Natural Treatment to Reverse Diabetes

Reverse Diabetes Now

Reverse Your Diabetes Today by Matt Traverso can be described as comprehensive eBook that reveals what can you do to reverse diabetes, what can you eat to reverse diabetes and what can reverse type 2 diabetes and part 1 diabetes conditions by natural means with 3 short weeks or fewer. Reverse Your Diabetes today is presented especially for those who are experiencing difficulty with their blood sugar levels. Within this book, readers will learn a step-by-step customized formula that helps to normalize their blood sugar levels and stop type-2 diabetes permanently. The best thing about this e-book is that it is very simple to apply. All recommendations that this treatment offers can be implemented by users at their own home and own pace. Reverse Diabetes Today PDF is an extremely comprehensive treatment that encourages people to make positive changes in daily habits, more concretely, dieting, regularly exercising, and weight managing routines to reverse diabetics. More here...

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Understanding Diabetes

Diabetes mellitus, or diabetes, is an illness in which there is an abnormally high level of glucose in the blood. Depending on how high your glucose level is and how long it has been high, you may feel fairly well, or you may be so sick that you require hospitalization. Usually, your doctor will test you for diabetes if you have symptoms such as thirst, frequent urination, weight loss, blurred vision, and fatigue. This chapter helps you understand how diabetes is defined and classified and how physicians test for the disease. The liver is in charge of taking up and releasing glucose into the bloodstream. After a meal, the blood carrying nutrients from digestion first flows through the liver, which removes the excess glucose. When the glucose level in the blood drops (for example, after fasting or exercising), the liver does the opposite and releases glucose into the bloodstream. The liver knows how to regulate the level of glucose in the blood because it receives signals from...

Carbohydratesinsulin resistance

Pregnancy is hyperlipidaemic and glucosuric. Although neither the absorption of glucose from the gut nor the halflife of insulin seems to change and the insulin response is well-maintained, by 6-12 weeks gestation, fasting plasma glucose concentrations fall by 0.11 mmol l, and by the end of the first trimester the increase in blood glucose following a carbohydrate load is less than outside pregnancy 12 . This increased sensitivity stimulates glycogen synthesis and storage, deposition of fat and transport of amino acids into cells. The uptake of amino acids by the mother for glu-coneogenesis may also be enhanced. Aftermid-pregnancy, resistance to the action of insulin develops progressively and plasma glucose concentrations rise, though remaining below non-pregnant levels (Fig. 2.7). Glucose crosses the placenta readily and the fetus uses glucose as its primary energy substrate, so this rise is presumably beneficial to the fetus. Fetal and maternal glucose concentrations are...

Other Types Of Diabetes

There are less common forms of diabetes in which there is a specific cause for the beta cell failure or problems with insulin function. Some of these conditions are extremely rare, so I discuss only the more common ones in the following sections. Diabetes Due to Gene Mutations Maturity onset diabetes of the young (MODY) refers to diabetes that occurs in childhood or adolescence (before age twenty-five) and is inherited in an autosomal dominant fashion that is, if you have the condition, half of your children are also likely to have it. About one in one hundred people with diabetes have MODY. There are six known genetic defects for this kind of diabetes. One of the genetic defects (called MODY 2) is in the gene that enables the beta cells to sense the body's glucose level (the glucose kinase gene) and so regulate insulin release. MODY 2 is usually easily controlled with oral medications that stimulate insulin release. People with this type of diabetes are usually not obese. About one...

Diabetic Amyotrophy And Mononeuropathies In Persons With Diabetes

There have been no prospective, population-based studies of diabetic amyotrophy and mononeuropathies in subjects with diabetes. However, some prevalence figures for these types of neuropathy can be derived from a few cross-sectional studies. In a cross-sectional survey based in Rochester, Minnesota, asymptomatic carpal tunnel syndrome (CTS) was found in 22 of those with type 1 diabetes and 29 of those with type 2 diabetes, whereas the corresponding prevalence for symptomatic cases was 11 and 6 , respectively (40). Ulnar and femoral cutaneous entrapment was found in 2 of type 1 diabetes and 1 of type 2 diabetes subjects. Cranial mononeuropathy and trun-cal radiculopathy were not observed in the Rochester population, whereas proximal asymmetric polyneuropathy was identified in 1 of type 1 diabetes and type 2 diabetes subjects (40). No incidence data were available for any of these types of neuropathy. In a cross-sectional, hospital-based study, O'Hare et al. (41) studied the presence of...

Diabetes And Problems With Skin And Nails

There are a number of skin and nail problems that are more commonly seen in people with diabetes. These include the following Acanthosis nigricans, a darkening of the skin at the back of the neck and under the armpit. The skin has a velvety feel. This condition occurs in people with type 2 diabetes who are very insulin resistant. It does not require any treatment. Necrobiosis lipoidica diabeticorum. This is seen mostly in people with type 1 diabetes. There is a thinning of the skin on the shins with a reddish yellowish discoloration. Sometimes it can be ulcerated in the middle. Treatment is usually with steroid injections or creams. Lipohypertrophy, a localized swelling, is caused by repeated insulin injections in one spot. Insulin absorption becomes more erratic in these areas. Stopping injections of insulin in the affected area usually leads to recovery. Shin spots, or diabetic dermopathy, are brown, oval patches on the shins (and sometimes on the forearms) of people with diabetes....

Autoantibodies in diabetes complications

The lack of an immune response to self when responses to environmental antigens are retained is due to immunological tolerance. The role of tolerance, or lack of tolerance, is important to the understanding of autoimmune diseases and transplantation immunobiology (Mackay 2000). A loss of natural tolerance (to self) underlies all autoimmune diseases. Many more individuals develop autoimmune phenomena than autoimmune disease. Immune-mediated (Type I) diabetes results from an organ-specific autoimmune-mediated loss of insulin-secreting P cells. This chronic destruction process involves both cellular and hormonal components detectable in the peripheral blood, months or even years, before the onset of clinical diabetes (Kukreja & Maclaren 1999). In order to elicit an immune response, a molecule must be recognized as non-self by the biological system. Proteins containing AGE are highly immunogenic and anti-AGE antibodies have been found in the sera of patients with diabetes (Reddy et...

Diabetes And Circulatory Problems

People with diabetes, especially those with type 2 diabetes, are two to five times more likely to have problems with circulation to the heart, the legs, and the head when compared to individuals without diabetes. This is because diabetes predisposes a person to a condition called atherosclerosis. If you imagine a blood vessel as a water or drainage pipe, then atherosclerosis is buildup in the pipe narrowing the channel and impairing the flow. In the case of the blood vessel the buildup, called plaque, consists of a core of inflammatory cells, cholesterol, and lipids with a fibrous cap of smooth muscle cells (see Figure 3-1). The plaque can narrow the blood vessel, impairing blood flow. Occasionally the fibrous cap can rupture, and when this happens a blood clot forms, causing an acute blockage of the blood vessel. If the acute blockage happens in one of the blood vessels to the heart, it results in a heart attack. If it occurs in one of the blood vessels supplying brain tissue, it...

Diabetes And Erectile Dysfunction

The ability to get an adequate erection depends upon adequate blood flow to the penis and intact nerve function. Men with diabetes whose nerves to the penis are damaged and or whose blood supply to the penis is reduced may not be able to get a strong erection. Before blaming nerve damage and blood supply problems for erectile dysfunction, however, it is important to exclude other causes such as low testosterone levels, medicines (for blood pressure and depression), alcohol, and cannabis (marijuana). Psychological issues such as depression, job stress, and other relationship problems may also contribute to erectile dysfunction. two hours, with some effect persisting for four hours. In clinical studies, people with diabetes mellitus using sildenafil reported 50 to 60 percent improvement in erectile function. The recommended doses of both vardenafil and tadalafil are 5 to 20 mg. Tadalafil has been shown to improve erectile function for up to thirty-six hours after dosing. In clinical...

Diabetes And Female Sexual Dysfunction

Women with diabetes are at increased risk for sexual arousal disorder that is, inadequate vaginal and clitoral swelling in response to sexual arousal. A small research study showed that in women with type 1 diabetes, sildenafil improved arousal, orgasm, and sexual enjoyment. A woman with diabetes should discuss problems of sexual arousal with her physician. The symptoms of diabetes depend upon the degree of insulin deficiency If the insulin deficiency is modest so that the glucose levels are only slightly elevated, there may be no symptoms and diabetes may be discovered on routine testing. If the insulin deficiency is moderate, the presentation may be of bladder infection, vaginal or penile yeast infection, or increased nighttime urination. If the insulin deficiency is severe, there may be thirst, frequent urination, weight loss, tiredness, and blurred vision. If untreated there can be progression to diabetes ketoacidosis (in type 1 patients) or hyperosmolar coma (in type 2 patients).

Autonomic Nervous System Diabetes Mellitus

It is well recognised that lower gastrointestinal symptoms, including diarrhoea and incontinence, are frequently reported by patients with diabetes, more so than in the general population, although the patho-genesis is unclear. A prevalence of 7 among a cohort of 540 diabetics has been reported 38 , with some degree of symptom fluctuation (improvement in some, new onset in others) over time. Abnormal gastrointestinal sensorimotor function (including internal sphincter dysfunction 39 and blunted rectal sensitivity) secondary to autonomic neuropathy, glycaemic control and psychological and sociodemo-graphic factors all contribute. However, within the limitations of those studies performed, symptoms suggestive of peripheral (and by inference, autonomic and enteric) neuropathy appear to be the strongest independent risk factors. Pudendal neuropathy may be found, associated with external sphincter weakness, and rapid transit of loose stool to the rectum may occur secondary to bacterial...

