Diabetes treatments: from supplements to foods

New research findings into traditional supplemental ingredients are driving new applications for diabetes health. Food formulators are taking note, and incorporating GRAS-approved ingredients into their offerings, and also utilising better-for-you ingredients. Todd Runestad surveys the changing diabetes landscape

Diabetes is closely linked to, in the early stage, metabolic syndrome, and on the later stage, obesity. Indeed, the latter two are so thoroughly linked that their combination has given rise to a new quasi-medical term: diabesity.

Diabetes itself is a group of diseases marked by high levels of blood glucose resulting from defects in insulin production, insulin action or both. As the need for insulin rises, the pancreas gradually loses its ability to produce it. Diabetes can lead to serious complications, from high blood pressure to kidney disease, stroke and premature death, but people with diabetes can take steps to control the disease and lower the risk of complications.

The opportunities this presents to food and supplements manufacturers are clear. And raw-materials suppliers are rising to the occasion to help with the reformulation, integration and introduction of new, novel and better-for-you ingredients to improve the healthiness profile of finished goods.

Alpha-lipoic acid: With metabolic syndrome on everyone's lips, it's notable that lipoic acid has been shown to benefit four of the five symptoms of the condition: excess weight, insulin resistance, atherogenic dyslipidaemia (specifically, low HDL cholesterol and elevated triglycerides), and high blood pressure.1 This makes it an excellent supplement for those wishing to prevent the occurrence of diabetes. But what of full-blown diabetes? For 30 years German doctors have prescribed 'the universal antioxidant' to patients with diabetic neuropathy. It has been shown to improve insulin action and to increase insulin-mediated glucose disposal — but mostly after parenteral administration.2

One recent study aimed to check that state of affairs. In a double-blind, placebo-controlled trial, 24 overweight middle-aged subjects were given 600mg alpha-lipoic acid, or placebo, twice daily for four weeks. Insulin sensitivity increased significantly — glucose disposal rate increased from about 3.2 to 5.9mg/kg/minute. The insulin sensitivity index also significantly increased, from about 4.7 to 7.7.3

In the past year, a few case studies have been published about a correlation between alpha-lipoic acid and what is called insulin autoimmune syndrome, a rare disease characterised by low blood-sugar levels and auto-antibodies to insulin.4 Although rare, and reported in only case studies, it probably bears paying some attention to.

Bitter melon (Momordica charantia): Locally known in Bangladesh as the bitter vegetable called karolla, it was first studied in 1999 in Bangladesh on 100 human subjects with moderate diabetes. Drinking an aqueous homogenised suspension of the vegetable pulp led to a significant reduction of both fasting and post-prandial serum glucose levels in 86 per cent of cases, while an additional five per cent showed lowering of only fasting serum-glucose levels.5

A class of chemicals called cucurbitane triterpinoids is the characteristic constituents of M charantia. These were first fractionated from an extract of bitter-melon dried gourds in 2006, by Japanese researchers.6 That kicked off a flurry of very recent animal research into its ability to improve glucose and insulin tolerance. In March 2008, Chinese researchers identified them as mediating glucose uptake and fatty acid oxidation in cells. Furthermore, the momordicosides enhanced fatty-acid oxidation and glucose disposal during glucose-tolerance tests in both insulin-sensitive as well as insulin-resistant mice. Several of the tested compounds had effects comparable to those of insulin.7

In April 2008, researchers from India reported that bitter-gourd extract improves insulin sensitivity, glucose tolerance and insulin signaling in rats induced to insulin resistance by a high-fat diet. Benefits in the 10-week study were seen after only two weeks.8

Cinnamon: Unlike bitter melon, cinnamon tastes good! Although used traditionally as a spice for foods, it has found most of its success from a health-benefit standpoint in the supplements world. There are two types of cinnamon typically found on the market: Cinnamomum zeylanicum nees or C cassia blume. The latter is the focus of scientific research, which finds it improves insulin's action.

