your legs, arms, or hands or cause problems with digesting food, going to the bathroom, or having sex.

Glucose And Memory

In contrast to acute hyperglycemia, chronic hyperglycemia exerts detrimental effects on cognition. T2DM and its precursor, impaired glucose tolerance, are common among aging adults. Adults above age 60 run a one in five chance of having T2DM (8) and a one in three chance of having either impaired glucose tolerance or T2DM (9). Most, though not all, studies have detected cognitive changes associated with T2DM (10-13). In older adults with T2DM, the most common cognitive deficit is a decline in list learning (12) other areas affected by diabetes may include attention, manual dexterity, reasoning, and psychomotor speed (10-13). Furthermore, there is evidence from rodents and humans that abnormal glucoregulation in the absence of diabetes can impair memory and global cognitive functioning (14-16). It is important to note that cognitive deficits associated with diabetes may, in part, be reversible with treatment for diabetes (11,17-19).


The American Diabetes Association (ADA) diagnostic criteria for diabetes and the two high-risk categories of pre-diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), updated in 2003 are defined in Table 1 (1). There are three ways to diagnose diabetes. Because of simplicity of use, acceptability to patients, and low cost, the fasting plasma glucose (PG) is the preferred diagnostic test. In the presence of symptoms of diabetes (polyuria, polydipsia, weight loss, etc.), a casual plasma glucose of greater or equal than 200mg dl is diagnostic. The 75-g oral glucose tolerance test (OGTT) is more sensitive and modestly more specific than fasting PG, but it is less reproducible and less frequently performed in clinical settings. In the absence of unequivocal hyperglycemia, any test used to diagnose diabetes must be confirmed on a subsequent day by a PG measured either in the fasting state or 2 h after an oral glucose load.

Subject Index

Acute stroke, hyperglycemia, see Hyperglycemia, in acute stroke ADA, see American Diabetes Association AD Assessment Scale-Cognitive Syndrome (BADS), 86 Behavioral Inattention Test (BIT), 86 Benton Test of Facial Matching, 89 Biomedical risk factors, of diabetic children and adolescents chronic hyperglycemia, 265-266 ketoacidosis, 264-265 psychological stress and mood disorder, 267 (BAEPs), 398, 399 Brain structure and cognitive functioning, in type 2 diabetic patients demographics and lifestyle, 305-306 depression, 309 genetic factors, 304-305 hyperglycemia and hypoglycemia, chronic hyperglycemia, 265-266 ketoacidosis, 264-265 psychological stress and mood 267-268 school performance, 254-256 See also Adults cognitive impairments, T1D Type 1 diabetes (T1D), in children and adolescents Cholecystokinin (CCK), 401 Cholinesterase inhibitors, in dementia treatment, 121, 438 See also Dementia Chronic hyperglycemia, in diabetic children and adolescents, 265-266 See also Type 1 diabetes...

Oxidative and Nitrosative Stress in Diabetes Induced Vascular Dysfunction

Superoxide anion may quench NO, thereby reducing the efficacy of a potent endothe-lium-derived vasodilator system that participates in the homeostatic regulation of the vasculature, and evidence suggests that during hyperglycemia, reduced NO availability exists (64). Hyperglycemia-induced superoxide generation contributes to the increased expression of NAD(P)H oxidase, which in turn generate more superoxide anion. Hyperglycemia also favors, through the activation of NF-kB an increased expression of iNOS, which may increase the generation of NO (65,66). Superoxide anion interacts with NO, forming the strong oxidant peroxynitrite (ONOO-), which attacks various biomolecules, leading to among other processes the production of a modified amino acid, nitrotyrosine (67). Although nitrotyrosine was initially considered a specific marker of peroxynitrite generation, other pathways can also induce tyrosine nitration. Thus, nitrotyrosine is now generally considered a collective index of reactive...

