Type II Diabetes Mellitus – 2011 Research Summary

by | May 16, 2011 | 2011, Diabetes, Pancreatic Health

Written by Marcia J. Egles MD. Foods which do not convert rapidly into blood sugar and exercise are recommended for diabetics and a number of supplements are also recommended.

Despite encouraging data that type II diabetes may be a largely preventable disease, the twenty-first century is seeing it in epidemic levels in the United States and worldwide.  As reported by the Center for Disease Control (CDC), from 1980 through 2007, the number of Americans with type II diabetes has more than tripled (from 5.6 million to 18 million) and continues to rise to now nearly 26 million.  Projections from the new 2010 census data by the CDC are even more grim with an expected 25% of the population being diabetic by 2040 (1,2). Worldwide Type II diabetes is reaching pandemic proportions, with no sign of abating (3).

The escalating rates of diabetes cause great human and financial burden, with estimated (2007) annual United States’ medical costs at more than 174 billion dollars (1). Much of the expense and misery of diabetes is attributable to its long-term complications which cause more cases of blindness, renal failure, and amputations than any other disease (4). In addition, diabetes is associated with a 2- to 5-fold increase in cardiovascular disease (CVD) (5, 6), which contributes to premature deaths, reducing life expectancy by up to 15 years. The diabetes-specific complications which occur in the tiny blood vessels of the eye’s retina and the kidneys can be reduced substantially by lowering chronic hyperglycemia (high blood sugar,7, 8).  Whether similar reductions decrease cardiovascular disease in type II diabetes is not as clear (9, 10).

The best documented strategy to avoid diabetes or to improve its course is to maintain a healthy body weight and to exercise.  This common knowledge continues to be backed by medical research.  Excellent evidence that even modest weight loss and exercise reduces the risk of type II diabetes is provided by many studies including the Diabetes Prevention Program published in the February, 2002 issue of the New England Journal of Medicine. This study reported a 58% reduction in new diabetes cases for adults at risk for diabetes who implemented a weight loss and exercise program compared to others who remained  more overweight and sedentary (11).  Similarly, a British meta-analysis estimates that lifestyle interventions can reduce the risk of progression of pre-diabetes to diabetes by about 60% (12).

Exercise

High-quality studies establishing the importance of exercise and fitness in diabetes were lacking until recently.  It is now well-established that regular physical exercise not only improves blood glucose control, but also can prevent or delay type II diabetes, along with positively affecting lipids, blood pressure, cardiovascular events, death rate, and quality of life. (13,14) The current recommendation of the American Diabetes Association is for diabetics to engage in 150 minutes per week of moderate to brisk physical activity ( 13). The exercise should be spread out over at least three days a week, with no breaks of longer than two days.

Many at risk for diabetes cannot or do not become active.  Even less ambitious regular physical exercise also appears to be of value.  A Finnish four  year study showed that high risk individuals who significantly increased their physical activity saw the most benefit in reducing the risk of the onset of diabetes, but also those who increased physical activities such as walking showed at least some benefit (15).

Diet and Dietary Supplements in Diabetes Prevention and Health

The known modifiable risk factors for type II diabetes are excessive body weight and sedentary lifestyle. Increasing age and a history of relatives having the disease also increase the likelihood of its development.  There is no drug or dietary supplement that has been shown to prevent diabetes.  This article seeks to review current medical research involving dietary and supplement information that may be of value to those affected by diabetes.

Diabetes is a disease of impaired carbohydrate metabolism.  Blood levels of the carbohydrate glucose (sugar) rise too high in the blood causing both immediate and long-term problems.  The hormone insulin which is produced in the pancreas lowers the blood glucose by moving the glucose into the body’s cells where it is converted to energy or, if there is excess, altered to be stored as fat.  In type I diabetes, the pancreas is unable to make sufficient insulin to lower the glucose appropriately.  A type I diabetic must receive insulin for survival.  In type II diabetes, the person makes insulin, and actually can have very high insulin levels, however the insulin does not work as well as it should.  The body’s cells are “impaired” to the glucose lowering effects of the insulin, and like the type I diabetic, the glucose in the blood rises while the body’s cells starve for glucose.   The extra glucose in the blood is processed through the kidneys and spills into the urine creating an overabundance of urine and severe thirst.  Dehydration ensues if the person is unable to keep up with the body’s loss of water to the urine.  Long-term complications of diabetes, some of which are attributed to chronically high blood glucose, include blood vessel disease affecting the brain, eyes, heart, kidneys, and muscles- essentially the entire body.