In a 2003 animal study, Chinese researchers found cinnamon extracts improve the metabolic action of insulin and help prevent insulin resistance in part by increasing glucose uptake into cells and enhancing the insulin-signaling pathway in muscle.9

Cinnamon's active ingredient appears to be double-linked polyphenol Type-A Polymers. These compounds increase insulin-dependent glucose metabolism in vitro by 20-fold, and mimic insulin.10,11 They also have been shown to reduce blood pressure — making cinnamon effective in preventing some symptoms of metabolic syndrome.

In a human study with 60 men and women with diabetes, those taking 1, 3 or 6g/day cinnamon for 40 days experienced decreases in fasting glucose levels of 18-29 per cent.12 A human study using a lower dose, 500mg/day for 12 weeks, gave 83 per cent of subjects an average eight per cent decrease in fasting blood-sugar levels.13

The active components in cinnamon are not destroyed by heat, so cinnamon could certainly play an enhanced role in processed foods — and even cinnamon sticks added to tea can be beneficial.

HCA: In recent years, Garcinia cambogia has been promoted for weight loss due to various possible effects it may have on the body. First, it is believed to interfere with an enzyme needed to store fat, possibly causing more fat from foods to be eliminated from the body. In addition, it may cause the body to use existing fat stores for energy during prolonged exercise. Ordinarily, carbohydrates are used before fats during exercise. In animal studies, hydroxycitric acid (HCA), a major component of Garcinia cambogia, also seemed to reduce appetite by raising the amount of serotonin in the body. In a 2007 animal study, HCA not only reduced food intake and body-weight gain in obese rats, but it also decreased inflammation, oxidative stress and insulin resistance compared to controls.14

Chromium: This mineral is at the heart of a biologically active complex called Glucose Tolerance Factor or 'GTF,' which is responsible for increasing the action of insulin in the body. Originally applied solely to supplements, it is now finding a home in bars, beverages and even chewing gums.

The two primary forms of chromium on the market are chromium picolinate and niacin-bound chromium polynicotinate. Both have research to back their efficacy.

In a 2006 review, researchers noted that 13 of 15 human clinical trials, including 11 randomised, controlled studies involving more than 1,500 subjects in the chromium-picolinate group, reported significant improvement in at least one outcome of glycaemic control. These areas included reduced blood glucose, insulin, cholesterol and triglyceride levels, and reduced requirements for hypoglycaemic medications.15

In a 2004 double-blind, placebo-controlled trial on niacin-bound chromium, subjects receiving 300mcg/day chromium for three months experienced significantly lowered fasting blood-glucose levels, and modest decreases in triglyceride levels as well as glycosylated haemoglobin, a measure of long-term glucose control.16

Combining chromium with other nutrients is also a developing trend. In 2002, researchers combined niacin-bound chromium with a water-soluble fraction of maitake mushroom and HCA. Diabetic rats receiving the combination had significantly reduced body weight, blood pressure and fasting blood-glucose levels.17

Chromium picolinate was combined with biotin, a water-soluble B-complex vitamin, in a 2006 human clinical trial with 43 patients with impaired glycaemic control. In this double-blind, placebo-controlled trial, those receiving 600mcg/day chromium with 2mg/day biotin for four weeks had a 9.7 per cent reduction in glucose during the two-hour oral glucose-tolerance tests, compared to a 5.1 per cent increase in the control group.18

The combination of chromium picolinate and biotin has been patented as Diachrome. In a 2005 analysis, economists at Widener University in Pennsylvania concluded that using this combination among the 1.17 million newly diagnosed patients with type-2 diabetes each year could deliver a lifetime cost savings of $42 billion, or $36,000 per patient.19

As well as chromium, the trace mineral selenium has been shown to influence blood-insulin levels and insulin effectiveness. Low levels of zinc are associated with diabetes and cardiovascular disease. And vanadium compounds have been shown to have insulinlike effects.20 Combining these trace minerals with chromium can offer intriguing intellectual-property opportunities for savvy developers.

