The targets are: HbA1c of 6% to 7.0% Preprandial blood glucose: 4.0 to 6.0 mmol/L (72 to 108 mg/dl) 2-hour postprandial blood glucose: 5.0 to 8.0 mmol/L (90 to 144 mg/dl)
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.
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.
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.
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.
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, Maitake Agaricus blazei as well as some others.
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 diabetes management 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.
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.
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.
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. However its benefit in type 2 diabetes is more controversial as there is much more variation in severity of type 2 cases. It has been suggested that some type 2 patients might do as well with home urine-testing alone. The best use of home blood-sugar monitoring is being researched.
Benefits of control and reduced hospital admission have been reported. 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. 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.
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, while others claim benefits for a high-fiber, 75% carbohydrate diet.
An article summarizing the view of the American Diabetes Association 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.
Patients with type 1 diabetes mellitus require direct injection of insulin as their bodies cannot produce enough (or even any) insulin. As of 2010, 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 tract. 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. 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. 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 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.
Second, hypoglycemia can affect a person’s thinking process, coordination, and state of consciousness. This disruption in brain functioning is called neuroglycopenia. Studies have demonstrated that the effects of neuroglycopenia impair driving ability. A study involving people with type 1 diabetes found that individuals reporting two or more hypoglycemia-related driving mishaps differ physiologically and behaviorally from their counterparts who report no such mishaps. For example, during hypoglycemia, drivers who had two or more mishaps reported fewer warning symptoms, their driving was more impaired, and their body released less epinephrine (a hormone that helps raise BG). Additionally, individuals with a history of hypoglycemia-related driving mishaps appear to use sugar at a faster rate and are relatively slower at processing information. These findings indicate that although anyone with type 1 diabetes may be at some risk of experiencing disruptive hypoglycemia while driving, there is a subgroup of type 1 drivers who are more vulnerable to such events.
Given the above research findings, it is recommended that drivers with type 1 diabetes with a history of driving mishaps should never drive when their BG is less than 70 mg/dl. Instead, these drivers are advised to treat hypoglycemia and delay driving until their BG is above 90 mg/dl. An internet-version of this training has also been shown to have significant beneficial results. Additional NIH funded research to develop internet interventions specifically to help improve driving safety in drivers with type 1 diabetes is currently underway.
Diabetic persons must increase their awareness towards the oral infections as they have a double impact on one's health. Firstly, people with diabetes are more likely to develop periodontal disease which causes increased blood sugar levels, often leading to diabetes complications. Severe periodontal disease can increase blood sugar, contributing to increased periods of time when the body functions with a high blood sugar. This puts diabetics at increased risk for diabetic complications.
The first symptoms of gum and teeth infections in diabetic persons are decreased salivary flow, burning mouth or tongue. Also, patients may experience signs as dry mouth which increases the incidence of decay. Poorly-controlled diabetes usually leads to gum problems recession as plaque creates more harmful proteins in the gums.
Tooth decay and cavities are some of the first oral problems that individuals with diabetes are at risk for. Increased blood sugar levels translate into greater sugars and acids that attack the teeth and lead to gum diseases. Gingivitis can also occur as a result of increased blood sugar levels along with an inappropriate oral hygiene. Periodontitis is an oral disease caused by untreated gingivitis and which destroys the soft tissue and bone that support the teeth. This disease may cause the gums to pull away from the teeth which may eventually loosen and fall out. Diabetic people tend to experience more severe periodontitis because diabetes lowers the ability to resist infection and also slows healing. At the same time, an oral infection such as periodontitis can make diabetes more difficult to control because it causes the blood sugar levels to rise.
To prevent further diabetic complications as well as serious oral problems, diabetic persons must keep their blood sugar levels under control and have a proper oral hygiene. A study in the Journal of Periodontology found that poorly controlled type 2 diabetic patients are more likely to develop periodontal disease than well-controlled diabetics are.
Dental care is therefore even more important for diabetic patients than for healthy individuals. Maintaining the teeth and gum healthy is done by taking some preventing measures such as regular appointments at a dentist and a very good oral hygiene. Also, oral health problems can be avoided by closely monitoring the blood sugar levels. Patients who keep better under control their blood sugar levels and diabetes are less likely to develop oral health problems when compared to diabetic patients who control their disease moderately or poorly.
