DiaVis®

Complementary Nutritional Support

Part I of the Diabetes and Nutrition series (see December 2008 issue) discussed the importance of diet and calories in helping to prevent type 2 diabetes, as well as the benefits of eating a low glycemic diet for better blood sugar control. Part II covered essential vitamins and minerals that can be compromised in diabetics - or those at risk for the disease - due to poor intake, faster excretion, or greater need (see January 2009 issue). The series concludes with a look at three complementary nutrients: alpha lipoic acid, quercetin and polyphenols. Evidence suggests this trio can play an important role in a diabetic's nutritional support team.

Protective Properties of Alpha Lipoic Acid

As mentioned in Part II, people with diabetes have higher levels of oxidative stress which can contribute to long-term complications. Antioxidants help counter oxidative stress, and alpha lipoic acid is a unique antioxidant. Made in the body and found in foods such as spinach, broccoli and potatoes, alpha lipoic acid can scavenge free radicals, and also appears to bolster levels of the antioxidant enzyme glutathione (1).

Because alpha lipoic appears to be particularly helpful in protecting nerve cells, it is being studied in neurodegenerative disorders such as Alzheimer's and Parkinson's disease. A number of trials (2) have also reported that high dose alpha lipoic eases symptoms such as pain and numbness in patients with diabetic neuropathy, a complication of diabetes.

Research in models of diabetic retinopathy suggests that this antioxidant could have a role in protecting the eye's retina as well. In one study (3), giving alpha lipoic early to diabetic mice reduced markers of oxidative stress, shored up glutathione levels and helped normalize electrical signals in the retina.

Multi-Faceted Quercetin

Quercetin is a flavonoid (part of the polyphenol family of compounds) and is present in a variety of fruits and vegetables such as onions, apples, citrus fruit, grapes and broccoli. Consuming plenty of flavonoids, especially quercetin, has been associated with lower incidence of heart disease and stroke. Quercetin's apparent ability to counter oxidative stress makes it an attractive candidate for the diabetic's nutrition arsenal.

In one clinical trial (4), diabetics had less oxidative damage to DNA within white blood cells when eating a high vs. a low quercetin diet. If results from laboratory studies are shown to hold true in people, quercetin may have a role in visual health as well. Quercetin has been shown to protect lab-grown human retinal pigment epithelial and cortical cells during oxidative stress (5).

Procyanidins Support Healthy Vessels, Vision

Procyanidins, plentiful in grapes and cocoa, have both antioxidant and anti-inflammatory actions. Importantly for diabetics, procyanidins extracted from pine (Pycnogenol®) may also help keep blood vessel walls strong and enhance compounds that help arteries dilate. This source of procyanidins has been tested in more than 1200 people with retinopathy and diabetic retinopathy in various trials, with reported results generally supporting benefit (6).

In a recent double-blind study (7) of diabetics with hypertension taking ACE inhibitor medication, 58% were able to achieve better blood pressure control at lower doses of medication after 3 months of Pycnogenol supplementation. Significant effects on other cardiovascular disease risk factors were also seen in the pine procyanidin group vs. placebo.

References

1. Peterson, et al. Critical Review: Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity. Life 60: 362-67, 2008.
   
2. Singh U, et al. Alpha-lipoic acid supplementation and diabetes. Nutr Rev 66:646-57, 2008.
   
3. Johnsen-Soriano S, et al. Early lipoic acid intake protects retina of diabetic mice. Free Rad Res 4:613-17, 2008.
   
4. Lean MEJ, et al. Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 48:176-181, 1999.
   
5. Hanneken A, et al. Flavonoids protect human retinal pigment epithelial cells from oxidative stress-induced death. Invest Ophthalmol Vis Sci 47:3164-77, 2006.
   
6. Schönlau F, et al. Pycnogenol for diabetic retinopathy: A review. Inter Ophthalmol 24:161-71, 2002.
   
7. Zibadi S, et al. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. Nutr Res 28:315-20, 2008.
   

Some Nutrients Can Be a Problem in Diabetes

Twenty-four million Americans - nearly 25% of those 60 and older - currently suffer from diabetes according to the Centers for Disease Control. Fifty seven million more have pre-diabetes which often leads to the full-blown disease. Meeting vitamin and mineral needs is important for everyone, but for those with diabetes - or those at risk for this condition - getting enough of certain nutrients can be a problem. Some nutrients may be compromised in diabetics due to poor intake, faster excretion, or greater need.

Vitamin D and B-Vitamin Shortfalls

Vitamin D is important for healthy bones and for its anti-inflammatory activity, and low levels are common in adults with type 2 diabetes. Up to 75% of young people with type 1 may also be deficient in vitamin D according to new evidence (1). A recent review of studies suggests that for lowering the risk of type 2 in women, 800 IU of this vitamin is more effective than 400 IU (2).