Fibre: The indigestible part of plants is known as fibre. Soluble fibres such as psyllium, flax, gums and oats form gels in the intestine and slow the rate of nutrient absorption, which helps reduce blood-sugar levels after meals are consumed. Insoluble fibres from whole grains increase bulk and slow down the movement of matter through the bowel. Both fibre types prolong gastric emptying and bind cholesterol to limit its absorption. Dietary fibre also inhibits the activity of alpha-amylase and postpones the release of glucose from starch.21

Water-soluble fibre, such as oat bran, helps balance blood sugar. Researchers tested post-meal glucose and insulin effects of whole-kernel rye bread, whole-meal rye bread containing oat beta-glucan concentrate, dark durum wheat pasta and white bread made from white wheat flour. Each product provided 50g carbohydrates. Upon eating, 10 men and 10 women with normal glucose tolerance had their fasting and eight post-meal blood samples collected at 15-30 minute intervals for three hours to determine levels of blood glucose, glucose-dependent insulinotropic polypeptide (GIP), glucagons-like peptide 1 (GLP-1), and serum insulin.

Glucose responses and the rate of gastric emptying after consumption of the two rye breads and pasta did not differ from the white wheat bread (with the exception of GLP-1 response to the rye bread containing oat beta-glucan). However, GIP and GLP-1 responses, which both stimulate insulin response, and insulin were lower after eating rye breads and pasta than white wheat bread. Researchers concluded the insulin response is determined more from the form of food rather than the amount of fibre or type of cereal in the food.22

A further study measured the effects of fibre enrichment of pasta and fat content on gastric emptying, GLP-1, glucose and insulin responses to a meal. Researchers added 1.7g psyllium, which was enough fibre to qualify for a US FDA claim for reduced cholesterol and risk of coronary heart disease. The psyllium-enriched pasta had no significant effect on gastric emptying or the area under the curve for GLP-1, insulin or glucose compared with the control pasta. However, when they added 30g sunflower oil and 3g sodium propionate, the 10 subjects experienced significant reductions in gastric emptying, an increase in GLP-1, and reduced glucose and insulin concentrations.23

Resistant starch: Recently, it has become accepted that there are not merely two forms of fibre, soluble and insoluble. A third type — resistant starch — has come on to the scene. These so-called nonglycaemic carbohydrates resist digestion in the small intestine, are fermented like some dietary fibres to provide long-term energy, and can increase insulin sensitivity in healthy people. In one study, 10 healthy people ate two identical meals, but one contained 60g resistant starch (Novelose 260, National Starch). The following morning, a fibre-free meal tolerance test was taken and postprandial insulin sensitivity assessed. Results showed that those eating the resistant starch meal the day before experienced lower postprandial blood glucose and insulin, with a higher insulin sensitivity the next day.24

In sum, seven published studies have shown beneficial effects of natural R-2 resistant starch on glucose and insulin response. When substituted for flour, it lowers the glycaemic response of foods in a dose-dependent manner.25

Beta-glucan: In 2006, researchers added a variable to the resistant-starch story by including different quantities of beta-glucan to muffins. While beta-glucan decreased glucose and insulin under the curve between 17 and 33 per cent, and resistant starch's numbers were 24 and 38 per cent, when both functional ingredients were combined, the result was 33 and 59 per cent for glucose and insulin, respectively.26

Before formulators go out and begin adding beta-glucan to meals, they would do well to heed the results of a recent test carried out in the Department of Food Science & Microbiology at the University of Milan in Italy.27 Researchers there added beta-glucan to barley flour or whole-wheat flour and made cookies and crackers. In general, they found that cookies responded better to the addition of barley fibre than crackers, highlighting the complexity of the effect barley fibre may exert when added to different food products to address glucose metabolism and diabetes.

