Life Extension Magazine®
The deadly effects of even slightly elevated glucose are fatally misunderstood. One reason for this calamity is physicians who continue to rely on obsolete blood glucose ranges. These doctors fail to recognize that any excess glucose creates lethal metabolic pathologies that are underlying factors behind multiple age-related diseases. People today thus suffer and die from diabetic-like complications without knowing their blood sugar (glucose) levels are too high! Life Extension® long ago argued that most aging people have elevated blood glucose. Our controversial position has been vindicated as mainstream medicine consistently lowers the upper-level threshold of acceptable (safe) fasting blood glucose. As new evidence accumulates, it has become abundantly clear that maturing individuals need to take aggressive actions to ensure their fasting and after-meal glucose levels are kept in safe ranges. Glucose Is Like GasolineOur body’s primary source of energy is glucose. All of our cells use it, and when there is not enough glucose available, our body shuts down in a similar way that a car engine stops when the gasoline tank is empty. When glucose is properly utilized, our cells produce energy efficiently. As cellular sensitivity to insulin diminishes, excess glucose accumulates in our bloodstream. Like spilled gasoline, excess blood glucose creates a highly combustible environment from which oxidative and inflammatory fires chronically erupt. Excess glucose not used for energy production converts to triglycerides that are either stored as unwanted body fat or accumulate in the blood where they contribute to the formation of atherosclerotic plaque.1-6 If you were filling your automobile with gasoline and the tank reached full, you would not keep pumping in more gas. Yet most people keep fueling their bodies with excess energy (glucose) with little regard to the deadly consequences. As an aging human, you face a daily onslaught of excess glucose that poses a greater risk to your safety than overflowing gasoline. Surplus glucose relentlessly reacts with your body’s proteins, causing damaging glycation reactions while fueling the fires of chronic inflammation and inciting the production of destructive free radicals.7-20 The Evolving Definition of Type 2 DiabetesMedical dictionaries define diabetes as a condition whereby the body is not able to regulate blood glucose levels, resulting in too much glucose being present in the blood. The debate is over what level of blood glucose is considered “too high.” Nearly four decades ago, we emphatically stated that fasting blood glucose should be below 100 (mg/dL). Yet from 1979 to 1997, the medical establishment dictated that one of the criteria for a diagnosis of diabetes was fasting glucose readings of 140 mg/dL or higher on two separate occasions. In 1997, the medical establishment revised the fasting glucose threshold for a diagnosis of diabetes to 126 mg/dL. In addition, the medical establishment (American Diabetes Association), characterized the so-called impaired fasting glucose threshold level at 110 mg/dL, which was subsequently lowered in 2003 to what Life Extension originally stated, i.e. that no one should have fasting glucose 100 mg/dL or higher. The problem is that we now know that the optimal fasting glucose ranges are 70-85 mg/dL based upon the totality of the scientific evidence.33 Those with glucose above 85 mg/dL are at increased risk of heart attack.34 This was shown in a study of nearly 2,000 men where fasting blood glucose levels were measured over a 22-year period. The startling results showed that men with fasting glucose over 85 (mg/dL) had a 40% increased risk of death from cardiovascular disease. The researchers who conducted this study stated “fasting blood glucose values in the upper normal range appears to be an important independent predictor of cardiovascular death in nondiabetic apparently healthy middle-aged men.”34 So pull out your latest blood test result and see where you stand. At a minimum, you want to see your fasting glucose below 86 mg/dL.
Why Any “Excess” Glucose is DangerousSugar damages cells via multiple mechanisms and is a causative factor in common diseases of aging.35-52 In a group of humans who reduced their food intake to calorie restriction levels, fasting glucose declined to an average of 74 mg/dL.23 This corresponds to animal studies in which caloric restriction induced significant reductions in blood glucose in conjunction with extension of life span.53-55 It is well established that cutting calorie intake reduces one’s risk of age-related diseases and slows markers of aging.56-62 One reason for this may be the reduction in blood glucose (and insulin) levels that occurs in response to ingesting fewer calories. In a study of 33,230 men, high glucose was independently associated with a 38% increase in deaths from digestive tract cancers.63 Other studies show that diabetics have even greater increased cancer risks.64-70 Diabetics suffer such horrific incidences of vascular disorders that some experts believe that coronary artery occlusion and diabetes should be classified as the same disease. In other words, if you are diabetic, you are almost certainly going to suffer coronary atherosclerosis. In a recent study involving 1,800 people, coronary disease rates were the same over a 10-year period in pre-diabetics compared to those with full-blown diabetes. The authors of the study commented that impaired fasting glucose significantly increased risk in comparison with the normal glucose group and concluded: “Early control of blood glucose is essential to prevention and control of coronary heart disease.”71 As people age, their fasting glucose levels usually increase as their health declines. Standard laboratory reference ranges allow an upper-limit of fasting glucose of 99 mg/dL. Yet the most effective anti-aging therapy—caloric restriction—lowers fasting glucose levels to the 70-85 mg/dL range. Recent studies indicate that keeping fasting glucose levels in the range of 70-85 mg/dL and not allowing after-meal glucose levels to spike higher than 40 mg/dL over your fasting value, favorably influences our longevity genes.72 The take-home lesson is that one can slash their risks of age-related diseases and possibly slow their rate of aging by tightly controlling blood glucose levels.
Shield Your Body From Excess GlucoseAn enormous volume of published data shows that by taking the proper compounds before meals, the surge of glucose into the bloodstream and the subsequent insulin spike can be mitigated.74-84 Nutrients that neutralize carbo-hydrate-degrading enzymes (like white kidney bean and brown seaweed extracts) are helpful.77,85 The addition of special fibers (like propolmannan) can slow the rate of carbohydrate absorption from the small intestine, thus further blunting the after-meal (postprandial) flow of glucose into the blood.86-89 Life Extension introduced a multi-ingredient powdered formula in 2010 that was designed to be taken before heavy meals to control the rate of fat and carbohydrate absorption. I cannot emphasize the critical importance for those with glucose levels above 85 mg/dL to take these kinds of compounds before meals that help shield one’s bloodstream against dangerous glucose-insulin spikes. Why Most Aging People Should Take MetforminMetformin is a drug approved to treat type 2 diabetes. It is also very effective for those at high risk of developing diabetes due to elevated blood sugar readings. The Diabetes Prevention Program showed that metformin can reduce the risk of developing diabetes in high risk patients by a whopping 31%, with the greatest benefit for those significantly overweight.90 Metformin improves insulin sensitivity,91-93 and inhibits the release of glycogen (the storage form for glucose) from the liver,94-98 thus lowering fasting glucose blood levels. Life Extension funded research showing that metformin may have calorie restriction mimetic properties in laboratory mice. The drug’s unique ability to reduce glucose-insulin blood levels and its super low-cost make it something you’ll want to ask your doctor about. Are Most of Us Pre-diabetic?In reviewing thousands of blood test results and published scientific studies, I have come to the conclusion that more than 75% of people over the age of 40-50 are suffering from some degree of prediabetic-related disorder inflicted by elevated blood sugar. These problems may silently smolder as kidney impairment,99,100 aberrant cell proliferation,101-109 and endothelial dysfunction110-117—or explode outwardly as a sudden-death heart attack.118-122 Young healthy people can usually maintain optimal glucose ranges, whereas glucose levels creep up as we age. The data showing that modestly elevated “normal” glucose increases disease risk cannot be ignored.119,123-127 Normal aging predisposes most of us to metabolic complications as a result of impaired glucose metabolism. If we fail to recognize this fact, we are doomed to suffer a plethora of degenerative conditions that were largely preventable. The good news is that there are nutrients, hormones, and drugs that healthy people can take to achieve optimal glucose readings, or at least reduce blood sugar levels to safer ranges. The section at the end of this article provides a concise description of simple steps you can take to slash your glucose levels.
