Life Extension Magazine®
Doctors Overlook Leading Cause of Premature Death
Despite a virtual mountain of scientific data showing the lethal dangers of high blood sugar, mainstream doctors are allowing their patients to needlessly suffer and die. It is not just elevated fasting glucose that leads to diabetic complications in non-diabetics. Startling findings reveal excess after-meal glucose surges inflict frightening damage throughout the body and are involved in the leading causes of death in America.
Scientifically reviewed by Dr. Gary Gonzalez, MD, in October 2024. Written by: William Faloon.
Diabetes is defined as a disease in which a person has high blood sugar. The problem is that physicians are failing to determine how low blood glucose needs to be to protect against dreaded diabetic complications. In a series of published studies, the definition of what constitutes diabetes, (or said differently, a person with high blood sugar) is about to be turned upside down. This is not a trivial matter. The term "diabetic complications" encompasses the most common diseases of aging, ranging from kidney failure1-3 and blindness,4-6 to heart disease,7-12 stroke,13,14 neuropathy,15,16 and even cancer.17-22 This means that most degenerative disease can be traced back to undiagnosed glucose control problems, which we assert will soon become the new definition of diabetes. High blood sugar appears to be the leading killer today, yet the medical mainstream is not properly diagnosing or treating it. The tragic result is an epidemic of diabetic complications that cripple and kill millions of Americans because simple steps are not being taken to suppress after-meal glucose spikes. As you are about to learn, it is not just elevated fasting glucose that creates diabetic complications. Excess after-meal glucose surges have turned into a silent diabetes plague, thus mandating new steps be taken to protect against what may be the leading cause of premature death. Fasting Glucose Is a Delayed Marker of DiabetesWhen people take blood tests to measure glucose levels, they are asked to fast for 8 to 12 hours. Doctors ask for this 8-12 hour fast because they want a consistent baseline to measure glucose and lipids in comparison with the general population. There is one problem with this. A person who suffers from dangerously high blood sugar several hours following a typical meal may artificially drop their fasting glucose to a safe range after fasting 8 or more hours. A person’s ability to clear their blood of excess glucose 8-12 hours after eating may persist for decades, thus masking what may be a dangerous postprandial (after-meal) spike in glucose. Even tests that measure long-term glycemic control like hemoglobin A1c may not adequately detect these post-meal glucose surges. This means that many of us spend a part of our day in an acute diabetic state. The lethal impact of these multi-hour glucose surges is just now being understood. As you will read, diabetic complications can develop years or even decades before full-blown type 2 diabetes is diagnosed. Consequences of Post-meal Glucose Surge
What happens in your blood during the first several hours after ingesting a high-carbohydrate meal has a lot to do with your risk of acquiring diabetic complications, even if you have not yet developed diabetes (as defined today). Glucose levels naturally rise in your blood after a high-carbohydrate meal and if you are healthy, glucose will quickly drop back to pre-meal ranges. If glucose rises too much and stays elevated too long, however, a tremendous amount of tissue damage is inflicted.23-27 Diabetics have sharply higher rates of heart attacks compared to non-diabetics.28-30 Yet even in many not considered diabetic, heart attack rates are 40% higher when fasting glucose levels are above 85 mg/dL.31 In a study where after-meal glucose spikes were impeded, heart attacks rates dropped an astounding 91%.32 Even when someone suffers a heart attack, the amount of damage to the heart muscle is significantly reduced when steps are taken ahead of time to reduce post-meal glucose surges.32-36 The Honolulu Heart Program found that the risk of coronary artery disease correlated with glucose levels measured one hour after a 50-gram oral glucose load. The incidence of coronary artery disease was twice as high in patients with postprandial glucose levels between 157 and 189 mg/dL compared to those with levels under 144 mg/dL.37 Another study showed the incidence of sudden death was doubled with postprandial glucose levels of 225 mg/dL or higher.38 The Whitehall Study of British male civil servants showed that blood glucose levels of 96 mg/dL or higher two hours after a meal were associated with a two-fold increase in mortality from coronary artery disease.39 Another British study, the Islington Diabetes Survey, reported that the incidence of major coronary artery disease was 17% in subjects with impaired glucose tolerance, typically defined as 2-hour postprandial glucose levels of 140-199 mg/dL, compared with 9% in subjects with normal glucose tolerance.40 The Oslo Study indicated that risk of fatal stroke in diabetic patients increased by 13% for each 18 mg/dL elevation in postprandial glucose.41 These studies consistently show sharply higher vascular disease in those with higher postprandial (after-meal) glucose spikes. Diabetic Complications Seen in Non-diabetics