Physiologic effects of nitric oxide on the vascular system

Hyperglycemia and endothelium-derived vasocative substances. Hyperglycemia decreased the bioavailability of nitric oxide (NO) and prostacyclin (PGI2) and increased the synthesis of vasoconstrictor prostanoids and endothelin (ET-1) via multiple mechanisms (see text). PLC, phospholipase C DAG, diacylglycerol PKC, protein kinase C eNOS, endothelial nitric oxide synthase Thr, thrombin NAD(P)H Ox, nicotinamide adenine dinucleotide phosphate oxidase O2-, superoxide anion OONO-, peroxynitrite MCP, monocyte chemoattractant protein-1 NFkb, nuclear factor K b TNF, tumor necrosis factor Ils, interleukins COX-2, cyclooxygense-2. (Reproduced with permission from ref. 127.) Fig. 1. Hyperglycemia and endothelium-derived vasocative substances. Hyperglycemia decreased the bioavailability of nitric oxide (NO) and prostacyclin (PGI2) and increased the synthesis of vasoconstrictor prostanoids and endothelin (ET-1) via multiple mechanisms (see text). PLC, phospholipase C DAG, diacylglycerol PKC,...

Drug or Chemicalinduced Diabetes

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

Oral Agent Combinations

Less than 20 of patients with type 2 diabetes presenting to primary care physicians offices with an initial glucose of 200-240 mg dL (hemoglobin A1-C of 9-10 ) will be able to reach a hemoglobin A1-C of less than 7 if treated with maximal doses of a sulfonylurea or metformin alone. With newer guidelines lowering the desired goal for hemoglobin A1-C to 6.5 , the majority of patients seen in primary care offices with this degree of hyperglycemia will require combination therapy to achieve the 6.5 A1-C goal. Even patients with initially good responses to a single agent will subsequently require a second or even a third agent in the future because of the progressive nature of type 2 diabetes, dietary indiscretion, and noncompliance.

Preconceptional Counseling

Overall, more than two-thirds of pregnancies are unplanned (3). Because first trimester hyperglycemia may lead to fetal malformations and pregnancy loss and because untreated target organ damage may worsen during early pregnancy, women contemplating pregnancy should be referred for preconceptional counseling to optimize maternal health, to tighten glycemic control, and to anticipate maternal diabetic, obstetric, and fetal complications. The preconceptional visit should include a thorough history of disease state, comorbidities, and an extensive maternal examination. Not only will women want to discuss how diabetes will affect the pregnancy but also they will wish to know how the pregnancy may impact their diabetes. Discussion of the anticipated risks may further include questions on how to achieve pregnancy.

Target Glycemic Values

Women will need to be educated regarding the changing goals for blood glucose concentrations in pregnancy (Table 2). As they learn to manage their diabetes in pregnancy, they will learn when adjustments to therapy should be considered based on the number of out of target glycemic values obtained over the course of their monitoring. Providers should inform their patients that if greater than 15 to 20 of values are outside the target range they should call their physician and relay their glucose concentrations. Women with consistently elevated fasting glucose concentrations should be encouraged to obtain a glucose concentration between 2 00 a.m. and 3 00 a.m. to assess for a Somogyi effect that is discovered with maternal hypoglycemia in the early am with maternal hyperglycemia at the am fasting.

Comments on Treatment with Basal Bolus Regimen

It is still unknown whether it is essential to address postprandial hyperglycemia by using rapid-acting insulin before the meals to reduce the risk of a cardiovascular event and late diabetic complications. Nevertheless, in many patients, especially with a poor endogenous insulin secretion, treatment of both basal and postprandial hyperglycaemia with a basal-bolus regimen is necessary to reach a target of HbAlc less than 6.5-7.0 . The practical burden imposed by the frequency of injections and glucose testing may be taken into consideration before choosing multiple injections in a subject with type 2 diabetes mellitus.