Don’t Be a Victim of Physician IgnoranceWe at Life Extension hear from members who say their doctor is not concerned that their fasting glucose level is a little over 100 mg/dL. The reason physicians don’t panic about this kind of high reading is that they are so used to seeing it in older individuals. As you have just learned, however, glucose readings over 85 mg/dL place aging humans at sharply elevated risks for cardiovascular disease. You don’t have to become a victim of physician apathy and ignorance. There are a myriad of steps you can take to drive down your glucose to safer ranges. The section beginning on the next page provides a menu of options to select from to gain glycemic control over your body. As more Americans wake up to the inadequacies of mainstream medicine, they are joining the Life Extension Foundation. One benefit of membership is being able to order your own blood tests at ultra-low prices. For instance, we offer a comprehensive blood chemistry test that measures glucose, triglycerides, LDL, HDL, total cholesterol, liver-kidney function, blood cell counts and more for only $35. You can order this test by calling 1-800-208-3444 (24 hours a day) and have your blood drawn in your area at your convenience. | ||||||||||||
Research Funded by Life Extension in 2010The Life Extension Foundation expanded its research funding in 2010, with special emphasis on grants to scientists working on cutting-edge cancer therapies. We selectively fund research that offers the best opportunity to discover a cure during the early clinical trial phase. In other words, when cancer patients enter our clinical trials, we take extraordinary efforts to give them the best chance of attaining a complete response or eradication of the disease. Pharmaceutical companies, on the other hand, conduct placebo-controlled studies on cancer patients to gather data with little regard to the human lives they know will be lost because of the barbaric way their studies are designed. Cancer research funded by Life Extension is not being done by pharmaceutical giants because it seldom involves a compound that can be patented. As members are aware, therapies that don’t have the potential to produce gigantic profits are neglected and even suppressed by the pharmaceutical industry. Life Extension supports a relentless campaign to reform corrupt governmental policies that deprive Americans of life-saving therapies. By exposing the lethal impact of medical ignorance, such as showing that doctors accept dangerously high glucose levels as being normal, we spare countless humans the ravages of debilitating and lethal diseases. Just once a year, we discount the price of every product we offer. During our annual Super Sale, members stock up on our most advanced formulations and enjoy considerable savings. I want to thank members for purchasing most of their supplements from the Life Extension Buyers Club. We use these sales to fund critical research projects aimed at eliminating disease and death, while battling oppressive government attempts to establish dictatorial control over your health and longevity. For longer life, William Faloon Proven Methods to Reduce Fasting and Postprandial Glucose LevelsScientific studies indicate that any amount of fasting glucose over 85 mg/dL incrementally adds to heart attack risk.34 If you can choose an ideal fasting glucose reading, it would probably be around 74 mg/dL.23 We know, however, that some people are challenged to keep their glucose under 100 mg/dL. What this means is that it is critically important for aging individuals to follow an aggressive program to suppress excess glucose as much as possible. The good news is that many approaches that reduce glucose also lower fasting insulin,31,128-130 LDL,86,128,131-134 triglycerides,21,22,28,128,130 and C-reactive protein,135 thereby slashing one’s risk of vascular disease,21,31,76,136 cancer,137-141 dementia142-146 and a host of other degenerative disorders. In this section, we succinctly describe drugs, hormones, nutrients and lifestyle changes that facilitate healthy glucose levels. Nutrient OptionsSince Life Extension members know it is best to take dietary supplements with meals, it should not be difficult for them to make it a routine practice to shield their bloodstream from excessive calorie absorption by taking the proper nutrients before most meals. An efficient way of obtaining nutrients that can impede the impact of carbohydrate and fat foods when taken before meals is a powdered drink mix that provides the nutrients in the box below:
For Sugar AddictsFor those whose glucose levels remain unacceptably high despite taking the powdered drink mix, there are encapsulated nutrients that work to specifically block the sucrase and glucosidase digestive enzymes. Sucrase breaks down sucrose and glucosidase converts all carbohydrates into glucose. Blocking these enzymes reduces the amount of glucose absorbed from dietary sources. One capsule containing L-arabinose and a special brown seaweed extract should be taken before eating sucrose (table sugar) containing foods.33,79,152,153 Enhancing Insulin SensitivityAging causes a loss of insulin sensitivity, which means that glucose that would normally be utilized by energy-producing cells instead either remains in the blood or converts to storage as trigly-ceride (in blood and fat cells) or glycogen in the liver. A new cinnamon extract has been developed to enhance the ability of insulin to drive blood glucose into muscle cells. This novel cinnamon compound that enhances insulin sensitivity is combined with brown seaweed extract (to inhibit the glucosidase enzyme) to provide additive control over glucose levels.29,77,153-157 Drug OptionsAn anti-diabetic drug that Life Extension suggests normal aging people consider taking to lower glucose is metformin. It is available in low-cost generic form. Metformin has a long history of safe human use, plus intriguing data to suggest that it may possess anti-aging properties.158,159 We think that those with excess blood glucose (above 80-85 mg/dL) should ask their doctor about it even if they are not diagnosed as diabetic. Some of the side benefits of metformin include weight loss160-162 and triglyceride reduction,163-165 which are in themselves proven heart attack risk reducers.