Peripheral neuropathy involves burning, tingling, and loss of sensation, usually of the lower extremities. It is a common diabetic complication that if left unchecked can result in gangrene that requires amputation to save the patient’s life.42,43 A study showed that many non-diabetics whose glucose elevates to 140 mg/dL or higher after an oral glucose tolerance test suffered the same type of neuropathy as seen in full-blown diabetics. These patients’ fasting glucose and hemoglobin A1c levels were not high, but if their blood glucose levels remained above 140 mg/dL two hours after ingesting 75 grams of pure glucose (a glucose tolerance test), there was a sudden and significant increase in incidence of diabetic neuropathy signs and symptoms.44 Another study found that 56% of neuropathy patients had glucose tolerance levels that fell in the pre-diabetic range, and these individuals suffered damage to their small nerve fibers.45 It has been anecdotally reported that neuropathic pain in the feet of patients worsens when glucose levels exceed 140 mg/dL and diminish when glucose is dropped below this range.44,46 Retinopathy occurs when high blood sugar damages tiny blood vessels in the retina of the eye. It is one of the most feared diabetic complications as it can lead to blindness. The American Diabetes Association thought that retinopathy did not occur until a glucose tolerance test showed glucose levels well over 200 mg/dL after two hours. However, in a large population study, one out of every twelve people with pre-diabetes showed signs of retinopathic changes occurring in their eyes. This study classified pre-diabetes as fasting glucose between 100-125 mg/dL or two-hour glucose tolerance readings between 150-199 mg/dL. These findings show that post-meal glucose spikes over 150 mg/dL are associated with tiny blood vessel changes that lead to diabetic retinopathy.4 Diabetics have higher rates of cancer that have been attributed to higher blood sugar and insulin levels.47-49 When glucose is elevated, the pancreas secretes excess insulin in an attempt to normalize it. Higher insulin levels are believed to stimulate cancer cell proliferation. A study that tracked 10,000 people for 10 years showed substantial increase in cancer in those with fasting glucose over 110 mg/dL or two-hour postprandial glucose levels over 160 mg/dL.50 Excess glucose also increases triglyceride levels, another vascular risk factor.51 Certain drugs like metformin that lower glucose and insulin also reduce artery-clogging triglycerides.52,53 These and other studies demonstrate that those who are unable to control their glucose peaks are prone to suffer diabetic complications. All of this confirms what Life Extension® previously published about the urgent need to protect against after-meal surges of glucose, insulin, and triglycerides. Clearly, the body does not like to be inundated with after-meal glucose spikes, yet too many Americans suffer from excess postprandial glucose throughout most of the day, and their doctors are not paying attention to the lethal risks this poses. Not only do glucose spikes acutely damage tissues, but they unfavorably alter gene expression in a way that may accelerate aging processes.54,55 This is one reason why calorie restriction has yielded such robust extensions in life span, along with sharply lower risks of degenerative diseases. Fortunately, there are several proven ways to curb after-meal glucose spikes that do not require severe calorie restriction. High Glucose Destroys Insulin-producing Cells
Not only do after-meal glucose surges create lethal diabetic complications, but they directly cause the destruction of the insulin-producing beta cells in the pancreas. Once enough beta cells die, there is insufficient insulin to control blood glucose levels. It is usually at this time of spiraling fasting glucose levels that full-blown type 2 diabetes is diagnosed…sometimes decades after high blood sugar has already damaged every tissue in the body.56,57 Beta cells secrete insulin in response to increases in blood glucose. Unfortunately, beta cells are quite sensitive to even slight increases in blood sugar. There is evidence of beta cell dysfunction when glucose levels stay over 100 mg/dL for more than a few hours.58 When analyzing this data further, scientists found that even small incremental increases in glucose over a two-hour period result in detectable beta