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Life Extension Magazine

Life Extension Magazine February 2014
As We See It  

When Will Doctors Recognize This Leading Cause of Death?

By William Faloon
William Faloon
William Faloon

Today’s cardiologists understand that oxidized cholesterol plays a role in the development of atherosclerosis.1

What may surprise you was the debate that raged last century as to whether one’s blood lipid levels had any relationship to heart attack risk.

In 1951, the first book that connected LDL cholesterol to heart disease was published by a group that included one of our early members, John Gofman, MD, PhD.2 The medical establishment at the time rebelled against this concept and issued an armada of withering criticisms against Dr. Gofman.3

In 1959 and 1965, the FDA proclaimed it illegal to promote foods low in saturated fat and cholesterol as being potentially protective against artery disease.4

Medical schools back then taught doctors that atherosclerosis was an inevitable accompaniment of aging about which nothing could be done. Despite epidemic numbers of middle-aged men succumbing to sudden death heart attack, very little was being done. Vocal opposition to the cholesterol theory of vascular disease continued into the 1980s.3

The purpose of this article is to remind Life Extension® members of a correctable risk factor that significantly increases risk of vascular and other diseases, but is not being taken seriously by mainstream physicians.

When Will Doctors Recognize This Leading Cause of Death?  

Excess glucose damages the delicate endothelium that lines our arteries, setting the stage for coronary and cerebral vascular disease.5 Previous articles published in Life Extension magazine have shown the deadly impact in response to high after-meal glucose levels.6-14

Acarbose is a prescription drug that inhibits the alpha-glucosidase enzyme in the intestines.15 People taking acarbose with meals reduce the amount of ingested carbohydrates that absorb into their bloodstream. Acarbose blunts deadly after-meal glucose surges that occur in response to eating sugars and starches.15-17

Results from seven long-term studies suggest acarbose may reduce heart attack risk by up to 64%.18 The initial data is so impressive that a study of 7,500 cardiac patients titled the Acarbose Cardiovascular Evaluation Trial has been initiated to see if acarbose can prevent heart attacks in people with impaired glucose tolerance and type II diabetes.19 Results from this study are expected to be released by 2016.

What has us excited about this research is that reducing after-meal glucose levels has the potential to prevent far more death and disease than lowering LDL-cholesterol. One reason is that elevated glucose not only promotes vascular disease, but is also associated with an increased risk of dementia, an increased risk of developing cancer, and worse outcomes in patients with cancer.18,20-29

Doctors Are Failing To Warn Their Patients

Aging people today are being told by their physicians that their glucose is “normal” when it’s usually at dangerously high levels. It is analogous to the 1960s-1970s when doctors viewed cholesterol levels of 300 mg/dL as normal.

Doctors in the 1960s-1970s were correct that diets rich in animal fat made high blood cholesterol quite normal, but at a cost of heart attack rates in middle-aged men much greater than today!30,31

It took many decades before mainstream medicine reduced the reference range of cholesterol considered safe to under 200 mg/dL.32

Today we have the same problem with glucose, where doctors tolerate fasting levels up to 110 mg/dL as “normal” in their aging patients.33 To optimally protect against degenerative disease, fasting glucose should be under 86 mg/dL.34

Even more insidious is data showing that blood sugar “spikes” that occur after meals dramatically increase the risk of cardiovascular disease,17,35,36 retinal damage,37 and cancer.38

Unless steps are taken to suppress after-meal sugar surges, the elevated glucose levels triggered by most large meals will incite a dangerous metabolic cascade that results in cell damage and accelerated aging.39

I am grateful to report that improved natural methods have been discovered to suppress deadly after-meal glucose surges.

Epidemic Of High Blood Sugar

Epidemic Of High Blood Sugar  

Most adults suffer from elevated blood sugar levels.40

One report evaluated 46,000 middle-age individuals and found more than 80% had fasting blood sugar of 85 mg/dL or greater.40 Another study involving over 11,000 middle-age and older individuals showed nearly 85% had fasting blood sugar of 85 mg/dL or greater.41

Since incidence of disease starts to increase when fasting blood sugar rises above 85 mg/dL, this means the majority of aging humans today endure chronic cellular damage associated with elevated blood sugar, along with the accumulation of surplus fat pounds.34

This epidemic of elevated blood sugar will continue to cause age-related disease until the medical profession realizes that their test values for defining “normal” blood sugar are antiquated.