Certified Diabetes Educator

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

The ADA and Other Sources of Diabetes Related Information

The American Diabetes Association has an excellent website, and it also publishes many self-help books for patients. You can also seek out local diabetes support groups through your local hospital or pharmacist or by searching on the Internet. There are support groups that cater to people with type 1 and type 2 diabetes, those using insulin pumps, and families who have children with diabetes. These groups enable people with diabetes to share experiences and enhance their knowledge about diabetes self-management. There are also many Internet websites devoted to diabetes. They vary in the quality of information they provide, so you may want to go to the websites of professional organizations like the ADA first. You can also look at the Canadian Diabetes Association and the British Diabetes Association websites (see Resources). Once you get good basic information, then you can go to websites that cater to specific issues like insulin pumps or diabetes and exercise. Information about...

Physiopathology of diabetes chronic complications

According to what has already been said, diabetes chronic complications occur as a consequence of persistent hyperglycemia (7). Hyperglycemia, in turn, promotes glucose auto-oxidation, AGEs formation and its interaction with RAGEs, activation of several isoformes of PKC, induction of poliol pathway and an increase of flux of hexosamine pathway (7). Mitochondrial role in retinopathy pathogenesis is supported by reports which show that retinal mitochondria presents a dysfunction in diabetes (30,31). Eight-month diabetic rats (a duration in which capillary cell apoptosis is seen in retina) present an increase of citocrome c release in citosol and of Bax pro-apoptotic protein in mitochondria (30,31). Besides, incubation of retinal capillary cells in a hyperglycemic environment results in these precise abnormalities, which are accompanied by increased cellular apoptosis (30).

Diabetes Medications 101

Let me make a few general comments about diabetes medications before I discuss them in detail in the following sections. Medicines for diabetes are only one component of the treatment of diabetes. To be successful in controlling the diabetes, you also need to consider other aspects of diabetes care, such as diet and exercise. Whether a specific medicine is suitable for you depends on The type of diabetes you have The discussion of medicines is complicated by the fact that each drug has at least two names the proprietary or brand name given by the pharmaceutical company and the generic name. After the pharmaceutical company patent runs out, a number of less expensive generic versions of the medicine become available. In my experience, generic diabetes medicines work just fine, and if one is available, I would switch to a generic drug. The tables in this chapter list the medicines by the generic names and the brand names. In the text of this chapter and the rest of the book, I refer to...

Expression of the Renin Angiotensin System in Diabetes

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

Type 2 diabetes and igt

Type 2 diabetes in the United States is increasing at an alarming rate it is predicted that as many as 10 of the country's population will have diabetes by the year 2025 (83). Individuals with type 2 diabetes pass through a stage of IGT prior to diabetes onset (Fig. 1) (84,85). Depending on the criteria used for the diagnosis of IGT, 30-40 million Americans now have IGT, with 20 or more of the elderly being affected (86). This compares with the 16 million individuals who now have type 2 diabetes. As the average lifespan of Americans continues to increase, the frequency of progression of IGT to type 2 diabetes will also probably increase. IGT has two major associated problems increased cardiovascular disease and the progression to type 2 diabetes. The risk of cardiovascular disease with IGT is not as great as that seen in overt type 2 diabetes, but it is clearly greater than in age-matched controls (87). Progression to type 2 diabetes increases if individuals with IGT decrease their...

Role of the reninangiotensin system in cardiovascular disease in diabetes

As reviewed elsewhere in this book, multiple factors, including hyperglycemia, insulin resistance, dyslipidemia, hypercoagulability, and inflammation contribute to the pathogenesis of atherosclerosis in DM. Although there is considerable evidence for a role of the RAS in vascular remodeling, inflammation, thrombosis, and atherogeneis (81-83), the role of this system in atherosclerosis in the context of the other diabetes-associated cardiovascular risk factors is not fully understood. There is a growing body of evidence from both clinical studies and experiments in diabetic rodent models suggesting that the RAS contributes to CVD in both type 1 and type 2 diabetes.

Outcomes in Diabetic Patients

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

Diabetes Medicine Combinations

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

Description Medical Diabetes

Diabetes mellitus (DM) is a chronic disorder of carbohydrate, protein, and fat metabolism in which there is a discrepancy between the amount of insulin required by the body and the amount of insulin available. DM affects over 10 million persons in the United States, and more than 35,000 people die from it each year. DM is classified into several categories (Table 1). The beta cells of the pancreas produce insulin and a protein called C-peptide, which are stored in the secretory granules of the beta cells and are released into the bloodstream as blood glucose levels increase. Insulin transports glucose and amino acids across the membranes of many body cells, particularly muscle and fat cells. It also increases the liver storage of glycogen, the chief carbohydrate storage material, and aids in the metabolism of triglycerides, nucleic acids, and proteins. Long-term complications such as disease of the large and small blood vessels lead to cardiovascular disease (coronary artery disease,...

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

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

Fastacting Insulin Preparations

There are four fast-acting insulin preparations Regular insulin Insulin lispro Insulin aspart Insulin glulisine Table 6-9 Characteristics of the Currently Available Insulins Table 6-9 Characteristics of the Currently Available Insulins Insulin Preparations Insulins lispro, aspart, glulisine Insulin glargine Insulin detemir

The Technical Side of Regular Insulin

Regular insulin consists of aggregates of six molecules of insulin complexed to two zinc ions (a hexamer). After subcutaneous (under the skin) injection, the regular insulin hexam-ers become diluted by the tissue fluids and become monomers (single molecules), which then enter the circulation and have their effects. a shorter period of time about four hours (rather than six hours). These properties make these insulins more effective at controlling the glucose rise after meals. Clinical studies have shown that when these insulin analogs are used in an optimal manner, you can achieve improved glucose control with less risk of hypoglycemia. However, there are some cautionary notes first, because the peak level of the insulin with the analogs is higher after a meal, it is important for you to be more precise in counting the carbohydrates you are consuming. Regular insulin is more forgiving of errors in carbohydrate counting. Also, if you were to consume a very fatty meal, which delays...

Longacting Insulin Preparations

There are three long-acting insulin preparations NPH insulin Insulin glargine (brand name Lantus) Insulin detemir (brand name Levemir) Mixing regular insulin with a fish protein called protamine forms a crystal (neutral protamine Hagedorn, NPH), which dissolves slowly when injected subcutane-ously, so that the effect on average lasts for about eight hours (shorter duration for very small doses and longer duration for large doses). The crystals of NPH insulin appear white to the naked eye, and they tend to settle in the insulin vial. This is why you should mix the NPH insulin (by rolling the bottle between the palms of your hands) before drawing it up in the syringe. Insulin glargine is human insulin that is modified so that it is soluble in a more acidic solution. It looks clear in the bottle, and when injected it precipitates in the tissues and is then slowly released into the bloodstream. Since it is acidic, the manufacturer recommends it should be given as a separate injection and...

And Insulin Sensitivity

There is growing evidence that inhibition of the RAS system by either ACE inhibition or AT1 receptor antagonism can increase insulin sensitivity and glucose utilization. Studies using euglycemic hyperinsulinemic clamps have shown that ACE inhibitor treatment improves insulin sensitivity in most (136-140), but not all (141,142) individuals with hypertension, obesity, and or type 2 diabetes. Similarly, although ATI antagonism has been reported to improve muscle sympathetic nerve activity and insulin sensitivity in obese hypertensive subjects (143) and increase basal and insulin-stimulated glucose oxidation in normotensive individuals with type 1 diabetes (144), other clinical studies have not observed improvement on insulin sensitivity and glucose homeostasis following treatment with AT1 receptor antagonists (139,145,146). In experimental rodent models, ACE inhibition has been shown to enhance glucose transport skeletal muscle and adipose tissue in insulin-resistant obese Zucker rats...

Insulin resistance is a state of inflammation

In addition to the fact that components of the metabolic syndrome contribute to cardiovascular disease, increasing data suggests insulin resistance is a proinflammatory state in itself. Adipose tissue secretes substances (adipokines) that decrease insulin-mediated glucose uptake and or promote vascular inflammation (Table 3). Adipocytokines circulate at higher levels in obese animals or in humans with increased viceral adiposity. Tumor necrosis factor-a (TNF-a) directly suppresses activation of tyrosine kinase on the insulin receptor, resulting in insulin resistance (22). TNF-a levels are not only high in atherosclerotic vessels, promoting inflammation, but are elevated in damaged myocardium and have been implicated in heart failure (23). Adiponectin (Acrp 30) also arises from fat but, in contrast to TNF-a, is low in the circulation of obese humans and animals, enhances insulin-mediated glucose uptake, and inhibits inflammatory responses (24). Leptin is another substance from fat...