cell failure. This study showed that more beta cells fail as a person’s blood sugar rose even within the so-called "normal range."58 Another study showed that beta cells start to die off when fasting glucose is over 110 mg/dL—a level that many doctors tell their patients not to worry about.59 This study indicates that people are killing off their vital insulin-producing beta cells by allowing glucose to spike too high after meals. Once enough beta cells have died, people become insulin-dependent diabetics with markedly shortened life spans. As we now know, when someone has fasting glucose over 110, it means they usually spend several hours after meals with sharply higher glucose levels. Laboratory studies show that prolonged exposure to high sugar levels destroys beta cells. When these beta cells are removed from high-sugar mediums, they can recover, but only if they were removed before a certain amount of time had passed.60,61 A huge portion of the population spends most of their day with glucose levels above those shown to injure or kill insulin-secreting beta cells. This explains how high blood sugar is in itself a direct cause of the destruction of beta cells needed for insulin production. It used to be thought that beta cells "burned out" because they were forced to overproduce insulin to suppress high blood sugar levels. We now know that high blood sugar itself is killing vital beta cells. Said differently, many type 2 diabetes cases are not caused because of insufficient insulin production. Instead, high blood sugar destroys beta cells, thus causing chronically elevated blood sugar (because of insufficient insulin secretion) that is eventually diagnosed as type 2 diabetes. The obvious solution is to keep after-meal glucose levels suppressed so beta cells don’t die! A New Definition of DiabetesDiabetes should be re-defined as "a disease in which a person has acute blood sugar spikes and/or chronically elevated blood sugar levels high enough to increase disease risk." The definition could be elaborated to include anyone with fasting glucose above 85 mg/dL and/or a 75-gram oral glucose tolerance test load that shows a rise from fasting glucose greater than 40 mg/dL after two hours. What this means is that if a person’s fasting glucose is 80 mg/dL, and their postprandial level is higher than 120 mg/dL two hours after a glucose tolerance test, they have less-than-optimal glycemic control that should be treated. The upper-limit number for after-meal glucose (120 mg/dL) in the preceding paragraph reflects ranges sought in people who practice calorie restriction. Others may argue that glucose-suppressing treatment should not be initiated until glucose readings are over 140 mg/dL two hours after an oral glucose challenge.23 This higher upper limit after-meal glucose level (140 mg/dL) is more practical for most aging humans to strive for. It is advantageous for all aging individuals to strive for fasting glucose levels below 86 mg/dL, which may not be feasible in everyone, as some of us are predisposed to higher glucose levels despite aggressive interventions. In any case, aging humans should view every meal (especially those high in carbohydrates) as a direct threat to their health and longevity. Proven methods should thus be implemented prior to all large meals to blunt postprandial glucose surges. This includes inhibiting amylase62-67 and glucosidase68,69 enzymes to impede absorption of glucose into the bloodstream, along with special fibers70-72 that delay emptying of food into the small intestine where rapid absorption of glucose from carbohydrate foods occurs. Nutrients, hormones, and drugs (already used by many Life Extension members) improve insulin sensitivity, which facilitates more efficient removal of glucose from the blood.73-81 Despite impeding glucose absorption and improving cellular glucose utilization, too many health-conscious members are not adequately controlling their blood glucose levels. The good news is that a standardized green coffee bean extract has demonstrated robust after-meal reductions in glucose spikes and functions via novel mechanisms not previously available.82,83 Why Do Aging People Have Too Much Glucose?We know that overconsumption of calories (especially refined carbohydrates) will acutely spike blood glucose and can eventually result in chronically elevated fasting glucose, which is how diabetes is defined today. Yet as people age, and pay closer attention to their diets, they still often suffer after-meal glucose surges that result in their bloodstreams being bloated with too much glucose for too many hours. This is caused by a variety of factors, including reduced insulin sensitivity that disables the ability of muscle cells to remove surplus glucose from blood for conversion to energy. There are other reasons, however, why certain individuals have not been able to reduce their glucose to safe ranges.