Endothelial Dysfunction

Atherosclerosis is the major contributor to CVD in diabetes. The initial lesion in atherosclerosis is endothelial cell dysfunction (ECD), which can be identified by the blunting of the NO-dependent vasodilation in response to acetylcholine and hyperemia (47). ECD is not only important in the initiation of atherosclerosis, but also in its progression and the appearance of cardiovascular events. In diabetes, ECD is multifactorial, involving hyperglycemia and its biochemical sequelae, oxidative stress, overexpression of cytokines and growth factors, and abnormalities in coagulation fibrinolysis and lipid metabolism (48). To understand the combined deleterious effects of these factors, it is important to appreciate the normal function of the EC and its critical role in overall homeostasis.

Insulin in the management of type diabetes

Insulin is the most the effective available medication for treating hyperglycemia in type 2 diabetes. If used appropriately, it can decrease any level of elevated A1C to, or close to, the desired goal. This chapter begins with a presentation of indications for insulin therapy in type 2 diabetes. Normal physiological insulin patterns will be reviewed, highlighting how awareness of these patterns can guide the development of insulin treatment regimens. The next section will provide an overview of the characteristics of available insulin preparations. The chapter will end with a discussion of potential strategies for initiating and advancing insulin therapy.

Effects Of Exercise In Diabetes Type Clinical Studies

Previous studies in nondiabetic patients have shown that exercise reduces hypertension, dyslipidemia, insulin resistance, and hyperglycemia (38, 42-45). In diabetics a number of small studies have been published, however, apart from lacking statistical power, their results were not uniform, and no large-scale studies have been performed so far. A meta-analysis of 14 trials, extracted from a total of 2700 potential articles, included 504 participants. Selection of the studies was based on a predetermined program of physical exercise lasting for a minimum of 8 weeks, supervision of exercise, and presence of type 2 diabetic control group (46). Of the 14 trials, 11 were randomized controlled trials, and 3 were case-control trials. The mean age of the participants was 55.0 7years, duration of diabetes was 4.3 4.6 years 50 of the participants were women. The exercise interventions consisted of three workouts per week lasting for a mean of 53 17min. Exercise consisted of walking or cycling...

Noninvasive Cgm Uses Reverse Ionophoresis To Sample Tissue Fluid

A noninvasive CGM system called the Glucowatch Biographer utilizes an electric current (reverse ionophoresis) to extract glucose-containing ISF from the skin (Animas Corporation, West Chester, PA, USA, http www.animas.com). Tissue fluid collected within a gel pad under the Glucowatch is analyzed for glucose using an enzyme-based, electrochemical technique. The system displays the absolute glucose concentration and the rate direction of change, every 10-15 minutes for patient interpretation. Programmable alarms are designed to warn the patient of impending hypo and hyperglycemia. The technology is limited by inadequate accuracy, long extraction time, long warm-up period (2 h), short gel pad lifetime (12 h), irritation of the skin and cost (37).

Managing Diabetes and Pregnancy

Despite increased first- and second-phase insulin release after a carbohydrate load in normal pregnancy, in the fed state there is a significant reduction in net insulin-mediated glucose disposal by the third trimester. The result is somewhat higher maternal blood glucose levels in nondiabetic subjects, and marked hyperglycemia in inadequately treated pregnant diabetic women. The contra-insulin effects of gestation are related to hPL, progesterone, cortisol, and prolactin, with the defects at the postreceptor level of muscle and hepatic cells. Due to the insulin resistance and enhanced ketogenesis of pregnancy, ketoacidosis is a great danger during gestation. Markedly increased doses of insulin are usually required to control hyperglycemia after the first trimester. Glucagon is well suppressed by glucose during pregnancy, and secretory responses of glucagon to amino acids are not increased above nonpregnant levels.

