With crisis comes opportunity. The combination of diabetes and obesity offers many ways to utilise 21st century nutritional ingredients to improve glucose tolerance and promote weight loss. Jack Challem surveys the landscape
Coined back in 1980, the term 'diabesity' has gained considerable traction in the past several years.1 Simply, diabesity refers to the interlaced epidemics of type 2 diabetes and obesity.
Being overweight or obese sets the stage for diabetes. In fact, gaining as little as 10 pounds (4.5kg) of excess weight promotes insulin resistance, the hallmark of diabetes.2 Being obese (13kg or more over your ideal weight) boosts the risk of diabetes by 80 times.3 Diabetes and obesity significantly increase the risk of many other health problems, including inflammatory disorders, coronary artery disease, Alzheimer's and even some types of cancer.
Current trends paint a grim public health picture. In the United States, two of every three adults are overweight or obese, and an estimated 100 million have some form of prediabetes. Twenty million people have type 2 diabetes, and that number now grows by one million each year. A recent report predicted that by the year 2030, 86 per cent of Americans will be overweight or obese, and the incidence of diabetes will increase 72 per cent. In the United Kingdom, two of every three adults are also overweight or obese, and an estimated 13.6 per cent of adults have diabetes.4
The prevalence of diabesity has also increased worldwide. The World Health Organization has reported that there are 1.7 billion overweight people in the world — almost three times the number of those who are undernourished. According to a 2007 article in the New England Journal of Medicine, diabetes cases will increase by 32 per cent in Europe, 164 per cent in the Middle East, 150 per cent in India, 104 per cent in China and 148 per cent in South America. Worldwide, an estimated 246 million people have diabetes, and that number is conservatively expected to climb to 420 million in less than 20 years.5
What can be done to stem the tide — or rather, this tsunami? Although improved eating habits are essential for normalising weight and blood glucose, many supplement ingredients can enhance insulin function, improve glucose tolerance, reduce appetite and help people lose weight.
Alpha-lipoic acid: In 1970, researchers at the University of Pennsylvania discovered that this vitaminlike nutrient increases cellular uptake and burning of blood glucose.6 In the early 1990s, Germany approved alpha-lipoic acid (thioctic acid) as a prescription drug for the treatment of diabetic nerve disease. It serves as an antioxidant and enzymatic cofactor in the Krebs cycle and, in people, improves insulin function and sensitivity.7,8,9 Maintaining normal insulin sensitivity — that is, insulin function — is crucial for controlling blood glucose.
Alpha-lipoic acid might also have benefits in reducing appetite and weight, and increasing metabolism, according to an animal study. The study by South Korean researchers found that alpha-lipoic acid regulates hypothalamic AMP-activated protein kinase (AMPK), which strongly influences appetite. Supplemental alpha-lipoic acid led to decreases in food intake and weight in laboratory rats.10
Alpha-lipoic acid consists of R and S isomers, but the R form is the biologically active isomer.11 Although available as an ingredient, R-lipoic acid is more expensive than alpha-lipoic acid.
Chromium: This essential dietary mineral enables insulin to transport glucose into cells. Symptoms of chromium deficiency — including elevated blood glucose, insulin, total cholesterol and triglyceride — resemble those of diabetes.
All forms of trivalent chromium seem to enhance glucose tolerance. However, research in recent years has focused on the chromium picolinate and chromium polynicotinate (niacin bound) forms, both of which can significantly reduce blood glucose and insulin levels.12 In one study, large doses (1,000mcg) of chromium picolinate led to substantial decreases in blood sugar and insulin levels after just four months.13 In another trial, supplements of niacin-bound chromium significantly decreased fasting blood sugar, with modest reductions in triglyceride and glycated haemoglobin (HbA1c) after three months.14,15
Biotin: The B-vitamin biotin enhances the benefits of chromium. Biotin is required for the manufacture of insulin, and it regulates genes involved in the metabolism of glucose, amino acids and fatty acids.16 A recent study of 348 people found that a combination of these nutrients led to an average six per cent decrease in fasting glucose.17 Doses up to 200,000mcg (200mg) have been found safe in humans, and in one study, even doses as high as 20,000mcg (20mg) were completely absorbed.18
Pycnogenol: This proprietary antioxidant extract of French maritime pine bark can reduce fasting blood sugar by about five per cent and postprandial blood sugar by about 10 per cent.19,20 It works in part by inhibiting alpha-glucosidase, a carbohydrate-digesting enzyme. This mechanism is similar to the diabetes drug acarbose, but experiments found pycnogenol 190 times more potent than acarbose in inhibiting alpha-glucosidase.19 Pycnogenol also has cardio-protective and anti-inflammatory benefits, important in reducing the risk of diabetic complications. It blocks the activity of the inflammation-promoting COX-2 enzyme.21 In a study of 30 patients with diabetes, European researchers found that pycnogenol (50mg, three times daily) reduced microcirculatory disease, which is involved in diabetic complications.22