The Hidden Causes of Glucose OverloadA lesser-known cause of glucose overload is that glucose stored in the body’s tissues (primarily the liver) is inappropriately released into the bloodstream. This pathological release of glucose occurs even though there is plenty of sugar in the blood from a meal that was just eaten. In those with healthy metabolisms, the liver stores glucose (as glycogen) and only releases enough to maintain a constant blood sugar level to protect against hypoglycemic events. This is called glycogenolysis.84 In healthy individuals, glycogenolysis is suppressed by 90% in the liver after a meal to protect against blood glucose overload.85,86 As people age and their blood sugar rises, this delicate balance destabilizes. High postprandial blood sugar stimulates an enzyme called glucose-6-phosphatase, which in turn prompts the excess release of stored glucose from tissues, even though there is already abundant glucose in the blood. People with high blood sugar levels lose control over normal glucose tissue release. Instead of turning it off in response to glucose flooding into their bloodstream from their last meal, they release too much. This contributes to the deadly after-meal glucose spikes that cause diabetic complications even among non-diabetics. The glucose-6-phosphatase enzyme has another dark side. It facilitates the creation of glucose from other substrates (amino acids, fatty acids, or lactate) in the body. This creation of new glucose is called gluconeogenesis.87 The significance of this process is that it explains how the body can break down any food (protein, fat or carbohydrate) into glucose. Gluconeogenesis is what causes some people to have high blood sugar even though they follow a "low-carb" diet. Elevated glucose-6-phosphatase prompts the release and creation of new glucose into the blood, whether or not you consume any carbohydrate calories. This twin phenomenon of glycogenolysis (release of stored glucose) and gluconeogenesis (creation of new glucose) explains why so many aging people suffer high blood sugar levels. For some people, even if they follow reduced-calorie diets, their bodies may still create too much glucose internally due to excess glucose-6-phosphatase. To understand why excess glucose-6-phosphatase is so deadly, aging people barely have the capacity to safely metabolize the calories they ingest throughout the day. As the body creates and releases too much glucose in the presence of excess glucose-6-phosphatase, each additional calorie can add to glucose spikes. So when a meal is consumed, glucose flows into the bloodstream. This in turn causes total blood glucose levels to skyrocket not just from the ingested carbohydrates, but also through the twin processes of gluconeogenesis and glycogenolysis. Blood sugar levels can then remain elevated for most of the day. Suppression of glucose-6-phosphatase is thus a critical missing link to blunting after-meal (postprandial) glucose surges that are an underlying cause of so many horrific (diabetic) complications. Green Coffee Bean Extract Suppresses Glucose-6-Phosphatase
A number of population studies identified coffee drinkers (who drank at least five cups a day) as being substantially less likely to get type 2 diabetes.88 Further research has suggested the compound responsible for this beneficial action on glucose metabolism is chlorogenic acid that is found abundantly in raw coffee beans. What chlorogenic acid does is inhibit the enzyme glucose-6-phosphatase, which reduces the release and creation of excess glucose in the body.89,90 This unique dual property of chlorogenic acid provides a powerful new weapon in our quest to attain optimal fasting and postprandial glucose levels. In a clinical trial of 56 subjects, 100 grams of glucose was given as an oral glucose challenge test. Study subjects were given escalating doses of standardized green coffee bean extract to measure its ability to reduce the postprandial glucose surge. At a dose of 400 mg of green coffee bean extract, there was a remarkable 32% reduction in the postprandial glucose surge.82 This translates into someone who normally suffers a dangerous postprandial blood glucose surge of 160 mg/dL reducing it to a safe 109 mg/dL. An article in this month’s issue describes the multi-faceted benefits of green coffee bean extract standardized for chlorogenic acid. If all it did was suppress after-meal glucose spikes, it would be well worth considering for anyone who has not been able to achieve optimal glucose control. Like so many other natural polyphenols, chlorogenic acid has demonstrated a wide range of additional protective properties.91-95
