-IBIS-1.7.6-
tx
endocrine system
diabetes mellitus
Nutrition


dietary guidelines
» eating principles
Decrease sucrose and other simple carbohydrates: all simple sugars, including fructose, should be markedly lowered. Fructose is often represented as a "healthy" food for diabetics because of its lack of insulin stimulation. However, a number of studies have shown that fructose consumption may also result in long term deleterious effects.
Note: In acute loading studies a synergism between glucose and fructose with regard to insulin secretion exists. Neither glucose or fructose, when given as the sole monosaccharide, stimulates insulin secretion as potently as glucose and fructose combined.
(Beck-Neilsin, et al. Am J Clin Nutr. 33:273; Hallfrisch J. et al. Am J Clin Nutr 43:151-59, 1986.)
• Increase complex carbohydrates to 60-70% of caloric intake; decrease fat to 20%
(Chait A. Contemp. Nutr. (2), Feb,1984.)
Increase consumption of foods with low glycemic indexes (especially legumes). Legumes in the morning have shown an extremely beneficial effect on blood glucose; in fact, they seem to keep the blood glucose at a fairly low level for almost 4-6 hours.
Treat food sensitivities
Fiber — foods high in water-soluble fiber: up to 80-100 gms per day.
guar gum (5 gms per meal)
pectin - up to 30 gms per day
oat bran (1 cup oats provides 9 gms fiber)
Reduce protein intake: Reduced protein intake is associated with lowered kidney damage caused by diabetes; some, but not necessarily all individuals, may experience improved glucose tolerance.
(Cohen D, et al. Brit Med J 1987;294:795-798; Evanoff G, et al. Arch Intern Med 1989;149:1129-1133; Gin H, et al. Nephron 1991;57:411-415.)

» for juvenile onset:
avoid dairy: Children who drink cow's milk at an earlier age may have an increased risk of IDDM. The proteins in cow's milk may be an inciting antigen to trigger off auto-antibodies to pancreatic cells due to their similarity to a protein in the human pancreas, the site of insulin production. Some research indicates that children with IDDM may exhibit heightened levels of antibodies that attack milk protein. Populations with higher milk consumption generally have a correspondingly high risk of IDDM.
(Maclaren N, Atkinson M. N Engl J Med 327(5):348-349; Dahl-Jorgensen K, et al. Diabetes Care 1991;14:1081-1083; Coleman DL, et al. Diabetes 1990;39:432-436; Gerstein H. Diabetes Care 1994;17:13-19;. Karajalainen J, et al. N Engl J Med 1992;327:302-307; Scott FWE, et al. Diabetes Care 1996;19:379-383; Atkinson MA, et al. N Engl J Med 1993;329:1853-1858.)

» for adult onset (Type 2) :
• low sugar, low cholesterol
• low fat diet of unsaturated fats
• calorie percentages: 70% complex carbohydrates, protein 12-15%, fat 15-18%
• high fiber
• low Sodium/Sodium-restricted diet
• avoid overeating! If overweight, reduce weight to normal range. Avoid mental and nervous stresses, especially worrying.
• eat in a pleasant environment and chew all food well. Eat 5-6 small meals through out the day instead of large meals.
• alkaline vegetarian diets can be helpful
• elimination/rotation diet, rotation diet, rotation diet expanded

therapeutic foods:
• cucumber, stringbeans (Airola, 72.)
• garlic, Jerusalem artichokes, burdock, parsley (Shefi)
• foods rich in Chromium and Zinc (Airola, 72.)
foods high in water-soluble fiber: flax seed, pectin, guar gum, oat bran, glucomannan, mucilage
(Florholmen J, et al. Acta Med Scand 1982;212:237-239; Rodríguez-Morán M, et al. Diabetes Its Complications 1998;12:273-278; Landin K, et al. Am J Clin Nutr 1992;56:1061-1065; Schwartz SE, et al. Am J Clin Nutr 1988;48:1413-1417; Hallfrisch J, et al. Am J Clin Nutr 1995;61:379-384; Doi K, et al. Lancet 1979;i:987-988.)
• complex whole grain and legume carbohydrates
• fenugreek seeds, 1-3 ounces per day, powdered
(Sharma RD, Raghuram TC. Nutr Res 1990;10:731-739; Raghuram TC, et al. Phytother Res 1994;8:83-86.)
• pumpkin, whole rice, yams, mung beans, squash, celery, peach, millet, onion, spinach, blueberry, peas, tofu, cabbage, daikon radish, mulberries (Ni, 122.)
• foods rich in Iodine, Silicon, Phosphorus: kelp, dulse, Swiss Chard, turnip greens, egg yolks, wheat germ, cod roe, lecithin, sesame seed butter, seed and nuts, raw goat milk (Jensen, 61.)
• garlic, wheat germ, liquid chlorophyll, alfalfa sprouts, buckwheat, watercress, rice polishings, apple, celery, cherries (Ni, 120.)
• onions, beans, legumes, soy, ginger, alfalfa, yogurt, brewer's yeast (Marz)
increase omega-3 and omega-6 fatty acids: vegetable, nut, seed oils, salmon, herring, mackerel, sardines, walnuts, flax seed oil, evening primrose oil, black currant oil
(Feskens EJM, et al. Diabetes Care 1991;14:935-941.)
vegetarian or vegan diet: reduced meat intake (especially reduced fat intake) can reduce heart disease, the leading cause of death among diabetics; furthermore, a vegan diet has been found to be especially helpful in reducing or reversing nerve damage due to diabetes.
(Snowdon DA, Phillips RL. Am J Publ Health 1985;75:507-512; Crane MG, Sample CJ. Am J Clin Nutr 1988;48:926; Crane MG, Sample C. J Nutr Med 1994;4:431-439.)
• spices: cinnamon, turmeric, bay leaf, cloves

» Kidney Xu (Deficiency) Diabetes:
• foods that tonify the Kidney

» Spleen and Stomach Xu (Deficiency) Diabetes:
• harmonize Spleen/Stomach foods

fresh juices:
• stringbean, cucumber, and celery (Airola, 71.)
• raw sauerkraut and lemon
• raw sauerkraut and tomato
• parsley tea
• huckleberry leaf tea (Shefi)
• stringbean, brussel sprout, carrot, and lettuce (Walker, 77.)
• watermelon and tomato (Chao-liang, Qing-rong, Bao-zhen, 62.)

eating principles
for Juvenile-Onset, Insulin-dependent (Type 1) :
• diet should be carefully calculated according to the type and amount of insulin used. Children need enough energy for growth, so supply adequate calories from complex carbohydrates. All other information concerning adult-onset is applicable.

fresh juices:
• bamboo shoots and celery, warm and drink (Ni, 33.)
• celery (Ni, 33.)

specific remedies:
• celery, yam, and pumpkin (Ni, 33.)
• pumpkin, yam, and potato pie (Ni, 122.)
• cook snow peas, blend into juice, drink 1/2 cup, twice daily (Ni, 47.)
• tea from spinach and chicken gizzards; l cup, three times daily (Ni, 49.)
• soup from cabbage, yam, winter melon, and lentils (Ni, 122.)
• steam tofu, cool, add sesame oil and slices of raw squash (Ni, 122.)
• soup from mung beans, peas, and barley (Ni, 122.)
• steam millet with yams and a few dates (Ni, 122.)
• drink daikon radish, celery, carrot, and spinach juice (Ni, 122.)
• crack open a fresh coconut and drink the juice, twice daily (Yin-fang and Cheng-jun, 86.)

See Exchange lists for diabetes

avoid:
food intolerances.
(Pots J, Lange M. Diabetes, 1977;26, supp. 1 #234 and Diabetes 1980;29:6; Philpott, Kalita, 1983.)
alcohol: Alcohol consumption will usually decrease glucose tolerance in those with diabetes and in the elderly. Alcohol intake by diabetics particularly increases the risk of diabetes-related damage to the eyes and nerves. In contrast, moderate alcohol consumption in healthy individuals can actually improve glucose tolerance.
(Goden G, et al. Diabetes 1993;42:28-34; Ben G, et al. Am J Med 1991;90:70; Young RJ, et al. Brit Med J 1984;288:1035; Connor H, Marks V. Human Nutr Appl Nutr 1985;39A:393-399; Kiechl S, et al. Brit Med J 1996;313:1040-1044; Facchini F, et al. Diabetes Care 1994;17:115; Rimm EB, et al. Brit Med J 1995;310:555-559; Stampfer MJ, et al. Am J Epidemiol 1988;128:549-558.)
coffee (Tuomilehto J, et al. Brit Med Journal March 1990;300:642-643.)
sugars (all types: malt, maltose, dextrose, corn syrup), candy, honey, molasses, dried fruits, concentrated sweets, concentrated juices, fried foods, caffeine, spicy foods, processed foods
trans-fatty acids, hydrogenated oils (margarine, vegetable shortenings, imitation butter spreads, most commercial peanut butters) oxidized fats (deep fried foods, fast food, ghee, barbequed meats)
Iron: Excess iron may stimulate the production of free radicals which can damage the beta cells of the pancreas, damage the insulin molecules that are secreted, or in some way effect the insulin receptors.
(Phelps, et al. Lancet 2:233-34, 1989; Cutler, P. Diabetes 1989;38:1207-1210.)