Food choices and activities are highly individual, but lifestyles that promote a normal body weight are extremely advantageous against diabetes.  In general foods that generate less glucose as they are digested, that is, ones with a lower “ glycemic load” are easier on a diabetic’s strained glycemic system.  Low glycemic foods would include foods low in carbohydrates.  Some carbohydrate type foods are more glycemic than others – sugary foods would be the highest glucose burden.  However some carbohydrate rich foods are more complex and are relatively difficult for the body to process into glucose.   Unrefined or whole grain foods and legumes would be examples. The presence of fiber in the food further slows the absorption of the glucose and can lower the glycemic load.

Several studies support the idea that diabetics do better in general with lower glycemic and higher fiber foods.  Brown rice, which is a less processed, higher fiber and lower glycemic alternative to the more popular white rice, is an example of one such beneficial food.  One study estimated that replacing 50 grams per day (uncooked, equal to one-third serving per day) of white rice with the same amount of brown rice was associated with a 16% reduced risk of diabetes ( 16).

Other relatively low-glycemic , high fiber food choices include nuts and seeds.  These are also sources of omega-3 fatty acids which have been demonstrated to be of value to both cardiovascular disease and to diabetes (  NHRI  reviewed ,17 ).  Walnuts in particular have been a focus of research and may improve blood vessel health in diabetics ( NHRI reviewed ,18 ).

An overall way of eating that has gained increasing recognition as beneficial especially to those with diabetes and heart disease is the Mediterranean diet (19).  The Mediterranean diet is rich in fruit, vegetables, nuts, legumes, whole grains, fish and low-fat dairy products with olive oil as its main source of fat.  Red wine is consumed in small to moderate quantities.  Meat and eggs are eaten in minimal amounts.  An ever-increasing number of studies, including clinical trials (20,21), underscores the particular benefits of this nutrient rich, high fiber style of eating in the management and prevention of diabetes.

In a recent four year study from Naples, Italy (20), a Mediterranean-style low-carbohydrate diet was compared with a low-fat diet of similar calories in 215 newly diagnosed, type II, overweight diabetics. Participants in one group were assigned to follow a Mediterranean diet with no more than half their daily calories from carbohydrates.  Participants in the other group were assigned to follow a low-fat diet similar to that recommended by the American Heart Association – with no more than 30 percent of its daily calories from fat and 10 percent from saturated fat.

Both diet groups saw benefits.  Of those on the Mediterranean diet, 56% were in control of their diabetes without the use of diabetic medications, compared to 30 per cent of the low-fat diet group. Participants assigned to the Mediterranean-style diet also lost more weight and experienced greater improvements in glycemic control and coronary risk measures than did those assigned to the low-fat diet.   This study emphasizes that for many type II diabetics, diabetes can be well controlled by diet.

Dietary Supplements in the Prevention and Treatment of Diabetes

Chromium

Chromium is a naturally occurring element found in tiny, “trace” amounts in a widespread variety of foods.  Chromium has been a logical focus of diabetes research, because of observations made in the development of intravenous food in the 1970’s.  Patients who were unable to eat were fed nutrients through their veins.  After many months of only intravenous food, they developed diabetes.  When trace amounts of chromium were added to the experimental intravenous food, the diabetes resolved (22).

Intravenous food (”TPN”) has since been formulated with trace chromium.  Although chromium has been shown to be involved in carbohydrate and lipid metabolism, and thought to affect insulin action, the molecular mechanisms concerning chromium remain unknown.  Similar cases of definite chromium deficiency in persons who are able to eat regular food have not been medically demonstrated.

The tantalizing possibility of chromium insufficiency as a cause of type II diabetes has been studied.   Despite the attention chromium has received, chromium’s role in diabetes remains uncertain.  To date, although studies have shown lower chromium levels in diabetics as compared with peers, chromium supplements have not demonstrated benefit in the prevention of diabetes (24).These studies have not been large clinical trials and doses and duration of chromium used have been variable.  No toxic concerns were reported with dosages of chromium picolate up to 1000 micrograms per day for 64 months (25).