Glucose Fuels Breast Cancer Risk

Life Extensions analysis of the published scientific literature has identified strong data suggesting increased breast cancer risk amongst women with so-called “normal” blood glucose levels. For example, premenopausal women with a blood sugar above 84 mg/dL had more than two-times the risk of developing breast cancer compared to those with a blood sugar below 84 mg/dL.44

Another study compared women with a fasting glucose under 100 mg/dL with those whose blood glucose was between 100-125 mg/dL. Women with the higher glucose readings had a 32% increased risk of breast cancer after multivariate analysis.61

A study of 10,633 women from Italy found significant relationships between blood sugar levels and breast cancer risk.45 In this study, women in the highest glucose quartile (median 96 mg/dL) had a 63% increased risk for breast cancer compared to those in the lowest quartile (median 73 mg/dL) after being “fully adjusted” for multiple variables. The authors stated in the discussion:

“…we found that elevated fasting glucose levels were significantly associated with subsequent occurrence of breast cancer. The association was significant both in pre- and postmenopausal women.”

The Glucose-Cancer Connection

In the United States, over 200,000 women are diagnosed with some form of breast cancer each year. Around 41,000 die from it.42 Most breast cancer victims’ lives are spared, but at the cost of surgical mutilation, radiation injury, systemic chemotherapy damage, and acute menopause caused by estrogen-blocking drugs.

With 12% of all American women destined to develop breast cancer,43 taking preventive steps make sense, especially if the same approach also slashes risk of dementia and heart attack…and helps shed fat pounds.

An abundance of published research links high-normal blood glucose levels to increased breast cancer risk.44-46 This fact alone emphasizes the importance of maintaining glucose at safe low-normal ranges.

In response to reports showing that type II diabetics suffer greater incidence and mortality from breast cancer,47-51 Life Extension conducted an analysis of the scientific literature to ascertain if there was a connection between higher “normal” blood glucose and breast cancer risk.

We identified twelve separate studies that examined blood glucose levels in relationship to incidence of breast cancer.47-58 Out of these twelve studies, nine showed an association of higher fasting glucose or other indicators of poor glycemic control with increased cancer risks.47-52,54,56,57

The take-home message in examining this data is to initiate steps to lower glucose (which also reduces insulin) in order to help prevent the most prevalent malignancy striking women today.

While glucose provides fuel for rapidly dividing cancer cells, insulin is a hormonal stimulator for cell growth and differentiation.44,48 The role of elevated glucose and insulin on cancer incidence and progression is being increasingly recognized and was the subject of a report on the CBS news magazine show 60 Minutes.59

A recent study looked at the risk of overall cancer death in relation to blood glucose levels. Those with fasting glucose averaging around100 mg/dL had 49% increased cancer death risk. Those with after-meal glucose above 199 mg/dL had 52% increased cancer death risk. This 19-year study of 2,438 people shows that elevated glucose levels markedly increase one’s risk of dying from cancer.60

High “Normal” Sugar Levels Shrink Brain Volume

In September 2012, Australian researchers published findings showing blood glucose at the high end of normal resulted in significant brain shrinkage.62,63

The shrinkage occurred in regions of the brain (hippocampus and amygdala) involved in memory and other critical functions. Atrophy (shrinkage) in these brain areas worsens memory.62,63

For this study, neuroscientists at Australian National University in Canberra studied 249 people in their early 60s. Each of them had blood sugar levels in the normal range. The study subjects’ brains were scanned at the beginning of the study, and again four years later.