Mitigating the Oxidative Flame-throwerA common complaint amongst newly-diagnosed diabetics is why so many complications develop so quickly. What they fail to understand is their delicate tissues may have been under assault from after-meal glucose surges for decades before full-blown type 2 diabetes was diagnosed. In the presence of excess glucose, tissues of the body undergo a hyper-oxidation effect analogous to being torched with a military flame-thrower. While antioxidants can suppress some of the oxidative flame, it is critical to block the underlying catalysts, which are the high blood sugar levels so many aging individuals suffer after every heavy meal. Scientific studies substantiate that acute damage occurs during after-meal glucose spikes, yet mainstream medicine continues to ignore this deadly phenomenon. On page 80 of this issue is an article about nutrients, hormones, and drugs that can help safely suppress fasting and postprandial glucose levels. Advanced Nutrient Formulas at Year’s Lowest PricesLife Extension members take advantage of the annual Super Sale to acquire our most up-to-date nutrient formulations at extra-discounted prices. Virtually every year, we upgrade our formulas to provide even more effective health-sustaining nutrients. Last year we introduced PQQ (pyrroloquinoline quinone) to induce the creation of new mitochondria in aging cells.96 PQQ became an overnight blockbuster as Life Extension members were astutely aware of the critical importance that healthy mitochondria play in forestalling aging processes. Mitochondrial insufficiency, in fact, is involved in the promotion of type 2 diabetes via its debilitating effects on cellular glucose utilization.97,98 In this month’s issue, you’ll discover a missing link that causes aging people to suffer acute post-meal glucose surges that trigger common age-related disorders. The good news is that most of you have been taking steps to shield your bloodstream against these acute glucose spikes. With the introduction of low-cost green coffee bean extract, aging humans can exert greater control over their blood glucose levels than ever before. Save Money While Supporting ResearchEvery time you purchase a Life Extension product, you contribute to research aimed at extending healthy human life span. The Life Extension Foundation® continues to fund a record number of scientific projects, while battling incompetent bureaucrats who seek to suffocate medical innovation. During the traditional winter Super Sale, all Life Extension formulas are discounted so that members can obtain up-to-date versions at the lowest prices of the year. Until January 31, 2012, members take advantage of Super Sale discounts to stock up on cutting–edge formulas designed to circumvent the underlying mechanisms of aging. For longer life,
William Faloon | |||||||||||||
| References | |||||||||||||
| 1. Bakris GL. Recognition, pathogenesis, and treatment of different stages of nephropathy in patients with type 2 diabetes mellitus. Mayo Clin Proc. 2011 May;86(5):444-56. 2. Bash, LD, Selvin E, Steffes M, Coresh J, Astor BC. Poor glycemic control in diabetes and the risk of incident kidney disease even in the absence of albuminuria and retinopathy: atherosclerosis risk in communities (ARIC) study. Arch Intern Med. 2008 Dec 8;168(22):2440-7. 3. Available at: http://www.diabetes.org/living-with-diabetes/complications/kidney-disease-nephropathy.html. Accessed October 27, 2011. 4. Beckley ET. ADA scientific sessions: Retinopathy found in pre-diabetes. DOC News. 2005 Aug; 2(8):1-10. 5. Cheng YJ, Gregg EW, Geiss LS. Association of A1C and fasting plasma glucose levels with diabetic retinopathy prevalence in the US population: implications for diabetes diagnostic thresholds. Diabetes Care. 2009 Nov;32(11):2027-32. 6. Available at: http://diabetes.niddk.nih.gov/dm/pubs/statistics/#allages. Accessed October 27, 2011. 7. 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. 8. 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. 9. 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. 10. Coutinho M, Gerstein H, Poque J, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events: a meta regression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999 Feb;22(2):233–40. 11. Pan WH, Cedres LB, Liu K, et al. Relationships of clinical diabetes and symptomatic hyperglycaemia to risk of coronary heart disease mortality in men and women. Am J Epidemiol. 