People with type 1 & 2 diabetes excrete more thiamin (vitamin B1,) and have low blood levels compared to those free of the disease. Researchers report that blood concentrations of thiamine were decreased by about 75% in type 1 & 2 diabetics vs. healthy controls (3). Thiamin plays a role in the body's metabolism of glucose, and low levels have been found to increase the risk of kidney, nerve and eye complications in animals.

Low B6 has been observed in those with type 1 and 2, and B6 levels generally decline with age. Older people are also at risk for sub-optimal levels of B12, a vitamin critical to proper nerve function. Diabetics have a greater risk for cataract, and riboflavin (B2) and thiamine have been linked to decreased risk. In an AREDS analysis, long-term multi use lowered cataract risk by 16-25%. Many of the participants in this trial were diabetic.

Antioxidants Help Combat Oxidative Stress

Diabetics have higher levels of oxidative stress - an imbalance between the production of damaging oxygen compounds and the body's ability to neutralize them. Oxidative stress contributes to long-term complications in diabetes such as vision (retinopathy), kidney (nephropathy), nerve (neuropathy) and heart disease.

Antioxidants such as vitamins C and E help counter oxidative stress. Vitamin C appears to be particularly important. Higher blood levels of this vitamin, for example, were linked to a 62% lower risk of developing diabetes in 21,000 people followed for 12 years (4). Additionally, in a large-scale government survey, long-term use of supplemental C, E and/or a multinutrient, lowered the risk of developing retinopathy (5).

Meaningful Minerals Can Be Missing

Magnesium, which is involved in maintaining artery health and sensitivity to insulin, is often low in diabetics with poor blood sugar control. If you are at risk for diabetes, note that research strongly suggests that better dietary magnesium intake lowers the risk of developing hypertension, metabolic syndrome and diabetes itself (6).

Zinc and chromium are minerals important for proper insulin function, and both have antioxidant activity. Urinary loss of zinc can be higher in type 1 and 2 diabetics (7). Evidence, too, suggests that chromium supports healthier blood glucose levels in people who are low in this trace mineral and have impaired glucose tolerance (8).

References

1. Svoren BM, et al. Significant vitamin D deficiency in youth with type 1 diabetes. J of Pediatrics 154:132-34 2009.
   
2. Pittas AG, et al. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 92:2017-29, 2007
   
3. hornally PF, et al. High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia 50:2164-70, 2007
   
4. Harding AH, et al. Plasma vitamin C level, fruit and vegetable consumption and the risk of new-onset type 2 diabetes mellitus-The European Prospective Investigation of Cancer-Norfolk Prospective Study. Arch Int Med 168:1493-99, 2008.
   
5. Millen AE, et al. Relations of serum ascorbic acid and alpha-tocopherol to diabetic retinopathy in the 3rd National Health and Nutrition Exam Survey. Am J Epidemiol 158:225-33, 2003.
   
6. Larsson A, et al. Magnesium intake and risk of type-2 diabetes: a meta-analysis J Int Med [ePub] 2007
   
7. Ross CA. In Modern Nutrition in Health and Disease. Shils ME et al Eds; Lippincott Williams & Wilkins Pub, 10th Ed, 2006.
   
8. Balk EM, et al. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care 30:2154-63, 2007.
   

Weight is Key to Fending off Type 2 Diabetes

A trio of studies published late last year in the journal Archives of Internal Medicine shed new light on the importance of diet in risk of developing type 2 diabetes - especially the role of calories. The bottom line from all three studies is that calories trump all else, and that our main goal in preventing type 2 should be to eat less high-calorie, low-benefit foods.

Fruit Drinks are Culprits; Fruits & Veggies Help

In the first study (1), which followed nearly 44,000 Afro-American women for 10 years, the risk of developing type 2 was 24% higher for those who consumed two or more soft drinks daily compared with women who drank them rarely. Sipping fruit drinks was even riskier, with a 31% increased risk for those drinking them twice daily.

Diet soft drinks as well as grapefruit and orange juice did not up the risk for diabetes. Unlike other fruit drinks, these juices contain mostly naturally occurring sugars which may have different metabolic effects than the high-fructose corn syrup used to sweeten other juice drinks.

In the second study(2), blood levels of vitamin C (an indicator of fruit and vegetable intake) and fruit and veggie consumption were measured in about 22,000 people without diabetes. After a dozen years, those with the highest vitamin C levels were 62% less likely to develop the disease. A similar but smaller risk reduction of 22% was observed for those eating even modest amounts of fruits and veggies.

