Diabetes management

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Diagnosis

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Template:Diabetes Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Karol Gema Hernandez, M.D. [2]

Overview

Diabetes is a chronic disease with no cure as of 2008. It is associated with an impaired glucose cycle, altering metabolism. Management of this disease may include lifestyle modifications such as achieving and maintaining proper weight, diet, exercise and foot care.

Management

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.

Complexities Relating to Management

The main complexities stem from the nature of the feedback loop itself, which is sought to be regulated:

  • The glucose cycle is a system which is affected by two factors: entry of glucose into the bloodstream and also blood levels of insulin to control its transport out of the bloodstream
  • As a system, it is sensitive to diet and exercise
  • It is affected by the need for user anticipation due to the complicating effects of time delays between any activity and the respective impact on the glucose system
  • Management is highly intrusive and compliance is an issue, since it relies upon user lifestyle change and (often) upon regular sampling and measuring of blood glucose levels, multiple times a day in many cases
  • It changes as people grow and develop
  • It is highly individual

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.

Early Advancements

Late 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.

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 control, and other lifestyle changes which impact the glucose cycle.

Blood Sugar Level

Blood 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). In the diabetic patient a before-meal level of <6.1 mmol/L (<110 mg/dL) and a level two hours after the start of a meal of <7.8 mmol/L (<140 mg/dL) is acceptable.[citation needed]

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.

Hypo and Hyperglycemia

Levels 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).

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.

A blood glucose test strip for an older style (ie, optical color sensing) monitoring system

Prolonged and elevated levels of glucose in the blood, which is left unchecked and untreated, will, over time, result in serious diabetic complications and sometimes even death. It is therefore highly important that a diabetic patient checks their blood levels either daily or every few days to see what levels they are achieving over a given period of time. There is also computer software for the PC which is available from blood testing manufacturers which can display results and trends over time. Type 1 patients will have to check on a more regular daily basis due to insulin therapy, which is a fine art to master.

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.

Glycemic Control

Glycemic 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.

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.

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.

Monitoring

An older style portable blood glucose meter. A blood sample is applied to an inserted strip (see image above) and color changes caused by reaction with blood glucose are measured by the meter.

Relying 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.

Personal (Home) Glucose Monitoring

Control and outcomes of both types 1 and 2 diabetes may be improved by patients using home glucose meters to regularly measure their glucose levels.[1] 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 essential 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.[2] However its benefit in type 2 diabetes is more controversial as there is much more variation in severity of type 2 cases.[3] It has been suggested that some type 2 patients might do as well with home urine-testing alone.[4] The best use of home blood-sugar monitoring is being researched.[5]

Benefits of control and reduced hospital admission have been reported.[6] 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 HbAc1 (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.[7] 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.[8]

HbA1c Test

A 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 cells 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.

Ongoing Monitoring

Recently, devices have been manufactured which provide ongoing monitoring of glucose levels on an automated basis during the day, for example:

  1. The Paradigm REAL-Time by Minimed, is a blood glucose monitoring device that provides blood glucose measurements to be made every five minutes. The patient can thus adjust an insulin infusion pump immediately and mimic the "feed-back" mechanism of a pancreas. Significant reductions in complications of therapy have been demonstrated[citation needed] and reductions in long-term complications from diabetes mellitus are projected.
  2. The US Food and Drug Administration has also approved a non-invasive blood glucose monitoring device, the GlucoWatch G2 Biographer. This allows checking blood glucose levels, while puncturing the skin as little as twice a day. Once calibrated with a blood sample, it pulls body fluids from the skin using small electrical currents, taking six readings an hour for as long as thirteen hours. It has not proven to be reliable enough, or convenient enough to be used in lieu of conventional blood monitoring. Other non-invasive methods like radio waves, ultrasound and energy waves are also being tested.

Approaches to Management

Insulin and Other Drug Based Approaches

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.[9]

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. There are several insulin application mechanisms under experimental development as of 2004. 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.[10] 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.

The 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.

Diet and Supplements

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,[11] while others claim benefits for a high-fiber, 75% carbohydrate diet.[12].

An article summarizing the view of the American Diabetes Association[13] 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.