For persons having type II diabetes, chromium supplements may hold some benefit.  The same review study(24) which concluded no benefits had been shown of chromium to the prevention of diabetes also asserted that their meta-analysis of 14 clinical trials showed,” Chromium supplementation significantly improved glycemia among patients with diabetes.”   Another review (26) observed that many of the chromium studies which showed no benefit used doses of less than 200 micrograms per day.  A more consistent clinical response is observed with daily supplementation of chromium greater than 200 micrograms per day for a duration of more than two months.  In addition, chromium picolate appears to be clinically more effective than chromium chloride in both human and animal studies.  Although the use of supplemental chromium has gained in acceptance among diabetes physicians (27), currently the American Diabetes Association does not endorse it because of the conflicting studies (28).

More clinical trials are in progress.  Supplements containing chromium picolinate in combination with biotin are undergoing extensive study with a dose of 600 micrograms per day plus 2 milligrams  daily of biotin (29).

Chromium has been reported to reverse corticosteroid-induced diabetes. In case studies of patients with steroid-induced diabetes treated with 600 micrograms per day chromium picolate, fasting blood glucose values fell from 250 to 150 mg/dl. The requirement for antidiabetic drugs was also reduced by 50% in these patients.  Chromium picolate at doses of 600 micrograms per day has been recognized by some diabetologists as valuable in the treatment of steroid–induced diabetes (30).

Vitamin C

The anti-oxidant vitamin C, or L- ascorbic acid, is an essential dietary nutrient in humans.  The nutritional disease of scurvy results from severe vitamin C deficiency.  As little as 10 mg daily of vitamin C will prevent scurvy.  The daily amounts of vitamin C for optimal health might be higher than that needed to avoid scurvy, with some experts advocating large daily amounts, in excess of 2 grams per day in some circumstances.  Other studies have warned against exceeding 300 mg per day and that adequate vitamin C is obtained by regularly eating ordinary amounts of fruits and vegetables ( 31).

Oxidative stress has been implicated in both the onset of type II diabetes and the worsening of its complications (32,33). The intriguing utility of the antioxidant vitamin C to the prevention and treatment of diabetes has received attention in medical research. Type II diabetics have been found in observational studies to have lower than normal levels of vitamin C and other antioxidants(34,35,36).

The first major clinical trial (37) looking at the potential of preventing type II diabetes by the long-term supplementation of antioxidant vitamins was reported in 2009.  This 9 year study, the Women’s Antioxidant Cardiovascular Study,(WACS), involved 8171 female health professionals over the age of 40 who were at risk for cardiovascular disease. They were randomly assigned to receive 500 mg of vitamin C daily, vitamin E ( RRR-alpha- tocopherol acetate, 600 IU every other day), beta-carotene ( 50 mg every other day), or placebos.  Although there was a slight but statistically insignificant reduction in the number of women who developed diabetes in the vitamin C group, the study concluded that it showed no significant overall effects of vitamin C, vitamin E or vitamin A on the risk of developing diabetes in women with high risk of heart disease.  This study also noted that a subgroup of women with high cholesterol, showed a less than expected number of new diabetes cases in the vitamin C group.  Further study with a larger number of this subgroup would be needed to determine if those with high cholesterol might lessen their risk of diabetes through treatment with vitamin C.   Because of the strength of preliminary studies which link low levels of vitamin C to type II diabetes, further clinical trials looking at vitamin C supplements will likely be reported.  At this time however, there is insufficient evidence for diabetologists to recommend that vitamin C supplements be given for the primary prevention of type II diabetes (37).

As to whether diabetics would benefit from vitamin C supplementation is a current ongoing question of research.   Similar in some respects to the vitamin C deficiency disease scurvy, patients with diabetes have fragility and poor healing of blood vessels and connective tissue.  Besides its importance as an antioxidant, vitamin C is essential to the body’s production and maintenance of collagen which is a key structural component of blood vessels and other body structures.

A 16-year study of 85,000 women, 2% of whom were diabetic, found that vitamin C supplement use (400 mg per day or more) was associated with significant reductions in the risk of fatal and nonfatal coronary heart disease in the entire vitamin C group as well as in those with diabetes (38).  Reaching an opposite conclusion, a 15-year study of postmenopausal women found that diabetic women who reported taking at least 300 mg per day of vitamin C from supplements when the study began were at significantly higher risk of death from coronary heart disease and stroke than those who did not take vitamin C supplements (39).  Neither of these two large, long studies were randomized controlled clinical trials. Clinical trials to date, which have been shorter in duration than these two long -term studies, have not found antioxidant supplementation that included vitamin C to reduce the risk of cardiovascular disease in diabetic or other high-risk individuals (40,41).