Features of Fetal Growth in Diabetic Pregnancies

Diabetes-associated accelerated growth, starting in early third trimester when fetal adipocyte proliferation and fetal storage occurs, is the most common problem in pregnancies with diabetes. In the second trimester, the growth of noninsulin-sensitive tissues, e.g., bones, accounts for the main difference in the fetal growth pattern. It has been shown that in this period a previous history of delivery of a macrosomic newborn appears to be the major determinant of growth expressing the strong influence of genetic factors (10), while in the third trimester variation of growth is determined to a greater extent by nutritional supply. Maternal hyperglycemia leads via transport by the placenta to fetal hyperglycemia and consequently to hyperinsulinism (Pedersen hypothesis) (11). Insulin is the strongest growth factor for insulin-sensitive tissue. Thus, a fetus with hyperinsulinism is characterized by asymmetric excessive growth mainly of the AC due to increased subcutaneous fat layers (Fig....

Localization Of The Renal Microvascular Dysregulation In Early Td

Diabetic hyperfiltration is evident not only in humans with T1D, but also in rodent models of T1D. Most experimental studies of renal hemodynamic and glomerular function in diabetes have utilized the streptozotocin (STZ)-treated rat. Renal cross-transplantation studies have established that STZ exerts minimal direct nephrotoxic effects, such that the renal functional changes evident in the STZ rat arise as a consequence of the induction of T1D (1). Within 3 d after STZ injection, renal and glomerular hypertrophy are evident (2), whereas hyperfiltration arises within 1 wk and remains evident for weeks to months (probably dependent on the magnitude of the hyperglycemia). The hyperfiltration can be substantial, as exemplified by our observation of an 80 increase in inulin clearance in Sprague-Dawley rats studied 2 wk after STZ treatment (3). Hence, although there are some limitations in the utility of the STZ rat in studying the processes occurring during advanced DN (2), the STZ rat...

Remission in Diabetes

African American subjects with Type 2 diabetes who present with severe hyperglycemia may develop long-lasting remissions (92, 93). At the time of presentation, these individuals require hospitalization for severe symptomatic hypergly-cemia (mean glucose 600 mg dl, 33.3 mM) and following a period of treatment, with anti-diabetic pharmacologic agents they are able to discontinue Long-term follow-up of 8 years showed that remission was maintained for a median of 40 months or 3.3 years (Figure 9A.6) (93). A small separate subset have been in remission for 10-15 years. Additionally, once in remission, the usual medical or surgical 'stresses' did not perturb glucose homeostasis and precipitate a relapse to hyperglycemia. To determine the frequency of remission, all newly diagnosed Type 2 diabetes subjects hospitalized with symptomatic hyperglycemia over 300 mg dl (16.7 mmol l), were treated intensively after discharge with multiple doses of insulin, diet and diabetes education. The...

The Role Of Advanced Glycosylation End Products

Despite the absence of a clear, convincing demonstration of a causal relationship between hyperglycemia and atherosclerosis, as would be provided by a successful interventional trial, there are much epidemiological data and in vitro experimentation to suggest such a linkage. Protein glycation is a clear mechanism by which hyperglycemia may give rise to diabetic complications (20). Taken together, it is apparent that AGEs can cause significant dysfunctional changes to the macrovascular endothelium in ways that can potentiate vessel wall atherogenesis, hypertension, or prothrombotic events (27). For these reasons, scrupulous glycemic control is important in type 1 diabetes. Clearly, elimination of hyperglycemia will minimize the microvascular complications of type 1 diabetes and may possible improve the risk of macrovascular complications. It should also be noted that albuminuria is quantitatively the greatest single risk factor for atherosclerosis in type 1 diabetes. Whether this...

Basement Membrane Thickening and Extracellular Matrix Expansion

Histologically, increases in type IV and VI collagen, fibronectin and laminin and decreases in proteoglycans are observed in the mesangium of diabetic patients with nephropathy and probably in the vascular endothelium in general (152,153). These effects can be replicated in mesangial cells incubated in increasing glucose levels that were prevented general PKC inhibitors (154-156). Additionally, increased expression of transforming growth factor (TGF)- P has been implicated in the development of mesangial expansion and basement membrane thickening in diabetes. Because PKC activation can increase the production of ECM and TGF-P, it is not surprising that several reports have shown that PKC inhibitors can also prevent hyperglycemia- or diabetes-induced increases in ECM and TGF-P in mesangial cells or renal glomeruli (98).

