Diabetes

Diabetes is a group of conditions in which sugar levels in the blood are abnormal. During digestion the body converts sugars, starches and other carbohydrates into glucose which is carried in the bloodstream to cells throughout the body. Glucose is then used for energy release or stored for later use. The hormone, insulin, which is manufactured in the beta cells of the pancreas, is necessary for this process and therefore for the control of blood sugar levels. Diabetes can occur when the body attacks and destroys the cells in the pancreas that produce insulin or when the body is unable to use the insulin the pancreas produces. Sugar then collects in the blood and in the urine. Fat metabolism is also disturbed in diabetes, with high blood levels of cholesterol and triglycerides. As many as 120 million people worldwide have diabetes and the World Health Organization estimates that by the year 2025 this number will rise to 250 million.

 

Types of Diabetes

Type I (Insulin-Dependent Diabetes)

Type I diabetes accounts for around 5 to 10 per cent of cases and is most often seen in children and young adults. It occurs when the body attacks and destroys the cells in the pancreas that make insulin. Insulin production either stops altogether or only a tiny amount is made. Type I diabetes begins suddenly and symptoms quickly become severe. It is treated with insulin injections, regular exercise and a diet low in sugar and fat. Control of Type I diabetes requires a person to balance the intake of food and the entry of insulin into the blood.

Type II (Non-Insulin-Dependent Diabetes)

This type of diabetes, which accounts for around 90 per cent of cases, is also known as maturity onset diabetes and occurs most often in adults aged over 40, especially in those who are obese. In Type II diabetes the pancreas produces some insulin but it is not used effectively. The progression of the disease is slow and symptoms are mild in the beginning. Type II diabetes can often be controlled by diet and exercise, which can improve a person's blood glucose response. Overweight people may need to slim down and some people may need medication or insulin injections to control blood sugar.

Other Types of Diabetes

There are other kinds of diabetes, such as gestational diabetes, which occurs in around 2 to 3 per cent of pregnant women and usually disappears after the birth of the baby. Such women are at increased risk of developing Type II diabetes later in life. Secondary diabetes is caused by damage to the pancreas from chemicals, certain medicines, or diseases such as cancer.

 

Symptoms of Diabetes

Symptoms of Type I diabetes, which usually occur suddenly, include frequent urination, excessive thirst, extreme hunger, dramatic weight loss, weakness, fatigue, blurred vision, nausea and vomiting. The symptoms of Type II diabetes usually occur less suddenly and include any of the above Type I symptoms and others such as recurring skin, gum or bladder infections; drowsiness; blurred vision; itching and tingling; or numbness in the hands and feet.

 

Causes of Diabetes

The exact causes of both types of diabetes are still unknown and there may be several factors that play a part, although how important each factor is remains unclear. In Type I diabetes, the body's immune system attacks the beta cells of the pancreas and it is likely that genetic factors play a role in this. It is also possible that a viral infection that causes the immune system to destroy pancreatic cells instead of the virus may be involved. Cow's milk in the first few months of life may increase the risk of developing Type I diabetes, possibly due to the immune system recognizing the similarity between a protein in milk and a protein on the surface of the body's beta cells.1

Those who are overweight, do not exercise, eat a poor diet, suffer from hypertension, have high cholesterol and triglyceride levels, are aged over 40, and who have a family history of diabetes, are at particular risk of Type II diabetes. In this disorder the pancreas may produce enough insulin, but excess fat may prevent the insulin from working properly. This is known as insulin resistance and is often reversible with weight loss. Women with unexplained miscarriages, stillbirths, or who have had babies weighing nine pounds or more at birth also seem to be at increased risk of Type II diabetes.

Diet also influences the development of diabetes. Recent research suggests that those who eat an Asian diet have less risk of developing Type II diabetes. In a 1996 study, Japanese American men in Hawaii who had a more Japanese lifestyle with a higher carbohydrate, lower fat, less animal protein-based diet had a lower risk of diabetes than Japanese American men who had a Western lifestyle.2 A 1997 study published in the Journal of the American Medical Association showed that women who ate diets low in cereal fiber and high in foods which cause sharp rises in blood sugar are at increased risk of Type II diabetes.3 Similar results have been seen in men.4 Exercise also appears to decrease the risk of Type II diabetes.