Metformin functions to reduce absorption of ingested carbohydrates,98,166,167 suppress appetite,168,169 enhance insulin sensitivity,91-93 and most uniquely, metformin inhibits the release of stored liver glucose (glycogen) back into the blood.95-98,170 One of the problems that frustrates so many people who follow a low-calorie diet, yet have persistently elevated glucose levels is that the liver improperly dumps too much glucose into the blood. This of course is a vital life function in a starvation state, but for aging individuals, excess hepatic release of glycogen (called gluconeogenesis) causes them to suffer chronically high glucose and insulin levels. Metformin inhibits gluconeogenesis.170,171 Another low-cost drug that lowers glucose levels is acarbose, which reduces the absorption of ingested carbohydrates by inhibiting the glucosidase and other sugar absorbing enzymes in the small intestine. A typical dose is 50-100 mg of acarbose taken before each meal. Some people experience intestinal side effects, but otherwise, acarbose is highly efficacious in reducing blood glucose levels and reducing several cardiac risk markers in the blood.21,31,76 There are of course other FDA-approved drugs that will lower your glucose levels. Many of these drugs, however, function by mechanisms that carry side effect risks. Life Extension stands on solid scientific ground in recommending that those with impaired glucose tolerance follow an aggressive program that involves eating healthier and smaller meals, exercising, and taking nutrients before meals that deflect the impact of excess calorie intake. Drugs like metformin may be considered for its multiple benefits that extend beyond mere glucose control. Acarbose should be utilized if glucose levels remain stubbornly high. Hormone OptionsNormal aging is accompanied by a sharp decline in hormones that are involved in maintaining insulin sensitivity and hepatic glucose control. Restoring DHEA (dehydroepiandrosterone) levels to youthful ranges in men and women may help enhance insulin sensitivity and glucose metabolism in the liver.173-177 Progressive doctors are realizing that in men, a testosterone deficiency can induce a serious reduction of insulin sensitivity. For men, restoring youthful levels of testosterone has been shown to be particularly beneficial in facilitating glucose control.178 Blood tests can assess your hormonal status so a man can replenish testosterone (and DHEA) to more youthful ranges. Optimal free testosterone blood levels in men are between 20-25 pg/mL.179
Life Extension has published articles showing that diabetic men can derive enormous benefits by restoring testosterone to youthful ranges, as opposed to overloading the body with excess insulin as mainstream doctors continue to do.180-182 Dietary OptionsOne can achieve remarkable control over glucose levels by altering their diet and exercising more. Below are three dietary options to consider:
SummaryFrom a practical approach, achieving optimal glucose readings on your next blood test will probably involve a combination of the various approaches described in this section. Each individual will respond differently. For some, a modest reduction in calorie intake and an increase in physical activity will sufficiently lower fasting and after-meal glucose levels. Most aging individuals, however, will need to take the powdered drink mix described on page 12 before the two heaviest meals of the day to impede the impact of ingested calories. Others should ask their doctor about the prescription drug suggestions such as metformin. When one questions the importance of doing all this, please know that the incidence of pre-diabetes, metabolic syndrome and type 2 diabetes is increasing at alarming rates. In fact, diseases related to glucose impairment are skyrocketing everywhere in the world that adopts unhealthy Western eating habits. A medical catastrophe is predicted for the United States as the vast majority of the population is now overweight and suffers frighteningly high levels of glucose, insulin and triglycerides. The single most important component of one’s longevity program may be the steps taken before meals to neutralize the toxic effects of excess calories most of us invariably ingest. Life Extension urges all members to enact a personal program designed to suppress fasting glucose levels to ranges of 80-85 mg/dL (or lower). Fortunately, there are a wide range of options that enable aging humans to accomplish this profoundly effective anti-aging feat. | ||||||||||||||||||||||||||
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1. Welin L, Eriksson H, Larsson B, et al. Triglycerides, a major coronary risk factor in elderly men. A study of men born in 1913. Eur Heart J. 1991 Jun;12(6):700-4. 2. Carlson LA, Bottiger LE, Ahfeldt PE. Risk factors for myocardial infarction in the Stockholm prospective study. A 14-year follow-up focusing on the role of plasma triglycerides and cholesterol. Acta Med Scand. 1979;206(5):351-60. 3. Jagla A, Schrezenmeir J. Postprandial triglycerides and endothelial function. Exp Clin Endocrinol Diabetes. 2001;109(4):S533-47. 4. Ebenbichler CF, Kirchmair R, Egger C, Patsch JR. Postprandial state and atherosclerosis. Curr Opin Lipidol. 1995 Oct;6(5):286-90. 5. Jacobson TA, Miller M, Schaefer EJ. Hypertriglyceridemia and cardiovascular risk reduction. Clin Ther. 2007 May;29(5):763-77. 6. Teno S, Uto Y, Nagashima H, et al. Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes. Diabetes Care. 2000 Sep;23(9):1401-6. 7. Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res. 2004 Sep 1;63(4):582-92. 8. Uribarri J, Cai W, Sandu O, Peppa M, Goldberg T, Vlassara H. Diet-derived advanced glycation end products are major contributors to the body’s AGE pool and induce inflammation in healthy subjects. Ann N Y Acad Sci. 2005 Jun;1043:461-6. 9. Toma L, Stancu CS, Botez GM, Sima AV, Simionescu M. Irreversibly glycated LDL induce oxidative and inflammatory state in human endothelial cells; added effect of high glucose. Biochem Biophys Res Commun. 2009 Dec 18;390(3):877-82. 10. Bonnefont-Rousselot D. Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care. 2002 Sep;5(5):561-8. 11. Esposito K, Nappo F, Marfella R, M et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002 Oct 15; 106(16):2067-2072. 12. Marfella R, Quagliaro L, Nappo F, Ceriello A, Giugliano D. Acute hyperglycemia induces an oxidative stress in healthy subjects. J Clin Invest. 2001 Aug; 108(4):635-6. 13. Ceriello A. Hyperglycaemia: the bridge between non-enzymatic glycation and oxidative stress in the pathogenesis of diabetic complications. Diabetes Nutr Metab. 1999 Feb;12(1):42-6. 14. Hirsch IB, Brownlee M. Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complications. 2005 May-Jun;19(3):178-81. 15. Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes. 2003 Nov;52(11):2795-804. 16. Ceriello A, 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 May;24(5):816-23. 17. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002 Mar 5;105(9):1135-43. 18. Bansilal S, Farkouh ME, Fuster V. Role of insulin resistance and hyperglycemia in the development of atherosclerosis. Am J Cardiol. 2007 Feb 19;99(4A):6B-14B. 19. Johnson RJ, Segal MS, Sautin Y, et al. Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr. 2007 Oct;86(4):899-906. 20. Tzotzas T, Samara M, Constantinidis T, Tziomalos K, Krassas G. Short-term administration of orlistat reduced daytime triglyceridemia in obese women with the metabolic syndrome. Angiology. 2007 Feb-Mar;58(1):26-33. 21. 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. 22. Udani J, Hardy M, Madsen DC. Blocking carbohydrate absorption and weight loss: a clinical trial using Phase 2 brand proprietary fractionated white bean extract. Altern Med Rev. 2004 Mar;9(1):63-9. 23. Walford RL, Harris SB, Gunion MW. The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11533-7. 24. Kemnitz JW, Roecker EB, Weindruch R, Elson DF, Baum ST, Bergman RN. Dietary restriction increases insulin sensitivity and lowers blood glucose in rhesus monkeys. Am. J Physiol. 1994 Apr;266(4, Pt. 1):E540-7. 25. Martins C, Morgan LM, Robertson MD. Effects of restrained eating behaviour on insulin sensitivity in normal-weight individuals. Physiol Behav. 2009 Mar 23;96(4-5):703-8. 26. Bischoff H. Pharmacology of alpha-glucosidase inhibition. Eur J Clin Invest. 1994 Aug;24 Suppl 3:3-10. 27. Kobayashi M, Ichitani M, Suzuki Y, et al. Black-tea polyphenols suppress postprandial hypertriacylglycerolemia by suppressing lymphatic transport of dietary fat in rats. J Agric Food Chem. 2009 Aug 12; 57(15):7131–6. 28. Juhel C, Armand M, Pafumi Y, Rosier C, Vandermander J, Lairon D. Green tea extract (AR25) inhibits lipolysis of triglycerides in gastric and duodenal medium in vitro. J Nutr Biochem. 2000 Jan;11(1):45-51. 29. Zhang J, Tiller C, Shen J, et al. Antidiabetic properties of polysaccharide- and polyphenolic-enriched fractions from the brown seaweed Ascophyllum nodosum. Can J Physiol Pharmacol. 2007 Nov;85(11):1116-23. 30. Ngondi JL, Etoundi BC, Nyangono CB, Mbofung CM, Oben JE. IGOB131, a novel seed extract of the West African plant Irvingia gabonensis, significantly reduces body weight and improves metabolic parameters in overweight humans in a randomized double-blind placebo controlled investigation. Lipids Health Dis. 2009 Mar 2;8:7. 31. Zeymer U. Cardiovascular benefits of acarbose in impaired glucose tolerance and type 2 diabetes. Int J Cardiol. 2006 Feb 8;107(1):11-20. 32. Osaki S, Kimura T, Sugimoto T, Hizukuri S, Iritani N. L-Arabinose feeding prevents increases due to dietary sucrose in lipogenic enzymes and triacylglycerol levels in rats. J Nutr. 2001;131:796-9. 33. McGlothin, P, Averill M. Glucose Control: The Sweet Spot in Longevity. The CR Way: Using the Secrets of Calorie Restriction for a Longer, Healthier Life. NY: HarperCollins; 2008:57-78. 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. Rossetti L, Giaccari A, DeFronzo RA. Glucose toxicity. Diabetes Care. 1990 Jun; 13:610-30. 36. Vlassara H. Advanced glycation end-products and atherosclerosis. Ann Med. 1996 Oct;28(5):419-26. 37. Stattin P, Björ O, Ferrari P, et al. Prospective study of hyperglycemia and cancer risk. Diabetes Care. 2007 Mar;30(3):561-7. 38. Levi B, Werman MJ. Long-term fructose consumption accelerates glycation and several age-related variables in male rats. J Nutr. 1998 Sep;128(9):1442-9. 39. Makino H, Shikata K, Kushiro M, et al. Roles of advanced glycation end-products in the progression of diabetic nephropathy. Nephrol Dial Transplant. 1996;11 Suppl 5:76-80. 40. Kimura C, Oike M, Koyama T, Ito Y. Impairment of endothelial nitric oxide production by acute glucose overload. Am J Physiol Endocrinol Metab. 2001 Jan;280(1):E171-8. 41. Winocour PD. Decreased platelet membrane fluidity due to glycation or acetylation of membrane proteins. Thromb Haemost. 1992 Nov 10;68(5):577-82. 42. Ziyadeh FN. Mediators of hyperglycemia and the pathogenesis of matrix accumulation in diabetic renal disease. Miner Electrolyte Metab. 1995;21(4-5):292-302. 43. Kikuchi S, Shinpo K, Takeuchi M, et al. Glycation—a sweet tempter for neuronal death. Brain Res Brain Res Rev. 2003 Mar;41(2-3):306-23. 44. El-Assaad W, Buteau J, Peyot ML, et al. Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death. Endocrinology. 2003 Sep;144(9):4154-63. 45. Maedler K, Spinas GA, Lehmann R, et al. Glucose induces beta-cell apoptosis via upregulation of the Fas receptor in human islets. Diabetes. 2001 Aug;50(8): 1683-90. 46. Agardh E, Hultberg B, Agardh C. Effects of inhibition of glycation and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats. Curr Eye Res. 2000 Jul;21(1):543-9. 47. Morohoshi M, Fujisawa K, Uchimura I, Numano F. The effect of glucose and advanced glycosylation end products on IL-6 production by human monocytes. Ann N Y Acad Sci. 1995 Jan 17;748:562-70. 48. Kaneto H, Fujii J, Suzuki K, et al. DNA cleavage induced by glycation of Cu,Zn-superoxide dismutase. Biochem J. 1994 Nov 15;304 (Pt 1):219-25. 49. Available at: http://apjcn.nhri.org.tw/server/APJCN/ProcNutSoc/2000+/2004/65.pdf. Accessed August 23, 2010. 50. Ceriello A. Impaired glucose tolerance and cardiovascular disease: the possible role of post-prandial hyperglycemia. Am Heart J. 2004 May;147(5):803-7. 