Comparing the before and after images, the researchers found significant brain shrinkage among those whose blood sugar levels were high but still below the World Health Organization’s threshold for pre-diabetes (fasting glucose under 110 mg/dL). The researchers report that these high normal levels may account for a 6% to 10% decrease in the volume of the hippocampus and amygdala.62,63

The lead researcher stated, “ It is this chronic exposure to high glucose levels that is more likely to lead to poorer brain health.” He cautioned that these findings should not be taken “lightly,” as the association between high normal blood sugar and brain shrinkage was “robust.”63

One Way To Protect Arteries Against After-Meal Glucose

One Way To Protect Arteries Against After-Meal Glucose  

Your risk of suffering a cardiovascular death is the greatest in the two-hour period after you eat a meal.64 That’s partly because during that time, you can experience dangerous blood sugar spikes that acutely impair blood flow through vital arteries, which can ultimately lead to a heart attack or stroke.65

Fortunately, you’re about to learn about new natural methods that significantly reduce the surge of glucose into your aging arteries. And while you may not entirely eliminate after-meal sugar surges, Life Extension members should feel assured that steps they long ago initiated confer protection against some of the damage glucose inflicts to their cardiovascular systems.

For example, a landmark study showed that gamma tocopherol limits the artery damaging impact of an after-meal glucose burst. This human study, published in January 2013, showed an expected 30-44% decrease in endothelial function in men after consuming 75 grams of pure glucose. Men who took gamma tocopherol five days in a row before the glucose challenge showed no significant loss of endothelial function.66

This well-designed study revealed how gamma tocopherol protected the arterial endothelium against glucose damage. Foundation members have supplemented with gamma tocopherol since as early as 1996. It’s still critical, however, to take steps before carbohydrate-containing meals to reduce the amount of glucose that enters your bloodstream.

Novel Approaches To Glucose Management

As mentioned in the beginning of this article, the drug acarbose functions by inhibiting the alpha-glucosidase enzyme.15 This limits the amount of glucose available for rapid absorption from dietary starch and sugar.

Initial studies indicate that acarbose may dramatically reduce cardiovascular risk.16 We’ll know definitively how well acarbose works when the results of a large human trial are released around 2016. You don’t have to wait until year 2016 to benefit.

Instead of taking the drug acarbose (which Life Extension has advocated for the past 7 years), consumers now have access to low-cost nutrients that have demonstrated alpha-glucosidase inhibiting properties.67-74

Scientists have identified three natural agents that when combined not only inhibit alpha glucosidase, but function by additional mechanisms to impede glucose absorption, reduce glucose over-production in the liver, and enhance clearance of excess glucose from the bloodstream.72,74-77

A discovery that has us very excited is a nutrient that in laboratory studies increases glucose uptake from the bloodstream into energy producing cells by up to 54%.78 It does this by stimulating an energy transporter called GLUT4 in cells, which is a mechanism by which the drug metformin beneficially lowers glucose.79

Another of these novel nutrient extracts inhibits a transport system in the small intestines that enables glucose to enter the bloodstream.75 The name of this glucose transport protein is sodium-dependent glucose transporter-1 or SGLT1 for short.80 A nutritional SGLT1 inhibitor impedes the ability of glucose to enter the bloodstream, thus providing another shield to guard your body against deadly after-meal sugar spikes.75,80

Few people realize that most of the glucose in our bloodstream after fasting comes from its production in the liver. This process is called gluconeogenesis and is an underlying culprit behind the difficulty in controlling many cases of type II diabetes.81 One of these novel nutrients has been shown to interfere with excess gluconeogenesis , which is a property by which the drug metformin beneficially helps lower insulin and glucose levels.77,82

Another of these nutrients has demonstrated effects that naturally increase the expression of beneficial PPAR-gamma in cells, which enables blood sugar levels to drop without stimulating excess insulin release.83

These nutrients, which function by four different mechanisms, have been combined into one low-cost formula to be taken before meals that contain glucose-spiking starches (bread, pasta, potatoes, and rice) or sugars.

Overwhelming evidence shows excess glucose to be a leading killer of Americans. Doctors are failing to recognize that even high normal blood sugar predisposes us to virtually all killer diseases.35,36,38 It is thus critical that consumers take steps to protect their aging bodies against the deadly impact of glucose overload.