Insulin Preparations Available in the United States

Short-Acting Insulins Regular insulin Insulin lispro (Humalog) Insulin aspart (Novolog) Insulin glulisine (Apidra) Long-Acting Insulins NPH insulin Insulin glargine (Lantus) Insulin detemir (Levemir) Premixed Insulins 70 percent NPH 30 percent regular (70 30 insulin) 50 percent NPH 50 percent regular (50 50 insulin) 75 percent NPL 25 percent insulin lispro (Humalog Mix 75 25) 50 percent NPL 50 percent insulin lispro (Humalog Mix 50 50) 70 percent insulin aspart protamine 30 percent insulin aspart (Novolog Mix 70 30) Inhaled Insulin Exubera (1 mg and 3 mg blister packets of powdered regular insulin)

Renin Angiotensin System Inhibition and New Onset Diabetes

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

Exubera Inhaled Insulin

Inhaled insulin is not a new insulin it is simply an old insulin (regular insulin) that is delivered into the body in a different way. You use an inhaler (very much like an asthma inhaler) to inhale the insulin powder, which is available in 1 mg and 3 mg blister packs. The 1 mg pack is equivalent to 3 units of insulin, and the 3 mg pack is about 8 units of insulin. Three 1 mg inhalations are not equivalent to one 3 mg inhalation you get one-third more insulin with the former. This is because three separate inhalations result in more insulin being absorbed than one larger-dose inhalation. Only about 10 percent of the delivered dose gets into the circulation, so an average adult has to inhale 300 to 400 units of insulin a day. The inhaled insulin is rapidly absorbed the insulin profile is very much like the injected fast-acting insulin analogs, except it lasts longer (up to six hours). The biggest unanswered question about inhaled insulin is whether it will damage the lungs if used for...

The role of insulin sensitizers

Activation of peroxisome proliferator-activated receptor-y (PPAR-y), in adipose tissue restores the adipokine balance to increase insulin sensitivity and to decrease vascular inflammation (32). The decrease in FFAs, TNF-a, leptin, and other adipokines and the reciprocal increase in adiponectin that occurs with PPAR-y ligand thiazolidinedione (TZD) administration probably contributes to the action of these ligands to enhance insulin-mediated glucose uptake. Because of these changes and the decrease in PAI-1 and IL-6, PPAR-y ligands also appear to attenuate the proinflammatory state. In addition, the ligands directly LDLR- - on high-fat diet (insulin-resistant diabetes model) I TRO (34) I RSG (35) I GW7845 (35) LDLR- - on high-fructose diet (non-insulin-resistant model) inhibit inflammatory processes in monocytes macrophages including cell migration and attachment, intercellular nitric oxide synthase (iNOS), interleukin, matrix metalloproteinase (MMP), and superoxide dismutase (SOD)...

Using An Insulin Pump

An insulin pump is a device the size of a pager. It contains a syringe or reservoir filled with a fast-acting insulin, a battery-powered syringe plunger, and a small computer to control the insulin delivery. The syringe is attached to tubing, which in turn is attached to a small plastic tube (cannula) inserted under the skin (see Figure 6-1). The pump can be programmed to put tiny drops of insulin into the subcutane- Figure 6-1 Insulin Pump ous tissues every three to ten minutes day and night this is the basal insulin. When you eat, you can program the pump to give a bolus of insulin for the food. Thus, when you are on the pump, you use only a fast-acting insulin to provide both your basal and bolus needs. Often, people with type 1 diabetes will decide to go on an insulin pump for their diabetes control. The pump does not check glucose levels, nor does it decide how much insulin to give. It does allow you to tailor your basal insulin to your needs. With a pump, you are better able to...

Spinal Electrophysiology In Diabetes

There have been occasional reports of conduction slowing in the spinal cord of diabetic rats as early as 2 weeks after onset of hyperglycemia (49), although others reported that months of diabetes were required to show slowing in both ascending and descending tracts (50,51). Again, little is known about the pathogenesis of the disorder and the extent to which it mirrors the early metabolic and later structurally mediated aetiology of PNS conduction slowing has not been established, although conduction slowing in the PNS does appear to precede that in the CNS (51). It may be worth noting that glucose levels in spinal cerebrospinal fluid of diabetic rats are markedly lower than in plasma of the same animals (52), so that spinal axons and lower motor neuron cell bodies are exposed to less glycemic stress than their PNS counterparts. Characterization of the response properties of spinal neurons that are triggered by peripheral sensory stimuli have been studied only in rats with short-term...

Spinal Neurochemistry In Diabetes

The structural and electrophysiological properties of the spinal cord during diabetes described earlier present a picture that resembles the paradox often noted in studies of the peripheral nerve, namely structural and electrophysiological indices of progressive degeneration and functional loss that are accompanied by increased activity in some sensory fibers and associated with hyperalgesia, allodynia, or spontaneous pain. There has been speculation that the spontaneous or enhanced activity of spinal sensory pathways is responsible for diabetic neuropathic pain and is secondary to enhanced excitatory input from peripheral nerve primary afferent fibers. This is difficult to verify in clinical studies, whereas evidence of spontaneous or exaggerated evoked activity of primary afferents in animal models of diabetes has been reported in some studies (56-59) but also discounted in others (60,61). Of course, electrical activity of sensory fibers is only one component of any altered input to...

Setting Up Your Insulin Pump

Show you how to fill a reservoir without getting bubbles and how to prime the tubing. An inch of bubble in your tubing is equivalent to half a unit of insulin. Thus, having bubbles in your tubing can reduce the amount of insulin you are getting and can lead to high glucose levels. Once the tubing is primed, you can insert the infusion set and attach the tubing. A 0.3- to 1.0-unit bolus may be needed to fill the dead space in the infusion set. The pump trainer should teach you how to use a pump using saline (salt water, as opposed to insulin). Ideally, you should do this for about a week before your planned initiation of insulin in the pump. During this time, you can practice changing sets, filling reservoirs, priming tubes, and adjusting basal and bolus doses.

Peroxisome Proliferator Activated Receptory Key Regulator of Adipogenesis and Insulin Sensitivity

PPAR-y was first identified as a part of a transcriptional complex essential for the differentiation of adipocytes, a cell type in which PPAR-y is highly expressed and critically involved (6). Homozygous PPAR-y-deficient animals die at about day 10 in utero as a result of various abnormalities including cardiac malformations and absent white fat (7-9). PPAR-y is also involved in lipid metabolism, with target genes such as human menopausal gonadotropin coenzyme A synthetase and apolipoprotein (apo)-A-I (10,11). Chemical screening and subsequent studies led to the serendipitous discovery that thiazolidinediones (TZDs) were insulin sensitizers that lower glucose by binding to PPAR-y. Used clinically as antidiabetic agents, the TZD class includes pioglitazone (Actos) and rosiglitazone (formerly BRL49653, now Avandia) (12,13). Troglitazone (ReZulin) was withdrawn from the market because of idiosyncratic liver failure. Naturally occurring PPAR-y ligands have been proposed, although with...

The Cure for Type 1 Diabetes

A pancreas transplant will cure type 1 diabetes. So why doesn't everyone with type 1 diabetes get a pancreas transplant There are two reasons. First, there are only a limited number of donor pancreata available a few thousand whereas there are about a million people with type 1 diabetes. Second, people who get an organ transplant have to be on medicines to prevent the body's immune system from attacking and rejecting the organ. These immunosuppressive medicines have serious side effects, such as making the individual more susceptible to infections and increasing the risk of developing a cancer in the future. You are likely to be offered a pancreas transplant if you have kidney failure and you are on a list for a donor kidney. Because getting two organs simultaneously has additional risks, some restrictions do apply. For example, if you have a history of heart attacks or strokes, you may not be a candidate for simultaneous pancreas-kidney transplant. A pancreas transplant alone that...

Stacking Insulin and Overaggressive Treatment of High Glucose Levels

Some people with diabetes do not like their glucose levels to be high, and they treat every high glucose level aggressively. These individuals who stack their insulin that is, give another dose of insulin before the first injection has had its full action can leave themselves open to hypoglycemia. A common mistake is to give insulin before a meal and then check the glucose level again an hour or two later and give additional insulin without realizing that the premeal insulin is still getting absorbed. To protect against stacking, the new insulin pumps have an insulin-on-board feature that keeps track of when the last insulin bolus was given and will remind the user that some of the previous insulin bolus is still getting absorbed if they attempt to give additional insulin.

Diabetes and vascular disease

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

Platelet function in subjects with diabetes mellitus

The activation of platelets and their participation in a thrombotic response to rupture of an atherosclerotic plaque are critical determinants of the extent of thrombosis, incremental plaque growth, and the development of occlusive thrombi. Increased adherence of platelets to vessel walls manifesting early atherosclerotic changes and the release of growth factors from a-granules can exacerbate the evolution of atherosclerosis. Patients with diabetes, particularly those with macrovascular disease, have an increased circulating platelet mass secondary to increased ploidy of megakaryocytes (28). Activation of platelets is increased with type 2 diabetes. This is reflected by increased concentrations in urine of a metabolite of thromboxane A2, thromboxane B2, and by the spontaneous aggregation of platelets (29-31) in blood. The prevalence of spontaneous aggregation of platelets correlates with the extent of elevation of concentrations of hemoglobin (Hb)A1c (30). Stringent glycemic control...