 

Managing Diabetes

Diabetes is a manageable condition, and with proper care, most people can live as they did before developing the disease. Successful management involves following a daily routine, which may include monitoring blood sugar levels, taking insulin or other medications, following a healthy diet and exercising regularly. Diabetics must avoid hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar) as both can lead to coma if left untreated. Many experts now believe that keeping blood sugar levels tightly controlled can help prevent complications. Monitoring metabolic parameters including blood glucose, glycated hemoglobin, lipids, blood pressure and body weight is crucial to ensuring good control of the disease.

 

Diabetic Complications

Diabetics are at increased risk of developing certain disorders such as heart, eye and kidney diseases; foot infections; and stroke. Increasing evidence suggests that many of these disorders arise as a result of oxidative damage to tissues. In diabetes, there may be an overproduction of free radicals and decreased efficiency of antioxidant defenses. Studies have shown lower levels of antioxidant vitamins and minerals in diabetic patients, especially those with complications.

Diabetics are at increased risk of cardiovascular disease as they have higher levels of harmful LDL cholesterol, which is more easily oxidized than other forms. The rate of this oxidation also appears to be higher in diabetics. This combination increases the risk of damage to arteries.

There are other compounds and processes that lead to diabetic complications. When glucose is metabolized, one of the compounds formed is sorbitol, which in nondiabetics is then converted to fructose and excreted. However, in diabetics, who often have high blood sugar, sorbitol accumulates and may lead to complications. Prolonged periods of high blood sugar cause glucose molecules to become attached to proteins, causing changes in structure and function. This is known as glycation. Proteins commonly affected include those in red blood cells, the lens of the eye and the myelin sheath that surrounds nerve cells. Vitamins and minerals play an important part in protecting against these alterations in metabolism.

Diabetes and Diet

It is vital for diabetics to maintain a desirable body weight and stabilize blood sugar and fat levels within a normal range in order to prevent or delay diabetic complications. The most important principle of diabetic diets is that they should be low in fat, especially saturated fat. They are also low in simple sugars and high in fiber. The American Diabetes Association (ADA) recommends that complex carbohydrates such as bread, pasta, potatoes and legumes make up 55 to 60 per cent of total calories; protein makes up around 20 per cent; and fat makes up 15 to 30 per cent.

The same food eaten by different people can produce different responses in blood sugar levels. It seems that the response is dependent upon the proportions of carbohydrate, protein and fat. A rating system known as the glycemic index (GI) ranks foods according to how fast their carbohydrate content is converted to glucose and enters the bloodstream. The lower the number, the slower the action. It may be advisable for people with diabetes to choose low GI foods wherever possible.

For many people, six small meals are easier to digest than three larger ones, as it is easier to dispose of smaller amounts of glucose because less insulin is needed. Sometimes eating meals and snacks at regular times will improve glucose levels.

A diet diary and glucose self-monitoring can be useful in helping a diabetic person to devise a diet appropriate for their lifestyle. Glucose meter readings indicate the body's response to meals, snacks, exercise, stress, illness and general habits. Many diabetics use the 'exchange list' system of food choices, in which foods are placed on one of six lists based upon their nutrient content. The six groups are: starch/bread, meat/substitutes, vegetables, fruit, milk, and fats. Portion sizes are also indicated to keep caloric value very close for all foods on the list. Meal plans usually indicate how many choices may be taken from a list for a meal or a snack.

Some diet plans involve the carbohydrate counting method. This involves making food choices so that an optimal amount of carbohydrate is present in the meal, the remainder of the calories are then allotted for protein and fat. Many vegetarians prefer to use carbohydrate counting, as animal products that appear on the meat and milk exchange lists are usually left out of the diet.

Vitamins, Minerals and Diabetes

Antioxidant Vitamins

Diabetes is associated with higher levels of oxidized blood fats, which can increase the risk of diabetic complications such as cardiovascular disease. Oxidative stress may be increased because of glucose attachment to proteins. Levels of antioxidants are also lower in diabetics, and this lower level of antioxidant protection is likely to contribute to the development of diabetic complications.5

Regular consumption of adequate amounts of antioxidant-rich foods, such as fruits and vegetables, is important in the prevention of diabetic complications. Antioxidant supplements may also be beneficial, as the amounts needed to give protection may be higher than those that can easily be obtained from the diet. Multivitamin mixtures with trace elements have been shown to protect diabetic patients against free radical damage.6

Vitamin C

Vitamin C metabolism is altered in diabetics. The cellular uptake of vitamin C is promoted by insulin and inhibited by high blood sugar; and as diabetics have low insulin levels, they are at greater risk of vitamin C deficiency. Most studies have found people with diabetes to have at least 30 per cent lower vitamin C concentrations than people without the disease. Levels seem to be lower in diabetic people as a result of the disease rather than as a result of poor dietary intake.7 This deficiency can lead to increased capillary permeability, poor wound-healing, increased cholesterol levels, and immune suppression; which all contribute to diabetic complications.

