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This article is about the management of diabetes mellitus. For more on the disease itself see diabetes mellitus. Main article: Diabetes mellitus See also: Prediabetes, Diabetes mellitus type 1, Diabetes mellitus type 2, Diabetes and pregnancy, Diabetic coma, Blood sugar, Impaired glucose tolerance, Diabetic diet, Antihypertensive agents, Diabetic hypoglycemia, Diabetic ketoacidosis, Diabetic nephropathy, Diabetic retinopathy, and Diabetes UK Diabetes is a chronic disease with no cure as of 2009[update]. It is associated with an impaired glucose cycle, altering metabolism. Management of this disease may include carefully managing diet, exercising, taking oral diabetes medication, using some form of insulin, maintaining proper circulation in extremities and may be further complicated by other external factors such as stress, illness, menses, injection site scarring, and other physiological factors unique to individual patients.
[edit] Overview of management[edit] Issues requiring management
The primary issue requiring management is the glucose cycle, whereby glucose in the bloodstream is made available to cells in the body, a process dependent upon the twin cycles of glucose entering the bloodstream, and insulin allowing appropriate uptake into the cells of the body. Both aspects can require management. [edit] Complexities relating to managementThe main complexities stem from the nature of the feedback loop itself, which is sought to be regulated:
As diabetes is a prime risk factor for cardiovascular disease, controlling other risk factors which may give rise to secondary conditions, as well as the diabetes itself, is one of the facets of diabetes management. Checking cholesterol, LDL, HDL and triglyceride levels may indicate hyperlipoproteinemia, which may warrant treatment with hypolipidemic drugs. Checking the blood pressure and keeping it within strict limits (using diet and antihypertensive treatment) protects against the retinal, renal and cardiovascular complications of diabetes. Regular follow-up by a podiatrist or other foot health specialists is encouraged to prevent the development of diabetic foot. Annual eye exams are suggested to monitor for progression of diabetic retinopathy. The expense, inconvenience and discomfort of frequent blood glucose measurements has been a significant challenge until recently. Recently newer devices which monitor glucose levels on an ongoing basis have been developed, as detailed below. [edit] Early advancementsLate in the nineteenth century, sugar in the urine (glycosuria) was associated with diabetes. Various doctors studied the connection. Frederick Madison Allen studied diabetes in 1909-12, then published a large volume, Studies Concerning Glycosuria and Diabetes, (Boston, 1913). He invented a fasting treatment for diabetes called the Allen treatment for diabetes. His diet was an early attempt at managing diabetes. [edit] Modern approaches
Modern approaches to diabetes primarily rely upon dietary and lifestyle management, often combined with regular ongoing blood glucose level monitoring. Diet management allows control and awareness of the types of nutrients entering the digestive system, and hence allows indirectly, significant control over changes in blood glucose levels. Blood glucose monitoring allows verification of these, and closer control, especially important since some symptoms of diabetes are not easy for the patient to notice without actual measurement. Other approaches include exercise and other lifestyle changes which impact the glucose cycle. In addition, a strong partnership between the patient and the primary healthcare provider – general practitioner or internist – is an essential tool in the successful management of diabetes. Often the primary care doctor makes the initial diagnosis of diabetes and provides the basic tools to get the patient started on a management program. Regular appointments with the primary care physician and a certified diabetes educator are some of the best things a patient can do in the early weeks after a diagnosis of diabetes. Upon the diagnosis of diabetes, the primary care physician, specialist, or endocrinologist will conduct a full physical and medical examination. A thorough assessment covers topics such as:
Diabetes can be very complicated, and the physician needs to have as much information as possible to help the patient establish an effective management plan. Physicians may often experience data overload resulting from hundreds of blood-glucose readings, insulin dosages and other health factors occurring between regular office visits which must be deciphered during a relatively brief visit with the patient to determine patterns and establish or modify a treatment plan.[1] The physician can also make referrals to a wide variety of professionals for additional health care support. In the UK a patient training course is available for newly diagnosed diabetics (see DESMOND).In a large city there may be a diabetes center where several specialists, such as diabetes educators and dietitians, work together as a team. In smaller towns, the health care team may come together a little differently depending on the types of practitioners in the area. By working together, doctors and patients can optimize the healthcare team to successfully manage diabetes over the long term. [edit] Blood sugar levelBlood sugar level is measured by means of a glucose meter, with the result either in mg/dL (milligrams per deciliter in the USA) or mmol/L (millimoles per litre in Canada and Europe) of blood. The average normal person should have a glucose level of around 4.5 to 7.0 mmol/L (80 to 125 mg/dL). Optimal management of diabetes involves patients measuring and recording their own blood glucose levels. By keeping a diary of their own blood glucose measurements and noting the effect of food and exercise, patients can modify their lifestyle to better control their diabetes. For patients on insulin, patient involvement is important in achieving effective dosing and timing. Some edible mushrooms are noted for the ability to lower blood sugar levels including Reishi,[2][3] Maitake[4][5][6][7][8][9] Agaricus blazei[10][11][12][13] as well as some others. [edit] Hypo and hyperglycemiaLevels which are significantly above or below this range are problematic and can in some cases be dangerous. A level of <3.8 mmol/L (<70 mg/dL) is usually described as a hypoglycemic attack (low blood sugar). Most diabetics know when they're going to "go hypo" and usually are able to eat some food or drink something sweet to raise levels. A patient who is hyperglycemic (high glucose) can also become temporarily hypoglycemic, under certain conditions (e.g. not eating regularly, or after strenuous exercise, followed by fatigue). Intensive efforts to achieve blood sugar levels close to normal have been shown to triple the risk of the most severe form of hypoglycemia, in which the patient requires assistance from by-standers in order to treat the episode.[14] There were annually 48,500 hospitalizations for diabetic hypoglycemia and 13,100 for diabetic hypoglycemia resulting in coma in the period 1989 to 1991, before intensive blood sugar control was as widely recommended as today.[15] One study found that hospital admissions for diabetic hypoglycemia increased by 50% from 1990-1993 to 1997-2000, as strict blood sugar control efforts became more common.[16] Among intensively controlled type 1 diabetics, 55% of episodes of severe hypoglycemia occur during sleep, and 6% of diabetics under age 40 die from nocturnal hypoglycemia in the so-called 'dead-in-bed syndrome,' while National Institute of Health statistics show that 2% to 4% of all diabetics die from hypoglycemia.[17] In children and adolescents following intensive blood sugar control, 21% of hypoglycemic episodes occurred without explanation.[18] In addition to the deaths caused by diabetic hypoglycemia, periods of severe low blood sugar can also cause permanent brain damage.[19] Interestingly, although diabetic nerve disease is usually associated with hyperglycemia, hypoglycemia as well can initiate or worsen neuropathy in diabetics intensively struggling to reduce their hyperglycemia.[20] Levels greater than 13-15 mmol/L (230-270 mg/dL) are considered high, and should be monitored closely to ensure that they reduce rather than continue to remain high. The patient is advised to seek urgent medical attention as soon as possible if blood sugar levels continue to rise after 2-3 tests. High blood sugar levels are known as hyperglycemia, which is not as easy to detect as hypoglycemia and usually happens over a period of days rather than hours or minutes. If left untreated, this can result in diabetic coma and death. Prolonged and elevated levels of glucose in the blood, which is left unchecked and untreated, will, over time, result in serious diabetic complications in those susceptible and sometimes even death. There is currently no way of testing for susceptibility to complications. Diabetics are therefore recommended to check their blood sugar levels either daily or every few days. There is also computer software available from blood testing manufacturers which can display results and trends over time. Type 1 diabetics normally check more often, due to insulin therapy. A history of blood sugar level results is especially useful for the diabetic to present to their doctor or physician in the monitoring and control of the disease. Failure to maintain a strict regimen of testing can accelerate symptoms of the condition, and it is therefore imperative that any diabetic patient strictly monitor their glucose levels regularly. [edit] Glycemic controlGlycemic control is a medical term referring to the typical levels of blood sugar (glucose) in a person with diabetes mellitus. Much evidence suggests that many of the long-term complications of diabetes, especially the microvascular complications, result from many years of hyperglycemia (elevated levels of glucose in the blood). Good glycemic control, in the sense of a "target" for treatment, has become an important goal of diabetes care, although recent research suggests that the complications of diabetes may be caused by genetic factors[21] or, in type 1 diabetics, by the continuing effects of the autoimmune disease which first caused the pancreas to lose its insulin-producing ability.