supplements

Thiamine 100 mg per day (2 week trial). Researchers have come up with variable results in treating diabetic neuropathies, with the best outcomes when B1 when individuals previously on a vitamin-deficient diet were supplemented with B1 and when B1 was used in combination with vitamins B6 and/or B12. Some studies have reported blood lower levels of B1 in diabetics.
(Vorhaus MG, et al. Am J Dig Dis 1935;2:541-557; Abbas ZG, Swai ABM. East African Med J 1997;74:804-848.; Stracke H, et al. Exp Clin Endocrinol Diabetes 1996;104:311-316; Haugen HN. Scand J Clin Lab Invest 1964;16:260-266.)
Vitamin B3: Niacin and/or niacinamide: 250 mg-1500 mg should be given especially at the early onset of IDDM; also for gestational diabetes However, some researchers have reported that several grams per day of niacin can impair glucose tolerance and should be avoided by individuals with diabetes.
(Mertz W, 1975, 129; Coelingh, 1975, 13ff; Clearly JP. et al. J Orthomol Med 1988;3:164-174; Clearly JP. J Nutr Med 1990;1:217–25; Vague P, et al. Lancet 1987;1:619-620; Lewis CM, et al. Diabetes Care 1992;15:121-123; Chase HP, et al. Diabetologia 1990;33:444-446; Mendola G, et al. Diabetologia 1989;32:160-162; Elliott RB, et al. J Pediatr Endocrinol Metabol 1996;9:501-509; Lampeter EF, et al. Diabetes 1998;47:980-984; Molnar GD, et al. Metabol 1964;13:181-189; Gaut ZN, et al. Metabol 1971:1031-1035.)
Vitamin B6 100 mg per day esp. with neuropathy; also for gestational diabetes and glucose intolerance associated with pregnancy and birth control pill use.
Vitamin B6 is especially beneficial for diabetic neuropathy. Most diabetics exhibit low blood levels of B6, especially those suffering from diabetic neuropathies. It should be noted that xanthurenic acid is often elevated in diabetics. In addition, B6 inhibits platelet aggregation and prevents thromboxane release. It also inhibits clotting by blocking the clotting activity of thrombin. 100 mg in humans can block platelet function for up to 52 hours. Passariello et al found that 1,800 mg per day of pyridoxine alpha-ketoglutarate was particularly effective in improving glucose tolerance in diabetics.
(Davis R, et al. Pathol 1976 Apr;8(2):151-156; Jones CL, Gonzalez V. J Am Podiatry Assoc 1978 Sep;68(9):646-653; Kotake Y, Murakami E. Am J Clinical Nut 1971 July; 826-829; Wilson RG, Davis RE. Pathol 1977;9:95-99; McCann VJ, Davis RE. Austral NZ Med 1978;8:259-261; Spellacy WN, et al. Am J Obstet Gynecol 1977;127:599-602; Coelingh HJT, Schreurs WHP. Brit Med J 1975;3:13-15; Spellacy WN, et al. Contraception 1972;6:265-273; Passariello N, et al. Internat J Clin Pharmacol Ther Toxicol 1983;21:252-256; Solomon LR, Cohen K. Diabetes 1989;38:881-886; Rao RH, et al. J Clin Endocrinol Metabol 1980;50:198-200.)
• Vitamin B12: plays a critical role in healthy nerve function. Oral doses of 300 to 500 mcg three times per day are usually beneficial. Researhcers have found that oral, intravenous, and intramuscular injection administration can usually reduce nerve damage caused due to diabetes.
(Yamane K, et al. Curr Ther Res 1995;56:656-670.)
Vitamin C: 2 - 3 g per day
Individuals with IDDM tend to exhibit low levels of vitamin C; those with NIDDM often experience improved glucose tolerance when supplementing with vitamin C. 2-4 grams per day decreases levels of sorbitol, a sugar, in red blood cells. This is important since sorbitol tends to accumulate in diabetics and cause damage to the eyes, nerves, and kidneys. During the 1970s Dr. Mann of Vanderbilt University theorized that vitamin C and glucose have the same transport mechanism because they are so similar structurally. As a result the excess glucose can inhibit vitamin C transport into cells and as a result may produce localized scurvy. The end organ pathologies of diabetes look very similar to that of scurvy. It may be that a chronic Vitamin C deficiency leads to the microangiopathy of diabetes.
(Som S, et al. Metabolism 1981 Jun;30(6):572-577; Friend, Time; USA Today, Life Section, Sept. 18, 1990; Cunningham JJ, et al. Metabol 1991;40:146-149; Davie SJ, et al. Diabetes 1992;41:167-173; Will JC, Tyers T. Nutr Rev 1996;54:193-202; Eriksson J, Kohvakka A. Ann Nutr Metabol 1995;39:217-223; Paolisso G, et al. J Am Coll Nutr 1995;14:387-392; Mayer-Davis E, et al. Ophthalmology 1998;105:2264-2270.)
• Vitamin D: Some evidence suggests that supplementation might facilitate increased insulin secretion in some individuals with NIDDM. It is known that the areas of the pancreas responsible for insulin production have vitamin D receptors and that the vitamin plays an important role in maintaining blood levels of insulin.
(Labriji-Mestaghanmi H, et al. J Endocrine Invest 1988;11:577-587; Boucher BJ. Br J Nutr 1998;79:315-327.)
Vitamin E: 100 IU and increase slowly to 400 IU, adjusting insulin dose, as needed; many researchers and practitioners have used 900 IU as a standard dose. Vitamin E protects the blood vessels of diabetics from damage in many ways, such as preventing excessively rapid clotting; animal research indicates that this may be especially important in reducing the incidence and severity of diabetic cataracts. Vitamin E may reduce the risk of IDDM by reducing oxidative damage in the pancreas. Some research indicates that vitamin E reduces glycosylation, an important index of diabetes. Most double-blind studies of individuals with NIDDM have found that vitamin E improves glucose tolerance.
(Salonen JT, et al. Brit Med J 1995;311:1124-1127; Bierenbaum ML, et al. Nutr Rep Internat 1985;31:1171-1180; Paolisso G, et al. Am J Clin Nutr 1993;57:650-656; Paolisso G, et al. Diabetes Care 1993;16:1433-1437; Tütüncü NB, et al. Diabetes Care 1998;21:1915-1918; Paolisso G, et al. Am J Clin Nutr 1994;59:1291-1296; Paolisso G, et al. Lancet 1994;343:596; Colette C, et al. Am J Clin Nutr 1988;47:256-261; Gisnger C, et al. Diabetes 1988;37:1260-1264; Ross WM, et al. Can J Ophthalmol 1982;17:61; Knekt P, et al. J Intern Med 1999;245:99-102; Ceriello A, et al. Diabetes Care 1991;14:68-72; Duntas L, et al. Curr Ther Res 1996;57:682-690; Reaven PD, et al. Diabetes Care 1995;18:807; Tütüncü NB, et al. Diabetes Care 1998;21:1915-1918.)
Warning: Vitamin E may reduce the insulin requirement. Diabetics on insulin should be started on 100 IU or less daily and the dosage raised slowly with adjustment of the insulin dose. Diabetic patients have tocopherol deficiencies which cause increased free-radical damage. Vitamin E, as an antioxidant, may help prevent diabetic complications. It also increases HDL-cholesterol levels and aids in fatty acid metabolism.
(Lubin B, 1982, p. 389; Vogelsang, A. Ann NY Acad Sci 393, 1982; Ozden I, et al. Diabetes Res 1989 Nov;12(3):123-124.)
Alpha-Lipoic Acid: Alpha-lipoic acid has been shown to be beneficial in type 1 and type 2 diabetes, by preventing various pathologies associated with this disease, such as reperfusion injury, macular degeneration, cataracts, and neuropathy. ALA is approved in Germany to treat diabetic neuropathy. The most commonly used therapeutic dosage to improve diabetic neuropathies is 600 mg per day. It has been used to reduce pain associated with nerve damage. ALA improves blood flow to peripheral nerves and stimulates regeneration of nerve fibers. A German study evaluating 800 mg per day of ALA in diabetics with damaged autonomic nervous systems was compared against a placebo. After 4 months, sympathetic systems showed improvement and autonomic nerve disorder decreased in the ALA group.
(Murray, M. 1996; 343-346; Ley, B. BL Publications. 1996; Schonheit, K, at al. Biochemica et Biophysica Acta 1995; 1271:335-342; Nagamatsu M, at al. Diabetes Care 1995; 18:1160-1167; Packer L, Witt EH, Tritschler HJ. Free Rad Biol Med 1995; 19:227-250; Garrett NE, Malcangio M, Dewhurst M, Tomlinson DR. Neurosci Lett 1997; 222: 191-194; Ziegler D, et al. Diabetes Care 1997; 20:369-373.)
Diabetic neuropathy: A three-week multicenter double-blind, placebo-controlled trial of alpha-lipoic acid administered intravenously at 1200, 600, or 100 mg was conducted in patients with diabetic neuropathy. Symptom scoring including pain, burning, paresthesia, and numbness was conducted at baseline and at each visit. Intravenous treatment with 600 mg/day for three weeks was superior to placebo in reducing symptoms of neuropathy and caused no significant adverse reactions.
(Ziegler D, et al. Diabetoogia 1995; 38: 1425-1433.)
In a non-blinded study of diabetic patients with both type 1 and 2 diabetes, 600 mg/day of alpha-lipoic acid was given for two weeks, followed by 300 mg/day for 10 weeks. Albuminuria decreased 50% as compared to placebo controls. A clinical improvement in neurological symptoms was found in the alpha-lipoic acid group but not in the control group.
(Kehler W, et al. 1993: 33-53.)
Blood sugar metabolism: ALA also improves the diabetic condition by improving blood sugar metabolism, by facilitating better conversion of sugar into energy. (Murray, M. 1996; 343-346) In 13 non-insulin-dependent diabetes mellitus patients, ALA increased insulin-stimulated glucose disposal. Metabolic clearance rate for glucose rose by 50% compared with the control group. (Jacob S, et al. Arzneimittel-Forschung 1995; 45(8): 872-874.) In heart tissue of diabetic rats, high doses of alpha-lipoic acid first normalized glucose uptake and utilization, and consequently normalized oxygen uptake, myocardial ATP levels, and cardiac output, while a low dose of alpha-lipoic acid normalized lactate and pyruvate production. (Strodter D, et al. Diabetes Res Clin Pract 1995; 29: 19-26.) In cell cultures, alpha-lipoic acid stimulated basal glucose transport and had a positive effect on insulin-stimulated glucose uptake. (Estrada DE, et al. Diabetes 1996 Dec; 45 (12): 1798-1804.) Alpha-lipoic acid administration prevented diabetes in 70% of diabetes induced animals. This effect was thought to be secondary to DHLA suppression of nitric oxide release from macrophages involved in islet cell inflammation. (Faust A, et al. Int J Immunopharmac 1994; 16: 61-66.)
Protein glycation: Glycation of protein caused by elevated blood and tissue glucose is believed to contribute to many of the complications seen in diabetes. These sugar-damaged proteins are referred to as advanced glycosylation end products (AGEs). AGEs increase with the length of hyperglycemia and are thought to be responsible for the kidney damage and advanced atherosclerosis seen in diabetes. (Packer L, et al. Free Rad Biol Med 1995; 19:227-250.) Packer and Kawabata found that noncovalent binding of alpha-lipoic acid to albumin protected proteins against glycation. (Kawabata T, Packer L. Biochem Biophys Res Comms 1994; 203: 99-104.)
Glucose disposal: Type II diabetic humans given an acute dose of alpha-lipoic acid (1000 mg intravenously) experienced 50% improvement in insulin-stimulated glucose disposal. (Jacob S, Henriksen EJ, Schiemann AL, Simon I, Clancy DE, Tritschler HJ, Jung W, Augustin HJ, Dietze GJ. Arzneimittelforschung 1995 Aug; 45(8): 872-874.) In an uncontrolled pilot study 20 patients with type II diabetes received daily alpha-lipoic acid (500 mg/500 ml NaCl, 0.9%) parenterally for ten days. An increase of insulin-stimulated glucose disposal of approximately 30% was reported; however, no changes in fasting plasma levels for glucose or insulin were found during the short period of treatment and observation. (Jacob S, et al. Exp Clin Endocrinol Diabetes 1996; 104: 284-288.)
Antioxidant function: Because many of the systemic complications of diabetes mellitus, such as polyneuropathy and cataract formation, appear to be secondary to free radical damage, alpha-lipoic acid and DHLA have been proposed as possible therapeutic agents in these conditions. When ALA was compared with antioxidant vitamin E, results failed to justify the higher cost of ALA over less-expensive and equally effective nutritional antioxidants. (Murray M. 1996; 343-346.)
Bioflavonoids: Rutin and Quercetin, 500 mg per day: inhibit aldose reductase and thus prevents glucose from being converted to sorbitol. This is important with regard to cataract formation. Quercetin also stabilizes cell membranes and acts as an antioxidant.
(Gaby AR. Townsend Letter 1985;32:307)
Biotin: May require up to 16 mg per day; a commonly used level for a clinical trial. Biotin helps as a cofactor for glucokinase, an enzyme that breaks down glucose into metabolic substrates for energy production. If glucokinase is inactive, the patient can develop diabetes. Researchers have found that the fasting glucose levels of indivduals with IDDM dropped by half when they supplemented with 16 mg biotin per day for one week. Similar results in indivduals with NIDDM have been reported after two months using 9 mg biotin per day. Other research indicates that biotin may reduce pain due to diabetic neuropathies in some individuals.
(Coggeshall JC, et al. Ann NY Acad Sci 1985;447:389-392; Maebashi M, et al. J Clin Biochem Nutr 1993;14:211-218; Koutsikos D, et al. Biomed Pharmacother 1990;44:511-514.)
Chromium: Chromium has been found to improve glucose tolerance for a wide range of indivduals, not only those with IDDM and NIDDM, but also for those considered prediabetic and women with gestational diabetes. Studies indicate that chromium exerts its beneficial effect by increasing sensitivity to insulin and thus can be of benefit even to those not suffering from glucose intolerance. Urberg and Zemel found that combining chromium with 100 mg of nicotinic acid (niacin) significantly enhanced its effectiveness in improving glucose tolerance, epsecially among the elderly.
(Schroeder HA. J Nutr 1969;97:237-242; Gaby AR, Wright JV. 1996, 54-64; Anderson RA, et al. Am J Clin Nutr 1991;54:909-916; Jovanovic-Peterson L, et al. J Am Coll Nutr 1995;14:530; Anderson RA, et al. Metabol 1983;32:894-899; Lee NA, Reasner CA. Diabetes Care 1994;17:1449–52.; Urberg M, Zemel MB. Metabol 1987;36:896-899.)
» Brewer’s yeast: 1 tablespoon three times daily, also contains glutathione. Brewer's yeast has been used in the treatment of diabetes for well over 100 years. However, caution is warranted in using this form of chromium supplementation in individuals who are sensitive to yeast.
(Mertz W, Schwarz K. Arch. Biochemical Biophys. 1959;85:292-295; Offenbacher E, Stunyer F. Diabetes 1980;29:919-925; Martinez OB, et al. Nutr Res 1985;5:609-620.)
» Chromium picolinate: 200 mcg per day is the most commonly used dose in clinical and research settings, though many practitioners prescribe 200 mcg twice daily or 500 mcg once daily. 1000 mcg per day can have pronounced beneficial effects on the management of adult-onset (Type 2) diabetes; also lowered cholesterol.
(Evans GW. Int J Biosocial Med Res 1989;11:163-180; Anderson RA, et al. Diabetes 1997 Nov;46(11):1786-1791.)
» Chromium (GTF) 200 mcg per day (Freund, 1979, 496; Martinez O. Nutr Res 1985;5:609-620; Liu V. Abernathy R. Am J Clin Nutr 1982;25(4):661-667.)
Lithium: Thirty-eight diabetic patients (aged 20-70 years) were treated with 100 mg per day of lithium carbonate for 624 days. The fasting blood glucose and 1-hour postprandial blood glucose concentrations decreased significantly in patients who were receiving insulin or oral hypoglycemic agents. In patients whose diabetes was being controlled by diet alone, addition of lithium resulted in a significant decrease in postprandial glucose and a nonsignificant decrease in fasting blood glucose. In many cases, the effect of lithium was marked (i.e., a greater than 30% reduction in blood glucose).
(Hu M, et al. Biol Trace Elem Res 1997;60:131-137.)
Magnesium: 300-500 mg per day. Diabetics show significantly lowered magnesium levels, especially those who suffer severe retinopathy. The lack of magnesium seems to increase the risk of cardiovascular disease. Magnesium is a cofactor in glycolysis and an important cell regulator. Evidence shows that magnesium may prevent retinopathy, increase HDL levels, decrease platelet aggregation, and prolong clotting time.
(McNair P, et al. Diabetes 1978;27:1075-1077; Mag Bulletin, 1983; Paolisso G, et al. Diabetes Care 1989;12:265-269; Eibl NL, et al. Diabetes Care 1995;18:188; Mimouni F, et al. Obstet Gynecol 1987;70:85-89; Sjorgren A, et al. Magnesium 1988;121:16-20; Paolisso G, et al. Am J Clin Nutr 1992;55:1161-1167; American Diabetes Association. Diabetes Care 1992;15:1065-1067.)
Manganese
Myo-inositol 1g per day (Salway JG, et al. Lancet 1978 Dec 16;2(8103):1282-1284.)
Phosphorus
Potassium
Thyroid: There have been studies done with IDDM patients showing that they have difficulty converting T4 to T3. Transport of glucose across cell membranes becomes impaired when thyroid hormone is deficient.
Vanadium: 15mg per day improved glucose tolerance.
(Badmaev V, et al. J Altern Complement Med 1999 Jun;5(3):273-291; Kiersztan A. Postepy Biochem. 1998;44(4):275-282; Fantus IG, Tsiani E. Mol Cell Biochem 1998 May;182(1-2):109-119; Cam MC, et al. Metabolism 1997 Jul;46(7):769-778.)
Zinc picolinate: 30mg per day. Zinc is involved in the synthesis, secretion and utilization of insulin. Diabetics require zinc supplementation because they tend to hyperexcrete zinc. Laboratory tests have shown that glucose tolerance has been increased in hyperglycemic mice through zinc supplementation.
Coenzyme Q10
Omega-3 fatty acids: These fats have many benefits on cardiovascular complications as well as improving the ability of insulin to bind onto receptor sites. Although generally considered safe, omega 3 fatty acids should be used with caution as there have been several short term studies showing that omega 3 fatty acids may actually impair glucose tolerance.
(Vessby B, Boberg M. J Intern Med. 228:165-171, 1990; Horwitz N. Med Tribune 1;13, July 8, 1987.)
Note: If the studies were carried out for a longer period of time there might have be an overall improvement in glucose control and that less insulin would be required to keep down blood sugars. In general, fats tend to slow down the rate of absorption of glucose and therefore tend to be favorable toward post-prandial glucose levels. (Marz, 1997)
Omega-6 fatty acids
Fenugreek seeds: Defatted fenugreek seed powder (100mg divided into 2 equal doses). Bordia et al found that when fenugreek was given in a dose of 2.5 g twice daily for 3 months, coronary artery disease patients with NIDDM demonstrated significantly decreased blood lipids (total cholesterol and triglycerides) without affecting the HDL-c. When administered in the same daily dose to NIDDM (non-CAD) patients (mild cases), fenugreek reduced significantly the blood sugar (fasting and post prandial). In severe NIDDM cases, blood sugar (both fasting and post prandial) was only slightly reduced.
(Sharma R, et al. Eur J Clin Nutr 1990 Apr;44(4):301-306; Bordia A, et al. Prostaglandins Leukot Essent Fatty Acids 1997 May;56(5):379-384; Khosla P, et al. Indian J Physiol Pharmacol 1995 Apr;39(2):173-174.)
Garlic: Decreases platelet aggregation and is useful at preventing the microangiopathy associated with diabetes. In addition it has been shown to lower blood glucose levels. (Bevo BO, Zahnd GR. Quart J Crude Drug Res 17:139-96, 1979; Sitprija S, et al. J Med Assoc Thai 1987 Mar;70 Suppl 2:223-227; Augusti KT, Sheela CG. Experientia 1996 Feb 15;52(2):115-120; Mel'chinskaia EN, et al. Biull Eksp Biol Med 1997 Nov;124(11):595-597; Sheela CG, Augusti KT. Indian J Exp Biol 1992 Jun;30(6):523-526.)
Gymnema sylvestre: Reported to assist in regeneration of Islets of Langerhans.
(Shanmugasundaram ER, et al. J Ethnopharmacol 1990 Oct;30(3):265-279; 281-294.)
Maitake mushrooms (Grifola frondosa): studies involving animals and humans have reported blood glucose reduction, as well as changes in plasma levels of insulin and triglyceride
(Kubo K, et al. Biol Pharm Bull 1994 Aug;17(8):1106-1110; Kubo K, Nanba H. 1996)
Vaccinium myrtillus: has long been used as a folk remedy in the treatment of diabetes. It increases capillary integrity and improves venous tone. It is specifically effective in the treatment of macular degeneration and cataracts. It has potent antioxidant properties.
(Salomaa VV, et al. Brit Med J 302:493-6, 1990; Cignarella A, et al. Thromb Res 1996 Dec 1;84(5):311-322.)