Several studies suggest that chronic vitamin C administration has beneficial effects on glucose and lipid metabolism in Type II diabetic patients. In a 1995 study, the effect of magnesium and vitamin C supplements on metabolic control was assessed in 56 diabetics. The study involved a 90-day run-in period followed by two 90-day treatment periods, during which patients received 600 mg of magnesium and 2 g of vitamin C per day. The results showed that vitamin C supplementation improved glycemic control, fasting blood glucose, cholesterol and triglycerides.8

Vitamin C supplementation is effective in reducing sorbitol accumulation in the red blood cells of diabetics. In a 58-day study carried out in 1994, researchers investigated the effect of two different doses of vitamin C supplements (100 or 600 mg) on young adults with Type I diabetes. The results showed that within 30 days, vitamin C supplementation at either dose normalized sorbitol levels in those with diabetes.9 Vitamin C may also help to reduce capillary fragility, which also contributes to complications. The ability of the arteries to dilate is impaired in diabetics. Vitamin C supplements improve the response.10 Drugs which are used to reduce sorbitol have many toxic side effects, and vitamin C therapy is beneficial in reducing sorbitol accumulation without the toxicity. Vitamin C has also been shown to reduce the attachment of glucose to proteins, and the damage this causes.

Vitamin E

Vitamin E supplements have been shown to have beneficial effects in diabetics. As an antioxidant, vitamin E reduces damage to cell membranes, improving glucose metabolism and enabling insulin to act more efficiently. It also reduces the attachment of glucose to proteins.11 Vitamin E has also been shown to have beneficial effects on cholesterol levels in diabetics by reducing the susceptibility of LDL to oxidative damage, thus limiting damage to arteries. Vitamin E also reduces blood clotting, another contributory factor to heart disease.

In a study published in 1996, Louisiana researchers examined whether 67 mg (100 IU) per day had any effect on blood lipid oxidation products and blood lipid profiles of 35 diabetic patients over a three-month period. The results showed that vitamin E supplementation significantly lowered lipid peroxidation products and lipid levels in diabetic patients.12

Type I Diabetes

The results of a 1997 study done in Italy show that vitamin E can protect against damage to beta cells which produce insulin in Type I diabetes patients. The one-year study involved 84 patients between 5 and 35 years of age. One group was treated with vitamin E supplements and the other group received nicotinic acid which has been shown to protect pancreatic beta cell function. All patients were under intensive insulin therapy with three to four injections a day. The results showed that vitamin E was as effective as nicotinic acid in protecting the beta cells.13

Nicotinamide

The nicotinamide form of niacin may prevent or delay clinical onset of Type I diabetes. Nicotinamide appears to interfere with the immune-mediated beta cell destruction by reducing production of harmful compounds and increasing the energy metabolism of the cell.

New Zealand researchers have carried out a controlled trial of oral nicotinamide in the prevention of the onset of diabetes mellitus in a group of high risk children. All eight of the untreated children developed diabetes during the follow-up period of the study, whereas only one of 14 treated children did.14 In 1996, the same researchers published the findings of a population-based diabetes prevention trial involving nicotinamide treatment of 173 children aged 5 to 8 at risk of Type I diabetes. The results showed a 50 per cent reduction in the development of diabetes in a five-year period, and suggest a protective effect of nicotinamide.15

Vitamin B6

Vitamin B6 deficiency causes symptoms such as low blood sugar, low insulin levels, degeneration of beta cells and an altered insulin response to sugar. Insulin sensitivity increases when vitamin B6 intake increases in people who are deficient.

Vitamin B12

The vitamin B12 deficiency disease, pernicious anemia, is not uncommon in Type I diabetics. Researchers have studied the effects of vitamin B12 on patients with diabetic nerve disease. Treatment has been shown to improve some of the symptoms.