With the extensive WACS clinical trial (37) using 500 mg daily of supplemental vitamin C for 9 years and finding no cardiovascular risk, perhaps a prudent approach for a diabetic would be to eat daily foods that contain vitamin C, and if choosing to use a supplement, to stay below 500mg vitamin C per day.  Diabetics should be aware that “megadose” vitamin C, that is, doses above 2 grams per day, has been reported to cause hyperglycemia (42).

Vitamin D

Similar to the state of vitamin C research, many strong medical studies have found an association of the onset of type II diabetes with low levels of vitamin D (43).  Any prevention of diabetes by supplementing vitamin D, however, has yet to be clearly demonstrated by clinical trial (44).

Aloe Vera

There is emerging evidence that products from the aloe plant may be efficacious for diabetics.  The range of aloe products is quite diverse, from many species of aloe and from three different parts of the plant.  Aloe studies are few in number, and not uniform with regards to dosage or product.  A pharmaceutical review of recent studies (45) concluded that a ”preponderance of evidence“ showed that oral aloe vera might beneficially reduce blood glucose levels in diabetics.   Because of currently insufficient data, however, this review board could not recommend the use of aloe vera for the management of diabetes or dyslipidemia.

Patients using an aloe preparation should be aware that since aloe can have the desirable effect of lowering blood sugar, it can also lower blood sugar dangerously too low, therefore, blood sugars must be carefully monitored.  Adverse effects such as diarrhea, with potentially serious electrolyte imbalances, can occur as aloe can act as a laxative.   Aloe should be discontinued one to two weeks prior to surgery as cases of prolonged  surgical bleeding have been reported with its use (46).

Cassia Cinnamon

One fairly well studied supplement used to help hyperglycemia in diabetics is cassia cinnamon. Animal and laboratory studies have indicated that cinnamon may mimic the effects of insulin and make cells more sensitive to insulin (47).

In diabetic patients, some studies have shown a favorable response; some no effect.  The most comprehensive review of cinnamon use in diabetics, published in 2008 by the journal Diabetes Care(46), found no metabolic benefits to the use of cinnamon by type I or type II diabetics.  Specifically, no benefits to fasting blood glucose, lipids, or cholesterol were observed in a meta-analysis of five small clinical trials.  An earlier small study, published by the same journal in December 2003 (47), had reported a modest reduction in blood sugar by diabetics using a quarter teaspoon to a teaspoon of cinnamon daily.    More studies on the effects of cinnamon in diabetes are still ongoing, but in the hierarchy of research studies, a meta-analysis of clinical trials is considered to be more reliable than a single clinical trial.

More recently, a 2009 study reported antioxidant effects of cinnamon studied in type II diabetics (50).  A twelve  week , small clinical trial in Britain in 2010 again reported small improvements in blood sugar and blood pressure in diabetics taking 2 grams of cinnamon daily (51).  In a 2009 a randomized controlled trial (52) with 109 type 2 diabetics whose A1c levels were 7 or higher at baseline, cassia cinnamon capsules at a dose of 1 g daily for 90 days, added to usual care, lowered their A1c by 0.83%. In contrast, those who received usual care but no cinnamon lowered their A1c by 0.37%. These investigators recommended cinnamon as an adjunct to diabetes care for patients with an A1c level greater than 7.0%.

Most people find cinnamon to be likable and it may help at least to a small degree in diabetes. Cinnamon’s safety record is excellent. (Coumadin patients need to know that cinnamon can prolong the protime.)  Cinnamon can make whole grains and other fiber-rich foods more appealing without adding calories, fat or salt. Two grams of cinnamon is a bit less than half a teaspoon.

Conclusion

Current medical research shows that Type II diabetes mellitus is a largely nutritional disease, the course of which can be significantly improved through lifestyle interventions such as advantageous food choices and exercise.  Diabetes is also a longterm, discouraging battle.  Those contending with its threats often suffer blame from themselves and criticism from those around them.  As with many chronic diseases, diabetics are at increased risk of clinical depression (53).  This review is offered in the hope that those seeking help with diabetes will find  encouraging information to bolster themselves against this disease.