In the last study(3), 60% of the nearly 49,000 women participants continued with their regular diet while 40% were assigned to a low fat diet with added fruits, veggies and grains. Although the diet was not designed for weight loss, those in the low-fat diet group lost about 5 pounds more over an 8 year period compared to the "usual diet" group. The researchers concluded that losing weight - rather than eating less fat - was more important in preventing type 2.

For Diabetics, Recommended Diet May Need Changing

or so suggests a new study(4) that is one of the longest and largest to assess the impact of foods with a low glycemic index (GI). Low GI foods don't raise blood sugar as much as foods with a higher GI.

People with type 2 were assigned to one of two diets. The first emphasized "brown foods" such as whole grain bread and breakfast cereal, brown rice and potatoes with the skin on. This high fiber, high cereal diet is what is usually recommended for those with diabetes.

The other diet focused on low GI foods which included beans, peas, lentils, pasta, quickly boiled rice and certain breads like pumpernickel and rye, as well as oatmeal and oat bran cereals.

Both diets were low in saturated and trans fats. Both groups were told to limit their consumption of white flour and to eat five servings of vegetables and three servings of fruit daily.

At the end of six months, people on the low GI diet kept their blood sugar under better control and had slight reductions in HA1C levels - a measure of blood sugar levels over time. They also experienced significant increases in "good" HDL cholesterol, which is good for heart health. That's important because diabetic men have twice the risk for heart disease and women four times the risk. Also, drugs used to control type 2 have not shown the expected benefits in terms of reducing heart disease.

The bottom line is that high fiber foods are fine, but include beans and nuts and try to eat more low GI foods

References

1. Palmer JR, et al. Sugar-Sweetened Beverages and Incidence of Type 2 Diabetes Mellitus in African American Women. Arch Int Med 168:1487-92, 2008.
   
2. Harding A-H, et al. Plasma Vitamin C Level, Fruit and Vegetable Consumption, and the Risk of New-Onset Type 2 Diabetes Mellitus: The European Prospective Investigation of Cancer-Norfolk Prospective Study. Arch Int Med 168:1493-99, 2008.
   
3. Tinker LF, et al. Low-Fat Dietary Pattern and Risk of Treated Diabetes Mellitus in Postmenopausal Women: The Women's Health Initiative Randomized Controlled Dietary Modification Trial. Arch Int Med 168:1500-11, 2008.
   
4. Jenkins DJ, et al. Effect of a low-glycemic index or a high-cereal fiber diet on type 2 diabetes: a randomized trial. JAMA 300:2742-53, 2008.
   

Physical Activity isn't Optional - it's a Must!

Physical activity simply means movement of the body that uses energy. Walking, gardening, briskly pushing a baby stroller, climbing the stairs, playing soccer or dancing are all good examples of being active.

Being physically active is a KEY element in living a longer, healthier, happier life. It can help relieve stress, provide an overall feeling of well-being, and reduce our risk of many chronic diseases such as heart disease and diabetes. It can also play a major role in weight control, and may even support better memory in older people.

Get Moving to Prevent & Treat Diabetes

Type 2 diabetes is one of the fastest growing public health problems worldwide. The relationship between staying physically active and the risk of developing diabetes has been assessed by a number of clinical trials. The results from these studies consistently tell us that regular physical activity reduces the risk of type 2 Diabetes by 15-60% (1).

If you already have diabetes, exercise and better health go hand in hand. Regular physical activity can help improve blood sugar control, as well as boost overall fitness and reduce the risk of heart disease and nerve damage. Exercise counteracts those risks by improving blood flow, increasing the heart's pumping power and decreasing cholesterol levels.

Physical Activity Fends Off 'Fat Gene' Effects

Becoming overweight often involves many factors from poor diet to "stress eating", couch potato behavior and genetics. While experts say there are probably many genetic differences that can influence obesity, one gene variation that has been linked to excess weight can be overcome by 3-4 hours of moderate physical activity daily according to a study conducted among the Amish people.

Scientists believe that about 30% of Caucasians with European ancestry have a variation in the FTO gene linked to obesity, including the Amish. That genetic variation can make people more susceptible to gaining weight, possibly by regulating food intake.

In the study, which involved over 700 Amish, re-searchers determined which people had the variation of the FTO gene linked to obesity (2). Among people with the variant, those who got about 3-4 hours of moderate physical activity a day weighed about 15 lbs. less on average than the least active people who had the variant. That included such activities as brisk walking, housecleaning and gardening.

People with the genetic variant were no more likely to be overweight than those who had a regular version of the gene, so long as they kept active. "It's only when you're not active that the gene hurts", according to the researchers. Physical activity - and lots of it - is a way to overcome the effects of this genetic inheritance.