Conclusion Linking Microvessels Diabetes And Neuropathy

Examples of sciatic nerves from nondiabetic (left) and diabetic (right) rats perfused with India ink to outline vasa nervorum in the distal nerve stump 2 weeks following transection. Note the large number of perfused vessels in epineurial area of the nondiabetics, but fewer in diabetics. (Bar 1 mm) (Reproduced with permission from ref. 134.)

Mechanisms responsible for hyperreactivity of platelets in people with diabetes

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

Antiplatelet therapy and diabetes

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

Insulin like Growth Factor IGFI

IGF-I is a polypeptide showing high similarity to insulin. Two different forms are distinguished IGF-I and IGF-II. IGF-I circulates in blood in the form of IGF-binding protein (IGF-BP), probably inhibiting activity of free IGF. IGF-I is a pivotal growth factor secreted as a result of stimulation by human growth hormone. Both in vivo and in vitro studies indicate its anti-apoptotic and anti-inflammatory properties (Goes et al., 1996 Sukhanov et al., 2007 Sun et al., 2010). There are reports that IGF-I has protective actions in ischaemic rat kidney due to inhibition of inflammatory cytokine production (Goes et al., 1996) and anti-apoptotic in Parkinson disease via inhibition of GSK-3P signalling pathway (Sun et al., 2010). IGF-I exerts its protective actions also in central nervous system and cardiomyocytes (Sun et al., 2010). In premature babies a small concentration of IGF-I is a risk factor of retinopathy of prematurity (Perez-Munuzuri et al., 2010). IGF-I deficiency after birth may...

Mechanisms responsible for a prothrombotic state associated with diabetes

Patients with DM have increased concentrations in blood of the prothrombotic factors fibrinogen, von Willebrand factor, and factor VII coagulant activity (77-79). Among the three coagulation factors, fibrinogen has been most strongly associated with the risk of development of CVD (80). Although the mechanisms responsible for increased concentrations of fibrinogen and von Willebrand factor have not yet been fully elucidated, elevated concentrations in blood of insulin and proinsulin may be determinants in people with type 2 diabetes. This possibility is suggested by the close correlation between concentrations of fibrinogen with those of insulin and proinsulin in healthy subjects (81). Because prediabetic subjects and people with early stages of diabetes have marked insulin resistance that leads to a compensatory increase in the concentrations in blood of insulin and proinsulin (82-84), the hyper(pro)insulinemia of type 2 diabetes is likely to underlie, at least in part, the typically...

Diabetes and fibrinolysis

Decreased fibrinolytic system capacity is observed consistently in blood from patients with DM, particularly those with type 2 diabetes (93,94). It has been known for many years that obesity is associated with impaired fibrinolysis (95) that elevated blood triglycerides and other hallmarks of hyperinsulinemia are associated with increased activity of PAI-1 (96) and that elevated PAI-1 is a marker of increased risk of acute MI as judged from its presence in survivors compared with age-matched subjects who had not experienced any manifestations of overt CAD (97). We found that impaired fibrinolysis in subjects with type 2 DM, not only under baseline conditions but also in response to physiological challenge, was attributable to augmented concentrations in blood of circulating PAI-1. Furthermore, obese diabetic subjects exhibited threefold elevations of PAI-1 in blood compared with values in nondiabetic subjects despite tissue-type plasminogen activator (t-PA) values that were virtually...

Effects of growth hormone and insulinlike growth factor 1 deficiency on ageing and longevity

Endocrinology & Diabetes Research Unit, Schneider Children's Medical Center of Israel and Sackler Faculty of Medicine, Tel Aviv University, Israel Abstract Present knowledge on the effects of growth hormone (GH) insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGF1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding...

Improving The Oral Activity Of Calcitonin And Insulin Through Chemical Modification

Insulin is the major hormonal regulator of glucose metabolism. It is a 51-amino acid polypeptide that is produced and secreted by the p-cells of pancreatic islets.64'65 All known vertebrate insulins are composed of two polypeptide chains that are linked to one another by two disulfide bonds, one between CysA7 and CysB7 and the other between CysA20 and CysB19. A third, intrachain disulfide bond connects CysA6 and A11. The amino acid sequence among vertebrate species is also highly conserved. One-third of the amino acid residues in the two insulin chains are strictly invariant, and more than one-third of the remaining amino acids are either invariant or highly conserved, suggesting unique structural requirements

Syndrome of Inappropriate Secretion of Antidiuretic Hormone and Diabetes Insipidus

Diabetes insipidus involves a lack of free water due to a partial or complete deficiency in ADH. The clinical symptoms include polyuria (urine output greater than 300 mL h or 500 mL 2 h), thirst, dehydration, hypovolemia, and polydipsia. Diabetes insipidus results from the destruction of at least 90 of the large neurons in the supraoptic and para-ventricular nuclei. The lesion often involves the supraoptic and hy-pophysial tract rather than the neuronal bodies themselves. The laboratory criteria for the diagnosis of diabetes insipidus are as follows.

Pathophysiology Of Microvascular Disease And Endothelial Dysfunction In Diabetes

The activation of the polyol pathway. On the other hand, according to the hypoxic hypothesis, the structural alterations detected in kidney, eye, and nerve microvascu-lature, including basement membrane thickening and endothelial cell proliferation, were considered as the main factor contributing to reduced blood flow and tissue ischemia (13). It is now apparent that both the metabolic and vascular pathways are linked. More specifically, endothelial dysfunction has been suggested as the common denominator between the metabolic and vascular abnormalities detected in diabetes (14). The impaired synthesis and or degradation of nitric oxide, the main vasodilator released by the endothelium, is believed to determine microvascular insufficiency, tissue hypoxia, and degeneration (15). Diabetes mellitus, even in the absence of complications, impairs the vascular reactivity that is the endothelium-dependent and -independent vasodilation in the skin microcirculation (16). Many glucose-related...

Nutrition in Type 1 Diabetes

Most people with type 1 diabetes are of normal body weight, and they usually do not need to be on a calorie-restricted diet. They also do not tend to have the cholesterol abnormalities that are commonly seen in patients with type 2 diabetes. The American Diabetes Association recommends that an adult should obtain These recommendations also apply to lean individuals without diabetes. In other words, this is a normal, healthy diet. You should have a good idea of how much carbohydrate you are going to eat at a meal, because it will affect how much insulin you should take before the meal. Estimating the carbohydrate content of a meal is called carbohydrate counting or carbohydrate exchange. You need two pieces of information to count carbohydrates

Macrovascular Disease And Diabetes An Overview

Both type 1 and type 2 diabetes are powerful and independent risk factors for coronary artery disease (CAD), stroke, and peripheral artery disease. More specifically, the Framingham study showed that type 2 diabetes is associated with approximately a twofold increase in CAD in men and a fourfold increase in women (41). It is also known that patients with diabetes have the same risk of acute myocardial infarction than patients without diabetes with a history of previous myocardial infarction, thus all patients with diabetes have to be considered in secondary prevention for CAD (42). Mortality from CAD in individuals with diabetes is also higher than in subjects without diabetes (43). As opposed to the clear influence of hyperglycemia in the development of microvas-cular complications in diabetes, hyperglycemia plays a less strong role in the development of macrovascular disease, in particular CAD, as shown by the UKPDS (10). Thus, the risk for macrovascular disease in diabetes seems to...

Your Diet for Type 2 Diabetes

People with type 2 diabetes are frequently overweight, so advice about nutrition is directed not only at controlling carbohydrate intake, but also at limiting calories. (I discuss caloric restriction and weight loss in Chapter 10.) If you have type 2 diabetes, there are several reasons why you still need to estimate the carbohydrate content of your food Abnormalities in insulin secretion mean that eating a high-carbohydrate meal results in high glucose levels immediately after the meal. You want to avoid these high postmeal glucose levels because they can contribute to increases in HbA1c levels (see Chapter 5). If you are using insulin injections, you need to count carbohydrates in order to adjust your insulin doses (just like people with type 1 diabetes). According to the ADA, a normal, healthy diet for people with diabetes should consist of The glucose rise after eating is due to the carbohydrates in the meal, and therefore all people with diabetes should learn carbohydrate...

Insulinlike Growth Factor1 IGF1

Growth hormone and IGF-I have been suspected of playing a role in the progression of diabetic retinopathy. In a previous era, hypophysectomy was shown to lead to regression of proliferative retinopathy in a study of 100 patients . Similarly, diabetic dwarfs with low systemic IGF-I levels due to growth hormone deficiency have a reduced incidence of proliferative DR compared with age- and sex matched diabetic patients. Such observations have raised interest in the use of growth hormone-inhibitory and antiproliferative somatostatin analogs to treat severe proliferative DR, however, a growth hormone receptor antagonist, pegvisomant, failed to induce regression of neovascularization . This negative result may have occurred because the treatment was initiated too late treatment may need to have started prior to the development of proliferative DR. In another small-scale trial (23 patients), octreotide (a somatostatin analog) treatment reduced the requirement for laser photocoagulation...