footnotes

[Alpha-lipoic acid in diabetic neuropathy. Action mechanism and therapy. Clinical picture and pathogenesis of diabetic neuropathy]. Internist (Berl) 1994 Jun;35(6 Alpha-liponsa):1-4. [Article in German]

Abbas ZG, Swai ABM. Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy. East African Med J 1997;74:804-808.

Abdel-Aziz MT, Abdou MS, Soliman K, et al. Effect of carnitine on blood lipid pattern in diabetic patients. Nutr Rep Internat 1984;29:1071-1079.

Abraira C, Derler J. Large variations of sucrose in constant carbohydrate diets in type II diabetes. Am J Med 1988;84:193-200.

Aharon Y, Mevorach M, Shamoon H. Vanadyl sulfate does not enhance insulin action in patients with type 1 diabetes. Diabetes Care 1998;21:2194. (Letter)

Albrink MJ, Ullrich IH, Blehschmidt NG, et al. The beneficial effect of fish oil supplements on serum lipids and clotting function of patients with type II diabetes mellitus. Diabetes 1986;35 (suppl 1):43A. (Abstract)

Almada AL, Harvey PW, Platt KJ. Effect of chronic oral glucosamine sulfate upon fasting insulin resistance index (FIRI) in nondiabetic individuals. Experimental Biology 2000; San Diego, CA; March 18, 2000.
Abstract: Previous animal studies have demonstrated that glucosamine sulfate can induce insulin resistance. In the present trial, 6 nondiabetic subjects received 500 mg tid of glucosamine sulfate (GS-500 brand) for 12 weeks. Fasting insulin levels showed an "increasing trend" in the glucosamine group when compared with controls after 12 weeks. However, these results were not statistically significant (P=0.25). Fasting glucose levels were unaffected. The researchers suggest that additional, more rigorous studies are needed to assess glucosamine's effects on insulin resistance.

American Diabetes Association. Magnesium supplementation in the treatment of diabetes. Diabetes Care 1992;15:1065-1067.

Anderson RA, Polansky MM, Bryden NA, et al. Chromium supplementation of human subjects: effects on glucose, insulin, and lipid variables. Metabol 1983;32:894-899.

Anderson RA, Polansky MM, Bryden NA, Canary JJ. Supplemental-chromium effects on glucose, insulin, glucagon, and urinary chromium losses in subjects consuming controlled low-chromium diets. Am J Clin Nutr 1991;54:909-916.

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):1786-1791.
Abstract: Double-blind, placebo-controlled study conducted at the USDA Human Research Center in collaboration with the Beijing Medical University, 180 men and women treated for Type 2 diabetes at two Beijing hospitals in a four-month study; there have not been any reported toxic effects.

Atkinson MA, Bowman MA, Kao K-J, et al. Lack of immune responsiveness to bovine serum albumin in insulin-dependent diabetes. N Engl J Med 1993;329:1853-1858.

Augusti KT, Sheela CG. Antiperoxide effect of S-allyl cysteine sulfoxide, an insulin secretagogue, in diabetic rats. Experientia 1996 Feb 15;52(2):115-120.
Abstract: Treatment of alloxan diabetic rats with the antioxidant S-allyl cysteine sulfoxide (SACS) isolated from garlic (Allium sativum Linn), ameliorated the diabetic condition almost to the same extent as did glibenclamide and insulin. In addition, SACS controlled lipid peroxidation better than the other two drugs. Furthermore, SACS significantly stimulated in vitro insulin secretion from B cells isolated from normal rats. Hence it can be surmised that the beneficial effects of SACS could be due to both its antioxidant and its secretagogue actions. The former effect is more predominant and the latter is only secondary. These effects highlight the therapeutic value of garlic, which is a component of many diets.

Badmaev V, Prakash S, Majeed M. Vanadium: a review of its potential role in the fight against diabetes. J Altern Complement Med 1999 Jun;5(3):273-291. (Review)
Abstract: The potential role of vanadium in human health is described as a building material of bones and teeth. However, another very interesting and promising application for vanadium in human health emerges from recent studies that evaluated the role of vanadium in the management of diabetes. Vanadium is present in a variety of foods that we commonly eat. Skim milk, lobster, vegetable oils, many vegetables, grains and cereals are rich source of vanadium (>1 ppm). Fruits, meats, fish, butter, cheese, and beverages are relatively poor sources of vanadium. The daily dietary intake in humans has been estimated to vary from 10 microg to 2 mg of elemental vanadium, depending on the environmental sources of this mineral in the air, water, and food of the particular region tested. In animals, vanadium has been shown essential (1-10 microg vanadium per gram of diet). There is only circumstantial evidence that vanadium is essential for humans. However, in doses ranging from 0.083 mmol/d to 0.42 mmol/d, vanadium has shown therapeutic potential in clinical studies with patients of both insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) type. Although vanadium has a significant biological potential, it has a poor therapeutic index, and attempts have been made to reduce the dose of vanadium required for therapeutic effectiveness. Organic forms of vanadium, as opposed to the inorganic sulfate salt of vanadium, are recognized as safer, more absorbable, and able to deliver a therapeutic effect up to 50% greater than the inorganic forms. The goal is to provide vanadium with better gastrointestinal absorption, and in a form that is best able to produce the desired biological effects. As a result, numerous organic complexes of vanadium have been developed including bis(maltolato)oxovanadium (BMOV), bis(cysteinamide N-octyl)oxovanadium known as Naglivan, bis(pyrrolidine-N-carbodithioato)oxovanadium, vanadyl-cysteine methyl ester, and bis-glycinato oxovanadium (BGOV). The health benefits of vanadium and the safety and efficacy of the available vanadium supplements are discussed in this review.

Baskaran K, Ahmath BK, Shanmugasundaram KR, Shanmugasundaram ERB. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol 1990;30:295-305.

Beck-Neilsin H, Pedersen O, Lendskov H. Impaired cellular insulin binding and sensitivity induced by high-fructose feeding in normal subjects. Am.J. Clin. Nut. 33:273.
Abstract: Normal human volunteers were fed their usual diet plus 1000 cal/day of fructose for one week. There was a significant reduction of both insulin binding to isolated monocytes and insulin sensitivity. In contrast, 1000cal of glucose under the same conditions did not significantly change insulin binding or sensitivity.

Bevo BO, Zahnd GR. Plants with oral hypoglycemic action. Quart J Crude Drug Res 17:139-96, 1979.
Abstract: Garlic has been shown to increase the release if insulin as well as sparing insulin.

Biewenga G, Haenen GR, Bast A. The role of lipoic acid in the treatment of diabetic polyneuropathy. Drug Metab Rev 1997 Nov;29(4):1025-1054. (Review)

Boden G, Chen X, Ruiz J, et al. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin dependent diabetes mellitus. Metabolism 1996;45:1130-1135.

Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1997 May;56(5):379-384.
Abstract: In a placebo-controlled study the effect of ginger and fenugreek was examined on blood lipids, blood sugar, platelet aggregation, fibrinogen and fibrinolytic activity. The subjects included in this study were healthy individuals, patients with coronary artery disease (CAD), and patients with non-insulin-dependent diabetes mellitus (NIDDM) who either had CAD or were without CAD. In patients with CAD powdered ginger administered in a dose of 4 g daily for 3 months did not affect ADP- and epinephrine-induced platelet aggregation. Also, no change in the fibrinolytic activity and fibrinogen level was observed. However, a single dose of 10 g powdered ginger administered to CAD patients produced a significant reduction in platelet aggregation induced by the two agonists. Ginger did not affect the blood lipids and blood sugar. Fenugreek given in a dose of 2.5 g twice daily for 3 months to healthy individuals did not affect the blood lipids and blood sugar (fasting and post prandial). However, administered in the same daily dose for the same duration to CAD patients also with NIDDM, fenugreek decreased significantly the blood lipids (total cholesterol and triglycerides) without affecting the HDL-c. When administered in the same daily dose to NIDDM (non-CAD) patients (mild cases), fenugreek reduced significantly the blood sugar (fasting and post prandial). In severe NIDDM cases, blood sugar (both fasting and post prandial) was only slightly reduced. The changes were not significant. Fenugreek administration did not affect platelet aggregation, fibrinolytic activity and fibrinogen.