Posted May 4, 2011.

REFERENCES:

  1. CDC National Diabetes Fact Sheet, 2007. See the CDC website.
  2. 2010  CDC data at the CDC website.
  3. Shaw JE et al.  Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010: 87: 4-14.
  4. Nathan DM. Long-term complications of diabetes mellitus. N Engl J Med. 1993;328:1676-85. [PMID: 8487827].
  5. Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979;241:2035-8. [PMID: 430798].
  6. Type 2 Diabetes Found to More Than Triple Heart Disease Risk from NHRI Greg Arnold.
  7. Comparison of prognosis for men with type 2 diabetes mellitus and men with cardiovascular disease”, Canadian Medical Association Journal, 2009; 180 (1), 40-47.  Posted January 27, 2009.
  8. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-65. [PMID: 9742977].
  9. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-53. [PMID: 9742976].
  10. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577-89. [PMID: 18784090].
  11. Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-59. [PMID: 18539917].
  12. The Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6);393-403.
  13. Clare L Gillies et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis  BMJ 2007;334:299 doi:10.1136/bmj.39063.689375.55.).
  14. Exercise and Type 2 Diabetes: American College of Sports Medicine and the American Diabetes Association: Joint Position Statement.  December 2010- volume 42-Issue 12 p.2282-2303.
  15. E. Morrato et al. Physical Activity in U.S. Adults With Diabetes and At Risk for Developing Diabetes  Diabetes Care Feb. 2007 doi: 10.2337/dc06-1128 Diabetes Care February 2007 vol. 30 no. 2 203-209.
  16. Laaksonen DE, Lindstrom J, Lakka TA, Eriksson JG, Niskanen L, Wikstrom K, et al. Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes2005;54:158-65.
  17. Sun Q.  White Rice, Brown Rice, and Risk of Type 2 Diabetes in US Men and Women. Arch Intern Med, 2010; 170 (11): 961-969. ( reviewed by NHRI article “ Brown Rice Found to Help Blood Sugar Heath” by Greg Arnold, DC, CSCS  posted June 23, 2010).
  18. Nut and Seed Consumption and Inflammatory Markers in the Multi-Ethnic Study of Atherosclerosis. American Journal of Epidemiology 2006;163(3):222-231. By Susan Sweeny Johnson, PhD, Biochem, Posted NHRI site August 7, 2008 at NHRI site.
  19. Ma, Yingying, et al. Effects of walnut consumption on endothelial function in type 2 diabetic subjects: a randomized controlled crossover trial.  Diabetes Care 33.2 (2010): 227+. By Greg Arnold, DC, CSCS,  Posted April 9, 2010 at NHRI site.
  20. Willett WC; Sacks, F; Trichopoulou, A; Drescher, G; Ferro-Luzzi, A; Helsing, E; Trichopoulos, D (June 1, 1995). “Mediterranean diet pyramid: a cultural model for healthy eating”. American Journal of Clinical Nutrition 61 (6): 14025–65.
  21. Katherine Esposito, MD, PhD  Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients With Newly Diagnosed Type 2 Diabetes, A Randomized Trial Ann Intern Med September 1, 2009 151:306-314.
  22. Ramon Estruch, Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors: A Randomized Trial  Ann Intern Med July 4, 2006 145:1-11.
  23. Freund H, Atamian S, Fischer JE: Chromium deficiency during total parenteral nutrition. JAMA 241:496–498, 1979.
  25. See the Oregon State University website. The Linus Pauling Institute.
  26. Ethan M. Balk et al. Effect of Chromium Supplementation on Glucose Metabolism and Lipids : A systematic review of randomized controlled trials Diabetes Care August 2007 vol. 30 no. 8 2154-2163.
  27. Jeejeebhoy KN: The role of chromium in nutrition and therapeutics and as a potential toxin. Nutr Rev 57:329–335, 1999.
  28. William T. Cefalu, MD and Frank B. Hu, MD, PHD Role of Chromium in Human Health and in Diabetes   Diabetes Care November 2004 vol. 27 no. 11 2741-2751.
  29. Anne Peters, MD  see the CDC website.
  30. Bantle JP et al  Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care 31 (Suppl. 1):S61-S78, 2008.