Definition And Natural History

It is known that diabetic nephropathy (DN) can be detected before the onset of decreased glomerular filtration rate (GFR) in most patients by detecting abnormal amounts of albumin in the urine. Two stages have been designated microalbuminuria (defined as urine albumin between 30 and 300 mg 24 h, 20-200 g min on a timed sample, or spot urine albumin to creatinine ratio 30-300 mg g) and albuminuria, also termed clinical albuminuria, macroalbuminuria, and overt nephropathy ( 300 mg 24 h, 200 g min on a timed sample, or spot urine albumin to creatinine ACR ratio 300 mg g). Short-term hyperglycemia, exercise, urinary tract infections, marked hypertension, heart failure, and acute, febrile illness can cause transient elevations (9) there is also marked day-to-day variability in albumin excretion, so that at least two of

Definition Of Type Diabetes Mellitus

The studies reviewed here use a variety of criteria to define type 2 diabetes. This is inevitable, given the long time period included. It was not possible to identify consistent criteria for all studies. However, the 1985 WHO criteria24 were used as a reference when possible since the majority of modern studies used them. In prevention trials, the development of any clinical diagnosis of diabetes or measured hyperglycemia meeting defined criteria was usually the outcome of the trial.

Atypical Diabetes of Childhood

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

Exacerbation of Retinopathy

Intensive therapy slows the rate of development and progression of mild to moderate retinopathy. In addition, in the DCCT it was found that retinopathy occasionally worsens in the first year after initiation of intensive therapy, which manifests as an increase in the number of soft exudates (due to retinal infarcts in the superficial layers) (2,89). This is felt to represent the closure of small retinal blood vessels that were narrowed but previously patent. Correction of hyperglycemia lowers plasma volume, which places marginal vessels at-risk. Increased availability of insulin-like growth factor-1 (IGF-1) may also contribute (90).

Comments on the Treatment with Biphasic Premix Insulin

The explanation for the results with biphasic pre-mix insulin versus basal insulins is that both postprandial and basal glycaemia are controlled by the biphasic premix insulin. In patients with high HbA1c, basal hyperglycemia plays a greater role for the HbA1c level than in a situation with low HbA1c, where postprandial hyper-glycemia contributes more to overall glycaemic control 44 . The biphasic premix insulin analogues have an advantage over basal insulin alone because they provide the rapid-acting insulin component that covers mealtime hyper-glycaemia. Therefore, it is not surprising that the premix insulin can reduce HbA1c more than intermediate-acting or the long-acting insulin analogues. Conversely, premixed regimens are relatively inflexible with their fixed ratio between the fast- and long-acting components. They can be difficult to intensify, because of risk of hypoglycaemia and weight gain.

Longterm complications of diabetes

Diabetes mellitus is a long-term disorder associated with a number of clinical problems causing ill health and death. Disease affecting the small blood vessels in the retina, kidney, and peripheral nerves appears to be most directly related to the duration and severity of the raised blood glucose (hyperglycemia). These complications are termed microvascular and may result in blindness, chronic renal failure requiring dialysis, and nerve damage to the feet contributing to the formation of foot deformity and ulceration. Large blood vessels are also affected ( macrovascular disease) in the heart, brain, and peripheral circulation. People with diabetes have higher rates of coronary heart disease,4849 stroke,50 and peripheral vascular disease51 compared to similar subjects of the same age and sex. This contributes significantly to the higher rates of ill health and early death in people with diabetes.