Boucher BJ. Inadequate vitamin D status: does it contribute to the disorders comprising syndrome ‘X’? Br J Nutr 1998;79:315-327. (Review)

Cam MC, Li WM, McNeill JH. Partial preservation of pancreatic beta-cells by vanadium: evidence for long-term amelioration of diabetes. Metabolism 1997 Jul;46(7):769-778.
Abstract: Streptozotocin (STZ)-diabetic rats treated with vanadium can remain euglycemic for up to 20 weeks following withdrawal from vanadium treatment. In this study, we examined the effects of short-term vanadium treatment in preventing or reversing the STZ-induced diabetic state. Male Wistar rats were untreated (D) or treated (DT) with vanadyl sulfate for 1 week before administering STZ. Treatment was subsequently maintained for 3 days (DT3) or 14 days (DT14) post-STZ, after which vanadium was withdrawn. At 4 to 5 weeks post-STZ and following long-term withdrawal from vanadium, DT14 rats demonstrated levels of food and fluid intake and glucose tolerance that were not significantly different from those of age-matched untreated nondiabetic rats, and had significantly reduced glycemic levels in the fed state compared with D and DT3 groups. The proportion of animals that were euglycemic (fed plasma glucose < 9.0 mmol/L) was significant in DT14 (five of 10) relative to D (one of 10) and DT3 (one of 10) (P = .01). All euglycemic animals had an improved pancreatic insulin content that, albeit low (12% of control), was strongly linked to euglycemia in the fed state (r = -.91, P < .0001). Moreover, the highly significant correlation persisted with the analysis of untreated STZ-rats alone (r = -.95, P < .0001). Similarly, improvements in glucose tolerance and insulin secretory function in euglycemic rats were strongly correlated with small changes in residual insulin content. Hence, as vanadium pretreatment did not prevent STZ-induced beta-cytotoxicity, the vanadium-induced amelioration of the diabetic state appears to be secondary to the preservation of a functional portion of pancreatic beta cells that initially survived STZ toxicity. The partial preservation of pancreatic beta cells, albeit small in proportion to the total insulin store, was both critical and sufficient for a long-term reversal of the diabetic state. These results suggest that apparently modest effects in preserving residual pancreatic insulin content can have profound consequences on glucose homeostasis and may bear important implications for interventions that have "limited" protective effects on beta cells.

Ceriello A, Giugliano D, Quatraro A, et al. Vitamin E reduction of protein glycosylation in diabetes. Diabetes Care 1991;14:68-72.

Chait A. Dietary management of diabetes mellitus. Contemp. Nutr. (2), Feb,1984. (also: ASDC J Dent Child 1984 Nov-Dec;51(6):455-457.)
Abstract: Diets that are proportionally high in carbohydrates have been shown to improve blood glucose control by enhancing insulin sensitivity, provided adequate insulin is present.

Chase HP, Butler-Simon N, Garg S, et al. A trial of nicotinamide in newly diagnosed patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1990;33:444-446.

Cignarella A, Nastasi M, Cavalli E, Puglisi L. Novel lipid-lowering properties of Vaccinium myrtillus L. leaves, a traditional antidiabetic treatment, in several models of rat dyslipidaemia: a comparison with ciprofibrate. Thromb Res 1996 Dec 1;84(5):311-322.
Abstract: Vaccinium myrtillus L. (blueberry) leaf infusions are traditionally used as a folk medicine treatment of diabetes. To further define this therapeutical action, a dried hydroalcoholic extract of the leaf was administered orally to streptozotocin-diabetic rats for 4 days. Plasma glucose levels were consistently found to drop by about 26% at two different stages of diabetes. Unexpectedly, plasma triglyceride (TG) were also decreased by 39% following treatment. Subsequent to the latter observation, possible lipid-lowering properties of the extract were investigated on other models of hyperlipidaemia and ciprofibrate, a well-established hypolipidaemic drug, was used as a reference compound. Both drug reduced TG levels of rats on hyperlipidaemic diet in a dose-dependent fashion. When administered at single doses over the same experimental period, blueberry and ciprofibrate were effective in lowering TG concentrations in ethanol-treated normolipidaemic animals and in genetically hyperlipidaemic Yoshida rats. Unlike ciprofibrate, however, blueberry failed to prevent the rise in plasma TG elicited by fructose and did not affect free fatty acid levels in any of the above experimental conditions. In rats treated with Triton WR-1339, blueberry feeding induced an hypolipidaemic activity one hour after injection but proved to be ineffective at later time points, thus suggesting that its hypolipidaemic action may reflect improved TG-rich lipoprotein catabolism. In addition, ciprofibrate and the extract were tested for antithrombotic activity using a collagen-triggered model of venous thrombosis in diabetic and Yoshida rats. Only ciprofibrate, however, significantly reduced thrombus formation in diabetics, possibly because of its effects on free fatty acid metabolism, whereas no effect was observed in Yoshida rats. In conclusion, the present findings indicate that active consituent(s) of Vaccinium myrtillus L. leaves may prove potentially useful for treatment of dyslipidaemiae associated with impaired TG-rich lipoprotein clearance.

Clearly JP. Vitamin B3 in the treatment of diabetes mellitus: case reports and review of the literature. J Nutr Med 1990;1:217-225.
Abstract: Nicotinamide may have a protective ß-cell effect in IDDM while niacin may help with insulin resistance in NIDDM. ß-cell injury may be associated with low NAD and ATP levels resulting in oxidative injury and organ failure. NAD levels are known to be low in diabetics. In the 40's niacinamide was used to reduce insulin requirements in the treatment of DM. In IDDM niacinamide is used to inhibit poly (ADP-ribose) synthetase leading to loss of of NAD in the ß-cells and subsequent loss of insulin production. Consider 100-200mg niacinamide at the onset of IDDM.

Clearly JP. The importance of oxidant injury as a cause of impaired mitochondrial oxidation in diabetes. J Orthomol Med 1988;3:164-174.
Abstract: Evidence is presented that diabetes is associated with reduced intracellular levels of NAD, which contribute to the organ damage seen in this condition. Experimental diabetes induced by chemical alkylating agents causes a reduction of NAD levels in the pancreas, which leads to metabolic failure and cell death. Treatment with niacin or niacinamide prevented experimental diabetes. 6 caes are presented in which improvement of diabetes followed treatment with niacin and other vitamins.

Coelingh HJT, Schreurs WHP. Improvement of oral glucose tolerance in gestational diabetes by pyridoxine. Brit Med J 1975;3:13-15.

Cohen D, Dodds R, Viberti G. Effect of protein restriction in insulin dependent diabetics at risk of nephropathy. Brit Med J 1987;294:795-798.

Colagiuri S, Miller JJ, Edwards RA. Metabolic effects of adding sucrose and aspartame to the diet of subjects with noninsulin-dependent diabetes mellitus. Am J Clin Nutr 1989;50:474-478.

Colette C, Pares-Herbute N, Monnier LH, Cartry E. Platelet function in type I diabetes: effects of supplementation with large doses of vitamin E. Am J Clin Nutr 1988;47:256-261.

Crane MG, Sample C. Regression of diabetic neuropathy with total vegetarian (vegan) diet. J Nutr Med 1994;4:431-439.

Crane MG, Sample CJ. Regression of diabetic neuropathy with vegan diet. Am J Clin Nutr 1988;48:926. (Abstract)

Cunningham JJ, Ellis SL, McVeigh KL, et al. Reduced mononuclear leukocyte ascorbic acid content in adults with insulin-dependent diabetes mellitus consuming adequate dietary vitamin C. Metabol 1991;40:146-149.

Cunningham JJ, Fu Aizhong, Mearkle PL, Brown RG. Hyerzincuria in individuals with insulin-dependent diabetes mellitus: concurrent zinc status and the effect of high-dose zinc supplementation. Metabolism 1994;43:1558-1562.

Cutler P. Deferoxamine therapy in high-ferritin diabetes. Diabetes 38:1207-1210, 1989.
Abstract: Serum ferritin levels were elevated in 9/18 poorly controlled NIDDM patients. None of the patients had a disorder known to cause iron storage. Serum iron and TIBC were normal in all cases. Because excess iron, as in hemochromatosis, is associated with diabetes and, because diabetes has been shown to improve after lowering the total body iron load through repeat venesection, all 9 patients with high serum ferritin and 7 of 9 with normal ferritin were treated with the iron chelating agent deferoxamine (10mg/kg IV in 500ml ringers lactate given over 2 hours, 2x/wk). The number of treatments ranged from 9-26 (mean=16). Treatments were stopped when ferritin became normal and patients were maintained without hypoglycemia agents. Of 9 patients with high serum ferritin, 8 had an improvement in blood sugar, which was frequently dramatic and occurred even though insulin or oral hypoglycemic agents were discontinued in all 8 patients. Serum cholesterol, triglycerides, and hemoglobin A1c levels also improved considerably in these patients. In all 7 patients with normal serum ferritin, and in 1 with high serum ferritin, treatment with deferoxamine failed to improve diabetic control. This study demonstrates that idiopathic iron overload is an important etiologic factor in as many as 50% of patients with poorly controlled diabetes. That percentage is likely to be somewhat lower in other clinics, since Dr. Cutler, who practices orthomolecular medicine, presumably eliminated other nutritional causes of poor diabetic control.

Dahl-Jorgensen K, Joner G, Hanssen KF. Relationship between cows’ milk consumption and incidence of IDDM in childhood. Diabetes Care 1991;14:1081-1083.

Davis RE, Calder JS, Curnow DH. Serum pyridoxal and folate concentrations in diabetics. Pathol 1976;8:151-156.
Abstract: Serum pyridoxal and folate concentrations were measured in 518 diabetics. There were 185 males and 333 females. The level of pyridoxal was significantly lower in the diabetics when compared with 371 'healthy' controls and 25% had levels below the lower limit of the normal range. No significant difference was observed between diabetics being treated by diet alone, oral hypoglycaemics or insulin. Only 20 patients had a reduced serum folate level and in 6 this was accompanied by a low pyridoxal concentration. The results suggest that diabetics may have an increased demand for pyridoxal.

de Valk HW, Verkaaik R, van Rijn HJM, et al. Oral magnesium supplementation in insulin-requiring type 2 diabetic patients. Diabet Med 1998;15:503-507.

Duntas L, Kemmer TP, Vorberg B, Scherbaum W. Administration of d-alpha-tocopherol in patients with insulin-dependent diabetes mellitus. Curr Ther Res 1996;57:682-690.

Eibl NL, Schnack CJ, Kopp H-P, et al. Hypomagnesemia in type II diabetes: effect of a 3-month replacement therapy. Diabetes Care 1995;18:188.

Elliott RB, Picher CC, Fergusson DM, Stewart AWAD. A population-based strategy to prevent insulin-dependent diabetes using nicotinamide. J Pediatr Endocrinol Metabol 1996;9:501-509.

Eriksson J, Kohvakka A. Magnesium and ascorbic acid supplementation in diabetes mellitus. Ann Nutr Metabol 1995;39:217-223.

Estrada DE, Ewart HS, Tsakiridis T, Volchuk A, Ramlal T, Tritschler H, Klip A. Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thioctic acid: participation of elements of the insulin signaling pathway. Diabetes 1996;45:1798-1804.
Abstract: Thioctic acid (alpha-lipoic acid), a natural cofactor in dehydrogenase complexes, is used in Germany in the treatment of symptoms of diabetic neuropathy. Thioctic acid improves insulin-responsive glucose utilization in rat muscle preparations and during insulin clamp studies performed in diabetic individuals. The aim of this study was to determine the direct effect of thioctic acid on glucose uptake and glucose transporters. In L6 muscle cells and 3T3-L1 adipocytes in culture, glucose uptake was rapidly increased by (R)-thioctic acid. The increment was higher than that elicited by the (S)-isomer or the racemic mixture and was comparable with that caused by insulin. In parallel to insulin action, the stimulation of glucose uptake by thioctic acid was abolished by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, in both cell lines. Thioctic acid provoked an upward shift of the glucose-uptake insulin dose-response curve. The molar content of GLUT1 and GLUT4 transporters was measured in both cell lines. 3T3-L1 adipocytes were shown to have >10 times more glucose transporters but similar ratios of GLUT4:GLUT1 than L6 myotubes. The effect of (R)-thioctic acid on glucose transporters was studied in the L6 myotubes. Its stimulatory effect on glucose uptake was associated with an intracellular redistribution of GLUT1 and GLUT4 glucose transporters, similar to that caused by insulin, with minimal effects on GLUT3 transporters. In conclusion, thioctic acid stimulates basal glucose transport and has a positive effect on insulin-stimulated glucose uptake. The stimulatory effect is dependent on phosphatidylinositol 3-kinase activity and may be explained by a redistribution of glucose transporters. This is evidence that a physiologically relevant compound can stimulate glucose transport via the insulin signaling pathway.

Evans GW. The effect of chromium picolinate on insulin controlled parameters in humans. Int J Biosocial Med Res 1989;11:163-180.