Specific diets

Glycemic index - lowering the glycemic index of one's diet can improve the control of diabetes.[14][15] This includes avoidance of such foods as potatoes,and white bread, and favoring legumes and whole grains.

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.[16]

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.[17][18][19]

Chromium and vanadium

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.[20][21][22][23] Chromium supplements such as chromium picolinate have been shown to improve glucose tolerance in people with type 2 diabetes,[24][25][26] although other studies have not replicated this result.[27] 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.[28]

Vanadium - A form of vanadium, vanadyl sulfate, seems to improve glucose control in people with type 2 diabetes.[29][30][31][32][33]

A pilot study has also found evidence that Tai Chi and Qigong reduce the severity of type 2 diabetes.[34] For a helpful presentation that highlights the importance of exercise in the prevention of diabetes, click here: [3]

References

  1. Gray A, Raikou M, McGuire A, Fenn P, Stevens R, Cull C, Stratton I, Adler A, Holman R, Turner R (2000). "Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomized controlled trial (UKPDS 41). United Kingdom Prospective Diabetes Study Group". BMJ. 320 (7246): 1373&ndash, 8. doi:10.1136/bmj.320.7246.1373. PMID 10818026.
  2. Evans JM, Newton RW, Ruta DA, MacDonald TM, Stevenson RJ, Morris AD (1999). "Frequency of blood glucose monitoring in relation to glycaemic control: observational study with diabetes database". BMJ. 319 (7202): 83&ndash, 6. PMID 10398627.
  3. Gallichan M (1997). "Self monitoring of glucose by people with diabetes: evidence based practice". BMJ. 314 (7085): 964&ndash, 7. PMID 9099125.
  4. Chantelau E, Nowicki S (1997). "Self monitoring of glucose by people with diabetes. Patients with non-insulin dependent diabetes should monitor urine rather than blood glucose". BMJ. 315 (7101): 185. PMID 9251556.
  5. Farmer A, Wade A, French DP, Goyder E, Kinmonth AL, Neil A (2005). "The DiGEM trial protocol—a randomized controlled trial to determine the effect on glycaemic control of different strategies of blood glucose self-monitoring in people with type 2 diabetes [ISRCTN47464659]". BMC Fam Pract. 6: 25. PMID 15960852.
  6. Kibriya MG, Ali L, Banik NG, Khan AK (1999). "Home monitoring of blood glucose (HMBG) in Type-2 diabetes mellitus in a developing country". Diabetes Res Clin Pract. 46 (3): 253&ndash, 7. doi:10.1016/S0168-8227(99)00093-5. PMID 10624792.
  7. Jaworska J, Dziemidok P, Kulik TB, Rudnicka-Drozak E (2004). "Frequency of self-monitoring and its effect on metabolic control in patients with type 2 diabetes". Ann Univ Mariae Curie Sklodowska [Med]. 59 (1): 310&ndash, 6. PMID 16146003.
  8. Roach P (2004). "Better systems, not guidelines, for glucose monitoring". BMJ. 329 (7479): E332. doi:10.1136/bmj.329.7479.E332. PMID 15591539.
  9. Tuomilehto J, Lindström J, Eriksson J, Valle T, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M (2001). "Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance". N Engl J Med. 344 (18): 1343–50. doi:10.1056/NEJM200105033441801. PMID 11333990.
  10. "Diabetes Mellitus Management". Diabetes Mellitus and Oral Health. Armenian Medical Network. 2006. Retrieved 2007-05-10. Text " Brian L. Mealey, DDS, MS " ignored (help)
  11. Garg, Abhimanyu (11 May 1994). "Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus". JAMA. 271 (18): 1421–8. doi:10.1001/jama.271.18.1421. Unknown parameter |coauthors= ignored (help)
  12. Kiehm, Tae (August 1976). "Beneficial effects of a high carbohydrate, high fiber diet on hyperglycemic diabetic men" (abstract). Am J Clin Nutr. 29: 895–99. PMID 941870. Unknown parameter |coauthors= ignored (help)