Vitamin K: This vitamin is required for the carboxylation of osteocalcin, one of the key proteins in bones. In 2007, researchers discovered that osteocalcin also functions as a metabolic hormone-regulating pancreatic beta-cell activity, insulin, glucose and the size of fat cells.23 Several human studies by Japanese researchers have found that vitamin K improves glucose tolerance. In 2008, researchers at Tufts University, Boston, reported that supplements of vitamin K1 (500mcg daily) led to significant improvements in fasting blood glucose and insulin after three years. The benefits, however, occurred in men and not women.24
Increasingly, attention is shifting from vitamin K1 to vitamin K2 — and specifically to the MK-4 and MK-7 forms of vitamin K2. Vitamin K2 appears better absorbed than vitamin K1. Synthetic MK-4 has a one-hour half life, meaning high pharmacological doses taken multiple times daily are required for a sustained benefit. Natural MK-7 has been shown to have a significantly longer half life, with an adequate dosage of 45mcg/day.25 Note: vitamin K supplements are contraindicated in people taking vitamin K-antagonist anticoagulants, such as warfarin, though MK-7 is said to be unlikely to have such effects at 45mcg/day.25
Vitamin D: Although vitamin D often seems like the latest miracle nutrient, its role in maintaining normal insulin function and glucose is well established. Part of the credit goes to calcium, which is also required for normal insulin function, and vitamin D is necessary for normal calcium utilization.26 A large clinical trial found that women who took 800IU vitamin D and 1,200mg calcium daily for 20 years were one third less likely to develop diabetes. Another study found that people taking 700IU vitamin D and 500mg calcium daily had virtually no increase in blood-glucose levels over three years, whereas blood-sugar levels increased more than 6mg/dl among people taking placebos.27
A study published in the January 2009 Journal of Pediatrics found 76 per cent of youths (ages 1.5 to 17.5 years, n=128) with type 1 diabetes had insufficient levels of vitamin D. Researchers at the Joslin Diabetes Center said subjects included those with recent onset of diabetes as well as those with long-established diabetes. They recommended children take 400IU/day vitamin D.
Resveratrol: Found in red wine and Japanese knotweed (Polygonum cuspidatum), resveratrol increases activity of SIRT1, a principal anti-ageing gene and one that also regulates insulin sensitivity.28 Mice given resveratrol maintained normal liver function and had relatively low levels of glucose, insulin and insulinlike growth factor-1.29 The average lifespan of the mice increased by about 15 per cent, which may be related to both changes in gene function and lower levels of glucose and insulin.30 In a small unpublished study of men with type 2 diabetes, researchers found that resveratrol reduced fasting blood sugar and improved insulin sensitivity.31 A study using 5g/day resveratrol to treat insulin resistance is currently underway at the University of California, San Francisco.32 Note: in 2007, GlaxoSmithKline paid $720 million to acquire Sirtris Pharmaceuticals, which has been researching resveratrol and developing similar synthetic molecules.33
Silymarin: This antioxidant extract of milk thistle (Silybum marianum) has long been used to enhance liver function, an organ that works in tandem with the pancreas to regulate blood glucose. Three clinical trials have clearly demonstrated the benefits of silymarin supplements in type 2 diabetes. In one of them, 51 patients with diabetes took 200mg silymarin three times daily for four months. The supplement led to a 15 per cent decrease in blood glucose, a 13 per cent decrease in glycated hemoglobin (HbA1C), and a 25 per cent drop in fasting insulin levels.34 One of the other studies found a 20 per cent decrease in fasting blood sugar, a 37 per cent decline in postprandial blood sugar and a 16 per cent decrease in HbA1c — plus an 8.5 per cent reduction in weight.35,36,37
Cinnamon: The research on cinnamon is conflicting, with some studies showing benefits and others not. In one of the positive studies, Richard A Anderson, PhD, of the US Department of Agriculture, and colleagues from Pakistan used cinnamon to treat 60 middle-age men and women with type 2 diabetes. After 40 days, fasting glucose decreased by 18-29 per cent. In addition, cholesterol levels declined by 7-27 per cent and triglyceride levels by 23-30 per cent.38
Soluble fibre: Soluble fibre — the type that turns into a gel when mixed with water — includes glucomannan, inulin and pectin. (Beta-glucan consists of both soluble and insoluble fibres.) The gel increases a sense of fullness and decreases appetite. In an article in the American Journal of Clinical Nutrition, researchers analyzed 14 human studies on glucomannan, which is obtained from Amorpholphallus konjac.39 Although glucomannan is best known for lowering cholesterol and triglyceride levels, it has impressive benefits in controlling blood glucose and weight. Daily glucomannan supplements were found to lower glucose by an average of 7.4mg/dl after five weeks. In addition, supplements promoted a 1.7lb weight loss over five weeks.39
Fenugreek: The seeds of this plant lower blood-glucose levels, and researchers have identified several possible mechanisms for the hypoglycaemic effect. Fenugreek is rich in 4-hydroxyisoleucine, an amino acid that increases insulin secretion. It also inhibits the activity of two carbohydrate-digesting enzymes, alpha-amylase and sucrase.40 Fenugreek also contains both soluble and insoluble fibre, which slow carbohydrate absorption and boost insulin activity.41 Clinical trials have found that fenugreek improves glucose tolerance in both type 1 and type 2 diabetes.42,43
As always, formulators must evaluate the research on individual ingredients, identify their markets and regulatory issues, and design cost-effective formulas for managing normal glucose tolerance.
Jack Challem is the author of Stop Prediabetes Now and The Food-Mood Solution, both published by John Wiley & Sons.
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