[22] Because blood sugar levels fluctuate throughout the day and glucose records are imperfect indicators of these changes, the percentage of hemoglobin which is glycosylated is used as a proxy measure of long-term glycemic control in research trials and clinical care of people with diabetes. This test, the hemoglobin A1c or glycosylated hemoglobin reflects average glucoses over the preceding 2–3 months. In nondiabetic persons with normal glucose metabolism the glycosylated hemoglobin is usually 4-6% by the most common methods (normal ranges may vary by method). "Perfect glycemic control" would mean that glucose levels were always normal (70-130 mg/dl, or 3.9-7.2 mmol/L) and indistinguishable from a person without diabetes. In reality, because of the imperfections of treatment measures, even "good glycemic control" describes blood glucose levels that average somewhat higher than normal much of the time. In addition, one survey of type 2 diabetics found that they rated the harm to their quality of life from intensive interventions to control their blood sugar to be just as severe as the harm resulting from intermediate levels of diabetic complications.[23] Accepted "target levels" of glucose and glycosylated hemoglobin that are considered good control have been lowered over the last 25 years, because of improvements in the tools of diabetes care, because of increasing evidence of the value of glycemic control in avoiding complications, and by the expectations of both patients and physicians. What is considered "good control" also varies by age and susceptibility of the patient to hypoglycemia. In the 1990s the American Diabetes Association conducted a publicity campaign to persuade patients and physicians to strive for average glucose and hemoglobin A1c values below 200 mg/dl (11 mmol/l) and 8%. Currently many patients and physicians attempt to do better than that. Poor glycemic control refers to persistently elevated blood glucose and glycosylated hemoglobin levels, which may range from 200-500 mg/dl (11-28 mmol/L) and 9-15% or higher over months and years before severe complications occur. [edit] MonitoringRelying on their own perceptions of symptoms of hyperglycemia or hypoglycemia is usually unsatisfactory as mild to moderate hyperglycemia causes no obvious symptoms in nearly all patients. Other considerations include the fact that, while food takes several hours to be digested and absorbed, insulin administration can have glucose lowering effects for as little as 2 hours or 24 hours or more (depending on the nature of the insulin preparation used and individual patient reaction). In addition, the onset and duration of the effects of oral hypoglycemic agents vary from type to type and from patient to patient. [edit] Personal (home) glucose monitoringControl and outcomes of both types 1 and 2 diabetes may be improved by patients using home glucose meters to regularly measure their glucose levels.[24] Glucose monitoring is both expensive (largely due to the cost of the consumable test strips) and requires significant commitment on the part of the patient. The effort and expense may be worthwhile for patients when they use the values to sensibly adjust food, exercise, and oral medications or insulin. These adjustments are generally made by the patients themselves following training by a clinician. Regular blood testing, especially in type 1 diabetics, is helpful to keep adequate control of glucose levels and to reduce the chance of long term side effects of the disease. There are many (at least 20+) different types of blood monitoring devices available on the market today; not every meter suits all patients and it is a specific matter of choice for the patient, in consultation with a physician or other experienced professional, to find a meter that they personally find comfortable to use. The principle of the devices is virtually the same: a small blood sample is collected and measured. In one type of meter, the electrochemical, a small blood sample is produced by the patient using a lancet (a sterile pointed needle). The blood droplet is usually collected at the bottom of a test strip, while the other end is inserted in the glucose meter. This test strip contains various chemicals so that when the blood is applied, a small electrical charge is created between two contacts. This charge will vary depending on the glucose levels within the blood. In older glucose meters, the drop of blood is placed on top of a strip. A chemical reaction occurs and the strip changes color. The meter then measures the color of the strip optically. Self-testing is clearly important in type I diabetes where the use of insulin therapy risks episodes of hypoglycaemia and home-testing allows for adjustment of dosage on each administration.