1986 Mar;123(3):504-16. 12. de Vegt F, Dekker JM, Ruhe 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. 13. Batty GD, Kivimäki M, Smith GD, Marmot MG, Shipley MJ. Post-challenge blood glucose concentration and stroke mortality rates in non-diabetic men in London: 38-year follow-up of the original Whitehall prospective cohort study. Diabetologia. 2008 July;51(7):1123-6. 14. Available at: http://diabetes.niddk.nih.gov/dm/pubs/stroke/. Accessed October 31, 2011. 15. Sumner CJ, Sheth S, Griffin JW, Cornblath DR, Polydefkis M. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology. 2003 Jan 14;60(1):108-11. 16. Hoffman-Snyder C, Smith BE, Ross MA, Hernandez J, Bosch EP. Value of the oral glucose tolerance test in the evaluation of chronic idiopathic axonal polyneuropathy. Arch Neurol. 2006 Aug;63(8):1075-9. 17. Kramer HU, Schottker B, Raum E, Brenner H. Type 2 diabetes mellitus and colorectal cancer: Meta-analysis on sex-specific differences. Eur J Cancer. 2011 Aug 31. 18. Tseng CH. Prostate cancer mortality in Taiwanese men: increasing age-standardized trend in general population and increased risk in diabetic men. Ann Med. 2011 Mar;43(2):142-50. 19. Tseng CH, Chong CK, Tseng CP, Chan TT. Age-related risk of mortality from bladder cancer in diabetic patients: a 12-year follow-up of a national cohort in Taiwan. Ann Med. 2009;41(5):371-9. 20. Cust AE, Kaaks R, Friedenreich C, Bonnet F, 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. 21. Rosato V, Tavani A, Bosetti C, et al. Metabolic syndrome and pancreatic cancer risk: a case-control study in Italy and meta-analysis. Metabolism. 2011 Oct;60(10):1372-8. 22. Stocks T, Lukanova A, Bjorge T, et al. Metabolic factors and the risk of colorectal cancer in 580,000 men and women in the metabolic syndrome and cancer project (Me-Can): Metabolic Syndrome Cancer Project (Me-Can) Group. Cancer. 2010 Dec 17. 23. 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. 24. Ceriello A. Mechanisms of tissue damage in the postprandial state. Int J Clin Pract Suppl. 2001 Sep;(123):7-12. 25. Vlassara H. Advanced glycation end-products and atherosclerosis. Ann Med. 1996 Oct;28(5):419-26. 26. 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 27. Ceriello A. Impaired glucose tolerance and cardiovascular disease: the possible role of post-prandial hyperglycemia. Am Heart J. 2004 May;147(5):803-7. 28. Wingard DL, Barrett-Connor E. Heart disease and diabetes. In: Harris MI, ed. Diabetes in America. 2nd ed. Bethesda, MD. National Institutes of Health; 1995:429-48. 29. Timmer JR, Hoekstra M, Nijsten MW, et al. Prognostic value of admission glycosylated hemoglobin and glucose in nondiabetic patients with ST-segment-elevation myocardial infarction treated with percutaneous coronary intervention. Circulation. 2011 Aug 9;124(6):704-11. 30. Einarson TR, Machado M, Henk Hemels ME. Blood glucose and subsequent cardiovascular disease: update of a meta-analysis. Curr Med Res Opin. 2011 Nov;27(11):2155-63. 31. 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. 32. Zeymer U. Cardiovascular benefits of acarbose in impaired glucose tolerance and type 2 diabetes. Int J Cardiol. 2006 Feb 8;107(1):11-20. 33. Minatoguchi S, Zhang Z, Bao N, et al. Acarbose reduces myocardial infarct size by preventing postprandial hyperglycemia and hydroxyl radical production and opening mitochondrial KATP channels in rabbits. J Cardiovasc Pharmacol. 2009 Jul;54(1):25-30. 34. 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. 35. 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. 36. Bavenholm PN, Efendic S. Postprandial hyperglycaemia and vascular damage--the benefits of acarbose. Diab Vasc Dis Res. 2006 Sep;3(2):72-9. 37. Donahue RP, Abbott RD, Reed DM, et al. Postchallenge glucose concentration and coronary heart disease in men of Japanese ancestry. Honolulu Heart Program. Diabetes. 1987 Jun;36(6):689-92. 38. Curb JD, Rodriguez BL, Burchfiel CM, et al: Sudden death, impaired glucose tolerance, and diabetes in Japanese American men. Circulation. 1995;91:2591-5. 39. Fuller JH, Shipley MJ, Rose G, et al: Coronary-heart-disease risk and impaired glucose tolerance. The Whitehall Study. Lancet. 1980 Jun 28; 1(8183):1373-6. 40. Jackson CA, Yudkin JS, Forrest RD: A comparison of the relationships of the glucose tolerance test and the glycated haemoglobin assay with diabetic vascular disease in the community. The Islington Diabetes Survey. Diabetes Res Clin Pract. 1992 Aug;17(2):111-23. 41. Haheim LL, Holme I, Hjermann I, et al: Nonfasting serum glucose and the risk of fatal stroke in diabetic and nondiabetic subjects. 