IGF1 and insulin secretion during ageing

In a similar defined population of healthy individuals (as mentioned earlier) insulin levels are usually increased with advancing age (Ruiz-Torres et al 1996). FIG. 1. IGF1 serum levels and insulin secretion of young (20 39 years old, n 22) and old (70 92, n 33) healthy men with corresponding anthropometrical manifestations. On the right are blood concentrations of the N-terminal peptide of procollagen type III (PIIIP). The figure shows the opposite age-dependent behaviour of the hormones mentioned. IGF1 concentrations were determined after alcohol extraction by radioimmunoassay and PIIIP. Daily insulin secretion was by means of 24 h C-peptide excretion, corrections and normalization of results as described (Ruiz-Torres et al 1996) LBM calculated according to Forbes & Bruining (1976) and adipose mass worked out on the basis of skin fold thickness and body density according to Durnin & Womersley (1974). FIG. 1. IGF1 serum levels and insulin secretion of young (20 39 years old, n...

Nerve Fatty Acid Metabolism In Diabetes

The impact of diabetes mellitus causes an inability of tissues to metabolize glucose properly and this, in turn, leads to accelerated triacylglycerol breakdown and enhanced P-oxidation of fatty acids. The resulting increase in fat catabolism, together with a depletion of Krebs cycle intermediates, produces a marked increase in ketone body formation. Glucose is the major metabolic fuel for the normal nerve axon and Schwann cells, although in its absence, the peripheral nerve is able to utilize ketone bodies for at least a portion of its energy needs (Winegrad and Simmons 1987). Under normal circumstances, the blood-brain barrier prevents entry of albumin-bound fatty acids into the tissue. Furthermore, nerve incubated with physiological concentrations of free fatty acid exhibits profound respiratory inhibition. Although fatty acids do not therefore constitute a significant energy source in the nerve, the tissue possess the enzymatic machinery to biosynthesize long-chain saturated and...

Effects of insulin and IGF1 on SMCs

More than a decade ago different publications showed that insulin stimulates SMC proliferation in vitro (Stout 1990). We have observed that in non-cultured cells, SMCs directly taken from the human artery, insulin stimulates collagen secretion. This effect was probably produced by activation of the IGF1 receptors, because addition of insulin receptor-blocking antibodies did not show any inhibition. On the contrary, antibodies blocking IGF1 receptors inhibited the insulin-induced collagen secretion. We concluded that insulin is able to change the SMC phenotype by acting as a growth factor (Ruiz-Torres et al 1998). Moreover, insulin stimulates the chemotaxis of SMCs directly dispersed from the human artery (Mu oz et al 1998). In these experiments this migration could be inhibited by insulin receptor-blocking antibodies, so we assumed that insulin was acting here through its specific receptors. Nevertheless, these results point out a very close relationship between the stimulating effect...

Adjust the Insulin Dose

Before exercise, adjust the bolus or basal insulin, or both, in anticipation of the exercise. A bolus of a fast-acting insulin analog lasts for about four hours, and the peak is at about one to one and a half hours. If you exercise within two hours, you will need to cut back on the premeal bolus (to 50 to 75 percent of your usual dose). Making an adjustment in basal insulin dosing is easier if you are on an insulin pump. If you are planning for exercise of long duration (longer than ninety minutes), you may want to cut back the amount of your basal insulin for up to two hours before the exercise. If you are participating in competitive sports, you may find that the adrenaline rush means that you may have to increase your basal insulin temporarily for up to two hours before the exercise. Adjusting the basal dosage of the long-acting insulins like glargine or detemir is trickier you can try cutting back to 50 to 80 percent of the dose on the days you exercise. Any high glucose levels...

The effect of insulin and IGF1 on the cytoskeleton in relation to SMC migration

10 min after insulin 10 imin after insulin + diltiazem FIG. 2. Insulin-induced F-actin reorganization near the membrane of human vascular smooth muscle cells showing a ruffling which does not appear when Ca2+ channels of these cells are blocked by diltiazem. The results are similar in the case of IGF1 (unpublished). 10 min after insulin 10 imin after insulin + diltiazem FIG. 2. Insulin-induced F-actin reorganization near the membrane of human vascular smooth muscle cells showing a ruffling which does not appear when Ca2+ channels of these cells are blocked by diltiazem. The results are similar in the case of IGF1 (unpublished). cytoskeletal types, the actin filaments are primarily responsible for many cell movements, for example for SMC migration (Alberts et al 1994, p 787 803). According to Bretscher's model of fibroblast locomotion, actin filaments depolymerize ahead of the nucleus, generating actin subunits which diffuse to the cell's front where actin filaments polymerize at the...

Effects of Estrogen on Risk Factors for Diabetes

The changes in lipid metabolism that occur with the menopause, including increased total and LDLC, triglycerides and Lp(a), and decreased HDL-C, resemble those of type 2 diabetes and the metabolic syndrome (12). Adverse changes in carbohydrate metabolism also emerge with the menopause including decreased insulin sensitivity and insulin secretion (128). These together with increased central adiposity contribute to the increased risk of CVD in postmenopausal women. The effects of estrogen on lipid parameters are discussed in detail in the first part of this chapter. A number of observational studies have also reported that estrogen improves insulin resistance in postmenopausal women, a factor that is predictive for the development of type 2 diabetes (125,129). Estrogen therapy also appears to prevent central fat distribution, a factor that is strongly associated with insulin resistance (126). Thus, estrogen can potentially prevent the insulin resistance associated with central obesity...

Effects of HRT on Carbohydrate Metabolism in Women With Diabetes

There is a degree of reluctance among health care professionals to prescribe HRT to women with diabetes. A community-based survey in London found that diabetic postmenopausal women were less than half as likely as the general population to be prescribed HRT (137). Doctors and health care professionals perceive HRT as detrimental for diabetic women because of fear about glycemic control as is also the case with the oral contraceptive pill (138). Yet there is no evidence that HRT results in deterioration of glycemic control in women with diabetes. In general, the available data indicate that HRT either improves or has neutral effects on carbohydrate metabolism in women with diabetes depending on the estrogen and or progestogen formulation used (Table 2). Oral estradiol has been shown to improve glucose metabolism and insulin sensitivity in diabetic women (132,139), whereas transdermal estradiol was found not to affect glycemic control (140). The addition of norethisterone does not...

Effects of HRT on Lipids in Women With Diabetes

Serum lipid parameters show an overall beneficial change on HRT in postmenopausal diabetic women. Unopposed oral estradiol increases HDL-C and reduces LDL-C, whereas the addition of norethisterone may not alter this beneficial effect (132,148). Oral CEE 0.625 mg daily has been shown to reduce total and LDL-Cin women with diabetes, although increasing HDL-C (149). In one study, the increase in HDL-C was less than among nondiabetic women (150). Not all studies have shown an increase in triglycerides with oral CEE (149), although one showed a greater increase among women with diabetes Regarding Lp(a), no significant differences were found among the groups studied in the NHANES III survey. However, in a randomized controlled study combined continuous HRT (CEE + MPA) has shown beneficial effects on Lp(a) in postmenopausal women with type 2 diabetes (153). Also, a significant reduction in Lp(a) and triglycerides has been reported following treatment with tibolone (154). Overall, the use of...

Effects of HRT on Endothelial Function in Postmenopausal Women With Diabetes

Endothelial dysfunction is the hallmark of diabetes and is regarded as an early manifestation of atherogenesis. In postmenopausal women with diabetes, multiple pathophysiological processes may contribute to endothelial dysfunction. These are diabetes- related, as a result of hyperglycemia and obesity insulin resistance and menopause-related as a result of loss of the protective effect of estrogen, as discussed earlier. Despite the importance of the endothelium, there is limited data on the effects of HRT on endothelial dysfunction in postmenopausal women with diabetes. In a recent study comparing healthy and diabetic postmenopausal women, Lim and associates (109) found that, although cutaneous vasodilation was impaired in postmenopausal women, it was able to be improved by HRT in nondiabetic subjects, but the improvement was less apparent in the diabetic cohort. However, the use of HRT in women with diabetes was associated with lower soluble ICAM levels, suggesting an attenuation in...

HRT and Risk of Cardiovascular Disease in Women With Diabetes

CVD is the most common cause of death in type 2 diabetes. This increased risk is particularly apparent in women with diabetes in which the relative protection afforded by the female sex is lost (107). For women without diabetes, prospective cohort surveys such as the Nurse's Health Cohort Study, suggest that estrogen therapy decreases the risk of CHD in postmenopausal women who were initially healthy at the time of enrollment (5). However, data from the HERS and WHI clinical trials have questioned the validity of epidemiological evidence by reporting an increased risk of CHD among women assigned to HRT (6,7). Little is known about the effect of HRT on CHD in women with diabetes. Secondary analyses among small subgroups of women with diabetes from case-control studies have been equivocal, some reporting a non significant reduced risk (168,169) and others nonsignificant increased risk of CHD with exposure to HRT (170). In a 3-year follow-up observational study of a cohort of25,000...

Relationship to Insulin Resistance and Diabetes

Although the exact mechanisms that lead to the development of PCOS are not clear it has been shown that insulin resistance and compensatory hyperinsulinemia possess the central role in the pathophysiology of the syndrome. Women with PCOS have both basal and glucose-stimulated hyperinsulinemia compared with weight-matched women and the high levels of insulin are thought to mediate the development of hyperandrogenemia, anovulation, and infertility. At the same time, insulin resistance and compensatory hyperinsulinemia are responsible for the cardiovascular risk factors. The hyperinsulin-ism correlates with the hyperandrogenism and occurs independent of obesity (180,181). The insulin resistance in at least 50 of PCOS women appears to be related to excessive serine phosphorylation of the insulin receptor (182). This abnormality is caused by a factor extrinsic to the insulin receptor, which is presumably a serine threonine kinase. Serine phosphorylation appears to modulate the activity of...