It’s Not Your Fault…
It’s Not Your Fault…

Your body has evolved potent enzymes to rapidly break down ingested foods for immediate absorption into your body. If it were not for these enzymes, your ancestry lineage would have perished eons ago from famine.

Not only do you readily break down the foods you eat, but surplus calories are stored as body fat. Almost 70% of Americans suffer from excess fat storage and experts believe this will become the leading cause of preventable disability and death.84

Glucose-spiking starches and sugars dominate modern dietary patterns.85 A life saving countermeasure is to inhibit specific enzymes that enable starches-sugars to readily covert to glucose that is excessively absorbed into the bloodstream. Fortunately, these carbohydrate enzyme inhibitors are available in a low-cost dietary supplement form.

Don’t Wait For A Diabetes Diagnosis

It might not surprise you to learn that some people are diagnosed with type II diabetes in a hospital emergency room. This can occur in response to a heart attack when a hospital blood lab reveals an ER patient’s glucose levels are very high.

What people fail to understand is that glucose-induced arterial damage starts long before sugar levels rise to where diabetes or pre-diabetes is clinically diagnosed.

A study released in 2013 showed that individuals with impaired fasting glucose levels (around 110mg/dL) have similar cardiovascular risk factors as diabetic patients (fasting glucose over 126 mg/dL). This study showed that 36% of patients with impaired fasting glucose had coronary artery disease compared to 42% of those with frank diabetes.86

The study also showed that those with impaired glucose tolerance or diabetes had nearly double the rate of hypertension and high cholesterol when compared to people with normal glucose. The authors of this study stated:

“… it is recommended to identify and treat impaired fasting glucose early since impaired fasting glucose patients’ distribution in coronary artery disease is comparable to diabetes mellitus.”86

Another 2013 study showed that people drinking just one 12-ounce sugar-sweetened soda a day increased their risk of developing type II diabetes by 18%. This study indicates that only a small amount of excess sugar ingestion each day creates havoc in one’s body over the long term.87

Some of you might smugly think that you haven’t touched a sugary soda in years, but the reality is that it’s hard to avoid consuming glucose-spiking foods and drinks. Even whole grains convert to glucose, and healthy fruit juices can saturate your bloodstream with more glucose than a 12-ounce soda.

Unless you zealously follow a diet devoid of starches and sugars, you likely will derive enormous benefit by taking nutrients before meals that impede glucose absorption, reduce liver over-production of glucose (gluconeogenesis), and facilitate efficient removal of glucose from the blood.

We discuss a novel glucose-regulating nutrient blend in the first article of this month’s issue. Price-conscious consumers will be impressed about the broad-spectrum protection against glucose overload they can obtain at a very modest cost.

Most Advanced Formulas At Year’s Lowest Prices

Every time you purchase a Life Extension product, you contribute to biomedical research aimed at extending your healthy life span.

Life Extension funds pioneering scientists seeking to reverse degenerative disease. We do this while simultaneously battling mindless bureaucrats who want to suffocate medical innovation.

During our 25th annual winter Super Sale, all Life Extension formulas are discounted so that members can obtain the newest ingredients and most up-to-date versions at the lowest prices of the year.

Members traditionally take advantage of Super Sale discounts to stock up on cutting–edge formulas designed to circumvent the underlying causes of aging, such as the spiraling increase in glucose that most physicians today accept as normal.