Fantus IG, Tsiani E. Multifunctional actions of vanadium compounds on insulin signaling pathways: evidence for preferential enhancement of metabolic versus mitogenic effects. Mol Cell Biochem 1998 May;182(1-2):109-119. (Review)
Abstract: The pathophysiologic importance of insulin resistance in diseases such as obesity and diabetes mellitus has led to great interest in defining the mechanism of insulin action as well as the means to overcome the biochemical defects responsible for the resistance. Vanadium compounds have been discovered to mimic many of the metabolic actions of insulin both in vitro and in vivo and improve glycemic control in human subjects with diabetes mellitus. Apart from its direct insulinmimetic actions, we found that vanadate modulates insulin metabolic effects by enhancing insulin sensitivity and prolonging insulin action. All of these actions appear to be related to protein tyrosine phosphatase (PTP) inhibition. However, in contrast to its stimulatory effects, vanadate inhibits basal and insulin-stimulated system A amino acid uptake and cell proliferation. The mechanism of these actions also appears to be related to PTP inhibition, consistent with the multiple roles of PTPs in regulating signal transduction. While the precise biochemical pathway of vanadate action is not yet known, it is clearly different from that of insulin in that the insulin receptor and phosphatidylinositol 3'-kinase do not seem to be essential for vanadate stimulation of glucose uptake and metabolism. The ability of vanadium compounds to 'bypass' defects in insulin action in diseases characterized by insulin resistance and their apparent preferential metabolic versus mitogenic signaling profile make them attractive as potential pharmacological agents.

Faust A, Burkart V, Ulrich H et al. Effect of lipoic acid on cyclophosphamide-induced diabetes and insulitis in nonobese diabetic mice. Int J Immunopharmac 1994;16:61-66.

Feskens EJM, Bowles CH, Kromhout D. Inverse association between fish intake and risk of glucose intolerance in normoglycemic elderly men and women. Diabetes Care 1991;14:935-941.

Florholmen J, Arvidsson-Lenner R, Jorde R, Burhol PG. The effect of Metamucil on postprandial blood glucose and plasma gastric inhibitory peptide in insulin-dependent diabetics. Acta Med Scand 1982;212:237-239.

Friend, Time USA Today, Life Section, Sept. 18, 1990.
Abstract: When measured against controls, people who were found to have certain types of cataracts had reduced levels of vitamin C in their blood. Following up this study it was shown that a daily dose of 800mg vitamin C was required to raise a person's blood vitamin C level enough to result in a lower level of cataract formation.

Gaby AR, Wright JV. Diabetes. In: Nutritional Therapy in Medical Practice: Reference Manual and Study Guide. Kent, WA: Wright/Gaby Seminars, 1996, 54-64. (Review)

Gaby AR, Wright JV. Nutritional protocols: diabetes mellitus. In: Nutritional Therapy in Medical Practice: Protocols and Supporting Information. Kent, WA: Wright/Gaby Seminars, 1996, 10.

Gaby AR. Preventing complications of diabetes. Townsend Letter 1985;32:307. (Editorial)

Garg A, Bananome A, Grundy SM, et al. Comparison of a high-carbohydrate diet with a high-monounsaturated-fat diet in patients with non-insulin dependent diabetes mellitus. N Engl J Med 1988;319:829-834.

Gaut ZN, Pocelinko R, Solomon HM, Thomas GB. Oral glucose tolerance, plasma insulin, and uric acid excretion in man during chronic administration in nicotinic acid. Metabol 1971:1031-1035.

Gerstein H. Cow milk exposure and type I diabetes mellitus. Diabetes Care 1994;17:13-19.

Gin H, Aparicio M, Potauz L, et al. Low-protein, low-phosphorus diet and tissue insulin sensitivity in insulin-dependent diabetic patients with chronic renal failure. Nephron 1991;57:411-415.

Gisnger C, Jeremy J, Speiser P, et al. Effect of vitamin E supplementation on platelet thromboxane A2 production in type I diabetic patients: Double-blind crossover trial. Diabetes 1988;37:1260-1264.

Glauber H, Wallace P, Griver K, Brechtel G. Adverse metabolic effect of omega-3 fatty acids in non-insulin-dependent diabetes mellitus. Ann Intern Med 1988;108:663-668.

Halberstam M, Cohen N, Schlimovich P, et al. Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects. Diabetes 1996;45:659-666.

Hallfrisch J, Scholfield DJ, Behall KM. Diets containing soluble oat extracts improve glucose and insulin responses of moderately hypercholesterolemic men and women. Am J Clin Nutr 1995;61:379-384.

Hallfrisch J, et al. The effects of fructose on blood lipid levels. Am J Clin Nutr 1986;43:151-59.
Abstract: 12 men with a hyperinsulinemic response to sucrose loading and suitable controls were each alternately fed a diet with either 15% fructose or 15% starch. Fructose caused a general increase in both the total serum cholesterol and in the LDL cholesterol in most subjects in both groups, while triglycerides rose significantly only in the hyperinsulinemic group.
NOTE: In acute loading studies the existence of a synergism between glucose and fructose with regard to insulin secretion exists. Neither glucose or fructose, when given as the sole monosaccharide, stimulates insulin secretion as potently as glucose and fructose combined.

Haugen HN. The blood concentration of thiamine in diabetes. Scand J Clin Lab Invest 1964;16:260-266.

Horwitz N. Fish oil decontrols diabetics. Med Tribune 1;13, July 8, 1987.
Abstract: In this review article it was noted that in a small group of NIDDM patients 8gms/day given over a period of 8wks significantly lowered both cholesterol and triglycerides by 11% and 33% respecitvely. However, both fasting glucose and postprandial glucose levels went up significantly. In another study 5.5gms/day of fish oil over 4 weeks resulted in a decrease secretion of insulin and also a rise in fasting and postprandial blood glucose.

Hu M, Wu H, Chao C. Assisting effects of lithium on hypoglycemic treatment in patients with diabetes. Biol Trace Elem Res 1997 Oct-Nov;60(1-2):131-137.
Abstract: In this article, we report the assisting effect of lithium on hypoglycemic treatment in patients with diabetes. Thirty-eight diabetic patients, 15 male and 23 female, aged 20-70 yr, 33 noninsulin-dependent diabetes mellitus (NIDDM) patients, and 5 insulin-dependent diabetes mellitus (IDDM) patients, were recruited in this study. Fasting and 1-h postprandial blood glucose (BG) profiles were undertaken from three groups of patients with diabetes before and after short-term of treatment of lithium carbonate. Group I was treated with diet only, Group II with oral hypoglycemic agents (OHA), and Group III with insulin. The fasting blood glucose (FBG) level and 1-h postprandial blood glucose (1-h PBG) level before and after treatment of lithium were: Group I: FBG: 7.67 +/- 0.48 vs. 7.13 +/- 0.82; 1-h PBG 15.13 +/- 0.88 vs. 10.33 +/- 0.96; Group II: FBG: 8.84 +/- 0.67 vs. 6.04 +/- 0.57; 1-h PBG: 12.33 +/- 0.72 vs. 9.95 +/- 0.82; Group III: FBG: 10.87 +/- 0.83 vs. 6.83 +/- 0.79; 1-h PBG: 12.45 +/- 0.93 vs. 9.17 +/- 1.00 mmol/L, respectively. The FBG and PBG of all three groups decreased significantly after lithium treatment, except the FBG in Group I. These data suggest that combined with other therapy, lithium could improve glucose metabolism in most patients with diabetes. Our results suggest that lithium has an assisting hypoglycemic effect on antidiabetic treatment.

Hounsom L, Horrobin DF, Tritschler H, Corder R, Tomlinson DR. A lipoic acid-gamma linolenic acid conjugate is effective against multiple indices of experimental diabetic neuropathy. Diabetologia 1998 Jul;41(7):839-843.
Abstract: Untreated streptozotocin-diabetic (7 weeks duration) rats showed reductions (all p < 0.01; percentages in brackets) in motor and sensory nerve conduction velocity (MNCV; 14%, SNCV; 17%) and in sciatic nerve contents of nerve growth factor (NGF; 57%), substance P (SP; 53%) and neuropeptide Y (NPY; 39%). Treatment with a gamma linolenic acid-alpha-lipoic acid conjugate (GLA-LA; 35 mg x day(-1) x rat(-1)) attenuated (p < 0.05) these reductions to MNCV (8%), SNCV (5%), NGF (19%), SP (23%), NPY (20%), such that the values in GLA-LA-treated diabetic rats did not differ significantly from those of control non-diabetic animals. Treatment with alpha-lipoic acid alone at 100 mg/kg i.p. was without effect on these variables except for NGF (33% reduction, p < 0.05) and treatment with the antioxidant, butylated hydroxytoluene (1.5% dietary supplement) did not affect any deficits. These data show that GLA-LA is effective in improving both electrophysiological and neurochemical correlates of experimental diabetic neuropathy.

Jacob S, Henriksen EJ, Schiemann AL, Simon I, Clancy DE, Tritschler HJ, Jung WI, Augustin HJ, Dietze GJ. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995 Aug;45(8):872-874.
Abstract: Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore pharmacological interventions should aim to improve insulin sensitivity. Alpha-lipoic acid (CAS 62-46-4, thioctic acid, ALA), a natural occurring compound frequently used for treatment of diabetic polyneuropathy, enhances glucose utilization in various experimental models. To see whether this compound also augments insulin mediated glucose disposal in NIDDM, 13 patients received either ALA (1000 mg/Thioctacid/500 ml NaCl, n = 7) or vehicle only (500 ml NaCl, n = 6) during a glucose-clamp study. Both groups were comparable in age, body-mass index and duration of diabetes and had a similar degree of insulin resistance at baseline. Acute parenteral administration of ALA resulted in a significant increase of insulin-stimulated glucose disposal; metabolic clearance rate (MCR) for glucose rose by about 50% (3.76 ml/kg/min = pre vs. 5.82 ml/kg/min = post, p < 0.05), whereas the control group did not show any significant change (3.57 ml/kg/min = pre vs. 3.91 ml/kg/min = post). This is the first clinical study to show that alpha-lipoic acid increases insulin stimulated glucose disposal in NIDDM. The mode of action of ALA and its potential use as an antihyperglycemic agent require further investigation.

Jacob S, Henriksen EJ, Tritschler HJ, Augustin HJ, Dietze GJ. Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid. Exp Clin Endocrinol Diabetes 1996;104(3):284-288.

Jahromi MA, Ray AB. Antihyperlipidemic effect of flavonoids from Pterocarpus marsupium. J Nat Prod. 1993 Jul;56(7):989-94.

Jones CL, Gonzalez V. Pyridoxine deficiency: a new factor in diabetic neuropathy. J Am Podiatry Assoc 1978 Sep;68(9):646-653.
Abstract: 10 IDDM patients who had signs and symptoms of peripheral neuropathy were found to excrete more xanthurenic acid than did the diabetics without neuropathy. Each was given 50mg B-6 three times daily for 6 weeks. Xanthurenic acid excretion became normal and the signs and symptoms of peripheral neuropathy became normal in all the patients. In addition, every patient remarked that their eyes felt better.

Jovanovic-Peterson L, Gutierrez M, Peterson CM. Chromium supplementation for gestational diabetic women improves glucose tolerance and decreases hyperinsulinemia. J Am Coll Nutr 1995;14:530. (Abstract)

Karajalainen J, Martin JM, Knip M, et al. A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus. N Engl J Med 1992;327:302-307.

Kawabata T, Packer L. Alpha-lipoate can protect against glycation of serum albumin, but not low density lipoprotein. Biochem Biophys Res Comms 1994;203:99-104.

Kehler W, Kuklinski B, Ruhlmann C, Plotz C. Diabetes mellitus-a free radical associated disease: Effects of adjuvant supplementation of antioxidants. In: Gries FA, Wessel K, eds. The role of antioxidants in diabetes mellitus: Oxygen radicals and anti-oxidants in diabetes. Frankfurt am Maine: pmi. Verl-Gruppe; 1993:33-53.

Khosla P, Gupta DD, Nagpal RK. Effect of Trigonella foenum graecum (Fenugreek) on blood glucose in normal and diabetic rats. Indian J Physiol Pharmacol 1995 Apr;39(2):173-174.

Kiersztan A. [Insulin-like effect of vanadium compounds]. Postepy Biochem. 1998;44(4):275-282. (Review)

Knekt P Reunanen A, Marniumi J, et al. Low vitamin E status is a potential risk factor for insulin-dependent diabetes mellitus. J Intern Med 1999;245:99-102.

Kotake Y, Murakami E. A Possible Diabetogenic Role for Tryptophan Metabolites and Effects of Xanthurenic Acid on Insulin. Am J Clinical Nut 1971 July; 826-829.
Abstract: It was found that people deficient in B6 had certain abnormalities in their tryptophan metabolism (see graph). They developed excess xanthurenic acid which has the ability to bind onto insulin making it inactive.