People with the genetic variant were no more likely to be overweight than those who had a regular version of the gene, so long as they kept active. "It's only when you're not active that the gene hurts", according to the researchers. Physical activity - and lots of it - is a way to overcome the effects of this genetic inheritance.

Physically Active People Retain Brain Power

A newly reported trial is the first to demonstrate that exercise can improve the ability to think, reason and remember in older people with mild cognitive impairment who were at risk for Alzheimer's (3).

In the study, subjects participated in a 6-month home-based program of physical activity. Some participants received instruction about physical activity, while others did not. For those that engaged in more physical activity, the cognitive benefits were not only apparent at the end of 6 months, but also lasted for an additional 12 months. The best part of all, is the program entailed an increase in physical activity of just 20 minutes per day.

References

1. QI L, et al. Genes, environment, and interactions in prevention of type 2 diabetes: a focus on physical activity and lifestyle changes. Curr Mol Med 8:519-32, 2008.
2. Rampersaud E, et al. Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Inter Med 168:1791-7, 2008.
3. Lautenschlager NT, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA 300:1027-37, 2008.

Science is Strong for the Med Style of Eating

A flood of studies over the past year have increased support for the Mediterranean (Med) style of eating. Some of the most recent findings include:

• A study published in the British Medical Journal reported that a Med style diet can lower the risk of developing diabetes by 83% in those with high adherence to the diet, and by 40% with moderate adherence;
  
• A study of nearly 400,000 people, published in the Archives of Internal Medicine, found that sticking to the Med diet reduced the risk of death from cardiovascular disease and cancer by 22% and 17% in men, 12% in women;
  
• Research reported in the medical journal of the American Academy of Neurology, found that adhering to the Med diet could extend the life of people suffering from Alzheimer's;
  
• A Med-style eating plan was shown to cut the risk of dying from cardiovascular disease by 30% in a study published in the American Journal of Clinical Nutrition.
  

In Head-to-Head Test, Med Diet Promotes Weight Loss and is Best for Diabetics

Results from a 2-year trial comparing weight loss with a low-carb, Med-style or low-fat diet, made the news last month. In this tightly controlled experiment, 322 overweight people were assigned to 1 of 3 types of diet: a low-fat diet based on American Heart Association guidelines, a low-carb diet based on the Atkins plan, and a Med style diet.

The biggest weight loss happened in the first 5 months, with people in all 3 groups regaining some of the lost weight as time went on. At the end of 2 years, the low-fat dieters lost about 6 pounds while the Med and low-carb groups both lost about 10 pounds.

While the weight loss was modest, it resulted in improved health markers, and there were subtle differences in the 3 diets studied. Men seemed to do better on the low-carb diet, losing 11 pounds versus about 9 on the Med diet. Women fared best on the Med diet, losing about 14 pounds compared with about 5 pounds on the low-carb eating plan. For all dieters, the ratio of good to bad cholesterol improved. But among the 36 diabetic participants, the Med diet had the most favorable effect on glycemic control. Diabetics had better blood glucose and insulin levels.

What is the Med Style Diet?

The med diet is rich in cereals, wine, fruits, vegetables, nuts, beans, whole grains, fish and olive oil - foods which provide carotenoids, vitamins A, C and E, polyphenols, essential minerals, and the omega-3 fats.

Common foods include pasta, bread (whole grain is best), rice and couscous, olives, avocados, grapes, eggplant, tomatoes, peppers, nuts and beans, cheese and yogurt. Moderate consumption of fish and poultry is encouraged, while red meat is advised only a few times per month.

If you're not yet following the Med style of eating, the Mediterranean Pyramid, endorsed by the Harvard School of Public Health and the World Health Organization, can serve as a model to help you get started.

Reference

1. Shai I, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. New England Journal of Medicine 359:229-41, 2008.

Insulin Resistance Basics

Insulin is a hormone released from the pancreas that helps the body use glucose or sugar in the blood. Insulin binds to receptors on cells like a key would fit into a lock. Once unlocked, glucose can enter cells to be used as energy or stored for future use. Insulin resistance occurs when the normal amount of insulin secreted is unable to unlock the doors of muscle, fat and liver cells. In order to maintain healthy levels of blood glucose, the pancreas must compensate by making and releasing additional insulin.

Insulin Resistance Leads to Bigger Problems

Eventually the pancreas isn't able to keep up with the demand for more insulin and excess glucose builds up in the bloodstream setting the stage for pre-diabetes. Studies have shown that most people with pre-diabetes go on to develop type 2 diabetes within 10 years if they don't make lifestyle changes.

Insulin resistance and pre-diabetes also raises the risk of heart disease. Many people with insulin resistance have excess weight around the waist (40" for men, 35" for women), low levels of the good HDL cholesterol (below 40 mg/dL for men, 50 mg/dL for women), high triglycerides (150 mg/dL or more), high blood pressure (130/85 mm), and small dense LDL particles (the "bad" cholesterol). This cluster of problems is referred to as the metabolic syndrome or insulin resistance syndrome.