For longer life,

For Longer Life

William Faloon

References

  1. Pirillo A, Norata GD, Catapano AL. LOX-1, OxLDL, and atherosclerosis. Mediators Inflamm. 2013;2013:152786.
  2. Dobbin EV, Gofman HF, Jones HC, Lyon L, Young C. The Low-Fat, Low-Cholesterol Diet. Garden City, NY: Doubleday; 1951.
  3. Available at: http://www.jlr.org/content/early/2004/04/21/jlr.R400003-JLR200.full.pdf. Accessed November 15, 2013.
  4. Federal Register: December 12, 1959. Reaffirmed by the FDA in the Federal Register: May 18, 1965.
  5. Mäkimattila S, Virkamäki A, Groop PH, et al. Chronic hyperglycemia impairs endothelial function and insulin sensitivity via different mechanisms in insulin-dependent diabetes mellitus. Circulation. 1996 Sep 15;94(6):1276-82.
  6. Available at: http://www.lef.org/magazine/mag2013/jul2013_Stop-Starch-Induced-Glucose-Surges_01.htm. Accessed October 4, 2013.
  7. Available at: http://www.lef.org/magazine/mag2013/feb2013_awsi_01.htm. Accessed October 4, 2013.
  8. Available at: http://www.lef.org/magazine/mag2013/feb2013_breakthrough-in-protecting-arteries-against-after-meal-glucose-spikes_01. Accessed October 4, 2013.
  9. Available at: http://www.lef.org/magazine/mag2012/feb2012_Doctors-Overlook-Leading-Cause-Premature-Death_01.htm. Accessed October 4, 2013.
  10. Available at: http://www.lef.org/magazine/mag2012/feb2012_Suppress-Deadly-After-Meal-Blood-Sugar-Surges_01.htm. Accessed October 4, 2013.
  11. Available at: http://www.lef.org/magazine/mag2012/feb2012_Proven-Methods-Reduce-Fasting-Postprandial-Glucose-Levels_01.htm. Accessed October 4, 2013.
  12. Available at: http://www.lef.org/magazine/mag2011/ss2011_Are-We-All-Pre-Diabetic_01.htm. Accessed October 4, 2013.
  13. Available at: http://www.lef.org/magazine/mag2011/jan2011_Glucose-The-Silent-Killer_01.htm. Accessed October 4, 2013.
  14. Available at: http://www.lef.org/magazine/mag2010/oct2010_Control-Fasting-After-Meal-Glucose-Levels_01.htm. Accessed October 4, 2013.
  15. Frantz S, Calvillo L, Tillmanns J, et al. Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury: prevention by the alpha-glucosidase inhibitor acarbose. FASEB J. 2005 Apr;19(6):591-3.
  16. Yamagishi S, Nakamura K, Takeuchi M. Inhibition of postprandial hyperglycemia by acarbose is a promising therapeutic strategy for the treatment of patients with the metabolic syndrome. Med Hypotheses. 2005;65(1):152-4.
  17. Bavenholm PN, Efendic S. Postprandial hyperglycaemia and vascular damage--the benefits of acarbose. Diab Vasc Dis Res. 2006 Sep;3(2):72-9.
  18. Hanefeld M, Cagatay M, Petrowitsch T, Neuser D, Petzinna D, Rupp M. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J. 2004 Jan;25(1):10-6.
  19. Available at: http://clinicaltrials.gov/show/NCT00829660. Accessed November 18, 2013.
  20. Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999 Feb;22(2):233-40.
  21. de Vegt F, Dekker JM, Ruhé HG, et al. Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia. 1999 Aug;42(8):926-31.
  22. Xu W, Qiu C, Winblad B, Fratiglioni L. The effect of borderline diabetes on the risk of dementia and Alzheimer’s disease. Diabetes. 2007 Jan;56(1):211-6.
  23. Ott A, Stolk RP, van HF, et al. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999 Dec 10;53(9):1937-42.
  24. Yaffe K, Blackwell T, Whitmer RA, Krueger K, Barrett Connor E. Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women. J Nutr Health Aging. 2006 Jul-Aug;10(4):293-5.
  25. Michaud DS, Fuchs CS, Liu S, Willett WC, Colditz GA, Giovannucci E. Dietary glycemic load, carbohydrate, sugar, and colorectal cancer risk in men and women. Cancer Epidemiol Biomarkers Prev. 2005; 14(1):138-47.