  13. American Diabetes Association (2006). "Nutrition Recommendations and Interventions for Diabetes–2006". Diabetes Care. 29: 2140–57. doi:10.2337/dc06-9914.
  14. Brand-Miller, J (1999). "Diets with a low glycemic index: from theory to practice". Nutr Today. 34: 64–72.
  15. Sheard et al (2004). "Dietary carbohydrate (amount and type) in the prevention and management of diabetes: a statement by the American Diabetes Association." Diabetes Care;27(9):2266-71
  16. Bernstein, Richard K (2007). Dr Bernstein's Diabetes Solution. New York, NY: Little, Brown and Company. ISBN 978-0-316-16716-1.
  17. Chandalia, M; et al. (2000). "Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus". New Engl J Med. 342: 1392–8. doi:10.1056/NEJM200005113421903.
  18. Rodríguez-Morán, M (1998). "Lipid- and glucose-lowering efficacy of plantago psyllium in type II diabetes". Diabetes Its Complications. 12: 273–8. doi:10.1016/S1056-8727(98)00003-8.
  19. Schwartz, SE (1988). "Sustained pectin ingestion: effect on gastric emptying and glucose tolerance in non-insulin-dependent diabetic patients". Am J Clin Nutr. 48: 1413–7.
  20. Sherman, L (1968). "Failure of trivalent chromium to improve hyperglycemia in diabetes mellitus". Metabolism. 17: 439–42. doi:10.1016/0026-0495(68)90066-8.
  21. Lee, NA (1994). "Beneficial effect of chromium supplementation on serum triglyceride levels in NIDDM". Diabetes Care. 17: 1449–52. doi:10.2337/diacare.17.12.1449.
  22. Hermann, J (1998). "Effects of chromium or copper supplementation on plasma lipids, plasma glucose and serum insulin in adults over age fifty". J Nutr Elderly. 18: 27–45. doi:10.1300/J052v18n01_03.
  23. Press, RI (1990 January). "The effect of chromium picolinate on serum cholesterol and apolipoprotein fractions in human subjects". West J Med. 152: 41–45. Check date values in: |year= (help)
  24. Evans, GW (1989). "The effect of chromium picolinate on insulin controlled parameters in humans". Int J Biosocial Med Res. 11: 163–80.
  25. Anderson, RA (1998). "Chromium, glucose intolerance and diabetes". J Am Coll Nutr. 17: 548–55.
  26. Anderson, RA (2000). "Chromium in the prevention and control of diabetes". Diabetes Metab. 26: 22–7.
  27. Kleefstra N, Houweling ST, Bakker SJ; et al. (2007). "Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled trial". Diabetes Care. 30 (5): 1092–6. doi:10.2337/dc06-2192. PMID 17303791.
  28. Balk EM, Tatsioni A, Lichtenstein AH, Lau J, Pittas AG (2007). "Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials". Diabetes Care. 30 (8): 2154–63. doi:10.2337/dc06-0996. PMID 17519436.
  29. Halberstam, M; et al. (1996). "Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects". Diabetes. 45: 659–66. doi:10.2337/diabetes.45.5.659.
  30. Boden, G; et al. (1996;). "Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin dependent diabetes mellitus". Metabolism. 45: 1130–5. doi:10.1016/S0026-0495(96)90013-X. Check date values in: |year= (help)
  31. Goldfine, AB; et al. (2000). "Metabolic effects of vanadyl sulfate in humans with non-insulin-dependent diabetes mellitus: in vivo and in vitro studies". Metabolism. 49: 400–10. doi:10.1016/S0026-0495(00)90418-9.
  32. Badmaev, V; et al. (1999). "Vanadium: a review of its potential role in the fight against diabetes". Altern Complement Med. (XX)|format= requires |url= (help). 5: 273–291. doi:10.1089/acm.1999.5.273.
  33. Goldwaser, I; et al. (1999). J Biol Chem. 274: 26617–26624 title = L-glutamic acid gamma-monohydroxamine. A potentiator of vanadium-evoked glucose metabolism in vitro and in vivo. doi:10.1074/jbc.274.37.26617. Missing or empty |title= (help)
  34. Melanie Christiansen (20 December, 2005). "Tai Chi a promising remedy for diabetes". Australian Broadcasting Corporation. Check date values in: |date= (help) - Pilot study of qigong and T'ai Chi in diabetes sufferers.

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