[25] However its benefit in type 2 diabetes is more controversial as there is much more variation in severity of type 2 cases.[26] It has been suggested that some type 2 patients might do as well with home urine-testing alone.[27] The best use of home blood-sugar monitoring is being researched.[28] Benefits of control and reduced hospital admission have been reported.[29] However, patients on oral medication who do not self-adjust their drug dosage will miss many of the benefits of self-testing, and so it is questionable in this group. This is particularly so for patients taking monotherapy with metformin who are not at risk of hypoglycaemia. Regular 6 monthly laboratory testing of HbA1c (glycated haemoglobin) provides some assurance of longterm effective control and allows the adjustment of the patient's routine medication dosages in such cases. High frequency of self-testing in type 2 diabetes has not been shown to be associated with improved control.[30] The argument is made, though, that type 2 patients with poor long term control despite home blood glucose monitoring, either have not had this integrated into their overall management, or are long overdue for tighter control by a switch from oral medication to injected insulin.[31] [edit] HbA1c testA useful test that has usually been done in a laboratory is the measurement of blood HbA1c levels. This is the ratio of glycosylated hemoglobin in relation to the total hemoglobin. Persistent raised plasma glucose levels cause the proportion of these molecules to go up. This is a test that measures the average amount of diabetic control over a period originally thought to be about 3 months (the average red blood cell lifetime), but more recently thought to be more strongly weighted to the most recent 2 to 4 weeks. In the non-diabetic, the HbA1C level ranges from 4.0-6.0%; patients with diabetes mellitus who manage to keep their HbA1C level below 6.5% are considered to have good glycemic control. The HbA1c test is not appropriate if there has been changes to diet or treatment within shorter time periods than 6 weeks or there is disturbance of red cell aging (e.g. recent bleeding or hemolytic anemia) or a hemoglobinopathy (e.g. sickle cell disease). In such cases the alternative Fructosamine test is used to indicate average control in the preceding 2 to 3 weeks. [edit] Ongoing monitoringMain article: Blood glucose monitoring Recently, devices have been manufactured which provide ongoing monitoring of glucose levels on an automated basis during the day, for example:
[edit] Approaches to management[edit] Insulin and other drug based approachesMain article: Anti-diabetic drug Currently, one goal for diabetics is to avoid or minimize chronic diabetic complications, as well as to avoid acute problems of hyperglycemia or hypoglycemia. Adequate control of diabetes leads to lower risk of complications associated with unmonitored diabetes including kidney failure (requiring dialysis or transplant), blindness, heart disease and limb amputation. The most prevalent form of medication is hypoglycemic treatment through either oral hypoglycemics and/or insulin therapy. There is emerging evidence that full-blown diabetes mellitus type 2 can be evaded in those with only mildly impaired glucose tolerance.[32] Patients with type 1 diabetes mellitus require direct injection of insulin as their bodies cannot produce enough (or even any) insulin. As of 2005, there is no other clinically available form of insulin administration other than injection for patients with type 1: injection can be done by insulin pump, by jet injector, or any of several forms of hypodermic needle. Non-injective methods of insulin administration have been unattainable as the insulin protein breaks down in the digestive track. There are several insulin application mechanisms under experimental development as of 2004, including a capsule that passes to the liver and delivers insulin into the bloodstream[33]. There have also been proposed vaccines for type I using glutamic acid decarboxylase (GAD), but these are currently not being tested by the pharmaceutical companies that have sublicensed the patents to them. For type 2 diabetics, diabetic management consists of a combination of diet, exercise, and weight loss, in any achievable combination depending on the patient. Obesity is very common in type 2 diabetes and contributes greatly to insulin resistance. Weight reduction and exercise improve tissue sensitivity to insulin and allow its proper use by target tissues.