  26. Chan JM, Wang F, Holly EA. Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case-control study. Cancer Causes Control. 2009 Aug;20(6):835-46.
  27. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM. Fasting serum glucose level and cancer risk in Korean men and women. JAMA. 2005 Jan 12;293(2):194-202.
  28. Lajous M, Willett W, Lazcano-Ponce E, Sanchez-Zamorano LM, Hernandez-Avila M, Romieu I. Glycemic load, glycemic index, and the risk of breast cancer among Mexican women. Cancer Causes Control. 2005; 16(10):1165-9.
  29. Barba M, Sperati F, Stranges S, et al. Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort. Ann Oncol. 2012 Jul;23(7):1838-45.
  30. Available at: http://www.cdc.gov/nchs/data/databriefs/db88.htm. Accessed November 18, 2013.
  31. Available at: http://www.forbes.com/sites/larryhusten/2011/10/13/coronary-heart-disease-prevalence-in-us-continues-to-decline/. Accessed November 18, 2013.
  32. Available at: http://www.mayoclinic.com/health/cholesterol-levels/CL00001. Accessed November 18, 2013.
  33. Available at: http://www.helpguide.org/harvard/understanding_diabetes.htm. Accessed November 18, 2013.
  34. Bjornholt JV, Erikssen G, Aaser E, et al. Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men. Diabetes Care. 1999 Jan;22(1):45-9.
  35. Cavalot F, Petrelli A, Traversa M, et al. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. J Clin Endocrinol Metab. 2006 Mar;91(3):813-9.
  36. Lin HJ, Lee BC, Ho YL, et al. Postprandial glucose improves the risk prediction of cardiovascular death beyond the metabolic syndrome in the nondiabetic population. Diabetes Care. 2009 Sep;32(9):1721-6
  37. Aizawa T, Katakura M, Naka M, Kondo T. Postprandial hyperglycemia is an independent risk for retinopathy in elderly patients with type 2 diabetes mellitus, especially in those with near-normal glycosylated hemoglobin. J Am Geriatr Soc. 2010 Jul;58(7):1408-9.
  38. Stattin P, Bjor O, Ferrari P, Lukanova A, et al. Prospective study of hyperglycemia and cancer risk. Diabetes Care. 2007 Mar;30(3):561-7.
  39. Monickaraj F, Aravind S, Gokulakrishnan K, et al. Accelerated aging as evidenced by increased telomere shortening and mitochondrial DNA depletion in patients with type 2 diabetes. Mol Cell Biochem. 2012 Jun;365(1-2):343-50.
  40. Nichols GA, Hillier TA, Brown JB. Normal fasting plasma glucose and risk of type 2 diabetes diagnosis. Am J Med. 2008 Jun;121(6):519-24.
  41. Kato M, Noda M, Suga H, Matsumoto M, Kanazawa Y. Fasting plasma glucose and incidence of diabetes—implication for the threshold for impaired fasting glucose: results from the population-based Omiya MA cohort study. J Atheroscler Thromb. 2009 16(6):857-61.
  42. Available at: http://www.cdc.gov/cancer/breast/statistics/. Accessed October 4, 2013.
  43. Available at: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-key-statistics. Accessed October 4, 2013.
  44. Muti P, Quattrin T, Grant BJB, et al. Fasting glucose is a risk factor for breast cancer: A prospective study. Cancer Epidemiol Biomarkers Prev. 2002 11(11):1361-8.
  45. Sieri S, Muti P, Claudia A, et al. Prospective study on the role of glucose metabolism in breast cancer occurrence. Int J Cancer. 2011; 130(4):921-9.
  46. Liao S, Li J, Wei W, et al. Association between diabetes mellitus and breast cancer risk: a meta-analysis of the literature. Asian Pac J Cancer Prev. 2011 12(4):1061-5.