18-year follow-up of the Oslo Study. Stroke. 1995 May;26(5):774-7. 42. Turns M. The diabetic foot: an overview of assessment and complications. Br J Nurs. 2011 Aug 11-Sep 8;20(15):S19-25. 43. Pereira de Godoy JM, Vasconcelos Ribeiro J, Caracanhas LA. Mortality and diabetes mellitus in amputations of the lower limbs for gas gangrene: a case report. Int J Low Extrem Wounds. 2008 Dec;7(4):239-40. 44. Singleton JR, Smith AG, Bromberg MB. Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy. Diabetes Care. 2001 Aug;24(8):1448-53. 45. Sumner CJ, Sheth S, Griffin JW, Cornblath DR, Polydefkis M. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology. 2003 Jan 14;60(1):108-11. 46. Tavee J, Zhou L. Small fiber neuropathy: A burning problem. Cleve Clin J Med. 2009 May;76(5):297-305. 47. Barone BB, Yeh HC, Snyder CF, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA. 2008 Dec 17;300(23):2754-64. 48. Seshasai SR, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011 Mar 3;364(9):829-41. 49. Hemminki K, Li X, Sundquist J, Sundquist K. Risk of cancer following hospitalization for type 2 diabetes. Oncologist. 2010;15(6):548-55. 50. Stattin P, Björ O, Ferrari P, et al. Prospective study of hyperglycemia and cancer risk. Diabetes Care. 2007 Mar;30(3):561-7. 51. Parvez A, Ihsanullah, Rafiq A, Ahmad N, Khan EH. Relationship of glycaemia and triglycerides with BMI in diabetic patients. J Ayub Med Coll Abbottabad. 2010 Apr-Jun;22(2):164-6. 52. 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. 53. 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. 54. Gleason CE, Gonzalez M, Harmon JS, Robertson RP. Determinants of glucose toxicity and its reversibility in pancreatic islet Beta-cell line, HIT-T15. Am J Physiol Endocrinol Metab. 2000;279: E997-E1002. 55. Yokoi T, Fukuo K, Yasuda O, et al. Apoptosis signal-regulating kinase 1 mediates cellular senescence induced by high glucose in endothelial cells. Diabetes. 2006 Jun;55(6):1660-5. 56. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003 Jan;52(1):102-10. 57. Biarnes M, Montolio M, Nacher V, Raurell M, Soler J, Montanya E. ß-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia. Diabetes. 2002 Jan;51(1):66-72. 58. Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, De Fronzo RA. Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study. Diabetologia. 2004 Jan;47(1):31-9. 59. Butler AE, Janson J, Bonner-Weir S, et al. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003 Jan;52(1):102-10. 60. Pehuet-Figoni M, Ballot E, Bach JF, Chatenoud L. Aberrant function and long-term survival of mouse beta cells exposed in vitro to high glucose concentrations. Cell Transplant. 1994 Sep-Oct;3(5):445-51. 61. Zhou YP, Marlen K, Palma JF, et al. Overexpression of repressive cAMP response element modulators in high glucose and fatty acid-treated rat islets. A common mechanism for glucose toxicity and lipotoxicity? J Biol Chem. 2003 Dec 19;278(51):51316-23. 62. Mosca M, Boniglia C, Carratu B, Giammarioli S, Nera V, Sanzini E. Determination of alpha-amylase inhibitor activity of phaseolamin from kidney bean (Phaseolus vulgaris) in dietary supplements by HPAEC-PAD. Anal Chim Acta. 2008 Jun 9;617(1-2):192-5. 63. 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. 64. 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. 65. 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. 66. 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. 67. InnoVactiv, Inc. Data on file. 68. Benalla W, Bellahcen S, Bnouham M. Antidiabetic medicinal plants as a source of alpha glucosidase inhibitors. Curr Diabetes Rev. 2010 Jul;6(4):247-54. 69. 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. 70. McCarty MF. Glucomannan minimizes the postprandial insulin surge: a potential adjuvant for hepatothermic therapy. Med Hypotheses. 2002 Jun;58(6):487-90. 71. 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. 72. 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. 73. 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. 74. 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. 75. 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. 76. 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. 77. 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. 78. 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. 79. Malin SK, Gerber R, Chipkin SR, Braun B. Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care. 2011 Oct 31. 80. 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. 81. 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. 