Salba: This novel grain from Argentina (Salvia hispanica) has been introduced into the market, and boasts high quantities of fibre and the omega-3 alpha-linolenic acid as well as protein, calcium, magnesium, iron and antioxidants. More to the point, it is showing benefit for diabetics.

In a study published in November 2007, researchers in Toronto (the town that made the Glycaemic Index famous) gave 20 diabetics either 37g/day Salba or wheat bran for 12 weeks while maintaining their conventional diabetes therapies. Compared with the control group, the Salba group experienced reduced systolic blood pressure by 6.3mmHg and C-reactive protein levels, a marker of inflammation.28

Bioactives for diabetes

Alpha-lipoic acid
Bitter melon (Momordica charantia)
Maitake mushrooms
Trace minerals selenium, zinc, vanadium
Resistant starch
Tea, coffee, wine

coffeeDRINK your diabetes away
Why put a functional bioactive into a drink when certain drinks themse
lves have demonstrated diabetes benefits? Next to water, the top liquids consumed worldwide are probably tea, coffee and wine, and it is precisely these three that have been shown to help, under certain conditions.

The most abundant green-tea catechin, epigallocatechin gallate (EGCG), has been shown to have glucose-lowering effects in animals by mimicking insulin and decreasing liver-glucose production.1 Further animal studies carried out by DSM with its Teavigo EGCG extract found it improved glucose tolerance and blood-glucose levels in food-deprived rats in a dose-dependent manner. It also increased insulin secretion and reduced triglyceride levels.2

Research published in April 2008 identified the polyphenolic content of tea as well as wine as being the mechanism for inhibiting the activity of alpha-glucosidase, an enzyme that triggers the absorption of glucose. Researchers tested red and white wines, and green, white, oolong and black teas. Notably, while red wine unsurprisingly contained 10 times the polyphenolic content compared to white wine, black tea had the highest content in the tea varieties, followed by white tea.3 Other researchers in 2008 identified black-tea polyphenols that mimic insulin and insulin-like growth factor-1.4

Other recent research unveiled at the summer 2007 American Chemical Society meeting could have ramifications for soft-drink developers who are battling the association between high-fructose corn syrup and diabetes. Researchers found that adding EGCG to soft drinks improved the beverages' levels of reactive carbonyls — the compounds associated with unbound fructose and glucose molecules, and found at higher levels in diabetics.5

Coffee has been shown to house the ability to improve insulin sensitivity, with decaffeinated coffee being even more beneficial. The issue at stake is researchers found it takes seven cups per day to have the effect.6

Even the superfruit pomegranate has ancillary benefits to diabetes — more specifically, metabolic-syndrome symptoms. A 2006 human clinical study in Iran found 40g/day pomegranate juice from concentrate for eight weeks led to significant reductions in total and LDL cholesterol, but no changes in HDL cholesterol or triglycerides.7


1. Waltner-Law ME, et al. Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J Biol Chem 2002 Sep 20;277(38):34933-40.
2. Wolfram S, et al. Epigallocatechin gallate supplementation alleviates diabetes in rodents. J Nutr 2006 Oct;136(10):2512-8.
3. Kwon Y, et al. Inhibitory potential of wine and tea against alpha-amylase and alpha-glucosidase for management of hyperglycemia linked to type-2 diabetes. J Food Biochem 2008;32(1):15-31.
4. Amy R, et al. Black tea polyphenols mimic insulin-insulin-like growth-factor 1 signalling to the longevisty factor FOXO1a. Aging Cell 2008 Feb;7(1):69-77.
5. http://portal.acs.org/portal/acs/corg/content?_nfpb=true&_pageLabel=PP_ARTICLEMAIN&node_id=223&content_id=WPCP_006925&use_sec=true&sec_url_var=region1
6. Hu G, et al. Joint association of coffee consumption and other factors to the risk of type 2 diabetes: a prospective study in Finland. Int J Obes 2006 Dec;30(12):1742-9.
7. Esmaillzadeh A, et al. Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia. Int J Vitam Nutr Res 2006 May;76(3):147-51.