The Insulin and Memory Connection

At the recent 3rd Annual World Congress on Insulin Resistance Syndrome in San Francisco, Dr. Suzanne Craft presented cutting edge research findings on how insulin affects the brain. According to Dr. Craft, how an older person's body processes insulin can also affect their memory.

Normally, the insulin secreted after eating can enhance memory. Researchers theorize that this action of insulin evolved to help primitive people remember where to find food. But while optimal insulin levels may help us remember the location of our favorite restaurant in today's world, too much of a good thing may contribute to brain aging and memory impairment later in life.

The chronically high insulin that occurs when the body is resistant to insulin can decrease glucose metabolism in certain brain circuits and provoke inflammation along with free radical damage. Finally, insulin that is too high may also raise the risk of Alzheimer's by promoting the release of beta-amyloid and slowing its breakdown. Beta-amyloid is the major protein found in the plaque and nerve tangles of Alzheimer's patients.

In a series of studies, Dr. Craft and her colleagues found that an anti-diabetic drug which makes the body more sensitive to insulin can improve mental function and memory recall in older patients with insulin resistance, including those diagnosed with early Alzheimer's. Treatments that can reduce high levels of circulating insulin and improve insulin sensitivity are promising therapeutic avenues for some older people with impaired memory, Dr. Craft concluded.

Can You Reverse Insulin Resistance?

Yes! According to Dr. Gerald Reaven who chaired the World Congress meeting, about 50% of insulin resistance and the metabolic syndrome can be attributed to underlying genetic susceptibility, while inactivity and being overweight contribute about 25% each. Physical activity and weight loss make the body more responsive to insulin. Exercise makes muscle cells more sensitive to insulin because they need it for energy. And reducing extra fat tissue around the middle is especially helpful because the fat distributed there is more metabolically active.

Be Active and Eat Well

Results from the 2001 Diabetes Prevention Program, an NIH-sponsored clinical trial, confirmed that losing weight - even just 5-7% of your body weight - and walking briskly or riding a bike 5 times weekly, can reduce the risk of diabetes by 58% in those with pre-diabetes. An estimated 39% of Americans have some degree of insulin resistance, and it usually has no overt symptoms. So as we set our health goals for 2006, remember that fighting fatness and improving fitness isn't optional. It is absolutely essential.

Type-2 diabetes has tripled in the last 30 years. We've also experienced a dramatic upsurge in obesity. Experts now use the term "diabesity" to make more people aware of the connection between these trends: Excess weight makes you more prone to type 2, and 80% of those who get the disease are overweight when they're diagnosed. Right now, more than 20 million Americans have blood sugar levels that are higher than normal but not yet in the diabetic range. Called "pre-diabetes" this condition can turn into the full-blown disease, especially in those who are overweight and under-active.

Your Best Defense is Offense

According to one encouraging study, making realistic changes to your diet and activity level can greatly reduce your chances of getting type 2 diabetes (1). The study looked at over 3200 people who were more likely to develop type 2 because their fasting blood sugar levels were too high. After being encouraged to eat a low fat diet and increase their physical activity, everyone was assigned to get specific diet and exercise advice, or the drug metformin (Glucophage) to lower blood sugar. Another group took a placebo.

The incidence of diabetes went down by 58% in people making lifestyle changes compared to those taking placebo. For those who got the drug, diabetes decreased by 31%. What's remarkable about these findings is not just that the lifestyle changes were better than the drug for preventing diabetes, but that the goals were modest enough to be reached by most people. The targets were to maintain a weight loss of at least 7% of initial body weight - that's only 10 lb for a 150 lb woman for example - and to do moderate physical activity for at least 2 hours weekly.

In a follow-up, the researchers looked at how the lifestyle and drug interventions affected study volunteers who had metabolic syndrome (MS) in addition to high blood sugar (2). The syndrome is defined as having 3 or more these characteristics: thick waist, high triglycerides, low HDL, high blood pressure or high fasting blood sugar. People with MS have a 5-fold greater risk for diabetes and are 3 times more likely to die of heart attack or stroke. Once again, the lifestyle changes were more effective than the drug in preventing people who didn't have MS from developing it. For those who already had MS, the lifestyle changes were better than the drug in helping the syndrome resolve.