Biotin

Biotin supplements may help to improve blood glucose control in diabetics by enhancing insulin sensitivity and increasing the activity of enzymes involved in glucose metabolism.16 Biotin in high doses may also be useful in the treatment of diabetic neuropathy. 17

Vitamin D

The alterations in mineral metabolism seen in diabetics may lead to changes in the vitamin D function. Vitamin D deficiency also impairs glucose metabolism by reducing insulin secretion which may increase the risk of diabetes. Vitamin D supplements are likely to be useful in preventing diabetes in areas where vitamin D deficiency is common.18

In a 1997 study looking at the links between environmental factors and Type II diabetes, vitamin D levels were assessed in 142 Dutch men aged from 70 to 88 years of age. Thirty-nine per cent were found to have low vitamin D levels and tests showed that low vitamin D levels increased the risk of glucose intolerance.19

Changes in Mineral Metabolism

There is evidence that the metabolism of several trace elements is altered in diabetes and that these nutrients might have specific roles in the progress of this disease. Diabetes can alter copper, zinc and magnesium status; and these changes in mineral metabolism are more pronounced in diabetic populations with specific complications. It is always clear whether differences in trace element status are a consequence of diabetes or, alternatively, whether they contribute to the disease. Recently, some essential trace elements such as vanadium and selenium have been shown to have insulin-like effects. It is very likely that chromium, manganese, vanadium, and selenium have a favorable effect on carbohydrate metabolism.

Magnesium

Magnesium deficiency is the most evident disturbance of mineral metabolism in both Type I and Type II diabetes, with up to 30 per cent of diabetics showing some evidence of magnesium depletion. The clinical consequences of magnesium deficiency include impaired insulin secretion and reduced tissue sensitivity to insulin, and increased risk of damage to blood vessels.

Magnesium excretion is increased in children with Type I diabetes, especially when the levels of glucose in the urine are high, as blood plasma magnesium levels in diabetes are closely dependent on blood glucose concentration. In Type II diabetes, magnesium deficiency seems to be associated with insulin resistance. It may also be involved in the development of diabetes complications and may contribute to the increased risk of sudden death associated with diabetes. Some studies suggest that magnesium deficiency may play a role in spontaneous abortion and birth defects in diabetic women.

Results from the ARIC study suggest that serum magnesium levels are low in those suffering from diabetes, and that intake is related to insulin levels. This study involved over 15,248 people, male and female, black and white, aged 45 to 64 years.20 Magnesium plays a role in the insulin-mediated uptake of glucose into cells, and deficiency may worsen control of diabetes.21 Low magnesium levels increase the risk of several disorders; including heart disease, eye disease and bone problems.

According to research presented at the 1997 annual meeting of the American Diabetes Association, low magnesium levels predict Type II diabetes in whites. Researchers from Johns Hopkins University Medical School examined blood levels of magnesium in over 12,000 nondiabetic, middle-aged African American and white subjects and monitored them for six years. No relationship was found between magnesium levels and diabetes in African Americans, but a relationship was seen in whites.

The ADA has recommended that diabetics with low magnesium levels should take supplements as they have been shown to improve glucose tolerance and insulin response and action. They may also help protect against diabetic complications including heart disease and eye disorders. In a 1994 study, Italian researchers investigated the effects of magnesium supplementation on glucose uptake and use in nine elderly Type II diabetic patients. Each patient was followed up for a period of three weeks before the study, and was then given either a placebo or a magnesium supplement for four weeks. At the end of this time, improvements in insulin sensitivity and glucose oxidation were seen in those taking magnesium.22 Magnesium supplements have also been shown to lower blood pressure in Type II diabetics.23

Chromium

Chromium, as part of a compound known as glucose tolerance factor (GTF), plays a role in blood sugar control primarily by increasing tissue sensitivity to insulin. When sufficient levels of chromium are present much lower amounts of insulin are required. Diabetes has been shown to develop as a consequence of chromium deficiency in experimental animals and in humans sustained by prolonged total parenteral nutrition.

Chromium deficiency is relatively common in patients with Type II diabetes and may impair the function of GTF, causing the uptake of glucose into cells to become less efficient. Impaired chromium metabolism may also play a role in diabetes of pregnancy.24 High insulin levels also seem to increase chromium excretion. Chromium deficiency may also lead to hypoglycemia or low blood sugar.