Branded ingredients take aim at diabetes
Fibre is recognised as a diabetics' best friend, but some fibres are more equal than others. Ingredients supplier Frutarom tested 19 different fibre types in vitro to see which was best in binding glucose. The top group: psyllium husk as well as its Fenulife fenugreek extract.

"The reduction of glucose absorption can be the mechanism for earlier observations that FenuLife can reduce postprandial blood glucose in vivo," says Marian Verbruggen, PhD, head of medical sciences and regulatory affairs for Frutarom. "FenuLife is superior to many other fibres marketed for the same application: blood-sugar reduction."

And yet, it seems, not all fenugreek is created equal either. TSI Health Science has a patent-pending fenugreek extract called Promilin, standardised to contain 20 per cent 4-hydroxyisoleucine. This amino-acid derivative assists the pancreas in producing insulin. TSI has conducted bioactivity testing on Promilin, showing it reduces glucose concentrations and stimulates insulin secretion across a range of concentrations.

"TSI is sponsoring clinical studies to further understand and validate benefit claims surrounding glucose transport/glycogen resynthesis, weight management and glucose metabolism in healthy people, as well as individuals with impaired glucose tolerance," says TSI president Larry Kolb.

NHS' Pycnogenol boasts more than 220 published studies over 35 years, everything from osteoarthritis relief to improved sperm quality. "Horphag Research, the exclusive worldwide suppliers of Pycnogenol, continues to invest around $1.5 million a year in Pycnogenol research. In total, about 5,000 patients have been studied," says Frank Schonlau, PhD, director of scientific communications for Horphag/NHS. Pycnogenol can also lower blood-glucose levels — a single dose of 50mg/day for three weeks is effective. Another clinical study showed Pycnogenol, in addition to oral diabetic drugs such as metformin, significantly lowered blood-glucose levels.

Supplier giant DSM is another firm committed to R&D. Its latest launch, InsuVital, is made from a casein milk protein and leverages hidden pancreatic reserves. In five studies, it shows a 30 per cent reduction in blood-glucose levels.

"It has high solubility and low viscosity," says Philip Rijken, head of nutrition science at DSM. "It has good taste and is transparent in solution. It is good for applications such as water, fruit juice, dairy and bars."

On the horizon, two Florida scientists have recently discovered a compound that exists in tropical fruits and vegetables and makes sugary foods safe for diabetics. Dubbed Emulin, it is going through its last stages of R&D.

"It's a sugar defense mechanism that can be added to any sugar-laden manufactured food," says Joseph Aherns, PhD, of ATM Metabolics. "It protects the body from the glycaemic impact of that food without altering the taste."


Select suppliers: offering diabetes solutions

Fibersol-2 is a digestion-resistant maltodextrin that is stable; has low viscosity; is transparent in solution; and adds virtually no flavour to beverages, baked goods, cereals, dairy and frozen dairy items, soups, meal replacements, dietary supplements, or medical and functional foods.

Beneo inulin and Beneo oligofructose are soluble dietary fibres that are not digested in the stomach or small intestine, but reach the large intestine intact. Here, unlike most other fibres, they are selectively fermented by intestinal flora and maintain optimal gut function.

Xtend sucromalt and isomaltulose are low-glycaemic, natural liquid sweeteners that provide food and beverage makers with a natural and slow-release carbohydrate syrup. These fully digestible, low-glycaemic syrups provide sweetness and body for beverages, bars, ice cream, jellies and yoghurts.

Cosucra Groupe Warcoing
Fibruline DS2 is a de-sugared inulin marketed as a low-calorie sweetener with a particular focus on the bakery and confectionery industries. DS2 contains one calorie per gram as opposed to four calories for regular sugar.

Litesse polydextrose is a low-glycaemic ingredient that can replace 10 per cent of flour in baked goods while providing many of its functional properties. It is 1kcal/g, adds fibre without affecting mouthfeel, and helps with moisture retention.