Blood flow velocity measurement in patients with diabetes mellitus

The diabetic pathological processes, which initially are subtle, affect retinal hemodynamics. In the normal retina, autoregulated vascular responses keep the blood flow constant over a range of systemic blood pressures and intraocular pressures (Riva, et al., 1981, Robinson, et al., 1986). Vessels are controlled through local factors, (Haefliger & Anderson, 1997, Matsugi, et al., 1997a, atsugi, et al., 1997b, Riva et al., 1981, Shepro & Morel, 1993) which primarily target smooth muscle cells in arterioles and capillary pericytes (Shepro & Morel, 1993, Sims, 1986). In patients with diabetes, however, there are changes in local vasoactive factors as well as in the response of pericytes to these factors (Bursell, et al., 1997, de la Rubia, et al., 1992, Gillies & Su, 1993, Joussen, et al., 2002, King, et al., 1994, Riva et al., 1981).

Blood flow velocity in patients with preretinopathy diabetes mellitus

After confirming blood flow velocity alternation in the patients with existing DR, a study was performed utilizing the RFI in order to discover hemodynamic changes in patients with diabetes mellitus before morphological changes occur in the retina. This study compared the blood-flow velocity in the retinal vasculature of adult-onset diabetic mellitus patients with no evidence of diabetic retinopathy (23 eyes of DM patients) to that of aged-matched healthy controls (51 eyes of 31). Retinal blood flow velocity was measured using the RFI. Measurement of systemic blood pressure, intraocular pressure, blood glucose level, glycosylated haemoglobin (HbA1C) and body mass index (BMI) were recorded, and heart rate recording from the RFI was obtained. The average blood-flow velocity in the arteries was 4.7+1.7 mm sec in the DM group. This was significantly higher than in the healthy subjects (4.1+0.9 mm sec, p 0.03, table 2). As expected, in both groups venous velocity was slower than in the...

What to Do if You Get Sick and Are on Insulin

Do not stop your insulin depending on the severity of the illness you may need the same or more insulin. If you have type 1 diabetes and you stop the insulin, you will go into DKA (see Chapter 3). If you are on a basal-bolus insulin regimen, take the same amount of the long-acting insulin as you normally do. If you are on a pump, keep the basal rates the same. Cover your carbohydrates with insulin in the usual way. If you have vomiting and you are not sure if you will keep the food down, you can give the insulin for the carbohydrates afterward. Correct any high glucose levels with fast-acting insulin analogs. If you have type 2 diabetes and are on premixed insulins twice a day, you may take the same amount of insulin if you know that you can keep some food down. If you are not sure that you will be able to eat, check with your doctor you may need to cut back on your premixed insulin to 50 to 75 percent of the dose. Contact your medical team (see Chapter 4) or go to the emergency room...

Diabetes and Pregnancy

Diabetes complicates about 8 percent of pregnancies each year. About 75 percent of these diabetic pregnancies are gestational diabetes that is, the woman is diagnosed as having diabetes during the pregnancy. Of the remaining, 23 percent involve preexisting type 2 diabetes and about 1 to 2 percent involves preexisting type 1 diabetes. The issues surrounding preexisting diabetes are slightly different from those faced by women who first develop diabetes during pregnancy. Women who have diabetes before they become pregnant have to deal with glucose control at conception and early in pregnancy. If there are any diabetes-related complications, these may also have an impact on the pregnancy. Women who have gestational diabetes are faced with learning all about diabetes, including watching their diet and taking insulin, while pregnant. This chapter gives you details on both situations.

Nondiabetic Neuropathies More Common In Patients With Diabetes

In addition to specific neuropathies, patients with diabetes appear more prone to develop some types of neuropathy than patients without diabetes. Pressure palsy is more common in diabetic individuals (52). Carpal tunnel syndrome occurs in 12 of diabetic patients (53) and the incidence of ulnar neuropathy because of microlesions at the elbow level is high in patients with diabetes too (54). Inflammatory, predominantly demyelinative neuropathy also must be differentiated from diabetic polyneuropathy, and may occur with a greater frequency in this population. This diagnosis must be suspected when an acute or subacute, often predominantly motor, demyelinating polyneuropathy occurs in a patient with diabetes. Electrophysiological features are those of a demyelinating neuropathy (55). The course and response to treatments are the same as in patients without diabetes. This rare condition is an acute disease that affects successively the air cavities of the face, the orbit, and the brain, in...

Diabetes and Insulin Resistance

Adiponectin's involvement in CVD is likely multifactorial, but one of its main roles is likely in affecting traditional risk factors associated with coronary artery disease (CAD), particularly diabetes. As one of the diabetes susceptibility genes and the adiponectin gene both localize to 3q27, mutation at this locus has been associated with both type 2 diabetes and decreased adiponectin (41). The majority of data for animal studies thus far suggest that adiponectin acts as an insulin-sensitizing hormone. Adiponectin-knockout mice develop insulin resistance either independently of diet or only after high-fat and high-sucrose diet, and treating these mice with adiponectin ameliorates their insulin resistance (35,42). The insulin resistance in adiponectin-deficient lipoatrophic and obese mice can partially be reversed via adiponectin administration and fully restored with both leptin and adiponectin supplementation (29). Furthermore, in a longitudinal study analyzing the progression of...

The Risk of Your Child Developing Diabetes

Prospective parents may be fearful of transmitting diabetes to their children. The risk of transmitting type 1 diabetes is quite low (6 percent if the father has type 1 diabetes and 3 percent if the mother has type 1 diabetes). The risk of transmitting the genetic risk is higher in type 2 diabetes if the mother has type 2 diabetes, the risk is about 18 percent, increasing to 50 percent if both parents have type 2 diabetes. The environment, however, plays a bigger role in the development of type 2 diabetes, regardless of the genetic risk.

Complications of Diabetes

Two aspects of diabetes complications need to be considered when a woman is contemplating pregnancy. First, there is the impact of the pregnancy on diabetic corn- Diabetic retinopathy New diabetic retinopathy can suddenly appear during pregnancy, and retinopathy that is already present can get worse. There are two possible reasons for the deterioration First, if your diabetes control has been poor and you suddenly tighten it over a short period Diabetic kidney disease If you have kidney disease secondary to your diabetes, pregnancy can make the kidney disease worse. Often the kidney disease will recover after delivery, but it may not if the prepregnancy kidney failure is more severe. Women with diabetic kidney disease who are contemplating pregnancy should therefore consider getting an opinion from a nephrologist (kidney doctor). Preeclampsia Preeclampsia is a serious condition where there is severe elevation in blood pressure, fluid retention, and protein loss. It occurs more often...

Treatment of Diabetes During Pregnancy

Although there is evidence that oral glyburide is safe in pregnancy, the current practice is to have women control their diabetes with insulin when they are pregnant. If you have type 2 diabetes and you are using oral agents for your diabetes, you will be switched over to insulin before you start trying to get pregnant. Not all insulins, however, are approved for use during pregnancy. The fast-acting insulin analogs insulin lispro and insulin aspart are safe. Currently, the only long-acting insulin used during pregnancy is NPH. Recently, a small study of insulin glargine used in thirty-two pregnancies did not show any problems. There is no information about using insulin detemir during pregnancy. least three months to achieve this. You may need to visit your diabetes team every two to three weeks during this time. Once you have stable glucose levels in the target range, with a normal HbA1c, then you can try to get pregnant. Once you are pregnant, your care will be transi-tioned to a...

Gestational Diabetes

During pregnancy, women are screened for diabetes at twenty-four to twenty-eight weeks, or at the very first visit if they are at very high risk of diabetes as indicated by the following risk factors There are family members with diabetes. Her ethnic background is a group that is particularly susceptible to diabetes. She had diabetes with a previous pregnancy or delivered a baby weighing more than nine pounds. There are two tests that can determine whether a woman has gestational diabetes. The first test is performed on all non-high-risk women at the twenty-four to twenty-eight week visit. If this test is normal, no further testing is necessary. If this first test is positive, however, a second test is performed about a week later. First test One-hour 50-gram glucose challenge screening test. In this test you take a drink that contains 50 grams of glucose (there is no need to fast beforehand). The blood glucose level is checked after one hour. If your glucose level is greater than 130...

Gestational Diabetes And Risk For Type 2 Nongestational Diabetes

If you have gestational diabetes, your risk of developing type 2 diabetes in the future is 5 to 50 percent. Therefore, you should have a two-hour 75-gram oral glucose tolerance test (OGTT) six to ten weeks after delivery. With tight glucose control and careful management of diabetes complications, women with diabetes can have healthy babies Diabetes complications can impact maternal and fetal health during the Gestational diabetes is diabetes that first appears during the pregnancy. If diet does not normalize the glucose levels, insulin therapy should be initiated. Usually gestational diabetes resolves after the pregnancy, but these women are at higher risk for developing type 2 diabetes in the future. Maintaining normal weight and exercising regularly may delay or prevent the onset of diabetes in women who have had gestational diabetes.