Poor oral hygiene is a great factor to take under consideration when it comes to oral problems and even more in people with diabetes. Diabetic people are advised to brush their teeth at least twice a day, and if possible, after all meals and snacks. However, brushing in the morning and at night is mandatory as well as flossing and using an anti-bacterial mouthwash. Individuals who suffer from diabetes are recommended to use toothpaste that contains fluoride as this has proved to be the most efficient in fighting oral infections and tooth decay. Flossing must be done at least once a day, as well because it is helpful in preventing oral problems by removing the plaque between the teeth, which is not removed when brushing.
Diabetic patients must get professional dental cleanings every six months. In cases when dental surgery is needed, it is necessary to take some special precautions such as adjusting diabetes medication or taking antibiotics to prevent infection. Looking for early signs of gum disease (redness, swelling, bleeding gums) and informing the dentist about them is also helpful in preventing further complications. Quitting smoking is recommended to avoid serious diabetes complications and oral diseases.
Diabetic persons are advised to make morning appointments to the dental care provider as during this time of the day the blood sugar levels tend to be better kept under control. Not least, individuals who suffer from diabetes must make sure both their physician and dental care provider are informed and aware of their condition, medical history and periodontal status.
Diabetes type 1 is caused by the destruction of enough beta cells to produce symptoms; these cells, which are found in the Islets of Langerhans in the pancreas, produce and secrete insulin, the single hormone responsible for allowing glucose to enter from the blood into cells (in addition to the hormone amylin, another hormone required for glucose homeostasis). Hence, the phrase "curing diabetes type 1" means "causing a maintenance or restoration of the endogenous ability of the body to produce insulin in response to the level of blood glucose" and cooperative operation with counterregulatory hormones.
This section deals only with approaches for curing the underlying condition of diabetes type 1, by enabling the body to endogenously, in vivo, produce insulin in response to the level of blood glucose. It does not cover other approaches, such as, for instance, closed-loop integrated glucometer/insulin pump products, which could potentially increase the quality-of-life for some who have diabetes type 1, and may by some be termed "artificial pancreas".
A biological approach to the artificial pancreas is to implant bioengineered tissue containing islet cells, which would secrete the amounts of insulin, amylin and glucagon needed in response to sensed glucose.
When islet cells have been transplanted via the Edmonton protocol, insulin production (and glycemic control) was restored, but at the expense of continued immunosuppression drugs. Encapsulation of the islet cells in a protective coating has been developed to block the immune response to transplanted cells, which relieves the burden of immunosuppression and benefits the longevity of the transplant.
One concept of the bio-artificial pancreas uses encapsulated islet cells to build an islet sheet which can be surgically implanted to function as an artificial pancreas.
This islet sheet design consists of:
Islet sheet with encapsulation research is pressing forward with large animal studies at the present, with plans for human clinical trials within a few years.
Clinical studies underway in New Zealand by Living Cell Technologies have encapsulated pig islet cells in a seaweed derived capsule. This approach has had very positive clinical studies and is currently underway in human trials as of 2008. So far, treatment using this method of cell encapsulation has been proven safe and effective and is the first to achieve insulin independence in human trials without immunosuppressant drugs.
Other researchers, most notably Dr. Aaron I. Vinik of the Strelitz Diabetes Research Institute of Eastern Virginia Medical School and a former colleague, Dr. Lawrence Rosenberg (now at McGill University) discovered in a protein they refer to as INGAP, which stands for Islet Neogenesis Associated Protein back in 1997. INGAP seems to be the product of a gene responsible for regenerating the islets that make insulin and other important hormones in the pancreas.
INGAP has had commercialization difficulties. Although it has appeared promising, commercial rights have changed hands repeatedly, having once been owned by Procter & Gamble Pharmaceuticals, which eventually dropped it. Rights were then acquired by GMP Companies. More recently, Kinexum Metabolics, Inc. has since sublicensed INGAP from GMP for further clinical trials. Kinexum has continued development under Dr. G. Alexander Fleming, an experienced metabolic drug developer, who headed diabetes drug review at the FDA for over a decade. As of 2008, the protein had undergone Phase 2 Human Clinical Trials, and developers were analyzing the results. At the American Diabetes Association's 68th Annual Scientific Sessions in San Francisco, Kinexum announced a Phase 2 human clinical trial with a combination therapy, consisting of DiaKine's Lisofylline (LSF) and Kinexum's INGAP peptide, which is expected to begin in late 2008. The trial will be unique in that patients who are beyond the 'newly diagnosed' period will be included in the study. Most current trials seeking to treat people with type 1 diabetes do not include those with established disease.