Take Charge of Your Diet

Eating more fiber can help substantially. Fiber from beans, peas, oats, fruits and vegetables slow down digestion to help you feel fuller longer. They also slow the entry of glucose into the bloodstream, helping to dampen insulin output. Eating more of this fiber helps keep blood levels of LDL cholesterol in check as well. You'll also want heart-healthy fiber from whole grains, such as wheat cereals, bran and brown rice. Focus on getting at least 2-3 servings of fish weekly. High intake of omega-3s from fish correlates with a lower incidence of type 2, and supplemental amounts in the range of 2-4 grams daily have been shown to bring down elevated triglycerides (3). Even more importantly, omega-3s reduce the risk of death from coronary heart disease in diabetic women (4). Finally, it's wise to take a complete multi to ensure that you get enough of the many vitamins and minerals involved in insulin and glucose metabolism such as chromium, zinc, magnesium and various antioxidants.

Even if you already have type 2, trimming down and getting active can improve long-term blood sugar control. And that helps reduce the extra risks that come along with diabetes such as heart and kidney disease, nerve and vision problems, and even a greater chance of developing dry eye (5). So let's all resolve to have our blood glucose checked, tune up our diets and get moving. The rewards are well worth the effort!

References

1. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New Engl J Med 346:393-403, 2002.
2. Orchard TJ et al. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: The Diabetes Prevention Program Randomized Trial. Annals Intern Med 142:611-19, 2005.
3. Krauss RM. AHA Dietary Guidelines. Revision 2000: A statement for healthcare professionals from the nutrition committee of the American Heart Association. AHA Reprint 71-0193.
4. Hu FB et al. Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Circulation 107:1852-7, 2003.
5. Kaiserman I et al. Dry eye in diabetic patients. Am J Ophthalmol 139:498-503, 2005.

Diabetes Prevalence is Increasing

Twenty four million Americans - or 8% of the population and nearly 25% of those 60 and older - currently suffer from diabetes according to 2007 prevalence data from the Centers for Disease Control (CDC). The 2007 figure is 3 million higher than 2005 prevalence data. The CDC reported that an additional 57 million had pre-diabetes, a condition that most often precedes a diagnosis of diabetes.

Diabetes can lead to damage of several different tissues, particularly those that are insulin insensitive such as the retina, kidney and nerves. Type 2 diabetes is most common, accounting for 90-95% of all diabetic patients. Both forms cause long-term complications such as neuropathy, nephropathy, cataract and retinopathy. Up to 21% of patients with type 2 diabetes have some signs of retinopathy at time of first diagnosis, and most will develop some degree of retinopathy over time.

The potential role of Pycnogenol (pine bark extract) in the treatment of type 2 diabetes is discussed in a 2008 systematic review (1) from the Ophthalmic Research Group at Aston University in Birmingham England.

Mechanism of Action of Pine Bark Extract

Pycnogenol is the brand name for a standardized extract of bark of the French maritime pine (Pinus pinaster). It contains bioactive anthocyanidins as does generic standardized pine bark extract. Pine bark extract (hereafter referred to as "Pycnogenol") has been shown to protect endothelial cells against oxidant-induced injury. Pycnogenol promotes a protective antioxidant state by up-regulating important enzymatic and non-enzymatic oxidant scavenging systems. It is a potent natural antioxidant and also has an affinity for proteins such as collagen, which may be responsible for the reduction of pathologically increased capillary permeability observed.

Pycnogenol significantly decreases nitrogen monoxide generation and it is thought that this function may result from a combination of several biological activities including its radical oxygen species and nitrogen monoxide scavenging activity, inhibition of the enzyme nitric oxide syntase (iNOS), and inhibition of iNOS-mRNA expression. Pycnogenol can readily cross the blood-brain barrier to provide antioxidant protection to central nervous system tissue. It is also reported to possess anti-inflammatory action.

Highlighted Clinical Studies

Supplementation of conventional diabetes treatment with 100 mg day) Pycnogenol for 12 weeks has been shown to lower glucose levels, and improve endothelial function (Liu et al., 2004). Glycosylated hemoglobin levels were significantly reduced after 1 month of supplementation. Plasma concentrations of the prostacyclin metabolite, 6-ketoprostaglandin F1, were elevated in both treatment groups, and considerably more pronounced in the Pycnogenol group (p < 0.001).

Pycnogenol is licensed in France for the treatment of diabetic retinopathy. In one investigation, a 6-month double-masked trial of Pycnogenol versus Dexium 500 (calcium dobesilate) was carried out with type 1 and 2 diabetic participants. The pharmacology of Dexium is similar to that of Pycnogenol except that it does not have such a high binding affinity for collagen. Pycnogenol was found to reduce exudates in the eyes of significantly more participants than Dexium. The authors concluded that Pycnogenol might also be beneficial for improvement of visual field loss (Leydhecker, 1986).