Endothelial dysfunction and diabetes mellitus

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

Public Schools and Diabetes Training

In the United States, the schools or day care centers that receive public funds are legally required to provide training to school staff on treating diabetes. The ADA has literature for teachers and child-care providers. Your health-care team can also help ensure that the staff members at your child's school are adequately trained. The degree of supervision by the staff of the school will vary with your child's age and abilities. may limit insulin use in order to lose weight. This leads to poor diabetes control and is harmful. Late adolescence ages fifteen to nineteen At this age your child will manage his or her diabetes fairly independently. You can help by guiding your teen to improve his or her coping skills and transition to full independence for college or work. Diabetes can impact the adolescent issues of smoking, alcohol, risky behaviors, and sexual activity. Smoking increases the risk for diabetes complications. Let your teenager know how alcohol causes hypoglycemia and what...

Adjusting Insulin Doses

Insulin dosages are based on weight of your child in kilograms (1 kg is equal to 2.2 pounds). The doses vary based on whether the child is in the honeymoon phase or not and whether he or she is going through puberty. During the honeymoon phase, your child will need very little insulin, and a simple insulin regimen with two or three injections a day may suffice. The basal insulin needs may be as low as 0.125 units per kilogram. The ratio for carbohydrate might be 1 unit of insulin for 60 to 75 grams carbohydrate, and your child may not need any insulin for corrections. Once the honeymoon phase is over, your child's basal insulin needs may go up to 0.25 units per kilogram, and the insulin to carbohydrate ratio may go up to 1 unit for 15 to 60 grams carbohydrate. He or she may also need insulin for correction, for example, 1 unit for every 50 to 200 mg dl blood glucose over her target. When your child goes through puberty, the insulin needs go up substantially this is principally because...

Mechanisms of Faecal Incontinence in Diabetes

As discussed elsewhere in this volume, defecation involves close integration of the peripheral autonomic and enteric nerves. Therefore, it is reasonable to infer that ischaemic or toxic damage to these nerves caused by diabetes can lead to disorders of defecation that will vary according to the site and type of nerve(s) that are affected. As mentioned, it is important to not attribute the disturbances in defecation that occur in patients with diabetes as necessarily complications of diabetes for example, patients with diabetes are also at risk for cognitive and mobility impairment, faecal retention, and obstetric trauma. It has been suggested that when anxiety and depression are taken into account, no specific gastrointestinal symptom is significantly associated with autonomic neuropathy 38 . Patients with long-standing diabetes are apparently more likely to be affected by nocturnal faecal incontinence than are nondiabetics with faecal incontinence, which may reflect neuropathy...

Insulin Resistance and Nitric Oxide

Although hyperglycemia plays an essential role in the pathophysiology of DM, elevated serum insulin levels may also play an important role in atherogenesis, specifically in noninsulin DM. Furthermore, insulin resistance is a known cardiac risk factor. Insulin mediates NO production through specific pathway, which includes insulin receptor tyrosine, phosphatidyl inositol 3-kinase and its downstream effector, akt (118,119). This increase in NO release, in turn, results in vasodilation (120). This endot-helial-dependent relaxation is accompanied by an increase in glucose transport and metabolism (121,122) and may also potentially result in the removal of postprandial glucose. Therefore, endothelial dysfunction may lead to insulin resistance. This argument is further strengthened by the findings of Petrie and coworkers (123), which showed a correlation between basal endothelial function and insulin sensitivity in healthy controls. This relationship was not seen with either nitroprusside...

Type 2 Diabetes in Children

The number of children that have type 2 diabetes is on the rise. Accurate numbers about how many children have this condition are hard to obtain, because the disease may have been present for a while before it is diagnosed. Anywhere between 8 to 46 percent of children with diabetes referred to pediatric centers have type 2 diabetes. The increase in childhood obesity is likely to be the main factor driving this increased incidence of type 2 diabetes. Your child might be diagnosed with diabetes during routine screening or because she may be unwell. The American Diabetes Association recommends screening any overweight child (more than 120 percent ideal body weight, body mass index greater than 85 percent) who has two of the following features Strong family history of type 2 diabetes (parents, siblings, uncles, aunts, grandparents, nephew, niece, half sibling) Evidence for insulin resistance or presence of conditions associated with insulin resistance, such as darkening of the skin under...

Treatment For Type 2 Diabetes In Children

The treatment options for children with type 2 diabetes are the same as those available for adults with type 2 diabetes. They include diet, exercise, and oral and inject- able medications including insulin. The problem with medications is that there is limited information about their long-term use in children.

The incretin effect in ageing and in type 2 diabetes

Incretin is the umbrella term to cover the multiple gut factors (now known to be hormones) which augment insulin response above that which can be attributed to glucose alone. This insulinotropic effect has been demonstrated by matching the time course of the plasma glucose excursion following an OGTT with both an i.v. infusion of glucose (Perley & Kipnis 1967) and during a hyperglycaemic clamp. In the hyperglycaemic clamp, plasma glucose was increased to * 11 mmol l for 2 h on two different occasions. In one, only glucose was infused, while in the second, an OGTT was administered at 60 min and the exogenous glucose infusion rate was adjusted during the second hour as the ingested glucose was being absorbed in this manner the plasma glucose level remained at the same plateau level in the second hour as in the first hour (Andersen et al 1978). During the second hour in the study, despite the constancy of the plasma glucose concentration, a marked potentiation of insulin secretion was...

How Diabetes Impacts Diseases of Aging

Elderly people with long-standing diabetes are more likely to have kidney disease, nerve damage, and circulation problems such as heart disease and stroke. They are less able to walk, do housework, prepare meals, and manage money when compared to age-matched individuals who do not have diabetes. Women with diabetes become disabled at approximately twice the rate of women without diabetes, and they have an increased risk of falls and hip fractures. Long-standing diabetes can affect bone quality, and diabetes increases the risk of fractures with falls. Neurological deterioration is greater in people with diabetes they are more likely to develop memory problems and have more rapid deterioration in memory with time. Part of the reason for the more severe deterioration in cognitive function may be the effect of diabetes on the blood vessels and increased risk of small strokes.

Institutional Aspects of Diabetes

Elderly people living in board and care and nursing facilities may have additional challenges regarding their diabetes management. They may have to rely on caregiv-ers to check their glucose levels and administer their diabetes medications. They may not have control over their meals. The staff may have limited understanding of diabetes management because type 2 diabetes is so much more common, people tend not to remember that older individuals can have type 1 diabetes. These type 1 patients may not get adequate insulin bolus for their meals. Due to limited supervision, sophisticated insulin basal-bolus regimens may not be realistic, and some level of control may have to be sacrificed for safety. In these situations, insulin injections once or twice a day may have to suffice. I would encourage family members to remain actively engaged in helping manage their elderly relative's diabetes care, and with their physician, carefully devise recommendations for the nursing staff in the...

Treatment of Diabetes Complications and Associated Disorders

Diabetes complications in elderly people are treated in the same ways as in younger individuals. Treating the lipid abnormalities (see Chapter 3) and blood pressure is equally beneficial in the elderly as in younger individuals. In fact, because the risk for heart attack and stroke is higher in the elderly, benefits may actually be greater than in the younger population. The blood pressure target is less than 140 80 if tolerated. ACE inhibitors and angiotensin receptor blockers (ARBs) can be used to lower blood pressure, but these medicines can raise the potassium and serum creati-nine levels. High potassium levels can be dangerous and affect the heart rhythm. Therefore, your doctor will ask you to get lab tests one week after you start taking these medicines to make sure that your potassium is in the safe range. Often, elderly people are on many different medications because they are being treated for other medical problems as well. In these situations, you need to watch out for drug...

Newly Diagnosed Type 1 Diabetes

When you are first diagnosed with type 1 diabetes, you will meet your diabetes management team, which consists of your physician, the diabetes educator, and the nutritionist. The physician will answer your questions about diabetes and recommend an initial insulin regimen. The nutritionist will teach you about carbohydrate counting, give you a carbohydrate exchange book (the ADA publishes a good one), and explain The diabetes educator will teach you how to use a glucose monitor, how to keep a logbook, and how often you should monitor your glucose levels and will set your target glucose levels. She will also teach you how to draw up insulin in a syringe and give an injection. Even if you were prescribed insulin pens from the start, you should still know how to draw up insulin in a syringe just in case a pen is not available. The educator will go over the symptoms of low glucose reactions and how to treat them. She will also show you how glucagon works and instruct you and a family...

Established Type 1 Diabetes

Currently, there is no way of preventing the decline in insulin secretion that occurs with time in those with type 1 diabetes. The honeymoon period can last only a few weeks, or it can last for more than a year or two. Generally speaking, children and young adults tend to have shorter honeymoons, whereas older individuals can maintain insulin secretion for several years. There are, however, many exceptions to this observation. As your insulin secretion declines, you will need more insulin to control the glucose. You may find that your glucose values drift upward overnight. This is a good time to add some long-acting basal insulin. Usually only a few units (2 to 3) of insu lin glargine or detemir might be necessary to start with, but then the doses go up with time. The ratios of insulin for carbohydrate and for correction also change, and more insulin is needed. The amount of insulin that you need will vary according to your age and weight a teenager going through puberty will need...