Chromium supplements have been successfully used to treat Type I and Type II diabetes, diabetes in pregnancy, and hypoglycemia. Chromium supplementation has been shown to lower fasting glucose levels, improve glucose tolerance and lower insulin levels in Type II diabetics. This helps to keep blood levels stable, thereby preventing damage to blood vessels and organs caused by high levels of blood sugar. The greatest benefits are seen in those who have severe deficiencies. Chromium acts to increase insulin sensitivity by improving insulin binding, insulin receptor number, insulin internalization, beta cell sensitivity and insulin receptor enzymes.25

According to the results of a Chinese study published in 1997, daily chromium supplements may help control blood sugar levels and insulin activity in Type II diabetics. The study, conducted by researchers at the US Department of Agriculture and Beijing Medical University, involved 180 Type II diabetics. Chinese subjects were chosen because of the likelihood that they had not previously used supplements. The subjects were divided into three groups: one group was given 1000 mcg of chromium picolinate, the second was given 200 mcg and the third group was given a placebo. After two months, the researchers assessed blood sugar and cholesterol levels. In the 1000 mcg group, levels were significantly reduced. In the 200 mcg group, it took four months to see a reduction in blood sugar levels, and this was not as significant as that seen in the first group.26

In a study published in 1996, researchers assessed the effects of daily supplements of 200 mcg of chromium and nicotinic acid on blood glucose and lipids, including total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. The patients were 14 healthy adults and five adults with Type II diabetes mellitus. The results showed lowered total and LDL cholesterol, triglycerides, and glucose concentrations in patients with Type II diabetes.27

Selenium

A selenium deficiency may reduce insulin secretion. As part of the antioxidant enzyme, glutathione peroxidase, selenium is important in protecting against oxidative damage.

Vanadium

Vanadium can mimic the effects of insulin on cells in laboratory experiments and reduce the blood sugar levels in rats from high to normal. These benefits are seen with low doses. There have been limited clinical trials with vanadium salts in Type II diabetics, indicating that vanadium may have therapeutic potential in the treatment of diabetes. 28

In a study published in 1996, researchers at the Albert Einstein College of Medicine in New York compared the effects of 100 mg/day of oral vanadyl sulfate in moderately obese diabetic and nondiabetic people. The results showed improvements in both liver and skeletal muscle insulin sensitivity in diabetics. Blood fat levels and oxidation were also reduced. Thus vanadium may also be useful in reducing the risk of atherosclerosis in diabetic people.29

Zinc

Alterations in zinc metabolism are seen in people with both Type I and Type II diabetes. Response to insulin may be decreased and excretion in the urine is increased, thus exacerbating the risk of deficiency with all the associated risks such as poor immune function and increased risk of birth defects.

Zinc deficiency has been shown to increase the risk for diabetes in diabetes-prone experimental animals, and low concentrations of zinc have also been shown in the blood of people recently diagnosed with Type I diabetes. The results of a 1995 Swedish study suggest that a low concentration of zinc in drinking water can increase the risk of childhood onset of the disease.30

Diabetics often excrete excess zinc in their urine and studies have shown beneficial effects of zinc supplementation. Zinc supplementation in animals improves glucose tolerance; and in a French study carried out in 1995, zinc gluconate supplements were shown to improve glucose assimilation in humans.31

Zinc deficiency may lead to slower growth in diabetic children, who may benefit from supplements. Zinc supplements may also be useful in protecting against pregnancy complications in diabetic women who are at risk, and may also improve wound-healing.

Other Nutrients

Essential Fatty Acids

Increased intakes of omega-3 oils may be beneficial in helping to reduce the risk of cardiovascular disease in diabetics. There were some concerns that omega-3 fatty acid supplements would worsen blood sugar control in diabetics but more recent studies suggest that this is not the case. In a 1997 Italian study, researchers evaluated the effect of omega-3 fatty acid supplements on 935 patients with high blood fat levels, both with and without glucose intolerance or diabetes. The results showed improvements in blood fat levels and no worsening of blood sugar control.32

Diabetics seem to have a reduced ability to convert linoleic acid to GLA. This may lead to defective nerve function as metabolites of GLA are known to be important in nerve membrane structure, nerve blood flow, and nerve conduction. In a 1993 double-blind, placebo-controlled study, UK researchers compared the effects of placebo and GLA (480 mg per day) on the course of mild diabetic neuropathy in 111 patients over a one-year period. They used various nerve conduction, sensation and reflex tests, and the results of these showed that the change over one year in response to GLA was more favorable than the change with placebo.33

Lipoic Acid

Lipoic acid has been used to treat diabetics by improving glucose transport and metabolism.34 High intakes may increase the absorption of glucose into muscle tissue in Type II diabetes.35 Lipoic acid may also decrease the damaging effects on proteins of high glucose levels.