[34] Patients who have poor diabetic control after lifestyle modifications are typically placed on oral hypoglycemics. Some Type 2 diabetics eventually fail to respond to these and must proceed to insulin therapy. Patient education and compliance with treatment is very important in managing the disease. Improper use of medications and insulin can be very dangerous causing hypo- or hyper-glycemic episodes. Insulin therapy requires close monitoring and a great deal of patient education, as improper administration is quite dangerous. For example, when food intake is reduced, less insulin is required. A previously satisfactory dosing may be too much if less food is consumed causing a hypoglycemic reaction if not intelligently adjusted. In addition, exercise decreases insulin requirements as exercise increases glucose uptake by body cells whose glucose uptake is controlled by insulin, and vice versa. In addition, there are available several types of insulin with varying times of onset and duration of action. Insulin therapy creates risk because of the inability to continuously know a person's blood glucose level and adjust insulin infusion appropriately. New advances in technology have overcome much of this problem. Small, portable insulin infusion pumps are available from several manufacturers. They allow a continuous infusion of small amounts of insulin to be delivered through the skin around the clock, plus the ability to give bolus doses when a person eats or has elevated blood glucose levels. This is very similar to how the pancreas works, but these pumps lack a continuous "feed-back" mechanism. Thus, the user is still at risk of giving too much or too little insulin unless blood glucose measurements are made. A further danger of insulin treatment is that while diabetic microangiopathy is usually explained as the result of hyperglycemia, studies in rats indicate that the higher than normal level of insulin diabetics inject to control their hyperglycemia may itself promote small blood vessel disease.[20] While there is no clear evidence that controlling hyperglycemia reduces diabetic macrovascular and cardiovascular disease, there are indications that intensive efforts to normalize blood glucose levels may worsen cardiovascular and all-cause diabetic mortality.[35] The U.S. Food and Drug Administration (FDA) has approved a treatment called Exenatide, based on the saliva of a Gila monster, to control blood sugar in patients with type 2 diabetes. [edit] Diet and supplementsMain article: Diabetic diet For most Type 1 diabetics there will always be a need for insulin injections throughout their life. However, both Type 1 and Type 2 diabetics can see dramatic normalization of their blood sugars through controlling their diet, and some Type 2 diabetics can fully control the disease by dietary modification. As diabetes can lead to many other complications it is critical to maintain blood sugars as close to normal as possible and diet is the leading factor in this level of control. The American Diabetes Association in 1994 recommended that 60-70% of caloric intake should be in the form of carbohydrates. This is somewhat controversial, with some researchers claiming that 40% is better,[36] while others claim benefits for a high-fiber, 75% carbohydrate diet.[37] An article summarizing the view of the American Diabetes Association[38] gives many recommendations and references to the research. One of the conclusions is that caloric intake must be limited to that which is necessary for maintaining a healthy weight. The methodology of the dietary therapy has attracted lots of attentions from many scientific researchers and the protocols are ranging from nutritional balancing to ambulatory diet-care.[39][40][41]
G.I. Diet - lowering the glycemic index of one's diet can improve the control of diabetes.[42][43] This includes avoidance of such foods as potatoes cooked in certain ways, and white bread, and instead favoring multi-grain and sourdough breads, legumes and whole grains—foods that are converted more slowly to glucose in the bloodstream. Low Carb Diet - It has been suggested that the gradual removal of carbohydrates from the diet and replacement with fatty foods such as nuts, seeds, meats, fish, oils, eggs, avocados, olives, and vegetables may help reverse diabetes. Fats would become the primary calorie source for the body, and complications due to insulin resistance would be minimized.[44] However, it's vitally important that such a diet is low in saturated fats. The American Diabetes Association explains: "saturated fat raises blood cholesterol. High blood cholesterol is a risk factor for heart disease. People with diabetes have more frequent heart disease."[45] High fiber diet - It has been shown that a high fiber diet works better than the diet recommended by the American Diabetes Association in controlling diabetes, and may control blood sugar levels with the same efficacy as oral diabetes drugs.[46][47][48]
Though not yet evaluated by the Food and Drug Administration, at least two studies have shown that cinnamon can act significantly reducing some effects of diabetes. One study on people used fine ground cinnamon (Cinnamomum cassia) for oral consumption. Another study used an extract (MHCP) on laboratory rats. The study on people published in 2003 conducted in the Department of Human Nutrition, NWFP Agricultural University, Peshawar, Pakistan concluded:
The study on laboratory rats at Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University published in 2001 used purified hydroxychalcone from cinnamon. The extract was named "MHCP". Part of the study's conclusion stated that "the MHCP is fully capable of mimicking insulin" and recommended further studies.[50][51] Other studies have failed to reproduce these results, and, because large doses of cinnamon are not innocuous, some experts advise against treatment of diabetes with cinnamon.[52]
Chromium - Cholesterol and triglycerides are risk factors in heart disease and diabetes, and studies show that chromium lowers levels of total cholesterol, LDL cholesterol, and triglycerides.[53][54][55][56] Chromium supplements such as chromium picolinate have been shown to improve glucose tolerance in people with type 2 diabetes,[57][58][59] although other studies have not replicated this result.[60] A meta analysis of these trials concluded that chromium supplements had no beneficial effect on healthy people, but that there might be an improvement in glucose metabolism in diabetics, although the authors stated that the evidence for this effect remains weak.[61] Vanadium - A form of vanadium, vanadyl sulfate, seems to improve glucose control in people with type 2 diabetes.[62][63][64][65][66] A pilot study has also found evidence that Tai Chi and Qigong reduce the severity of type 2 diabetes.[67] Benfotiamine, a pro-vitamin of vitamin B1 which has been in use in Europe as an over-the-counter medicine for alcoholic neuropathy for the past half century with no significant side-effects or toxicity, has recently been found to block the major metabolic pathways by which excess blood glucose in the body is transformed into the advanced glycation endproducts (AGEs) which cause diabetic complications.[68] Studies have shown that taking oral benfotiamine can prevent diabetic retinopathy,[69] diabetic neuropathy,[70] and diabetic nephropathy[71] independently of any affect on the blood sugar levels of the patient. In theory, taking benfotiamine might allow patients to be less scrupulous in trying to normalize blood sugar levels and thus free them from the danger of hypoglycemia and the stress of stringent blood sugar monitoring, while still protecting them against the negative effects of hyperglycemia. Research is ongoing to establish the full significance of benfotiamine in the treatment of diabetes. Traditional plant treatments for diabetes A study was made of the effects on glucose homeostasis in normal and streptozotocin (induced) diabetic mice of eleven plants that have been used as traditional treatments for diabetes. The mice were given diets containing dried leaves from the following plants: agrimony (Agrimonia eupatoria), alfalfa (Medicago sativa), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra). The study concluded that "The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice".[72] Mushrooms Aloe vera Oral administration of aloe vera might be a useful adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia[citation needed]. Ten controlled clinical trials were found to reach that conclusion in four independent literature searches. However, caveats reported in each study led the researchers to conclude that aloe vera's clinical effectiveness was not yet sufficiently defined in 1999.[80] [edit] Other Treatment RegimensArtificial Intelligence researcher Dr. Cynthia Marling, of the Ohio University Russ College of Engineering and Technology, in collaboration with the Appalachian Rural Health Institute Diabetes Center, is developing a case based reasoning system to aid in diabetes management. The goal of the project is to provide automated intelligent decision support to diabetes patients and their professional care providers by interpreting the ever increasing quantities of data provided by current diabetes management technology and translating it into better care without time consuming manual effort on the part of an endocrinologist or diabetologist.[81] This type of Artificial Intelligence-based treatment shows some promise with initial testing of a prototype system producing best practice treatment advice which anaylizing physicians deemed to have some degree of benefit over 70% of the time and advice of neutral benefit another nearly 25% of the time.[1] Use of a "Diabetes Coach" is becoming an increasingly popular way to manage diabetes. A Diabetes Coach is usually a Certified diabetes educator (CDE) who is trained to help people in all aspects of caring for their diabetes. The CDE can advise the patient on diet, medications, proper use of insulin injections and pumps, exercise, and other ways to manage diabetes while living a healthy and active lifestyle. CDEs can be found locally or by contacting a company which provides personalized diabetes care using CDEs, such as Fit4D. Diabetes Coaches can speak to a patient on a pay-per-call basis or via a monthly plan. [edit] Cure