InsuVital hydrolysed casein stimulates secretion of insulin from the pancreas. It is available as a powder for foods and drinks.

Fenulife is a concentrate of the beneficial galactomannans in fenugreek used for supplements. By regulating sugar absorption, it turns fast carbs into slow carbs.

GTC Nutrition
OatVantage oat beta-glucan has a glycaemic response of about one fifth that of glucose. It increases viscosity of stomach contents, which slows stomach emptying, prolongs the absorption of energy from a meal and decreases fat absorption. These effects exert control over insulin release.

Integrity Nutraceuticals
Cinnulin PF is the only patented aqueous cinnamon extract available, manufactured through a water-based process using no chemical solvents. It is useful for healthy glucose levels, body composition, blood pressure and antioxidant function in healthy individuals. It is a water-soluble cinnamon suitable for capsules, tablets, powder or liquid.

InterHealth Nutraceuticals
ChromeMate is a unique, patented form of biologically active niacin-bound chromium called chromium nicotinate or polynicotinate that increases the safety and effectiveness of chromium, an essential trace mineral required for normal insulin function.

FiberAid soluble fibre is an arabinogalactan sourced from the larch tree. GRAS affirmed, it is water soluble, stable to heat, pH and salt concentration.

Maitake Products
Grifron SX-Fraction is a proprietary ingredient to maintain healthy blood-sugar levels and support healthy sensitivity to insulin.

National Starch
Hi-Maize resistant starch, as a substitute for flour, decreases glycaemic and insulin impact, and increases insulin sensitivity. It can be used in low-moisture food systems to also improve texture and processing properties.

Nutraceutical Group
Viscofiber is a high-viscosity and high-concentration oat beta-glucan soluble fibre. Up to 12 times more concentrated than oat bran, Viscofiber improves glycaemic response and glucose management, among other benefits.

Nutrition 21
Chromax chromium picolinate is a highly absorbable form of chromium that provides the body with the chromium it needs to help promote healthy blood sugar, fight food cravings and support cardiovascular health. Diachrome Diabetes Essentials are powered by Chromax and biotin.

Phase 2 for supplements and StarchLite for foods is derived from the white kidney bean. It reduces absorption of starch calories and reduces the glycaemic index of white bread when added to the recipe.

Source One Global Partners
Sytrinol is a proprietary formula of citrus bioflavonoids and palm tocotrienols. As well as proving to be a novel cholesterol and triglyceride-lowering supplement, Sytrinol also improves glycaemic control in individuals with metabolic syndrome.

Toyo Bio-Pharma
Toyo Kan-Sho, derived from the leaves and stems of the sweet-potato plant, supports healthy blood-glucose levels, maintains healthy blood pressure already within normal range and promotes liver health by regulating fat accumulation.