51. Alderman JM, Flurkey K, Brooks NL, et al. Neuroendocrine inhibition of glucose production and resistance to cancer in dwarf mice. Exp Gerontol. 2009 Jan-Feb;44(1-2):26-33. 52. 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. 53. Bluher M, Kahn BB, Kahn CR. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science. 2003 Jan 24;299(5606):572-4. 54. Lane MA, Ingram DK, Roth GS. Calorie restriction in nonhuman primates: effects on diabetes and cardiovascular risk. Toxicol Sci. 1999 Dec;52(2 Suppl.):41-8. 55. Ugochukwu NH, Figgers CL. Modulation of the flux patterns in carbohydrate metabolism in the livers of streptozoticin-induced diabetic rats by dietary caloric restriction. Pharmacol Res. 2006 Sep;54(3):172-80. 56. Lefevre M, Redman LM, Heilbronn LK, et al. Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis. 2009 Mar;203(1):206-13. 57. Kritchevsky D. Caloric restriction and cancer. J Nutr Sci Vitaminol. 2001 Feb; 47(1):13-9. 58. Weindruch R. Effect of caloric restriction on age-associated cancers. Exp Gerontol. 1992 Sep-Dec;27(5-6):575-81. 59. Colman RJ, Anderson RM, Johnson SC, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009 Jul 10;325(5937):201-4. 60. Weindruch R, Walford RL, Fligiel S, Guthrie D. The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J Nutr. 1986 Apr;116(4):641-54. 61. Hsieh EA, Chai CM, Hellerstein MK. Effects of caloric restriction on cell proliferation in several tissues in mice: role of intermittent feeding. Am J Physiol Endocrinol Metab. 2005 May;288(5):E965-72. 62. Mukherjee P, El-Abbadi MM, Kasperzyk JL, Ranes MK, Seyfried TN. Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. Br J Cancer. 2002 May 20;86(10):1615-21. 63. Matthews CE, Sui X, LaMonte MJ, Adams SA, Hébert JR, Blair SN. Metabolic syndrome and risk of death from cancers of the digestive system. Metabolism. 2010 Aug;59(8):1231-9. 64. Noto H, Osame K, Sasazuki T, Noda M. Substantially increased risk of cancer in patients with diabetes mellitus A systematic review and meta-analysis of epidemiologic evidence in Japan. J Diabetes Complications. 2010 Sept-Oct;24(5):345-53. 65. Flood A, Strayer L, Schairer C, Schatzkin A. Diabetes and risk of incident colorectal cancer in a prospective cohort of women. Cancer Causes Control. 2010 Aug;21(8):1277-84. 66. 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. 67. 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. 68. Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A, Barzi F, Woodward M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer. 2005;92(11):2076–83. 69. Chari ST, Leibson CL, Rabe KG, et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology. 2008 Jan;134(1):95-101. 70. Gapstur SM, Gann PH, Lowe W, Liu K, Colangelo L, Dyer A. Abnormal glucose metabolism and pancreatic cancer mortality. JAMA. 2000 May 17;283(19):2552-8. 71. Li Q, Chen AH, Song XD, et al. Analysis of glucose levels and the risk for coronary heart disease in elderly patients in Guangzhou Haizhu district. Nan Fang Yi Ke Da Xue Xue Bao. 2010 Jun;30(6):1275-8. 72. Available at: http://www.livingthecrway.com/home/blog/09-07-20/High_Glucose_after_Meals_is_a_Risk_Factor.aspx. Accessed August 2, 2010. 73. Available at: http://www.idf.org/webdata/docs/Guideline_PMG_final.pdf. Accessed July 29, 2010. 74. Tormo MA, Gil-Exojo I, Romero de Tejada A, Campillo JE. White bean amylase inhibitor administered orally reduces glycaemia in type 2 diabetic rats. Br J Nutr. 2006 Sep;96(3):539-44. 75. Henness S, Perry CM. Orlistat: a review of its use in the management of obesity. Drugs. 2006;66(12):1625-56. 76. Oyama T, Saiki A, Endoh K, et al. Effect of acarbose, an alpha-glucosidase inhibitor, on serum lipoprotein lipase mass levels and common carotid artery intima-media thickness in type 2 diabetes mellitus treated by sulfonylurea. J Atheroscler Thromb. 2008 Jun;15(3):154-9. 77. Lamela M, Anca J, Villar R, Otero J, Calleja JM. Hypoglycemic activity of several seaweed extracts. J Ethnopharmacol. 1989 Nov;27(1-2):35-43. 78. Seri K, Sanai K, Matsuo N, Kawakubo K, Xue C, Inoue S. L-arabinose selectively inhibits intestinal sucrase in an uncompetitive manner and suppresses glycemic response after sucrose ingestion in animals. Metabolism. 1996 Nov;45(11):1368-74. 79. Preuss HG, Echard B, Bagchi D, Stohs S. Inhibition by natural dietary substances of gastrointestinal absorption of starch and sucrose in rats and pigs: 1. Acute studies. Int J Med Sci. 2007 Aug 6;4(4):196-202. 80. McCarty MF. Glucomannan minimizes the postprandial insulin surge: a potential adjuvant for hepatothermic therapy. Med Hypotheses. 2002 Jun;58(6):487-90. 81. Vuksan V, Jenkins DJ, Spadafora P, et al. Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled metabolic trial. Diabetes Care. 1999 Jun;22(6):913-9. 82. Biorklund M, van Rees A, Mensink RP, Onning G. Changes in serum lipids and postprandial glucose and insulin concentrations after consumption of beverages with beta-glucans from oats or barley: a randomised dose-controlled trial. Eur J Clin Nutr. 2005 Nov;59(11):1272-81. 83. Poppitt SD, van Drunen JD, McGill AT, Mulvey TB, Leahy FE. Supplementation of a high-carbohydrate breakfast with barley beta-glucan improves postprandial glycaemic response for meals but not beverages. Asia Pac J Clin Nutr. 2007; 16(1):16-24. 84. Balk EM, Tatsioni A, Lichtenstein AH, Lau J, Pittas AG. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care. 2007 Aug;30(8):2154-63. 85. Obiro WC, Zhang T, Jiang B. The nutraceutical role of the Phaseolus vulgaris alpha-amylase inhibitor. Br J Nutr. 2008 Jul;100(1):1-12 86. Sood N, Baker WL, Coleman CI. Effect of glucomannan on plasma lipid and glucose concentrations, body weight, and blood pressure: systematic review and meta-analysis. Am J Clin Nutr. 2008 Oct;88(4):1167-75. 87. Heilbronn LK, Noakes M, Clifton PM. The effect of high- and low-glycemic index energy restricted diets on plasma lipid and glucose profiles in type 2 diabetic subjects with varying glycemic control. J Am Coll Nutr. 2002 Apr;21(2):120-7. 88. Walsh DE, Yaghoubian V, Behforooz A. Effect of glucomannan on obese patients: a clinical study. Int J Obes. 1984; 8(4):289-93. 