Kubo K, Aoki H, Nanba H.Anti-diabetic activity present in the fruit body of Grifola frondosa (Maitake). I. Biol Pharm Bull 1994 Aug;17(8):1106-1110.
Abstract: The fruit body of Grifola frondosa (maitake), Basidiomycetes was confirmed to contain substances with anti-diabetic activity. When 1 g/d of powdered fruit body of maitake was given orally to a genetically diabetic mouse (KK-Ay), blood glucose reduction was observed, in contrast to the control group in which the blood glucose increased with ageing. Moreover, levels of insulin and triglyceride in plasma demonstrated a change similar to blood glucose with feeding of maitake. Ether-ethanol-soluble (ES) and hot water-soluble (WS) fractions were prepared from the fruit body and their hypoglycemic activity was examined. Blood glucose-lowering activity was found when ES-fraction or WS-50% ethanol float (X) fraction was administered orally, but other WS-fractions were inactive. These results suggest that the anti-diabetic activity was present not only in the ES-fraction consisting of lipid but also in the X-fraction of peptidoglycan (sugar:protein = 65:35).

Kubo K, Nanba H. Anti-Diabetic Mechanism of Maitake (Grifola frondosa). Mushroom Biology and Mushroom Products. Royce (ed.) Penn State Univ.:1996.

Labriji-Mestaghanmi H, Billaudel B, Garnier PE, Sutter BCJ. Vitamin D and pancreatic islet function. 2. Time course for changes in insulin secretion and content during vitamin deprivation and repletion. J Endocrine Invest 1988;11:577-587.

Lampeter EF, Klinghammer A, Scherbaum WA, et al. The Deutsche Nicotinamide Intervention Study. An attempt to prevent type 1 diabetes. Diabetes 1998;47:980-984.

Landin K, Holm G, Tengborn L, Smith U. Guar gum improves insulin sensitivity, blood lipids, blood pressure, and fibrinolysis in healthy men. Am J Clin Nutr 1992;56:1061-1065.

Leatherdale BA, Panesar RK, Singh G, et al. Improvement of glucose tolerance due to Momordica charantia (karela). Br Med J 1981;282:1823-1824.

Lee NA, Reasner CA. Beneficial effect of chromium supplementation on serum triglyceride levels in NIDDM. Diabetes Care 1994;17:1449-1452.

Lettle GJ, Emmett PM, Heaton KW. Glucose and insulin responses to manufactured and whole-food snacks. Am J Clin Nutr 1987;45:86-91.

Lewis CM, Canafax DM, Sprafka JM, Bazrbosa JJ. Double-blind randomized trail of nicotinamide on early-onset diabetes. Diabetes Care 1992;15:121-123.

Liu V, Abernathy R. Chromium and insulin in young subjects with normal glucose tolerance. Am J Clin Nutr 1982;25(4):661-667.
Abstract: 20 normal college students were found to have an inverse relationship of peak glucose and chromium levels. It was also found that the amount of insulin required for the lower serum glucose levels was lower in the students who had the highest chromium levels.

Loghmani E, Rickard K, Washburne L, et al. Glycemic response to sucrose-containing mixed meals in diets of children with insulin-dependent diabetes mellitus. J Pediatr 1991;119:531-537.

Low PA, Nickander KK, Tritschler HJ. The roles of oxidative stress and antioxidant treatment in experimental diabetic neuropathy. Diabetes 1997 Sep;46 Suppl 2:S38-42.
Abstract: Oxidative stress is present in the diabetic state. Our work has focused on its presence in peripheral nerves. Antioxidant enzymes are reduced in peripheral nerves and are further reduced in diabetic nerves. That lipid peroxidation will cause neuropathy is supported by evidence of the development of neuropathy de novo when normal nerves are rendered alpha-tocopherol deficient and by the augmentation of the conduction deficit in diabetic nerves subjected to this insult. Oxidative stress appears to be primarily due to the processes of nerve ischemia and hyperglycemia auto-oxidation. The indexes of oxidative stress include an increase in nerve, dorsal root, and sympathetic ganglia lipid hydroperoxides and conjugated dienes. The most reliable and sensitive index, however, is a reduction in reduced glutathione. Experimental diabetic neuropathy results in myelinopathy of dorsal roots and a vacuolar neuropathy of dorsal root ganglion. The vacuoles are mitochondrial; we posit that lipid peroxidation causes mitochondrial DNA mutations that increase reduced oxygen species, causing further damage to mitochondrial respiratory chain and function and resulting in a sensory neuropathy. Alpha-lipoic acid is a potent antioxidant that prevents lipid peroxidation in vitro and in vivo. We evaluated the efficacy of the drug in doses of 20, 50, and 100 mg/kg administered intraperitoneally in preventing the biochemical, electrophysiological, and nerve blood flow deficits in the peripheral nerves of experimental diabetic neuropathy. Alpha-lipoic acid dose- and time-dependently prevented the deficits in nerve conduction and nerve blood flow and biochemical abnormalities (reductions in reduced glutathione and lipid peroxidation). The nerve blood flow deficit was 50% (P < 0.001). Supplementation dose-dependently prevented the deficit; at the highest concentration, nerve blood flow was not different from that of control nerves. Digital nerve conduction underwent a dose-dependent improvement at 1 month (P < 0.05). By 3 months, all treated groups had lost their deficit. The antioxidant drug is potentially efficacious for human diabetic sensory neuropathy.

Maclaren N, Atkinson M. Is insulin-dependent diabetes mellitus environmentally induced? N Engl J Med 1992 Jul 30;327(5):348-349. (Editorial)
Abstract: In this editorial it is noted that only one in every three pairs of identical twins affected by IDDM becomes concordant for the disease and that the incidence of IDDM is increasing. Along with the fact that certain viruses can stimulate the body to make autoantibodies to pancreatic cells and that numerous antibodies have been found against very specific tissues of the pancreas it seems certain that an environmental etiology is likely. In rat studies substitutions of various proteins markedly affect the frequency of diabetes. It is noted that an increased frequency of antibodies to cow's milk proteins in children with newly diagnosed IDDM parallels the frequency with which cow's milk is consumed worldwide. Lastly, in the review they mentioned that two of their patients in whom IDDM recently developed at one year of age had never had products containing cow's milk.

Martinez, O. Dietary chromium and effect of chromium supplementation on glucose tolerance of elderly Canadian women. Nutr Res 1985;5:609-620.
Abstract: A double blind study of 85 elderly women ages 59-83, 62% of whom were on medications that could affect glucose metabolism, were divided into "high risk" and "low risk" categories on the basis of a 2 hour GTT and received either trivalent Chromium or placebo. After 10 weeks there was no significant difference between experimental subjects and controls except for a small but significant improvement after a GTT in the high risk, non-medicated group. This sub-group was found to have a significantly lower median chromium intake compared to the experimental low risk non-medicated group, suggesting that sub-optimal chromium status may account for the difference. Because it appears that drugs may have obscured this effect in the medicated subjects, the researchers suggest that future studies omit mediated subjects.

Mcchegiani E, Boemi M, Fumelli P, Fabris N. Zinc-dependent low thymic hormone level in type I diabetes. Diabetes 1989;12:932-937.

McNair P, Christiansen C, Madsbad S, et al. Hypomagnesemia, a risk factor in diabetic retinopathy. Diabetes 1978;27:1075-1077.

Mel'chinskaia EN, Popovtseva ON, Gromnatskii NI. [Immunologic aspects of alisate in diabetes mellitus patients]. Biull Eksp Biol Med 1997 Nov;124(11):595-597. [Article in Russian]

Mendola G, Casamitjana R, Gomis R. Effect of nicotinamide therapy upon B-cell function in newly diagnosed type 1 (insulin-dependent) diabetic patients. Diabetologia 1989;32:160-162.

Mertz W., Schwarz, K. Chromium(lll) and the glucose tolerance factor. Arch. Biochemical Biophys. 1959;85:292-295.

Mertz W. Chromium in human nutrition: a review. J Nutr 1993 Apr;123(4):626-633.
Abstract: This review summarizes the results of 15 controlled studies supplementing defined Cr(III) compounds to subjects with impaired glucose tolerance. Three of these (3-4 mumol Cr/d for > 2 mo) produced no beneficial effects: serum glucose, insulin and lipid concentrations remained unchanged. The remaining 12 interventions improved the efficiency of insulin or the blood lipid profile of subjects (ranging from malnourished children and healthy middle-aged individuals to insulin-requiring diabetics). In addition, three cases of impaired glucose tolerance after long-term total parenteral alimentation responding to Cr supplementation have been reported. Chromium potentiates the action of insulin in vitro and in vivo; maximal in vitro activity requires a special chemical form, termed Glucose Tolerance Factor and tentatively identified as a Cr-nicotinic acid complex. Its complete structural identification is a major challenge to chromium research. The development and validation of a procedure to diagnose chromium status is the second challenge. Such a test would allow the assessment of incidence and severity of deficiency in the population and the selection of deficiency in the population and the selection of chromium-responsive individuals. The third challenge is the definition of chromium's mode of action on parameters of lipid metabolism that have been reported from some studies but not others. Future research along these lines might establish whether chromium deficiency is a factor in the much discussed "Syndrome X" of insulin resistance.

Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev 1998 Jun;56(6):174-177. (Review)

Mimouni F, Miodovnik M, Tsang RC, et al. Decreased maternal serum magnesium concentration and adverse fetal outcome in insulin-dependent diabetic women. Obstet Gynecol 1987;70:85-89.

Molnar GD, Berge KG, Rosevear JW, et al. The effect of nicotinic acid in diabetes mellitus. Metabol 1964;13:181-189.

Murray M. Encyclopedia of Nutritional Supplements. Rocklin, CA: Prima Publishing, 1996; 343-346.

Nakamura T, Higashi A, Nishiyama S, et al. Kinetics of zinc status in children with IDDM. Diabetes Care 1991;14:553-557.

Nichols T. Alpha-Lipoic Acid: Biological Effects and Clinical Implications. Alt Med Rev 1997;2(3):177-183.

Niewoehner CB, Allen JI, Boosalis M, et al. Role of zinc supplementation in type II diabetes mellitus. Am J Med 1986;81:63-68.

Nuttall FW. Dietary fiber in the management of diabetes. Diabetes 1993;42:503-508.

Offenbacher E. Stunyer F. Beneficial effect of chromium-rich yeast on glucose tolerance and blood lipids in elderly patients. Diabetes 1980;29:919-925.
Abstract: 24 elderly patients, including 8 NIDDM patients, randomly received either 9gms of brewers yeast which was rich in chromium or the equivalent amount of chromium-poor tortula yeast. After 8 weeks, glucose tolerance, insulin sensitivity and total lipids improved only in the group receiving the brewers yeast

Offenbacher EG, Li-Sunyer FX. Improvement of glucose tolerance and blood lipids in elderly subjects. Am J Clin Nutr 1980;33:916. (Abstract)

Okuda Y, Mizutani M, Ogawa M, et al. Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus. J Diabetes Complications 1996;10:280-287.

Onofrj M, Fulgente T, Mechionda D, et al. L-acetylcarnitine as a new therapeutic approach for peripheral neuropathies with pain. Int J Clin Pharmacol Res 1995;15:9-15.

Ozden I, Deniz G, Tasali E, Ulusarac A, Altug T, Buyukdevrim S. The effect of vitamin E on glycosylated hemoglobin levels in diabetic rats: a preliminary report. Diabetes Res 1989 Nov;12(3):123-124.
Abstract: The effect of vitamin E (D-alpha-tocopherol acetate) on glycosylated hemoglobin levels was investigated in streptozotocin-diabetic rats. The animals were divided into four groups: (a) Group 1: control group, (b) Group 2: diabetic group, (c) Group 3: diabetic group treated with low-dose vitamin E and (d) Group 4: diabetic group treated with high-dose vitamin E. Starting 24 hr after streptozotocin injections (60 mg/kg), Groups 3 and 4 received intraperitoneal injections of vitamin E on days 1, 4, 7, 11, 14, 18 and 21 at doses of 500 mg/kg and 1,000 mg/kg respectively. Vitamin E treatment did not prevent weight loss or improve glycemic control in diabetic animals but significantly suppressed the increase in glycosylated hemoglobin in Group 4 (7.7 +/- 0.6 mumols fructose/g hemoglobin versus 5.5 +/- 0.2 mumols fructose/g hemoglobin in Group 2 and Group 4 respectively). These levels were still significantly higher than the levels in healthy control group animals (2.6 +/- 0.1 mumols fructose/g hemoglobin). Further studies on the suppressive effect of vitamin E are warranted.

Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med 1997;22(1-2):359-378. (Review)
Abstract: Reactive oxygen species are thought to be involved in a number of types of acute and chronic pathologic conditions in the brain and neural tissue. The metabolic antioxidant alpha-lipoate (thioctic acid, 1, 2-dithiolane-3-pentanoic acid; 1, 2-dithiolane-3 valeric acid; and 6, 8-dithiooctanoic acid) is a low molecular weight substance that is absorbed from the diet and crosses the blood-brain barrier. alpha-Lipoate is taken up and reduced in cells and tissues to dihydrolipoate, which is also exported to the extracellular medium; hence, protection is afforded to both intracellular and extracellular environments. Both alpha-lipoate and especially dihydrolipoate have been shown to be potent antioxidants, to regenerate through redox cycling other antioxidants like vitamin C and vitamin E, and to raise intracellular glutathione levels. Thus, it would seem an ideal substance in the treatment of oxidative brain and neural disorders involving free radical processes. Examination of current research reveals protective effects of these compounds in cerebral ischemia-reperfusion, excitotoxic amino acid brain injury, mitochondrial dysfunction, diabetes and diabetic neuropathy, inborn errors of metabolism, and other causes of acute or chronic damage to brain or neural tissue. Very few neuropharmacological intervention strategies are currently available for the treatment of stroke and numerous other brain disorders involving free radical injury. We propose that the various metabolic antioxidant properties of alpha-lipoate relate to its possible therapeutic roles in a variety of brain and neuronal tissue pathologies: thiols are central to antioxidant defense in brain and other tissues. The most important thiol antioxidant, glutathione, cannot be directly administered, whereas alpha-lipoic acid can. In vitro, animal, and preliminary human studies indicate that alpha-lipoate may be effective in numerous neurodegenerative disorders.

Paolisso G, Balbi V, Volpe C, et al. Metabolic benefits deriving from chronic vitamin C supplementation in aged non-insulin dependent diabetics. J Am Coll Nutr 1995;14:387-392.

Paolisso G, D’Amore A, Galzerano D, et al. Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly type II diabetic patients. Diabetes Care 1993;16:1433-1437.

Paolisso G, D’Amore A, Giugliano D, et al. Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin dependent diabetic patients. Am J Clin Nutr 1993;57:650-656.

Paolisso G, D'Amore A, Balbi V, Volpe C, Galzerano D, Giugliano D, Sgambato S, Varricchio M, D'Onofrio F. Plasma vitamin C affects glucose homeostasis in healthy subjects and in non-insulin-dependent diabetics. Am J Physiol. 1994 Feb;266(2 Pt 1):E261-268.

Paolisso G, Di Maro G, Galzerano D, et al. Pharmacological doses of vitamin E and insulin action in elderly subjects. Am J Clin Nutr 1994;59:1291-1296.

Paolisso G, Gambardella A, Galzerano D, et al. Antioxidants in adipose tissue and risk of myocardial infarction. Lancet 1994;343:596. (Letter)

Paolisso G, Scheen A, D’Onofrio FD, Lefebvre P. Magnesium and glucose homeostasis. Diabetologia 1990;33:511-514. (Review)

Paolisso G, Sgambato S, Gambardella A, et al. Daily magnesium supplements improve glucose handling in elderly subjects. Am J Clin Nutr 1992;55:1161-1167.

Paolisso G, Sgambato S, Pizza G, et al. Improved insulin response and action by chronic magnesium administration in aged NIDDM subjects. Diabetes Care 1989;12:265-269.

Passariello N, Fici F, Giugliano D, et al. Effects of pyridoxine alpha-ketoglutarate on blood glucose and lactate in type I and II diabetics. Internat J Clin Pharmacol Ther Toxicol 1983;21:252-256.

Phelps, Chapman, Hall, Brand, and Mackinnon. Prevalence of genetic hemochromatosis among diabetic patients. Lancet 1989;2:233-234.
Abstract: Among 418 patients attending a diabetic clinic, 21(5%) had persistently high serum ferritin levels and 5 of these had transferrin saturations consistently over 55%. Idiopathic hemochromatosis was confirmed by liver biopsy in 4 patients. The prevalence of unrecognized idiopathic hemochromatosis was 9.6 per 1000, compared to a general population prevalence of 4 per 1000. Note that heterozygous hemosiderosis affects up to 8-9% of the population.

Philpott, Kalita. Victory Over Diabetes, a Bio-Ecologic Triumph. Keats Pub, Inc.,1983.
Case: Carl, a 15 year old boy diagnosed as a juvenile-onset diabetic by two physicians, was receiving insulin to control his blood sugar. He had other signs and symptoms such as weakness, headaches, irritability, depression, and lethargy. Individual foods were tested for maladaptive reaction and it was found that wheat, oats, and milk produced hyperglycemic reactions above 230mg %. In addition, a 30 minute test exposure to auto exhaust produced a shift in blood glucose from 90 to over 180. When placed on a hypoallergenic diet, his blood glucose stayed in the normal range and his signs and symptoms cleared.
Case: A 38 year-old who had been diagnosed as a chronic schizophrenic for 15 years was tested and found to have hyperglycemic reactions, all of which were over 200, to 6 foods. The highest reaction was to cane sugar. This person when tested for maple syrup and honey showed only a rise at one hour of 135 and 110 respectively.

Pidduck HG, Wren PJJ, Price Evans DA. Hyperzincuria of diabetes mellitus and possible genetic implications of this observation. Diabetes 1970;19:240-247.

Popp-Snijders C, Schouten J, et al. Dietary supplementation of omega-3 fatty acids improves insulin sensitivity in non-insulin dependent diabetes. Neth J Med 1985;28:531-532.

Popp-Snijders C, Schouten JA, Heine RJ, et al. Dietary supplementation of omega-3 polyunsaturated fatty acids improves insulin sensitivity in non-insulin-dependent diabetes. Diabetes Res 1987;4:141-147.

Pots J, Lange M. Avoidance provocative food testing in assessing diabetes responsiveness. Diabetes, vol 26, supp. 1 #234, 1977 and Diabetes 29, 6, 1980.
Abstract: Potts working on IDDM (adult-onset)patients, found that 2/3rds of these were able to go off all their insulin with good control of their blood glucose following withdrawal from their maladaptive reactive substances. The remaining 1/3rd were able to reduce their insulin requirements by an average of 70%.

Rao KVR, Seshiah V, Kumar TV. Effect of zinc sulfate therapy on control and lipids in type I diabetes. JAPI 1987;35:52. (Abstract)

Rao RH, Vigg BL, Rao KSJ. Failure of pyridoxine to improve glucose tolerance in diabetics. J Clin Endocrinol Metabol 1980;50:198-200.

Reaven PD, Barnett J, Herold DA, Edelman S. Effect of vitamin E on susceptibility of low-density lipoprotein and low-density lipoprotein subfractions to oxidation and on protein glycation in NIDDM. Diabetes Care 1995;18:807.

Rodríguez-Morán M, Guerrero-Romero F, Lazcano-Burciaga G. Lipid- and glucose-lowering efficacy of plantago psyllium in type II diabetes. Diabetes: Its Complications 1998;12:273-278.

Roy S, Sen CK, Tritschler HJ, Packer L. Modulation of cellular reducing equivalent homeostasis by alpha-lipoic acid. Mechanisms and implications for diabetes and ischemic injury. Biochem Pharmacol 1997 Feb 7;53(3):393-399.
Abstract: The therapeutic potential of alpha-lipoic acid (thioctic acid) was evaluated with respect to its influence on cellular reducing equivalent homeostasis. The requirement of NADH and NADPH as cofactors in the cellular reduction of alpha-lipoic acid to dihydrolipoate has been reported in various cells and tissues. However, there is no direct evidence describing the influence of such reduction of alpha-lipoate on the levels of cellular reducing equivalents and homeostasis of the NAD(P)H/NAD(P) ratio. Treatment of the human Wurzburg T-cell line with 0.5 mM alpha-lipoate for 24 hr resulted in a 30% decrease in cellular NADH levels. alpha-Lipoate treatment also decreased cellular NADPH, but this effect was relatively less and slower compared with that of NADH. A concentration-dependent increase in glucose uptake was observed in Wurzburg cells treated with alpha-lipoate. Parallel decreases (30%) in cellular NADH/NAD+ and in lactate/pyruvate ratios were observed in alpha-lipoate-treated cells. Such a decrease in the NADH/NAD+ ratio following treatment with alpha-lipoate may have direct implications in diabetes, ischemia-reperfusion injury, and other pathologies where reductive (high NADH/NAD+ ratio) and oxidant (excess reactive oxygen species) imbalances are considered as major factors contributing to metabolic disorders. Under conditions of reductive stress, alpha-lipoate decreases high NADH levels in the cell by utilizing it as a co-factor for its own reduction process, whereas in oxidative stress both alpha-lipoate and its reduced form, dihydrolipoate, may protect by direct scavenging of free radicals and recycling other antioxidants from their oxidized forms.

Salomaa VV, et al Glucose tolerance and blood pressure: long term follow up in middle aged men. Brit Med J 1990;302:493-496.
Abstract: 1815 men were studied from 1974-86. In 1974, about half were normal and the other half had at least one risk factor for cardiovascular disease such as hypertension or glucose intolerance. Those who were hypertensive in 1986 had higher glucose levels in 1974. Glucose concentration in 1968 correlated with hypertension in 1986, even amongst those who were normotensive to begin with.

Salonen JT, Nyssonen K, Tuomainen T-P, et al. Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E concentrations: a four year follow up study in men. Brit Med J 1995;311:1124-1127.

Salway JG, Whitehead L, Finnegan JA, Karunanayaka A, Barnett D, Payne RB. Effect of myo-inositol on peripheral-nerve function in diabetes. Lancet 1978 Dec 16;2(8103):1282-1284.
Abstract: Myo-Inositol, 500 mg twice a day, given to seven diabetic patients for two weeks, increased the amplitude of the evoked action potentials of the median, sural, and popliteal nerves by an average of 76%, 160%, and 40%, respectively. There was no significant change in the conduction velocities of these nerves, myo-Inositol may be valuable in the treatment of diabetic neuropathy.

Schroeder HA. Serum cholesterol and glucose levels in rats fed refined and less refined sugars and chromium. J Nutr 1969;97:237-242.

Schwartz SE, Levine RA, Weinstock RS, et al. Sustained pectin ingestion: effect on gastric emptying and glucose tolerance in non-insulin-dependent diabetic patients. Am J Clin Nutr 1988;48:1413-1417.

Scott FWE, Norris JM, Kolb H. Milk and type I diabetes. Diabetes Care 1996;19:379-383. (Review)

Shanmugasundaram ER, Gopinath KL, Radha Shanmugasundaram K, Rajendran VM. Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given Gymnema sylvestre leaf extracts. J Ethnopharmacol 1990 Oct;30(3):265-279.
Abstract: Two water soluble extracts, GS3 and GS4, obtained from the leaves of Gymnema sylvestre, were tested in streptozotocin treated rats for their effects on blood glucose homeostasis and pancreatic endocrine tissue. In the diabetic rats, fasting blood glucose levels returned to normal after 60 days of GS3 and after 20 days of GS4 oral administration. Blood collected during the conduct of oral glucose tolerance tests was used to assay for serum insulin. GS3 and GS4 therapy led to a rise in serum insulin to levels closer to normal fasting levels. In diabetic rat pancreas, both GS3 and GS4 were able to double the islet number and beta cell number. This herbal therapy appears to bring about blood glucose homeostasis through increased serum insulin levels provided by repair/regeneration of the endocrine pancreas.

Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol. 1990 Oct;30(3):281-294.
Abstract: GS4, a water-soluble extract of the leaves of Gymnema sylvestre, was administered (400 mg/day) to 27 patients with insulin-dependent diabetes mellitus (IDDM) on insulin therapy. Insulin requirements came down together with fasting blood glucose and glycosylated haemoglobin (HbA1c) and glycosylated plasma protein levels. While serum lipids returned to near normal levels with GS4 therapy, glycosylated haemoglobin and glycosylated plasma protein levels remained higher than controls. IDDM patients on insulin therapy only showed no significant reduction in serum lipids, HbA1c or glycosylated plasma proteins when followed up after 10-12 months. GS4 therapy appears to enhance endogenous insulin, possibly by regeneration/revitalisation of the residual beta cells in insulin-dependent diabetes mellitus.

Sharma RD, Raghuram TC, Rao NS.Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr 1990 Apr;44(4):301-306.
Abstract: The effect of fenugreek seeds (Trigonella foenum graecum) on blood glucose and the serum lipid profile was evaluated in insulin-dependent (Type I) diabetic patients. Isocaloric diets with and without fenugreek were each given randomly for 10 d. Defatted fenugreek seed powder (100 g), divided into two equal doses, was incorporated into the diet and served during lunch and dinner. The fenugreek diet significantly reduced fasting blood sugar and improved the glucose tolerance test. There was a 54 per cent reduction in 24-h urinary glucose excretion. Serum total cholesterol, LDL and VLDL cholesterol and triglycerides were also significantly reduced. The HDL cholesterol fraction, however, remained unchanged. These results indicate the usefulness of fenugreek seeds in the management of diabetes.

Sheela CG, Augusti KT. Antidiabetic effects of S-allyl cysteine sulphoxide isolated from garlic Allium sativum Linn. Indian J Exp Biol 1992 Jun;30(6):523-526.
Abstract: S-allyl cysteine sulphoxide (SACS), a sulphur containing amino acid of garlic which is the precursor of allicin and garlic oil, has been found to show significant antidiabetic effects in alloxan diabetic rats. Administration of it at a dose of 200 mg/kg body weight decreased significantly the concentration of serum lipids, blood glucose and activities of serum enzymes like alkaline phosphatase, acid phosphatase and lactate dehydrogenase and liver glucose-6-phosphatase. It increased significantly liver and intestinal HMG CoA reductase activity and liver hexokinase activity.