Another double-masked, placebo-controlled trial investigated the effect of 150 mg day of Pycnogenol on objective parameters in patients with retinopathies associated with diabetes, atherosclerosis and hypertension (Spadea, 2001). Examination of the ocular fundus showed a significant improvement in those treated with Pycnogenol, as well as improvements in electrophysiology and fluoroangiography measures. The group taking Pycnogenol also experienced a significant reduction in vascular permeability and an improvement in the blood-retinal barrier.

Finally, in a very recent double-blind study (2) of hypertensive type 2 diabetics taking ACE inhibitors, 125 mg of Pycnogenol for 12 weeks was reported to decrease use of ACE inhibitors by 50%. Fifty eight percent achieved blood pressure control, and LDL levels and fasting blood glucose levels were improved vs. placebo.

References

1. Bartlett HE and Eperjesi F. Nutritional supplementation for type 2 diabetes: a systematic review. Ophthal Physiol Opt 28: 503-523, 2008.
2. Zibadi S, et al. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. Nutr Res 28:315-20, 2008.

Pycnogenol® is a registered trademark of Horphag Research Ltd. Use of this product is protected by one ore more of U.S. patents #5,720,956 / #6,372,266 and other international patents.

There's a growing interest in nutrigenomics - the study of how different foods may interact with specific genes to modify the risk of chronic diseases. The underlying premise is that the influence of diet on health is related to individuals' genetic or phenotypic make-up. The aim is to identify the bioactive molecules in the diet that affect health by altering gene expression. As with any emerging field, there are knowledge gaps to close and questions about whether testing and targeted nutrition therapy will be cost effective public health strategies. However knowledge is increasing.

For example, researchers are identifying genotypes that appear to put meat consumers more at risk for colorectal cancer (1), and finding genetic variations that may increase susceptibility to osteoporosis and require early intervention with calcium and other nutrients (2). We've also learned that a common polymorphism of one gene is linked to elevated homocysteine levels and increased risk of heart disease when folic acid intake is low (3,4).

Predicting Who Can Benefit from Vitamin E

Researchers from Israel's Institute of Technology are pursuing another line of inquiry. It's known that people vary in their phenotype of haptoglobin (Hp), a blood protein that attaches to free hemoglobin and is used clinically to assess the rate of red blood cells destruction. Hp is also an antioxidant protein that prevents hemoglobin-induced tissue oxidation. The Hp gene locus is polymorphic, and people can inherit one of 3 different haptoglobin types referred to as Hp 1:1, Hp 2:1 and Hp 2:2. These inherited variations appear to influence response to antioxidant therapy.

The Israeli team tested this hypothesis in the Women's Angiographic Vitamin and Estrogen Trial (WAVE), a prospective study that evaluated the effects of vitamins C and E with or without hormone replacement therapy in treating atherosclerosis in post-menopausal women - a study that failed to find any benefit in taking antioxidants. In analyzing data from this trial, the Israeli researchers found significant benefit of the vitamins in slowing coronary artery stenoses, but only in women with a certain haptoglobin type (5).

Vitamin E May Benefit Haptoglobin 2:2 Diabetics

Hp 2:2 is a very poor antioxidant compared to other Hp types, and Hp 2:2 appears to be predictive of heart disease in diabetics who tend to generate more free radicals. About 40% of diabetics are estimated to have the Hp 2:2 form. In the newest study, the team analyzed serum samples from the Heart Outcomes Prevention Evaluation (HOPE) trial, another trial that showed no benefit for 400 IU vitamin E supplementation on cardiovascular risk in all patients. When analyzed by Hp type, those diabetics with Hp 2:2 who took vitamin E had an apparent 43% reduction in risk of heart attack.

Large Scale Trial Underway

According to the researchers at Technion, a large-scale, 5-year study of some 2000 diabetics with Hp 2:2 is being conducted. If this larger study confirms the results seen so far, vitamin E might represent a way to reduce the risk of CVD and heart attack in a significant proportion of diabetics. It may also help explain the disparity in results from antioxidant trials in recent years.

Other research teams have reported links between Hp 2:2 and refractory hypertension, risk of gestational diabetes and other disorders (7). If further research corroborates the predictive value of haptoglobin type, it may be a useful tool to identifying those who can benefit from targeted nutrition strategies.

References

• Murtaugh MA et al. The CYP1A1 genotype may alter the association of meat consumption pattersn and preparation with the risk of colorectal cancer in men and women. J Nutr 135:179-186, 2005.
• Napoli N et al. Effect of CYP1A1 Gene Polymorphisms on Estrogen Metabolism and Bone Density. J Bone Miner Res. 20(2):232-9, 2005.
• Jacques PF et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation.93:7-9, 1996.
• Klerk M et al. MTHFR 677C3T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA.288:2023-2031, 2002.
• Levy AP et al. The effect of vitamin therapy on the progression of coronary artery atherosclerosis varies by haptoglobin type in postmenopausal women. Diabetes Care 27:925-930, 2004.
• Levy AP et al. The effect of vitamin E supplementation on cardiovascular risk in diabetic individuals with different haptoglobin phenotypes. Diabetes Care 27:2767, 2004
• Sadrzadeh SM et al. Haptoglobin phenotypes in health and disorders. Review. Am J Clin Pathol.121 Suppl:S97-104, 2004.