Optimizing Your Basal Insulin Dose

Ideally, if your basal insulin (insulin glargine, detemir, NPH, or pump basal) dose is correct, then even if you did not eat and had your normal activity, your glucose levels will stay in the normal range. This is usually not true in practice, and there is always some drift in your glucose levels. This is because of the day-to-day variability in the absorption of the injected insulin and the way the body responds to the insulin. Your goal is to minimize the upward and downward drift of your glucose levels. So, how do you determine if your basal insulin dose is correct You do this by looking at your glucose levels after eliminating the variables of food, exercise, and bolus insulin. Usually, overnight is the easiest time to assess your basal insulin needs Provided your glucose at bedtime is in the safe range say 100 to 150 mg dl, then you can set your alarm and check blood glucose levels at 2 a.m. and then again at 6 a.m. and 9 a.m. If your glucose levels drift up or down, you need...

Optimizing Your Bolus Insulin Dose

Once you are satisfied with your basal glucose control, you can look at the bolus insulin. Before you can do this, you have to know how to count carbohydrates (see Chapter 8). The way you assess your bolus ratio for carbohydrates is to eat your usual meal and give the calculated dose of insulin. Then check your blood glucose after the meal and find out how high it goes you are trying to keep it below 180 mg dl. Check three times, and if the glucose goes much higher than 180 consistently, you need to increase the ratio. For example, if you gave 1 unit for 15 grams carbohydrate at breakfast, try using 1 unit per 12 grams of carbohydrate, and check again. Sometimes, if you change the ratio, you find that your peak after the meal is below 180 mg dl, but then you go low later on. If this happens, you have a number of options Why do you have a correction insulin bolus The correction insulin is to correct the drift upward in your glucose levels because the basal insulin is not perfect. The...

Polycystic Ovarian Syndrome and Insulin Resistance

The association between insulin resistance and PCOS has been well recognized for almost two decades. Insulin resistance refers to an impairment of insulin-stimulated glucose uptake largely in skeletal muscle and an impairment in insulin-mediated inhibition of hepatic glucose output. In skeletal muscle and fat, insulin initiates several intracellular signals culminating in GLUT 4-mediated glucose uptake. Insulin also has a vasodilator effect on the normal skeletal muscle vasculature mediated by stimulation of endothelium-derived nitric oxide (NO). In endothelial cells in vitro, insulin-stimulated NO production shares signaling pathways similar to those mediating glucose uptake in muscle and fat (15-17). The presence of insulin resistance leads to increased p-cell insulin secretion with compensatory hyperinsulinemia. Type 2 diabetes mellitus (DM) develops when insulin resistance is accompanied by p-cell dysfunction (15). Although a controlled randomized study has not been performed to...

Thyroid Disease in Diabetes Mellitus

The most frequent autoimmune disease in type 1 diabetes affects the thyroid. The etiology of autoimmunity in pancreas and thyroid is a T cell-mediated disease and seems to be due to common genetic susceptibility. Two immune regulatory genes (HLA human leukocyte antigen and CTLA-4 cytotoxic T lymphocyte-associated protein 4) contribute to the susceptibility for both diseases 5, 23 . This locus, also known as the IDDM 12 gene, seems to play a major role in development of autoimmune polyglandular syndrome type 2 (APS-2). Positivity for thyroid auto antibodies in children with type 1 diabetes shows considerable variability in different countries. Incidence and prevalence numbers vary between 3 and 50 3, 18, 19, 33, 36 compared to a suggested rate of 3-10 in non diabetic children and adolescents 17, 26, 38 . The largest cohort analysis was published by Kordonouri et al. 19 reporting a rate of 21.6 of thyroid antibodies in a group of 7,097 children and adolescents with type 1 diabetes. In...

Lower Extremity Arterial Disease And Diabetes

The concomitant occurrence of atherosclerotic peripheral vascular disease and peripheral neuropathy in patients with diabetes is the main factor in the development of diabetic foot pathology. Although neuropathy has proven the main risk factor for foot ulceration, peripheral arterial disease of the lower extremities is considered the major risk factor for lower-extremity amputation and it is also accompanied by a high likelihood for cardiovascular and cerebrovascular diseases (45). The rate of lower extremity amputation in the population with diabetes is 15 times that seen in the population without diabetes and within 4 years of the first amputation about 50 of contralateral limbs are lost (46,47). Life expectancy is also consistently reduced, as a result (48). Although the underlying pathogenesis of atherosclerotic disease in diabetics is similar to that noted in nondiabetics, there are significant differences. As previously mentioned, diabetics have a fourfold higher prevalence of...

Mechanisms responsible for the overexpression of pai1 in diabetes

Increased expression of PAI-1 in diabetes is undoubtedly multifactorial. A direct effect of insulin on the expression of PAI-1 has been suggested by a positive correlation between the concentration of insulin and PAI-1 in vivo (93,94,96,100-103,106). Triglycerides and their constituents (fatty acids) appear to contribute to the overexpression of PAI-1 in view of the fact that both insulin and triglycerides independently increase expression of PAI-1 by human hepatoma cells in vitro (105,107-109). Liver steatosis is another determinant of elevated concentrations of PAI-1, perhaps indicative of the response of both to derangements in the tumor necrosis factor signaling pathway (110). Insulin and triglycerides exert a synergistic increase in accumulation of PAI-1 in conditioned media when both are present in pathophysiological concentrations (105). Analogous results are obtained with insulin in combination with very low-density lipoprotein-triglyceride, emulsified triglycerides, or...

Oxidative and Nitrosative Stress in Diabetes Induced Vascular Dysfunction

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

Working with Small Insulin Doses

Giving the small doses of insulin can be challenging. Eli Lilly and Novo Nordisk make pens that will deliver in half units, but the minimum dose is 1 unit. Becton, Dickinson and Company makes an ultrafine short-needle insulin syringe with half-unit markings. You can also ask your pharmacy to dilute the insulin. Eli Lilly makes a diluent for NPH, regular, and Humalog insulin. Similarly, Novo Nordisk makes a diluent for Novolin regular, and this can also be used for NovoLog. For U50 insulin, the insulin is diluted by 50 percent, so 1 ml contains 50 units of insulin. If you draw up 1 unit on an insulin syringe, you are giving 0.5 units. For U10 insulin, the insulin is diluted by 90 percent, so 1 ml contains 10 units of insulin. If you draw up 1 unit on an insulin syringe, you are giving 0.1 units. The diluted insulin does not last as long, and you may need a new diluted batch every two weeks. If you use diluted insulin for your child, it is very important that all caregivers are aware of...

Diabetes is an atherosclerosis risk equivalent

In contrast to the microvascular complications of diabetes, such as nephropathy and retinopathy, atherosclerosis occurs early in the process of type 2 diabetes. Based on the observation that patients with diabetes without known atherosclerosis have the same 7-yr incidence rate of fatal or nonfatal myocardial infarction (MI) as nondiabetic patients with documented coronary artery disease, the National Cholesterol Education Program (NCEP) has defined diabetes as an atherosclerosis risk equivalent (1). This equivalency suggests that atherosclerosis is present at the time the diagnosis of type 2 diabetes is made. Therefore, early in the disease process, therapeutic strategies to prevent or arrest cardiovascular disease must be employed, and appropriate target goals for atherosclerosis risk factors need to be achieved (Table 1). Moreover, because of the well-documented acceleration of atherosclerosis in the diabetic milieu, therapeutic goals in patients with diabetes are more stringent...

The coagulation system and diabetes mellitus

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

Microangiopathy Diabetes And The Peripheral Nervous System Experimental Studies

Tuck and colleagues (22) initially reported that experimental diabetes of rats was associated with a decline of sciatic nerve blood flow and endoneurial hypoxia. Several other laboratories have reported similar findings and a variety of interventions have been reported to both correct nerve blood flow and diabetic electrophysiological abnormalities in tandem (see review 2 ). A large number of such studies through their findings have consequently implied that reductions in nerve blood flow initiate the changes of diabetic neuropathy. Although this body of work has undoubtedly provided evidence of a linkage, cause and effect has not been proven. A number of the reports have arisen from relatively few experimental laboratories (33,34,64-97). Similarly, the spectrum of agents reported to correct blood flow and conduction slowing has been very wide. As such, this range of apparently beneficial interventions raises the strong possibility that they exert parallel benefits on separate, but...

Glucose tolerance glucose utilization and insulin secretion in ageing

Ageing is associated with an increased incidence of hypertension, macrovascular disease and type 2 diabetes (non-insulin-dependent diabetes). It has been suggested that a common mechanism may be responsible for all of these pathological states since all of these conditions often cluster in the same individual. Epidemiological and clinical data have consistently demonstrated an association between insulin resistance and or hyperinsulinaemia and glucose intolerance, dyslipidaemia and elevated systolic blood pressures. Therefore, insulin resistance and hyperinsulinaemia have been proposed as the causal link among the elements of the clusters. The elderly are more glucose intolerant and insulin resistant, but it remains controversial whether this decrease in function is due to an inevitable consequence of 'biological ageing' or due to environmental or lifestyle variables, noticeably increased adiposity altered fat distribution and physical inactivity. An increase of these...

Supplements For Diabetics

Supplements For Diabetics

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

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