;South Korea
In January 2006, a team of South Korean scientists has grown pancreatic beta cells, which can help treat diabetes, from stem cells taken from the umbilical cord blood of newborn babies.
;Brazil
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.[48] 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 immunosuppression 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 that it significantly increased in the whole group of patients, regardless the need of daily exogenous insulin use.
However, there were no control subjects, which means that all of the processes could have been completely or partially natural. Secondly, no theory for the mechanism of cure has been promoted. It is too early to say whether the results will be positive or negative in the long run.
;University of North Carolina In September 2008, scientists from the University of North Carolina at Chapel Hill School of Medicine have announced their success in transforming cells from human skin into cells that produce insulin.
The skin cells were first transformed into stem cells and then had been differentiated into insulin-secreting cells.
However, other scientists have doubts, as the research papers fail to detail the new cells' glucose responsiveness and the amount of insulin they are capable of producing.
Technology for gene therapy is advancing rapidly such that there are multiple pathways possible to support endocrine function, with potential to practically cure diabetes.
Gene therapy can be used to manufacture insulin directly: an oral medication, consisting of viral vectors containing the insulin sequence, is digested and delivers its genes to the upper intestines. Those intestinal cells will then behave like any viral infected cell, and will reproduce the insulin protein. The virus can be controlled to infect only the cells which respond to the presence of glucose, such that insulin is produced only in the presence of high glucose levels. Due to the limited numbers of vectors delivered, very few intestinal cells would actually be impacted and would die off naturally in a few days. Therefore by varying the amount of oral medication used, the amount of insulin created by gene therapy can be increased or decreased as needed. As the insulin producing intestinal cells die off, they are boosted by additional oral medications. Gene therapy might eventually be used to cure the cause of beta cell destruction, thereby curing the new diabetes patient before the beta cell destruction is complete and irreversible. Gene therapy can be used to turn duodenum cells and duodenum adult stem cells into beta cells which produce insulin and amylin naturally. By delivering beta cell DNA to the intestine cells in the duodenum, a few intestine cells will turn into beta cells, and subsequently adult stem cells will develop into beta cells. This makes the supply of beta cells in the duodenum self replenishing, and the beta cells will produce insulin in proportional response to carbohydrates consumed.
;Yonsei University
Scientists in the South Korean university of Yonsei have, in 2000, succeeded in reversing diabetes in mice and rats. Using a viral vector, a DNA encoding the production of an insulin analog was injected to the animals, which remained non-diabetic for at least the eight months duration of the study. 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. Only those type 1 diabetics who have received either a pancreas or a kidney-pancreas transplant (often when they have developed diabetic kidney disease (i.e., 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. 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. 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.
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.
Testosterone replacement therapy may improve glucose tolerance and insulin sensitivity in diabetic hypogonadal men. The mechanisms by which testosterone decreases insulin resistance is under study. Moreover testosterone may have a protective effect on pancreatic beta cells, which is possibly exerted by androgen-receptor-mediated mechanisms and influence of inflammatory cytokines.
Recently it has been suggested that a type of gastric bypass surgery may normalize blood glucose levels in 80-100% of severely obese patients with diabetes. The precise causal mechanisms are being intensively researched; its results may not simply be attributable to weight loss, as the improvement in blood sugars seems to precede any change in body mass. This approach may become a treatment for some people with type 2 diabetes, but has not yet been studied in prospective clinical trials. This surgery may have the additional benefit of reducing the death rate from all causes by up to 40% in severely obese people. A small number of normal to moderately obese patients with type 2 diabetes have successfully undergone similar operations.
MODY is another classification of diabetes and it can be treated by early lifesyle management and medical management. it has to be treated in the early stage, so as to provide a good health.
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