Mechanisms Of Action In Humans Glucose Production

Accelerated endogenous glucose production is thought to be a key factor in the development of fasting hyperglycemia in type 2 diabetes (21,22). In patients with type 2 diabetes metformin has been shown to inhibit endogenous glucose production in most (23-29), but not all studies (summarized in Ref. 30) to various degrees (from a nonsignificant 10 up to a significant 30 (Fig. 4) (30). This could largely be accounted for by inhibition of gluconeogenesis (24,31) although an additional inhibitory effect of metformin on glycogen breakdown is likely (24,25). The observation in many studies that in the basal postabsorptive state overall glucose disposal (metabolic plasma clearance rate of glucose) did not change while endogenous glucose production decreased (23-25,28,29,32) suggests that the improvement in glycemic control is largely attributable to the effect of metformin on glucose production.

Clinical Presentation Of Type Diabetes In The Elderly Diagnosis

Criteria for the diagnosis of diabetes by American Diabetes Association (ADA) or World Health Organization (WHO) criteria do not differ by age (14,15). However, there are important differences in the characteristic glucose profile of older adults. Fasting glucose levels increase modestly with age, but a more dramatic increase in post-challenge (or postprandial) glucose levels has been reported in most studies (Fig. 2) (16,17). In fact, the increased prevalence of undiagnosed diabetes and IGR in the elderly population is primarily a consequence of the substantial increase in post-challenge, rather than fasting, hyperglycemia. New cases of diabetes (which account for approximately half of diabetes cases in people 65 years) may be missed if fasting glucose levels alone are used for diagnosis (18). Screening for diabetes using an oral glucose tolerance test (OGTT) has the added advantage of detecting the presence of IGT, thus allowing for appropriate interventions aimed at reducing...

Priority Aims and Suggested Measures

A multifactorial intervention targeting hyperglycemia and cardiovascular risk factors in individuals with diabetes is most effective. Both individual measures of diabetes care as well as comprehensive measures of performance on multifactorial interventions are recommended. A randomized controlled trial has shown a 50 reduction in major cardiovascular events through a multifactorial intervention targeting hyperglycemia, hypertension, dyslipidemia, microalbuminuria, aspirin and ACE inhibitor use in individuals with microalbuminuria (Gaede, 2003).

Mechanisms Of Pkcactivation

Diabetes and by hyperglycemia appears to be related to increase in de novo synthesis of DAG through glycolytic pathway 15, 18 . It is also possible that the increases in free fatty acids in diabetic state may enhance the synthesis of DAG levels 25, 27-29 . We and others have found that the elevation of DAG level is directly responsible for the activation of PKC in glomeruli of diabetic rats and cultured mesangial cells exposed to high glucose concentrations 15, 17, 30 . The role of increasing DAG in causing PKC activation by hyperglycemia is support by the studies of using high doses of vitamin E or inhibitors of DAG kinase which decrease the metabolism of DAG to phosphatidic acid 31 . Vitamin E treatment at high doses, equivalent to 1500-1800 unit day, in animal models of diabetes and in diabetic patients, improved renal hyperfiltration associated with normalization of DAG PKC pathway through activation of DAG kinase 32, 33 .

Increased Mitochondrial Electron Transport

In many cell types under physiological conditions, mitochondria are the major intracellular source of ROS production (39). In an elegant series of studies conducted predominantly in cultured bovine aortic endothelial cells, Brownlee and coworkers (34) implicated overproduction of superoxide by the mitochondrial electron transport chain, induced by hyperglycemia and or fatty acids, as a potential major source of ROS generation in diabetes. Overproduction of superoxide by mitochondria, in turn, may be a key mechanism by which hyperglycemia increases activity of the polyol and hexosamine pathways, the formation of AGE and activation of protein kinase C (PKC), all of which have been implicated in the pathogenesis of vascular and renal injury in diabetes (34). This proposed common pathogenetic mechanism for expression of multiple cellular actions of high ambient concentrations of glucose has previously been reviewed in detail by Brownlee et al. (34). Briefly, in cells in which glucose...