  47. Larsson SC, Mantzuros CS, Wolk A. Diabetes mellitus and risk of breast cancer: A meta-analysis. Int J Cancer. 2007 121(4):856-62.
  48. Xue F and Michels KB. Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence. Am J Clin Nutr. 2007; 86(4):s823-35.
  49. Alokail MS, Al-Daghri NM, Al-Attas OS, Hussain T. Combined effects of obesity and type 2 diabetes contribute to increased breast cancer risk in premenopausal women. Cardiovasc Diabetol. 2009 Jun 23;8:33.
  50. Vona-Davis L, Howard-McNatt M, and Rose DP. Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer. Obes Rev. 2007; 8(5):395-408.
  51. Bjorge T, Lukanova A, Jonsson H, et al. Metabolic syndrome and breast cancer in the Me-Can (metabolic syndrome and cancer) Project. Cancer Epidemiol Biomarkers Prev. 2010; 19:1737-45.
  52. Boyle P, Koechlin A, Pizot C, et al. Blood glucose concentrations and breast cancer risk in women without diabetes: a meta-analysis. Eur J Nutr. 2013 Aug;52(5):1533-40.
  53. Rapp K, Schroeder J, Klenk J, et al. Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia. 2006; 49(5):945-52.
  54. Manjer J, Kaaks R, Riboli E, et al. Risk of breast cancer in relation to anthropometry, blood pressure, blood lipids and glucose metabolism: a prospective study within the Malmö Preventive Project. Eur J Cancer Prev. 2001; 10(1):33-42.
  55. Contiero P, Berrino F, Tagliabue G, et al. Fasting blood glucose and long-term prognosis of non-metastatic breast cancer: a cohort study. Breast Cancer Res Treat. 2013 Apr;138(3):951-9.
  56. Lawlor DA, Smith GD, and Ebrahim S. Hyperinsulinaemia and increased risk of breast cancer: findings from the British women’s heart and health study. Cancer Causes Control. 2004; 15(3):267-75.
  57. Osaki Y, Taniguchi S, Tahara A, et al. Metabolic syndrome and incidence of liver and breast cancers in Japan. Cancer Epidemiol. 2012; 36(2):141-7.
  58. Kabat GC, Kim M, Caan BJ, et al. Repeated measures of serum glucose and insulin in relation to postmenopausal breast cancer. Int J Cancer. 2009 Dec 1;125(11):2704-10.
  59. Available at: http://www.cbsnews.com/8301-18560_162-57407294/is-sugar-toxic/?tag=contentMain;contentBody. Accessed October 4, 2013.
  60. Hirakawa Y, Ninomiya T, Mukai N, et al. Association between glucose tolerance level and cancer death in a general Japanese population: the Hisayama Study. Am J Epidemiol. 2012 Nov 15;176(10):856-64.
  61. Mink PJ, Shahar E, Rosamond WD, Alberg AJ, Folsom AR. Serum insulin and glucose levels and breast cancer incidence: the atherosclerosis risk in communities study. Am J Epidemiol. 2002 Aug 15;156(4):349-52.
  62. Cherbuin N, Sachdev P, Anstey KJ. Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study. Neurology. 2012 Sep 4;79(10):1019-26.
  63. Available at: http://www.webmd.com/brain/news/20120904/normal-blood-sugar-levels-may-harm-brain. Accessed October 4, 2013.
  64. Lin HJ, Lee BC, Ho YL, et al. Postprandial glucose improves the risk prediction of cardiovascular death beyond the metabolic syndrome in the nondiabetic population. Diabetes Care. 2009 Sep;32(9):1721-6.
  65. Nitenberg A, Cosson E, Pham I. Postprandial endothelial dysfunction: role of glucose, lipids and insulin. Diabetes Metab. 2006 Sep;32 Spec No2:2S28-33.
  66. Mah E, Noh SK, Ballard KD, Park HJ, Volek JS, Bruno RS. Supplementation of a γ-tocopherol-rich mixture of tocopherols in healthy men protects against vascular endothelial dysfunction induced by postprandial hyperglycemia. J Nutr Biochem. 2013 Jan;24(1):196-203.