89. Wu H, Dwyer KM, Fan Z, et al. Dietary fiber and progression of atherosclerosis: the Los Angeles Atherosclerosis Study. Am J Clin Nutr. 2003 Dec;78(6):1085-91. 90. Available at: http://www.lifeextension.com/Vitamins-Supplements/Item01492/Optimized-Irvingia-with-Phase-3-Calorie-Control-Complex.html. Accessed August 2, 2010. 91. Moon RJ. The addition of metformin in type 1 diabetes improves insulin sensitivity, diabetic control, body composition and patient well-being. Diabetes Obes Metab. 2007 Jan;9(1):143-5. 92. Sir T, Castillo T, Munoz S, Lopez G, Calvillan M. Effects of metformin on insulin resistance in obese and hyperandrogenic women. Rev Med Chil.1997 Dec;125(12):1457-63. 93. Giugliano D, De Rosa N, Di Maro G, et al. Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women. Diabetes Care. 1993 Oct;16(10):1387-90. 94. Zander M, Taskiran M, Toft-Nielsen MB, Madsbad S, Holst JJ. Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes. Diabetes Care. 2001 Apr;24(4):720-5. 95. Saenz A, Fernandez-Esteban I, Mataix A, Ausejo M, Roque M, Moher D. Metformin monotherapy for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005 Jul 20;(3). 96. Wiernsperger NF, Bailey CJ. The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms. Drugs. 1999; 58 Suppl 1:31-9. 97. Mithieux G, Guignot L, Bordet JC, Wiernsperger N. Intrahepatic mechanisms underlying the effect of metformin in decreasing basal glucose production in rats fed a high-fat diet. Diabetes. 2002 Jan;51(1):139-43. 98. Davidson MB, Peters AL. An overview of metformin in the treatment of type 2 diabetes mellitus. Am J Med. 1997 Jan;102(1):99-110. 99. Fioretto P, Bruseghin M, Berto I, Gallina P, Manzato E, Mussap M. Renal protection in diabetes: role of glycemic control. J Am Soc Nephrol. 2006 Apr;17(4 Suppl 2):S86-9. 100.Bilous R. Microvascular disease: what does the UKPDS tell us about diabetic nephropathy? Diabet Med. 2008 Aug;25 Suppl 2:25-9. 101.Stocks T, Rapp K, Bjørge T, et al. Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (me-can): analysis of six prospective cohorts. PLoS Med. 2009 Dec;6(12):e1000201. 102.Cowey S, Hardy RW. The metabolic syndrome: A high-risk state for cancer? Am J Pathol. 2006 Nov;169(5):1505-22. 103.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. 104.Wu L, Derynck R. Essential role of TGF-beta signaling in glucose-induced cell hypertrophy. Dev Cell. 2009 Jul;17(1):35-48. 105.Kabat GC, Kim M, Chlebowski RT, et al. A longitudinal study of the metabolic syndrome and risk of postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev. 2009 Jul;18(7):2046-53. 106.Pannala R, Basu A, Petersen GM, Chari ST. New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol. 2009 Jan;10(1):88-95. 107.Cust AE, Kaaks R, Friedenreich C, et al. Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer. 2007 Sep;14(3):755-67. 108.Jones SC, Saunders HJ, Qi W, Pollock CA. Intermittent high glucose enhances cell growth and collagen synthesis in cultured human tubulointerstitial cells. Diabetologia. 1999 Sep;42(9):1113-9. 109.Ceriello A, Quagliaro L, Piconi L, et al. Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes. 2004 Mar;53(3):701-10. 110.Esper RJ, Vilariño JO, Machado RA, Paragano A. Endothelial dysfunction in normal and abnormal glucose metabolism. Adv Cardiol. 2008; 45:17-43. 111.Rodriguez CJ, Miyake Y, Grahame-Clarke C, et al. Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus. Am J Cardiol. 2005 Nov 1;96(9):1273-7. 112.Williams SB, Goldfine AB, Timimi FK, et al. Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation. 1998 May 5;97(17):1695-701. 113.Kawano H, Motoyama T, Hirashima O, et al. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol. 1999 Jul; 34(1):146-54. 114.Nappo F, Esposito K, Cioffi M, et al. Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: role of fat and carbohydrate meals. J Am Coll Cardiol. 2002 Apr 3;39(7):1145-50. 115.Hink U, Tsilimingas N, Wendt M, Munzel T. Mechanisms underlying endothelial dysfunction in diabetes mellitus: therapeutic implications. Treat Endocrinol. 2003;2(5):293-304. 116.Lteif AA, Han K, Mather KJ. Obesity, insulin resistance, and the metabolic syndrome: determinants of endothelial dysfunction in whites and blacks. Circulation. 2005 Jul 5;112(1):32-8. 117.Panus C, Mota M, Vladu D, Vanghelie L, Raducanu CL. The endothelial dysfunction in diabetes mellitus. Rom J Intern Med. 2003; 41(1):27-33. 118.Dziewierz A, Giszterowicz D, Siudak Z, Rakowski T, Dubiel JS, Dudek D. Admission glucose level and in-hospital outcomes in diabetic and non-diabetic patients with acute myocardial infarction. Clin Res Cardiol. 2010 May 11. 119.Selvin E, Coresh J, Golden SH, Brancati FL, Folsom AR, Steffes MW. Glycemic control and coronary heart disease risk in persons with and without diabetes: the atherosclerosis risk in communities study. Arch Intern Med. 2005 Sep 12;165(16):1910-6. 120.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. 121.Ceriello A. The postprandial state and cardiovascular disease: relevance to diabetes mellitus. Diabetes Metab Res Rev. 2000 Mar-Apr;16(2):125-32. 122.Liu S, Willett WC, Stampfer MJ, et al. A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Am J Clin Nutr. 2000 Jun; 71(6):1455-61. 123.Zavaroni I, Bonora E, Pagliara M, et al. Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance. N Engl J Med. 1989 Mar 16;320(11):702-6. 124.Levitan EB, Song Y, Ford ES, Liu S. Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta-analysis of prospective studies. Arch Intern Med. 2004 Oct 25;164(19):2147-55. 125.Sorkin JD, Muller DC, Fleg JL, Andres R. The relation of fasting and 2-h postchallenge plasma glucose concentrations to mortality: data from the Baltimore Longitudinal Study of Aging with a critical review of the literature. Diabetes Care. 2005 Nov; 28(11):2626-32. 126.Held C, Gerstein HC, Yusuf S, et al. Glucose levels predict hospitalization for congestive heart failure in patients at high cardiovascular risk. Circulation. 2007 Mar 20;115(11):1371-5. 127.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. 