1. Pershadsingh HA. Alpha-lipoic acid: physiologic mechanisms and indications for the treatment of metabolic syndrome. Expert Opin Investig Drugs. 2007 Mar;16(3):291-302.
2. Evans JL, Goldfine ID. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes Technol Ther 2000 Autumn;2(3):401-13.
3. Kamenova P. Improvement of insulin sensitivity in patients with type 2 diabetes mellitus after oral administration of alpha-lipoic acid. Hormones 2006 Oct-Dec;5(4):251-8.
4. Furukawa N, et al. Possible relevance of alpha lipoic acid contained in a health supplement in a case of insulin autoimmune syndrome. Diabetes Res Clin Pract 2007 Mar;75(3):366-7.
5. Ahmad N, et al. Effect of Momordica charantia (Karolla) extracts on fasting and postprandial serum glucose levels in NIDDM patients. Bangladesh Med Res Counc Bull 1999 Apr;25(1):11-3.
6. Harinantenaina L, et al. Momordica charantia constituents and antidiabetic screening of the isolated major compounds. Chem Pharm Bull (Tokyo) 2006 Jul;54(7):1017-21.
7. Tan MJ, et al. Antidiabetic Activities of Triterpenoids Isolated from Bitter Melon Associated with Activation of the AMPK Pathway. Chem Biol 2008 Mar;15(3):263-73.
8. Sridhar MG, et al. Bitter gourd (Momordica charantia) improves insulin sensitivity by increasing skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat-fed rats. Br J Nutr. 2008 Apr;99(4):806-12.
9. Qin B, et al. Cinnamon extract (traditional herb) potentiates in vivo insulin-regulated glucose utilization via enhancing insulin signaling in rats. Diabetes Res Clin Prac 2003;62:139-48.
10. Anderson RA, et al. Isolation and characterization of polyphoenol Type-A Polymers from cinnamon with insulin-like biological activity. J Agric Food Chem 2004;52:65-70.
11. Khan A, et al. Insulin potentiating factor and chromium content of selected foods and spices. Biol Trace Elem Res 1990;24:183-8.
12. Khan A, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26(12):3215-8.
13. Ziegenfguss TN, et al. Effects of a proprietary water-soluble extract on metabolic syndrome. Diabetes Care 2006.
14. Asghar M, et al. Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation, insulin resistance, and body weight in developing obese Zucker rats. Mol Cell Biochem 2007 Oct;304(1-2):93-9.
15. Broadhurst CL, Domenico P. Clinical studies on chromium picolinate supplementation in diabetes mellitus — a review. Diabetes Technol Ther 2006 Dec;8(6):677-87.
16. Bagchi M, et al. Efficacy and Toxicological Assessment of a Novel, Niacin-Bound Chromium in Ameliorating Metabolic Disorders, 10th International Congress of Toxicology-Finland 197:abs. 354, July 2004.
17. Talpur, et al. Effects of niacin-bound chromium, Maitake mushroom fraction SX and (-)-hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats. Mol Cell Biochem 2003 Oct;252(1-2):369-77.
18. Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther 2006 Dec;8(6):636-43.
19. Fuhr JP Jr, et al. Use of chromium picolinate and biotin in the management of type 2 diabetes: an economic analysis. Dis Manag 2005 Aug;8(4):265-75.
20. Bagchi D. Beneficial roles of chromium, selenium, zinc and vanadium on insulin resistant syndrome. J Am Coll Nutr 2001;20(5):581, Abs. 79.
21. Ou S, et al. In vitro study of possible role of dietary fiber in lowering postprandial serum glucose. J Agric Food Chem 2001 Feb;49(2):1026-9.
22. Juntunen KS, et al. Postprandial glucose, insulin, and incretin responses to grain products in healthy subjects. Am J Clin Nutr 2002 Feb;75(2):254-62.
23. Frost GS, et al. The effects of fiber enrichment of pasta and fat content on gastric emptying, GLP-1, glucose, and insulin responses to a meal. Eur J Clin Nutr 2003 Feb;57(2):293-8.
24. Robertson MD, et al. Prior short-term consumption of resistant starch enhances postprandial insulin sensitivity in healthy subjects. Diabetologia 2003 May;46(5):659-65.
25. Vonk RJ, et al. Digestion of so-called resistant starch sources in the human small intestine. Am J Clin Nutr 2000 Aug;72(2):432-8.
26. Behall KM, et al. Consumption of both resistant starch and beta-glucan improves postprandial plasma glucose and insulin in women. Diabetes Care 2006 May;29(5):976-81.
27. Casiraghi MC, et al. Post-prandial responses to cereal products enriched with barley beta-glucan. J Am Coll Nutr 2006 Aug;25(4):313-20.
28. Vuksan V, et al. Supplementation of conventional therapy with the novel grain Salba (Salvia hispanica L.) improves major and emerging cardiovascular risk factors in type 2 diabetes: results of a randomized controlled trial. Diabetes Care 2007 Nov;30(11):2804-10.

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