Survey of Every Patient with Diabetes

Treatment with diet should be started. Only in patients with the classic symptoms of hyperglycemia and blood glucose levels 20 mM should insulin therapy be considered at this point. Sometimes, external factors are responsible for hyperglycemia infection, psychological stress and increased a glucose intake. It is wise to wait for a while on the results of educational and dietary measures before starting tablets or insulin.

Combined with fetal growth

Tight glucose control I have religiously clung to the notion that maternal hyperglycemia is the root of all evil in pregnancies complicated by diabetes. What persuaded her to question her opinion and the approach she had practiced for decades As mentioned earlier there is evidence that rising maternal glycemia implicates a risk for diabetes-related morbidity for the offspring not only in preexisting diabetes but also in GDM. Blinded evaluation of maternal glucose values has demonstrated a slow and continuous increase in complications, mainly macrosomia and C-section, in the prediabetic glucose range (15). However, while there might be a definable glucose threshold for an increased risk of congenital abnormalities (16, 17), there does not seem to be a clear threshold for macrosomia or other neonatal complications that are the major concerns in GDM. Maternal glucose and excessive growth do not correlate in a linear fashion, and the development of macrosomia seems to be only partly...

Maternal Diabetes Does It Matter Which Type

In a study of IGT in the offspring of mothers with type 1, type 2 and gestational diabetes, Silverman et al. found that the risk of IGT was not different by type of maternal diabetes (26). Rather, IGT was closely related to the amniotic fluid insulin levels, which are indicative of the degree of fetal hyper-insulinemia. Sobngwi et al. also confirmed that IGT and defective insulin secretory response in adults are associated with exposure to pregestational type 1 diabetes in utero (43). The control population in this study was a group of adult offspring of fathers with type 1 diabetes, in order to control for confounding by genetic susceptibility. These results further support the conclusion that hyperglycemia and other fuel alterations in pregnancies complicated by diabetes, and not the etiology of the mother's diabetes, are the important factors influencing risk of obesity and glucose metabolism abnormalities in the offspring. In the Pima Indian population, Franks et al. found that...

Abnormalities in coagulation

Attention has been directed at fibrinogen levels and dynamics in diabetes for a variety of reasons. The most important one is the fact that the plasma level of fibrinogen has been shown to be an independent risk factor for thrombotic events in population-based studies (260-262). In diabetes, plasma fibrinogen levels are found to be elevated, particularly in patients with hyperglycemia (263-265). Insulin deficiency leads to an increase in fibrinogen synthesis in IDDM, and infusion of insulin will decrease the fibrinogen synthetic rate (266). Interestingly, fibrinogen survival is decreased in diabetes, and this abnormality can be reversed by administration of insulin or by administration of heparin, suggesting that intravascular fibrin formation may be taking place (262). Exercise may also affect plasma fibrinogen and it has been shown that exercise conditioning will lower plasma fibrinogen levels in NIDDM individuals (267). The above findings suggest that there may be increased fibrin...

Gene Expression Profiling in Diabetic Nephropathy With Structure Function Correlation

To screen for genes that show correlation with different phenotypic outcome in diabetic mouse models, we used a cross-sectional design and performed microarray analysis on 24-wk-old STZ-treated C57B6J and 129svJ mice and db db mice with established renal pathology (22). In parallel with functional genomics characterization, each individual mouse underwent a detailed renal phenotype analysis. Mice treated with low-dose STZ (50 mg kg ipx5 doses) developed diabetes and moderately severe albuminuria (twice the control). In mice with C57B6 J background, the mesangial changes were mild or absent. Mice with 129SvJ genetic background, developed significant glomerular changes. However, these were not significantly different from the age-matched controls. The db db mice are insulin resistant and developed type 2 diabetes at 8 wk of age. Albuminuria was detected as early as 3-4 wk after the development of hyperglycemia. The glomerular histology was characterized by severe diffuse mesangial...