128.Lucas CP, Boldrin MN, Reaven GM. Effect of orlistat added to diet (30% of calories from fat) on plasma lipids, glucose, and insulin in obese patients with hypercholesterolemia. Am J Cardiol. 2003 Apr 15;91(8):961-4. 129.Behall KM, Scholfield DJ, Hallfrisch JG, Liljeberg-Elmståhl HG. Consumption of both resistant starch and beta-glucan improves postprandial plasma glucose and insulin in women. Diabetes Care. 2006 May;29(5):976-81. 130.Nizami F, Farooqui MS, Munir SM, Rizvi TJ. Effect of fiber bread on themanagement of diabetes mellitus. J Coll Physicians Surg Pak. 2004 Nov;14(11):673-6. 131.Ngondi JL, Oben JE, Minka SR. The effect of Irvingia gabonensis seeds on body weight and blood lipids of obese subjects in Cameroon. Lipids Health Dis. 2005 May 25;4:12. 132.Anderson JW, Allgood LD, Turner J, Oeltgen PR, Daggy BP. Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia. Am J Clin Nutr. 1999 Oct;70(4):466-73. 133.Chandalia M, Garg A, Lutjohann D, von Bergmann K, Grundy SM, Brinkley LJ. Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. N Engl J Med. 2000 May 11;342(19):1392-8. 134.Smith U, Holm G. Effect of a modified guar gum preparation on glucose and lipid levels in diabetics and healthy volunteers. Atherosclerosis. 1982 Oct;45(1):1-10. 135.Borges RL, Ribeiro-Filho FF, Carvalho KM, Zanella MT. Impact of weight loss on adipocytokines, C-reactive protein and insulin sensitivity in hypertensive women with central obesity. Arq Bras Cardiol. 2007 Dec;89(6):409-14. 136.Vasdev S, Gill V, Singal P. Role of advanced glycation end products in hypertension and atherosclerosis: therapeutic implications. Cell Biochem Biophys. 2007;49(1):48-63. 137.Available at: http://www.bmj.com/cgi/reprint/330/7503/1304. Accessed August 10, 2010. 138.Patel R, Krishnan R, Ramchandani A, Maru G. Polymeric black tea polyphenols inhibit mouse skin chemical carcinogenesis by decreasing cell proliferation. Cell Prolif. 2008 Jun;41(3):532-53. 139.Letchoumy PV, Mohan KV, Prathiba D, Hara Y, Nagini S. Comparative evaluation of antiproliferative, antiangiogenic and apoptosis inducing potential of black tea polyphenols in the hamster buccal pouch carcinogenesis model. J Carcinog. 2007 Dec 3;6:19. 140.Prasad S, Kaur J, Roy P, Kalra N, Shukla Y. Theaflavins induce G2/M arrest by modulating expression of p21waf1/cip1, cdc25C and cyclin B in human prostate carcinoma PC-3 cells. Life Sci. 2007 Oct 13;81(17-18):1323-31. 141.Shoji Y, Nakashima H. Glucose-lowering effect of powder formulation of African black tea extract in KK-A(y)/TaJcl diabetic mouse. Arch Pharm Res. 2006 Sep;29(9):786-94. 142.Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA. 2009 Apr 15;301(15):1565-72. 143.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. 144.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. 145.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. 146.Abbatecola AM, Rizzo MR, Barbieri M, et al. Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics. Neurology. 2006; 67(2):235-40. 147.Gonzalez Canga A, Fernández Martínez N, Sahagún AM, et al. Glucomannan: properties and therapeutic applications. Nutr Hosp. 2004 Jan-Feb;19(1):45-50. 148.Celleno L, Tolaini MV, D’Amore A, Perricone NV, Preuss HG. A Dietary supplement containing standardized Phaseolus vulgaris extract influences body composition of overweight men and women. Int J Med Sci. 2007 Jan 24;4(1):45-52. 149.Oben JE, Ngondi JL, Momo CN, Agbor GA, Sobgui CS. The use of a Cissus quadrangularis/Irvingia gabonensis combination in the management of weight loss: a double-blind placebo-controlled study. Lipids Health Dis. 2008 Mar 31;7:12. 150.Oben JE, Ngondi JL, Blum K. Inhibition of Irvingia gabonensis seed extract (OB131) on adipogenesis as mediated via down regulation of the PPARgamma and leptin genes and up-regulation of the adiponectin gene. Lipids Health Dis. 2008 Nov 13;7:44. 151.Bose M, Lambert JD, Ju J, Reuhl KR, Shapses SA, Yang CS. The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat-fed mice. J Nutr. 2008 Sep;138(9):1677-83. 152.Iwai K. Antidiabetic and antioxidant effects of polyphenols in brown alga Ecklonia stolonifera in genetically diabetic KK-A(y) mice. Plant Foods Hum Nutr. 2008 Dec;63(4):163-9. 153.Available at: http://www.naturalproductsinsider.com/news/2009/12/insea2-reduces-glycemic-response.aspx#. Accessed August 12, 2010. 154.Hlebowicz J, Darwiche G, Bjorgell O, Almer LO. Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety in healthy subjects. Am J Clin Nutr. 2007 Jun;85(6):1552-6. 155.Qin B, Nagasaki M, Ren M, Bajotto G, Oshida Y, Sato Y. Cinnamon extract prevents the insulin resistance induced by a high-fructose diet. Horm Metab Res. 2004 Feb;36(2):119-25. 156.Khan A, Safdar M, Muzaffar Ali Khan M, Nawak Khattak K, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003 Dec;26(12):3215-8. 157.Broadhurst CL, Polansky MM, Anderson RA. Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro. J Agric Food Chem. 2000 Mar;48(3):849-52. 158.Anisimov VN, Berstein LM, Egormin PA, et al. Metformin slows down aging and extends life span of female SHR mice. Cell Cycle. 2008 Sep 1;7(17):2769-73. 159.Onken B, Driscoll M. Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1. PLoS One. 2010 Jan 18;5(1):e8758. 160.Fontbonne A., Charles MA, Juhan-Vague I, et al. The effect of metformin on the metabolic abnormalities associated with upper body fat distribution. Results of the BIGPRO 1 trial. Diabetes Care. 1996 Sept; 19:920-6. 161.Guthrie R. Treatment of non-insulin-dependent diabetes mellitus with metformin. J Am Board Fam Pract. 1997 May-Jun;10(3):213-21. 162.Paolisso G, Amato L, Eccellente R, et al. Effect of metformin on food intake in obese subjects. Eur J Clin Invest. 1998 Jun;28(6):441-6. 163.Emral R, Koseoglulari O, Tonyukuk V, Uysal AR, Kamel N, Corapcioglu D. The effect of short-term glycemic regulation with gliclazide and metformin on postprandial lipemia. Exp Clin Endocrinol Diabetes. 2005 Feb;113(2):80-4. 164.Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007 Jul 18;298(3):299-308. 165.Hollenbeck CB, Johnston P, Varasteh BB, Chen YD, Reaven GM. Effects of metformin on glucose, insulin and lipid metabolism in patients with mild hypertriglyceridaemia and non-insulin dependent diabetes by glucose tolerance test criteria. Diabete Metab. 