Lipoic acid may be beneficial in improving nerve blood flow, reducing oxidative stress, and improving nerve conduction in diabetic neuropathy.36 The effects of lipoic acid on diabetic neuropathy have been studied in two German randomized, double-blind placebo-controlled trials. In the first of these, 328 patients with Type II diabetes and symptoms of peripheral neuropathy were treated with either intravenous infusion of lipoic acid or placebo for three weeks. The results showed improvements in symptoms. In another study, patients with NIDDM and cardiac autonomic neuropathy were treated with a daily oral dose of 800 mg lipoic acid or placebo for four months. Two out of four symptoms test measurements were significantly improved in those taking the lipoic acid compared with placebo.37

Herbal Medicine and Diabetes

Herbal medicines will not replace insulin therapy where it is necessary, and anyone who is thinking of or is currently using herbs to control blood sugar should consult their health practitioner. However, there are many herbs which have been used to treat diabetes and its complications. These include gymnena (Gymnema sylvestre), fenugreek (Trigonella foenum-graecum), garlic (Allium sativum), onion (Allium cepa). Other herbs such as ginkgo (Ginkgo biloba), hawthorn (Crataegus oxyacantha) and bilberry (Vaccinium myrtillus) may be useful in preventing the vascular complications commonly seen in diabetic patients.

1 Atkinson MA; Ellis TM. Infants diets and insulin-dependent diabetes: evaluating the "cows' milk hypothesis" and a role for anti-bovine serum albumin immunity. J Am Coll Nutr, 1997 Aug, 16:4, 334-4

2 Huang B; Rodriguez BL; Burchfiel CM; Chyou PH; Curb JD; Yano K. Acculturation and prevalence of diabetes among Japanese-American men in Hawaii. Am J Epidemiol, 1996 Oct, 144:7, 674-81

3 Salmerón J; Manson JE; Stampfer MJ; Colditz GA; Wing AL; Willett WC. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. JAMA, 1997 Feb, 277:6, 472-7

4 Salmerón J; Ascherio A; Rimm EB; Colditz GA; Spiegelman D; Jenkins DJ; Stampfer MJ; Wing AL; Willett WC Dietary fiber, glycemic load, and risk of NIDDM in men. Diabetes Care, 1997 Apr, 20:4, 545-50

5 Maxwell SR; Thomason H; Sandler D; Leguen C; Baxter MA; Thorpe GH; Jones AF; Barnett AH. Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus. Eur J Clin Invest, 1997 Jun, 27:6, 484-90

6 Holecek V; Racek J; Jerábek Z. Administration of multivitamin combinations and trace elements in diabetes. Cas Lek Cesk, 1995 Feb, 134:3, 80-3

7 Sinclair AJ; Taylor PB; Lunec J; Girling AJ; Barnett AH Low plasma ascorbate levels in patients with type 2 diabetes mellitus consuming adequate dietary vitamin C. Diabet Med, 1994 Nov, 11:9, 893-8

8 Eriksson J; Kohvakka A Magnesium and ascorbic acid supplementation in diabetes mellitus. Ann Nutr Metab, 1995, 39:4, 217-23

9 Cunningham JJ; Mearkle PL; Brown RG Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus. J Am Coll Nutr, 1994 Aug, 13:4, 344-5

10 Timimi FK; Ting HH; Haley EA; Roddy MA; Ganz P; Creager MA Vitamin C improves endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol, 1998 Mar, 31:3, 552-7

11 Jain SK; McVie R; Jaramillo JJ; Palmer M; Smith T. Effect of modest vitamin E supplementation on blood glycated hemoglobin and triglyceride levels and red cell indices in type I diabetic patients. J Am Coll Nutr, 1996 Oct, 15:5, 458-61

12 Jain SK; McVie R; Jaramillo JJ; Palmer M; Smith T; Meachum ZD; Little RL The effect of modest vitamin E supplementation on lipid peroxidation products and other cardiovascular risk factors in diabetic patients. Lipids, 1996 Mar, 31 Suppl:, S87-90

13 Pozzilli P et al. Vitamin E and nicotinamide have similar effects in maintaining residual beta cell function in recent onset insulin-dependent diabetes (the IMDIAB IV study). Eur J Endocrinol, 1997 Sep, 137:3, 234-9