82. Nagendran MV. Effect of Green Coffee Bean Extract (GCE), High in Chlorogenic Acids, on Glucose Metabolism. Poster presentation number: 45-LB-P. Obesity 2011, the 29th Annual Scientific Meeting of the Obesity Society. Orlando, Florida. October 1-5, 2011. 83. Henry-Vitrac C, Ibarra A, Roller M, Mérillon JM, Vitrac X.Contribution of chlorogenic acids to the inhibition of human hepatic glucose-6-phosphatase activity in vitro by Svetol, a standardized decaffeinated green coffee extract. J Agric Food Chem. 2010 Apr 14;58(7):4141-4. 84. Ramnanan CJ, Edgerton DS, Kraft G, Cherrington AD. Physiologic action of glucagon on liver glucose metabolism. Diabetes Obes Metab. 2011 Oct;13 Suppl 1:118-25. 85. Petersen KF, Laurent D, Rothman DL, Cline GW, Shulman GI. Mechanism by which glucose and insulin inhibit net hepatic glycogenolysis in humans. J Clin Invest. 1998 Mar 15;101(6):1203-9. 86. Available at: http://www.medscape.org/viewarticle/491410_3. Accessed November 4, 2011. 87. Basu R, Chandramouli V, Dicke B, Landau B, Rizza R. Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis as well as gluconeogenesis. Diabetes. 2005 Jul;54(7):1942-8. 88. Zhang Y, Lee ET, Cowan LD, Fabsitz RR, Howard BV. Coffee consumption and the incidence of type 2 diabetes in men and women with normal glucose tolerance: The Strong Heart Study. Nutr Metab Cardiovasc Dis. 2011 Jun;21(6):418-23. 89. Hemmerle H, Burger HJ, Below P, et al. Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of hepatic glucose-6-phosphate translocase. J Med Chem. 1997 Jan 17;40(2):137-45. 90. Arion WJ, Canfield WK, Ramos FC, et al. Chlorogenic acid and hydroxynitrobenzaldehyde: new inhibitors of hepatic glucose 6-phosphatase. Arch Biochem Biophys. 1997 Mar 15;339(2):315-22. 91. Yukawa GS, Mune M, Otani H, et al. Effects of coffee consumption on oxidative susceptibility of low-density lipoproteins and serum lipid levels in humans. Biochemistry (Mosc). 2004 Jan;69(1):70-4. 92. Jiang Y, Kusama K, Satoh K, Takayama E, Watanabe S, Sakagami H. Induction of cytotoxicity by chlorogenic acid in human oral tumor cell lines. Phytomedicine. 2000 Dec;7(6):483-91. 93. Rodriguez de Sotillo DV, Hadley M. Chlorogenic acid modifies plasma and liver of: cholesterol, triacylglycerol, and minerals in (fa/fa) Zucker rats. J Nutr Biochem. 2002 Dec;13(12):717-26. 94. Thom E. The effect of chlorogenic acid enriched coffee on glucose absorption in healthy volunteers and its effect on body mass when used long-term in overweight and obese people. J Int Med Res. 2007 Nov-Dec;35(6):900-8. 95. Johnston KL, Clifford MN, Morgan LM. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine. Am J Clin Nutr. 2003 Oct;78(4):728-33. 96. Chowanadisai W, Bauerly KA, Tchaparian E, Wong A, Cortopassi GA, Rucker RB. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alphaexpression. J Biol Chem. 2010 Jan 1;285(1):142-52. 97. Gallagher EJ, Leroith D, Karnieli E. Insulin resistance in obesity as the underlying cause for the metabolic syndrome. Mt Sinai J Med. 2010 Sep-Oct;77(5):511-23. 98. Ren J, Pulakat L, Whaley-Connell A, Sowers JR. Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease. J Mol Med (Berl). 2010 Oct;88(10):993-1001. 99. Ceriello A, Falleti E, Bortolotti N, et al: Increased circulating intercellular adhesion molecule-1 levels in type II diabetic patients: the possible role of metabolic control and oxidative stress. Metabolism. 1996 Apr;45(4):498-501. 100. Folli F, Corradi D, Fanti P, et al. The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro- and macrovascular complications:avenues for a mechanistic-based therapeutic approach. Curr Diabetes Rev. 2011 Aug 15. 101. Ceriello A, Quatraro A, Marchi E, et al. Impaired fibrinolytic response to increased thrombin activation in type 1 diabetes mellitus: effects of the glycosaminoglycan sulodexide. Diabetes Metab. 1993 Mar-Apr;19(2):225-9. 102. Bucala R, Cerami A, Vlassara H. Advanced glycosylation end products in diabetic complications. biochemical basis and prospects for therapeutic intervention. Diabetes Rev. 1995;3:258-68. 103. Soran H, Durrington PN. Susceptibility of LDL and its subfractions to glycation. Curr Opin Lipidol. 2011 Aug;22(4):254-61. 104. Barlovic DP, Soro-Paavonen A, Jandeleit-Dahm KA. RAGE biology, atherosclerosis and diabetes. Clin Sci (Lond). 2011 Jul;121(2):43-55. 105. Available at: http://www.idf.org/webdata/docs/Guideline_PMG_final.pdf. Accessed October 28, 2011. |
Wellness
Specialists
1-800-226-2370 - This service is FREE
7:30 AM - 12 AM (ET) Mon-Fri | 9 AM - 12 AM (ET) Sat-Sun