  31. CA Albarracon et al. Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes. Diabetes Metab Res Rev 24:41-51, 2008.
  32. Ravina A, Slezak L, Mirsky N, Bryden NA, Anderson RA: Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium. Diabet Med 16:164–167, 1999.
  33. A review of vitamin C dosage may be found at the Linus Pauling website.
  34. JL Evans et al. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 2003; 52:1–8. Abstract/FREE Full Text.
  35. A.Ceriella, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004;24:816–23. Abstract/FREE Full Text.
  36. Sargeant LA et al, Vitamin C and hyperglycemia in the European Prospective Investigation into Cancer–Norfolk (EPIC-Norfolk) study: a population-based study. Diabetes Care 2000;23:726–32. Abstract/FREE Full Text.
  37. Sinclair AJ et al.  Low plasma ascorbate levels have been reported in patients with type 2 diabetes mellitus consuming adequate dietary vitamin C. Diabet Med 1994;11:893–8.
  38. Montonen J. et al Dietary antioxidant intake and risk of type 2 diabetes. Diabetes Care 2004;27:362–6.     Abstract/FREE Full Text.
  39. Yiqing Song, Nancy Cook et al.  Effects of vitamins C and E and b-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial.  Am J Clin Nutr August 2009 vol. 90 no. 2 429-437.
  40. Osganian SK, Stampfer MJ, Rimm E, et al. Vitamin C and risk of coronary heart disease in women. J Am Coll Cardiol. 2003;42(2):246-252.
  41. Lee DH, Folsom AR, Harnack L, Halliwell B, Jacobs DR, Jr. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am J Clin Nutr. 2004;80(5):1194-1200.
  42. Waters DD, Alderman EL, Hsia J, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA. 2002;288(19):2432-2440.
  43. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):23-33.
  44. CJ Johnson, et al Megadose of vitamin C delays insulin response to a glucose challenge in normoglycemic adults Am J Clin Nutr November 1994 60: 5 735-738.
  45. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab (2007) 92:2017–29.
  46. Alison Avenell; Jonathan A. Cook; Graeme S. MacLennan; Gladys C. McPherson  Vitamin D Supplementation and Type 2 Diabetes: A Substudy of a Randomised Placebo-controlled Trial in Older People (RECORD Trial, ISRCTN 51647438).
  47. Minh Q. Ngo, Pharm.D.; Nancy N. Nguyen, Pharm.D.; Sachin A. Shah, Pharm.D. Oral Aloe Vera for Treatment of Diabetes Mellitus and DyslipidemiaPosted: 11/16/2010; American Journal of Health-System Pharmacy. 2010;67(21):1804-1811. © 2010 American Society of Health-System Pharmacists, Inc.
  48. Laura Shane-McWhorter, PharmD, Dietary Supplements for Diabetes: An Evaluation of Commonly Used Products Diabetes Spectrum November 20, 2009 vol. 22 no. 4 206-213.
  49. Anderson RA, Broadhurst CL, Polansky MM, et al. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. J Agric Food Chem. 2004;52:65-70.
  50. William L. Baker et al. Effect of Cinnamon on Glucose Control and Lipid Parameters Diabetes Care  January 2008 31:41-43; , doi:10.2337/dc07-1711.
  51. Khan A, Safdar M, Khan MMA, Khattak KN, Anderson RA: Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 26:3215–3218, 2003.
  52. Roussel AM, Hininger I, Benaraba R, Ziegenfuss TN, Anderson RA. “Antioxidant effects of a cinnamon extract in people with impaired fasting glucose that are overweight or obese.” J Am Coll Nutr. 2009 28(1):16-21.
  53. Akilen R, Tsiami A, Devendra D, Robinson N Glycated Haemoglobin and Blood Pressure-Lowering Effect of Cinnamon in Multi-Ethnic Type 2 Diabetic Patients in the UK: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial Diab Med. 2010;27:1159-1167.
  54. Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial. J Am Board Fam Med. 2009;22:507-512. Abstract.
  55. Arie Nouwen, PHD  Prevalence of Depression in Individuals With Impaired Glucose Metabolism or Undiagnosed Diabetes: A systematic review and meta-analysis of the European Depression in Diabetes (EDID) Research Consortium  doi: 10.2337/dc10-1414 Diabetes Care February 25, 2011 vol. 34 no. 3 752-762.