Main article: Cure for diabetes mellitus type 1 There is no practical cure, at this time, for type 1 diabetes. The fact that type 1 diabetes is due to the failure of one of the cell types of a single organ with a relatively simple function (i.e. the failure of the beta cells in the Islets of Langerhans) has led to the study of several possible schemes to cure this form of diabetes mostly by replacing the pancreas or just the beta cells.[82] Only those type 1 diabetics who have received either a pancreas or a kidney-pancreas transplant (often when they have developed diabetic kidney disease (ie, nephropathy) and become insulin-independent) may now be considered "cured" from their diabetes. A simultaneous pancreas-kidney transplant is a promising solution, showing similar or improved survival rates over a kidney transplant alone.[83] Still, they generally remain on long-term immunosuppressive drugs and there is a possibility that the immune system will mount a host versus graft response against the transplanted organ.[82] Transplants of exogenous beta cells have been performed experimentally in both mice and humans, but this measure is not yet practical in regular clinical practice partly due to the limited number of beta cell donors. Thus far, like any such transplant, it has provoked an immune reaction and long-term immunosuppressive drugs have been needed to protect the transplanted tissue.[84] An alternative technique has been proposed to place transplanted beta cells in a semi-permeable container, isolating and protecting them from the immune system. Stem cell research has also been suggested as a potential avenue for a cure since it may permit regrowth of Islet cells which are genetically part of the treated individual, thus perhaps eliminating the need for immuno-suppressants.[82] This new method autologous nonmyeloablative hematopoietic stem cell transplantation was developed by a research team composed by Brazilian and American scientists (Dr. Julio Voltarelli, Dr. Carlos Eduardo Couri, Dr Richard Burt, and colleagues) and it was the first study to use stem cell therapy in human diabetes mellitus. This was initially tested in mice and in 2007 there was the first publication of stem cell therapy to treat this form of diabetes. Until 2009, there was 23 patients included and followed for a mean period of 29.8 months (ranging from 7 to 58 months). In the trial, severe immunosuppresion with high doses of cyclophosphamide and anti-thymocyte globulin is used with the aim of "turning off" the immunologic system", and then autologous hematopoietic stem cells are reinfused to regenerate a new one. In summary it is a kind of "immunologic reset" that blocks the autoimmune attack against residual pancreatic insulin-producing cells. Until December 2009, 12 patients remained continuously insulin-free for periods raging from 14 to 52 months and 8 patients became transiently insulin-free for periods ranging from 6 to 47 months. Of these last 8 patients, 2 became insulin-free again after the use of sitagliptin, a DPP-4 inhibitor approved only to treat type 2 diabetic patients and this is also the first study to document the use and complete insulin-independendce in humans with type 1 diabetes with this medication. In parallel with insulin suspension, indirect measures of endogenous insulin secretion revealed thate it significantly increased in the whole group of patients, regardless the need of daily exogenous insulin use.[85] Microscopic or nanotechnological approaches are under investigation as well, in one proposed case with implanted stores of insulin metered out by a rapid response valve sensitive to blood glucose levels. At least two approaches have been demonstrated in vitro. These are, in some sense, closed-loop insulin pumps.
Type 2 diabetes is usually first treated by increasing physical activity, and eliminating saturated fat and reducing sugar and carbohydrate intake with a goal of losing weight. These can restore insulin sensitivity even when the weight loss is modest, for example around 5 kg (10 to 15 lb), most especially when it is in abdominal fat deposits. Diets that are very low in saturated fats can reverse insulin resistance.[86][87] Testosterone replacement therapy can improve glucose tolerance and insulin sensitivity in diabetic hypogonadal men. The mechanisms by which testosterone decreases insulin resistance is under study.[88] Moreover testosterone has a protective effect on pancreatic beta cells, which is possibly exerted by androgen-receptor-mediated mechanisms and influence of inflammatory cytokines.[89] Recently it has been shown that a type of gastric bypass surgery can normalize blood glucose levels in 80-100% of severely obese patients with diabetes. The precise causal mechanisms are being intensively researched; its results are not simply attributable to weight loss, as the improvement in blood sugars precedes any change in body mass. This approach may become a standard treatment for some people with type 2 diabetes in the relatively near future.[90] This surgery has the additional benefit of reducing the death rate from all causes by up to 40% in severely obese people.[91] A small number of normal to moderately obese patients with type 2 diabetes have successfully undergone similar operations.[92][93] [edit] References
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