Sitprija S, Plengvidhya C, Kangkaya V, Bhuvapanich S, Tunkayoon M. Garlic and diabetes mellitus phase II clinical trial. J Med Assoc Thai 1987 Mar;70 Suppl 2:223-227.

Sjorgren A, Floren CH, Nilsson A. Oral administration of magnesium hydroxide to subjects with insulin dependent diabetes mellitus. Magnesium 1988;121:16-20.

Smellie WS, O’Reilly D St J, Martin BJ, Santamaria J. Magnesium replacement and glucose tolerance in elderly subjects. Am J Clin Nutr 1993;57:594-595. (Letter)

Snowdon DA, Phillips RL. Does a vegetarian diet reduce the occurrence of diabetes? Am J Publ Health 1985;75:507-512.

Solomon LR, Cohen K. Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. Diabetes 1989;38:881-886.

Som S, Basu S, Mukherjee D, Deb S, Choudhury PR, Mukherjee S, Chatterjee SN, Chatterjee IB. Ascorbic acid metabolism in diabetes mellitus. Metabolism 1981 Jun;30(6):572-577.
Abstract: In contrast to normal subjects diabetic patients and very low plasma ascorbic acid and significantly high (p less than 0.001) dehydroascorbic acid irrespective of age, sex, duration of the disease, type of treatment, and glycemic control. However, there was no significant difference between the mean leukocyte ascorbate concentrations of the two populations. The in vitro rates of dehydroascorbate reduction in the hemolysate and the erythrocyte reduced glutathione levels and the glucose-6-phosphate dehydrogenase activities, which regulate the dehydroascorbate reduction, were similar in normal and diabetic subjects. The turnover of ascorbic acid was higher in the diabetics than that in the normal volunteers. Experiments with diabetic rats indicated that the increased turnover of ascorbic acid was probably due to increased oxidation of ascorbate to dehydroascorbate in tissue mitochondria. Ascorbic acid supplementation at a dose of 500 mg per day for a brief period of 15 days resulted in an increase in the plasma ascorbate level temporarily, but it did not lower the blood glucose level of the diabetic patients.

Spellacy WN, Buhi WC, Birk SA. The effects of vitamin B6 on carbohydrate metabolism in women taking steroid contraceptives: preliminary report. Contraception 1972;6:265-273.

Spellacy WN, Buhi WC, Birk SA. Vitamin B6 treatment of gestational diabetes mellitus. Am J Obstet Gynecol 1977;127:599-602.

Srivastava Y, Venkatakrishna-bhatt H, Verma Y, et al. Antidiabetic and adaptogenic properties of Momordica charantia extract: An experimental and clinical evaluation. Phytother Res 1993;7:285-289.

Stackpoole PW, Alig J, Kilgore LL, et al. Lipodystrophic diabetes mellitus. Investigations of lipoprotein metabolism and the effects of omega-3 fatty acid administration in two patients. Metabol 1988;37:944-951.

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):E185-191.
Abstract: The racemic mixture of the antioxidant alpha-lipoic acid (ALA) enhances insulin-stimulated glucose metabolism in insulin-resistant humans and animals. We determined the individual effects of the pure R-(+) and S-(-) enantiomers of ALA on glucose metabolism in skeletal muscle of an animal model of insulin resistance, hyperinsulinemia, and dyslipidemia: the obese Zucker (fa/fa) rat. Obese rats were treated intraperitoneally acutely (100 mg/kg body wt for 1 h) or chronically [10 days with 30 mg/kg of R-(+)-ALA or 50 mg/kg of S-(-)-ALA]. Glucose transport [2-deoxyglucose (2-DG) uptake], glycogen synthesis, and glucose oxidation were determined in the epitrochlearis muscles in the absence or presence of insulin (13.3 nM). Acutely, R-(+)-ALA increased insulin-mediated 2-DG-uptake by 64% (P < 0.05), whereas S-(-)-ALA had no significant effect. Although chronic R-(+)-ALA treatment significantly reduced plasma insulin (17%) and free fatty acids (FFA; 35%) relative to vehicle-treated obese animals, S-(-)-ALA treatment further increased insulin (15%) and had no effect on FFA. Insulin-stimulated 2-DG uptake was increased by 65% by chronic R-(+)-ALA treatment, whereas S-(-)-ALA administration resulted in only a 29% improvement. Chronic R-(+)-ALA treatment elicited a 26% increase in insulin-stimulated glycogen synthesis and a 33% enhancement of insulin-stimulated glucose oxidation. No significant increase in these parameters was observed after S-(-)-ALA treatment. Glucose transporter (GLUT-4) protein was unchanged after chronic R-(+)-ALA treatment but was reduced to 81 +/- 6% of obese control with S-(-)-ALA treatment. Therefore, chronic parenteral treatment with the antioxidant ALA enhances insulin-stimulated glucose transport and non-oxidative and oxidative glucose metabolism in insulin-resistant rat skeletal muscle, with the R-(+) enantiomer being much more effective than the S-(-) enantiomer.

Strodter D, Lehmann E, Lehmann U, et al. The influence of thioctic acid on metabolism and function of the diabetic heart. Diabetes Res Clin Pract 1995;29:19-26.

Tuomilehto J et al. Coffee consumption as a trigger for IDDM in childhood. Brit Med Journal March 1990;300:642-643.
Abstract: Finland has the highest incidence of IDDM in the world. The incidence has increaseed during recent years as has the consumption of coffee. In data derived from the Diabetes Epidem. Research International Study Group regarding coffee consumption there was an association between the annual average national coffee consumption per person and the age standardized incidence of IDDM. Countries with the highest coffee consumption per capita had the highest incidence of IDDM. Caffeine, the most widely used psychotropic agent, could be a risk factor in utero of IDDM. Its half life is prolonged in pregnancy and is known to cross the placenta into the fetus. Pregnant women who consume large amounts of coffee have increased risk to spontaneous abortions, premature deliveries and giving birth to infants with low birth weight.

Tütüncü NB, Bayraktar M, Varli K. Reversal of defective nerve condition with vitamin E supplementation in type 2 diabetes. Diabetes Care 1998;21:1915-1918.

Urberg M, Zemel MB. Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in elderly humans. Metabol 1987;36:896-899.

Vague P, Vialettes B, Lassmann Vague V, Vailo JJ. Nicotinaminde may extend remission phase in IDDM. Lancet 1987;1:619-620.
Abstract: In newly diagnosed IDDM functional Beta cells can be protected by halting the autoimmune process thru the regeneration of Beta cells, or by increasing their resistance to destruction. In animal studies, high-dose B3 prevented induction of diabetes by alloxan or streptozotocin, improved the condition of partly pancreatectomized diabetic rats, and prevented or delayed the onset of autoimmune diabetes. B3 restored normal intracellular levels of NAD in pancreatic islets, thereby preventing Beta cell damage or improving regeneratio. In the present study 16 IDDM received B3 (n=7; 3 g/day) or placebo (n=9). beginning one week after the start of insulin therapy, in a double blind trial. Insulin could be discontinued in 6 (85.7%) patients taking B3, compared to 5 (55.6%) patients taking placebo (p<0.05). Although complete remission for more than 2 years rarely occurs in IDDM, 3 patients treated with B3 for 18 months remained in remission for more than 2 years. These results suggest that B3 reduces destruction of Beta cells and enhaces their regeneration, thereby extending remission time.

Vandongen R, Mori TA, Codde JP, et al. Hypercholesterolaemic effect of fish oil in insulin-dependent diabetic patients. Med J Austral 1988;148:141-143.

Vessby B, Boberg M. Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with NIDDM. J Intern Med. 1990;228:165-171.
Abstract: 14 patients with NIDDM were randomly assigned to receive 10g/dday of fish oil in the form of MaxEPA or placebo (olive oil), in a double-blined cross-over trial. Each supplementation period last 8 weeks before switching. There was a statistically significant difference between the two groups with glucose concentrations going up in the MaxEPA treated group and down in the Olive oil supplemented group.

Vogelsang A. Vitamin E in the treatment of DM. Ann NY Acad Sci 1982;393..
Abstract: Warning- Vitamin E may reduce the insulin requirement. Diabetics on insulin should be started on 100 IU or less daily and the dosage raised slowly with adjustment of the insulin dose.

Wei I, Ulchaker M, Sheehan J. Effect of omega-3 fatty acids (FA) in non-obese non-insulin dependent diabetes (NIDDM). Am Clin Nutr 1988;47:775. (Abstract)

Welihinda J, Karunanaya E, Sheriff MHB, Jayasinghe K. Effect of Momardica charantia on the glucose tolerance in maturity onset diabetes. J Ethnopharm 1986;17:277-282.

Will JC, Tyers T. Does diabetes mellitus increase the requirement for vitamin C? Nutr Rev 1996;54:193-202. (Review)

Wilson RG, Davis RE. Serum pyridoxal concentrations in children with diabetes mellitus. Pathol 1977;9:95-99.Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes 1997 Sep;46 Suppl 2:S62-66.
Abstract: Antioxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes, providing a rationale for a potential therapeutic value in diabetic patients. The effects of the antioxidant alpha-lipoic acid (thioctic acid) were studied in two multicenter, randomized, double-blind placebo-controlled trials. In the Alpha-Lipoic Acid in Diabetic Neuropathy Study, 328 patients with NIDDM and symptomatic peripheral neuropathy were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (ALA 1,200 mg; 600 mg; 100 mg) or placebo (PLAC) over 3 weeks. The total symptom score (TSS) (pain, burning, paresthesia, and numbness) in the feet decreased significantly from baseline to day 19 in ALA 1,200 and ALA 600 vs. PLAC. Each of the four individual symptom scores was significantly lower in ALA 600 than in PLAC after 19 days (all P < 0.05). The total scale of the Hamburg Pain Adjective List (HPAL) was significantly reduced in ALA 1,200 and ALA 600 compared with PLAC after 19 days (both P < 0.05). In the Deutsche Kardiale Autonome Neuropathie Studie, patients with NIDDM and cardiac autonomic neuropathy diagnosed by reduced heart rate variability were randomly assigned to treatment with a daily oral dose of 800 mg alpha-lipoic acid (ALA) (n = 39) or placebo (n = 34) for 4 months. Two out of four parameters of heart rate variability at rest were significantly improved in ALA compared with placebo. A trend toward a favorable effect of ALA was noted for the remaining two indexes. In both studies, no significant adverse events were observed. In conclusion, intravenous treatment with alpha-lipoic acid (600 mg/day) over 3 weeks is safe and effective in reducing symptoms of diabetic peripheral neuropathy, and oral treatment with 800 mg/day for 4 months may improve cardiac autonomic dysfunction in NIDDM.

Ziegler D, Hanefield M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicenter randomized controlled trial (ALADIN Study). Diabetologia 1995;38:1425-1433.

Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie. Diabetes Care 1997 Mar;20(3):369-73
Abstract: OBJECTIVE: To evaluate the efficacy and safety of oral treatment with the antioxidant alpha-lipoic acid (ALA) in NIDDM patients with cardiac autonomic neuropathy (CAN), assessed by heart rate variability (HRV). RESEARCH DESIGN AND METHODS: In a randomized, double-blind placebo-controlled multicenter trial (Deutsche Kardiale Autonome Neuropathie [DEKAN] Study), NIDDM patients with reduced HRV were randomly assigned to treatment with daily oral dose of 800 mg ALA (n = 39) or placebo (n = 34) for 4 months. Parameters of HRV at rest included the coefficient of variation (CV), root mean square successive difference (RMSSD), and spectral power in the low-frequency (LF; 0.05-0.15 Hz) and high-frequency (HF; 0.15-0.5 Hz) bands. In addition, cardiovascular autonomic symptoms were assessed. RESULTS: Seventeen patients dropped out of the study (ALA n = 10; placebo n = 7). Mean blood pressure and HbA1 levels did not differ between the groups at baseline and during the study, but heart rate at baseline was higher in the group treated with ALA (P < 0.05). RMSSD increased from baseline to 4 months by 1.5 ms (-37.6 to 77.1) [median (minimum-maximum)] in the group given ALA and decreased by -0.1 ms (-19.2 to 32.8) in the placebo group (P < 0.05 for ALA vs. placebo). Power spectrum in the LF band increased by 0.06 bpm2 (-0. 09 to 0.62) in ALA, whereas it declined by -0.01 bpm2 (-0.48 to 1.86) in placebo (P < 0.05 for ALA vs. placebo). Furthermore, there was a trend toward a favorable effect of ALA versus placebo for the CV and HF band power spectrum (P = 0.097 and P = 0.094 for ALA vs. placebo). The changes in cardiovascular autonomic symptoms did not differ significantly between the groups during the period studied. No differences between the groups were noted regarding the rates of adverse events. CONCLUSIONS: These findings suggest that treatment with ALA using a well-tolerated oral dose of 800 mg/day for 4 months may slightly improve CAN in NIDDM patients.