1991 Sep-Oct;17(5):483-9. 166.Wilcock C, Bailey CJ. Reconsideration of inhibitory effect of metformin on intestinal glucose absorption. J Pharm Pharmacol. 1991 Feb;43(2):120-1. 167.Ikeda T, Iwata K, Murakami H. Inhibitory effect of metformin on intestinal glucose absorption in the perfused rat intestine. Biochem Pharmacol. 2000 Apr 1;59(7):887-90. 168.Lee A, Morley JE. Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes. Obes Res. 1998 Jan;6(1):47-53. 169.Mannucci E, Ognibene A, Cremasco F, et al. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care. 2001 Mar;24(3):489-94. 170.Hundal RS, Krssak M, Dufour S, et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes. 2000 Dec;49(12):2063-9. 171.Otto M, Breinholt J, Westergaard N. Metformin inhibits glycogen synthesis and gluconeogenesis in cultured rat hepatocytes. Diabetes Obes Metab. 2003 May;5(3):189-94. 172.Carlsen SM, Følling I, Grill V, Bjerve KS, Schneede J, Refsum H. Metformin increases total serum homocysteine levels in non-diabetic male patients with coronary heart disease. Scand J Clin Lab Invest. 1997 Oct;57(6):521-7. 173.Dhatariya K, Bigelow ML, Nair KS. Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women. Diabetes. 2005 Mar;54(3):765-9. 174.Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA. 2004 Nov 10;292(18):2243-8. 175.Boudou P, Sobngwi E, Ibrahim F, et al. Hyperglycaemia acutely decreases circulating dehydroepiandrosterone levels in healthy men. Clin Endocrinol (Oxf). 2006 Jan;64(1):46-52. 176. Diamond P, Cusan L, Gomez JL, Bélanger A, Labrie F. Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women. J Endocrinol. 1996 Sep;150 Suppl:S43-50. 177.Yamashita R, Saito T, Satoh S, Aoki K, Kaburagi Y, Sekihara H. Effects of dehydroepiandrosterone on gluconeogenic enzymes and glucose uptake in human hepatoma cell line, HepG2. Endocr J. 2005 Dec;52(6):727-33. 178. Kapoor D, Malkin CJ, Channer KS, Jones TH. Androgens, insulin resistance and vascular disease in men. Clin Endocrinol (Oxf). 2005 Sep;63(3):239-50. 179.Faloon W. Physician’s guide: Using blood tests to safely induce weight loss. Life Extension Magazine. 2009 Jun;15(6):42-63. 180.Bain J. The many faces of testosterone. Clin Interv Aging. 2007; 2(4):567-76. 181.Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ, McKinlay JB. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab. 2006 Mar;91(3):843-50. 182.Traish AM, Saad F, Guay AT. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl. 2009 Jan-Feb;30(1):23-32. 183.Paniagua JA, de la Sacristana AG, Sánchez E, et al. A MUFA-rich diet improves posprandial glucose, lipid and GLP-1 responses in insulin-resistant subjects. J Am Coll Nutr. 2007 Oct;26(5):434-44. 184.Tzima N, Pitsavos C, Panagiotakos DB, et al. Mediterranean diet and insulin sensitivity, lipid profile and blood pressure levels, in overweight and obese people; the Attica study. Lipids Health Dis. 2007 Sep 19;6:22. 185.Chrysohoou C, Panagiotakos DB, Pitsavos C, Das UN, Stefanadis C. Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: The ATTICA Study. J Am Coll Cardiol. 2004 Jul 7;44(1):152-8. 186.Gaby AR. Adverse effects of dietary fructose. Altern Med Rev. 2005 Dec;10(4):294-306. 187.Hallfrisch J, Ellwood KC, Michaelis OE 4th, Reiser S, O’Dorisio TM, Prather ES. Effects of dietary fructose on plasma glucose and hormone responses in normal and hyperinsulinemic men. J Nutr. 1983 Sep;113(9):1819-26. 188.Tokita Y, Hirayama Y, Sekikawa A, et al. Fructose ingestion enhances atherosclerosis and deposition of advanced glycated end-products in cholesterol-fed rabbits. J Atheroscler Thromb. 2005 12(5):260-7. 189.Beck-Nielsen H, Pedersen O, Lindskov HO. Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects. Am J Clin Nutr. 1980 Feb;33(2):273-8. 190.McPherson JD, Shilton BH, Walton DJ. Role of fructose in glycation and cross-linking of proteins. Biochemistry. 1988 Mar 22;27(6):1901-7. 191.Van Wymelbeke V, Beridot-Therond ME, de La Gueronniere V, Fantino M. Influence of repeated consumption of beverages containing sucrose or intense sweeteners on food intake. Eur J Clin Nutr. 2004 Jan;58(1):154-61. 192.Palmer JR, Boggs DA, Krishnan S, Hu FB, Singer M, Rosenberg L. Sugar-sweetened beverages and incidence of type 2 diabetes mellitus in African American women. Arch Intern Med. 2008 Jul 28;168(14):1487-92. 193.Yudkin J, Eisa O. Dietary sucrose and oestradiol concentration in young men. Ann Nutr Metab. 1988 32(2):53-5. 194.Blacklock NJ. Sucrose and idiopathic renal stone. Nutr Health. 1987 5(1-2):9-17. 195.Tjaderhane L, Larmas M. A high sucrose diet decreases the mechanical strength of bones in growing rats. J Nutr. 1998 Oct;128(10):1807-10. 196.Torronen R, Sarkkinen E, Tapola N, Hautaniemi E, Kilpi K, Niskanen L. Berries modify the postprandial plasma glucose response to sucrose in healthy subjects. Br J Nutr. 2010 Apr;103(8):1094-7. 197.Moeller SM, Fryhofer SA, Osbahr AJ 3rd, Robinowitz CB; Council on Science and Public Health, American Medical Association. The effects of high fructose syrup. J Am Coll Nutr. 2009 Dec;28(6):619-26. 198.Angelopoulos TJ, Lowndes J, Zukley L, et al. The effect of high-fructose corn syrup consumption on triglycerides and uric acid. J Nutr. 2009 Jun;139(6):1242S-1245S. 199.Stanhope KL, Havel PJ. Endocrine and metabolic effects of consuming beverages sweetened with fructose, glucose, sucrose, or high-fructose corn syrup. Am J Clin Nutr. 2008 Dec;88(6):1733S-1737S. 200. Forshee RA, Storey ML, Allison DB, et al. A critical examination of the evidence relating high fructose corn syrup and weight gain. Crit Rev Food Sci Nutr. 2007 47(6):561-82. 201.Ouyang X, Cirillo P, Sautin Y, et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol. 2008 Jun;48(6):993-9. 202.Willcox DC, Willcox BJ, Todoriki H, Suzuki M. The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load. J Am Coll Nutr. 2009 Aug;28 Suppl:500S-516S. 203.Brand-Miller J, McMillan-Price J, Steinbeck K, Caterson I. Dietary glycemic index: health implications. J Am Coll Nutr. 2009 Aug;28 Suppl:446S-449S. |