14 Elliott RB; Chase HP. Prevention or delay of type 1 (insulin-dependent) diabetes mellitus in children using nicotinamide. Diabetologia, 1991 May, 34:5, 362-5

15 Elliott RB; Pilcher CC; Fergusson DM; Stewart AW A population based strategy to prevent insulin-dependent diabetes using nicotinamide. Pediatr Endocrinol Metab, 1996 Sep, 9:5, 501-9

16 Koutsikos D et al. Oral glucose tolerance test after high-dose i.v. biotin administration in normoglucemic hemodialysis patients. Ren Fail, 1996 Jan, 18:1, 131-7

17 Koutsikos D et al. Biotin for diabetic peripheral neuropathy. Biomed Pharmacother. 1990; 44: 511-514

18 Boucher BJ; Mannan N; Noonan K; Hales CN; Evans SJ Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. Diabetologia, 1995 Oct, 38:10, 1239-45

19 Baynes KC; Boucher BJ; Feskens EJ; Kromhout D Vitamin D, glucose tolerance and insulinaemia in elderly men. Diabetologia, 1997 Mar, 40:3, 344-7

20 Ma J et al. Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities. J Clin Epidemiol, 1995 Jul, 48:7, 927-40

21 Paolisso G; Barbagallo M Hypertension, diabetes mellitus, and insulin resistance: the role of intracellular magnesium. Am J Hypertens, 1997 Mar, 10:3, 346-55

22 Paolisso G et al. Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type II) diabetic patients. J Clin Endocrinol Metab, 1994 Jun, 78:6, 1510-4

23 Gilleran G; OLeary M; Bartlett WA; Vinall H; Jones AF; Dodson PM Effects of dietary sodium substitution with potassium and magnesium in hypertensive type II diabetics: a randomised blind controlled parallel study. J Hum Hypertens, 1996 Aug, 10:8, 517-21

24 Aharoni A; Tesler B; Paltieli Y; Tal J; Dori Z; Sharf M Hair chromium content of women with gestational diabetes compared with nondiabetic pregnant women. Am J Clin Nutr, 1992 Jan, 55:1, 104-7

25 Anderson RA Nutritional factors influencing the glucose/insulin system: chromium. J Am Coll Nutr, 1997 Oct, 16:5, 404-10

26 Anderson RA; Cheng N; Bryden NA; Polansky MM; Cheng N; Chi J; Feng J. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes, 1997 Nov, 46:11, 1786-91

27 Thomas VL; Gropper SS. Effect of chromium nicotinic acid supplementation on selected cardiovascular disease risk factors. Biol Trace Elem Res, 1996 Dec, 55:3, 297-305

28 Verma S; Cam MC; McNeill JH. Nutritional factors that can favorably influence the glucose/insulin system: vanadium. J Am Coll Nutr, 1998 Feb, 17:1, 11-8

29 Halberstam M; Cohen N; Shlimovich P; Rossetti L; Shamoon H Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects. Diabetes, 1996 May, 45:5, 659-66

30 Haglund B; Ryckenberg K; Selinus O; Dahlquist G Evidence of a relationship between childhood-onset type I diabetes and low groundwater concentration of zinc. Diabetes Care, 1996 Aug, 19:8, 873-5

31 Brun JF; Guintrand Hugret R; Fons C; Carvajal J; Fedou C; Fussellier M; Bardet L; Orsetti A Effects of oral zinc gluconate on glucose effectiveness and insulin sensitivity in humans. Biol Trace Elem Res, 1995 Jan, 47:1-3, 385-91

32 Collier PM; Ursell A; Zaremba K; Payne CM; Staughton RC; Sanders T. Effect of regular consumption of oily fish compared with white fish on chronic plaque psoriasis. Eur J Clin Nutr, 1993 Apr, 47:4, 251-4

33 Mayser P et al. Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, multicenter trial. J Am Acad Dermatol, 1998 Apr, 38:4, 539-47

34 Streeper RS; Henriksen EJ; Jacob S; Hokama JY; Fogt DL; Tritschler HJ Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Am J Physiol, 1997 Jul, 273:1 Pt 1, E185-91

35 Jacob S et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung, 45: 8, 1995 Aug, 872-4

36 Nagamatsu M et al. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care, 18: 8, 1995 Aug, 1160-7

37 Ziegler D; Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes, 1997 Sep, 46 S

S

Suppl 2:, S62-63-61