  67. Mohamed Sham Shihabudeen H, Hansi Priscilla D, Thirumurugan K. Cinnamon extract inhibits α-glucosidase activity and dampens postprandial glucose excursion in diabetic rats. Nutr Metab (Lond). 2011 Jun 29;8(1):46.
  68. Li Y, Wen S, Kota BP, et al. Punica granatum flower extract, a potent alpha-glucosidase inhibitor, improves postprandial hyperglycemia in Zucker diabetic fatty rats. J Ethnopharmacol. 2005 Jun 3;99(2):239-44. [pomegranate]
  69. Schäfer A, Högger P. Oligomeric procyanidins of French maritime pine bark extract (Pycnogenol) effectively inhibit alpha-glucosidase. Diabetes Res Clin Pract. 2007 Jul;77(1):41-6.
  70. Zhi-yun Du, Rong-rong Liu, Wei-yan Shao, et al. Alpha-glucosidase inhibition of natural curcuminoids and curcumin analogs. Eur J Med Chem. 2006 Feb;41(2):213-8.
  71. Hogan S, Zhang L, Li J, Sun S, Canning C, Zhou K. Antioxidant rich grape pomace extract suppresses postprandial hyperglycemia in diabetic mice by specifically inhibiting alpha-glucosidase. Nutr Metab (Lond). 2010;7:71.
  72. He H, Lu YH. Comparison of inhibitory activities and mechanisms of five mulberry plant bioactive components against α-glucosidase. J Agric Food Chem. 2013 Aug 28;61(34):8110-9.
  73. Ma CM, Hattori M, Daneshtalab M, Wang L. Chlorogenic acid derivatives with alkyl chains of different lengths and orientations: potent alpha-glucosidase inhibitors. J Med Chem. 2008 Oct 9;51(19):6188-94.
  74. Mulimani VH, Supriya D. Alpha amylase inhibitors in sorghum (Sorghum bicolor). Plant Foods Hum Nutr. 1993 Nov;44(3):261-6.
  75. Masumoto S, Akimoto Y, Oike H, Kobori M. Dietary phloridzin reduces blood glucose levels and reverses Sglt1 expression in the small intestine in streptozotocin-induced diabetic mice. J Agric Food Chem. 2009 Jun 10;57(11):4651-6.
  76. Osorio H, Bautista R, Rios A, et al. Effect of phlorizin on SGLT2 expression in the kidney of diabetic rats. J Nephrol. 2010 Sep-Oct;23(5):541-6.
  77. Andallu B, Varadacharyulu NC. Gluconeogenic substrates and hepatic gluconeogenic enzymes in streptozotocin-diabetic rats: effect of mulberry ( Morus indica L.) leaves. J Med Food. 2007 Mar;10(1):41-8.
  78. Naowaboot J, Pannangpetch P, Kukongviriyapan V, Prawan A, Kukongviriyapan U, Itharat A. Mulberry leaf extract stimulates glucose uptake and GLUT4 translocation in rat adipocytes. Am J Chin Med. 2012; 40(1):163-75.
  79. Carvajal R, Rosas C, Kohan K, et al. Metformin augments the levels of molecules that regulate the expression of the insulin-dependent glucose transporter GLUT4 in the endometria of hyperinsulinemic PCOS patients. Hum Reprod. 2013 Aug;28(8):2235-44.
  80. Available at: http://onlinelibrary.wiley.com/doi/10.1111/j.2040-1124.2012.00227.x/full. Accessed October 4, 2013.
  81. Magnusson I, Rothman DL, Katz LD, Shulman RG, Shulman GI. Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J Clin Invest. 1992 Oct;90(4):1323-7.
  82. Kim YD, Park KG, Lee YS, et al. Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diabetes. 2008 Feb;57(2):306-14.
  83. Park JH, Lee SH, Chung IM, Park Y. Sorghum extract exerts an anti-diabetic effect by improving insulin sensitivity via PPAR-gamma in mice fed a high-fat diet. Nutr Res Pract. 2012 Aug;6(4):322-7.
  84. Available at: http://www.cdc.gov/nchs/fastats/overwt.htm. Accessed November 20, 2013.
  85. The Endocrine Society. Moderately reduced carbohydrate diet keeps people feeling full longer. ScienceDaily. 2009 June 12.
  86. Available at: https://www.aace.com/files/abstracts-2013.pdf. Accessed October 4, 2013.
  87. InterAct consortium. Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct. Diabetologia. 2013 Jul;56(7):1520-30.