In earlier EduFacts communiqués we have summarized reports in the literature evaluating the relationships between dietary intake levels/serum levels of dietary carotenoids and risk of age-related macular degeneration (volume 2, numbers 1, 4, 8, 9, 10, 11, and 14) and cataract (volume 2, number 13; volume 3, numbers 3 and 4). A recent evaluation of the Third National Health and Nutrition Examination Survey (NHANES III) data explored the relationship between diabetes mellitus and serum carotenoid levels (1).

The article points out that diabetes is a condition characterized by oxidative stress. This etiology is hypothesized based on demonstrated increased reactive oxygen species and, lipid peroxidation and increased free radical activity. The authors hypothesize that oxidative stress may result in a lowering of antioxidant concentrations in glucose-intolerant patients.

Methods:

Phase I of NHANES III was conducted between 1988 and 1991. This was a cross sectional survey using a sophisticated design enabling generalization of results to the non-institutionalized U.S. civilian population. Of the phase I subjects, 1665 had oral glucose tolerance tests yielding valid glucose tolerance status. Patients were classified as: 1) normal, 2) impaired glucose tolerance, and 3) newly diagnosed diabetes according to World Health Organization criteria. Five carotenoids were assayed at the CDC laboratory: alpha-carotene, beta-carotene, cryptoxanthin, lutein /zeaxanthin and lycopene. Covariate-adjusted geometric means of these carotenoids were computed for the 3 groups. The covariates included socio-demographic variables, physical activity, alcohol consumption, dietary intake (single 24-hour recall), vitamin use, serum cholesterol, HDL, BP, body mass index and activity levels.

Results:

Beta-carotene levels and lycopene levels (adjusted geometric means) decreased linearly with glucose tolerance status.

The authors concluded that the NHANES III data suggest that serum carotenoid concentrations are associated with insulin-resistance and glucose tolerance status. The ordinal status from normal to impaired to new diabetes showed a linear trend with respect to the levels of beta-carotene and lycopene.

References

• Ford ES, Will JC, Bowman BA, and Venkat Narayan KM. Diabetes Mellitus and Serum Carotenoids: Findings from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 1999;149:168-176.

See EduFacts volume 2, number 16 for a summary of another Diabetes-related nutritional study

Investigators from the Beaver Dam Eye Study presented an evaluation of the role of vitamin intake in diabetic retinopathy at the 1998 annual meeting of the Society for Epidemiologic Research in Chicago (1). Past evaluations of The Nutritional Factors in Eye Disease Study (as part of the Beaver Dam eye Study), have provided some evidence of decreased risk of lens opacities associated with increased antioxidant intake (see EduFacts Volume 2, number 7).

Methods:

In the recent report, the relationship of vitamins C and E (through diet and supplements) and the incidence and progression of diabetic retinopathy was explored. Beaver Dam Eye Study Participants with diabetes at baseline were asked to provide retrospective information on diet and supplements using a modified Block Food Frequency Questionnaire. Of 230 patients with diabetes at baseline, 166 patients provided this information and were followed for 5 years. Incidence and progression of retinopathy were determined by grading of fundus photos.

Results:

Incidence of retinopathy was 28% (47 of 166 participants). Odd's Ratios (relative risks) were computed for risk of retinopathy among those at the highest quintile level of each micronutrient vs. those at the lowest quintile level.

Multivariate analysis was performed to control for factors such as gender, insulin use, diastolic BP etc. Relative risk for highest quintile vitamin C intake level vs. lowest quintile was 0.6 - indicating a 40% decrease in risk (p=0.06 for trend). Overall citrus food intake at the highest quintile level had a relative risk of 0.2 compared with lowest quintile intake. This was an 80% reduction in risk (p=0.03). Vitamin E was not associated with lowered risk of retinopathy in this study. The authors suggested further research in this area.

ScienceBased Health's OcularProtect® provides a complete range of antioxidant vitamins and other nutrients important for maintaining ocular health

References

• Millen AE, Mares-Perlman JA, Klein R, Klein BEK, et al. Relationship of Vitamins C and E To the Incidence and Progression of Diabetic Retinopathy. Am J Epidemiol 1998;147(11)(suppl., s53, Abstract Number 212) - Presented at the 31st Annual Meeting of the Society for Epidemiologic Research, 1998, Chicago.