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Back To Vidyya Is There a Role for Dietary Supplements in the Management of Diabetes?

Abstracts From Clinical Studies


Lessons from Observational Studies Evaluating Magnesium Intakes: Can They Predict Outcomes for Clinical Interventions?

W.H. Linda Kao, Ph.D

Abstract

Type 2 diabetes mellitus imposes a substantial public health burden in the United States. It affects approximately 15 million Americans and leads to an excess risk of blindness, renal failure, lower extremity amputation, and cardiovascular disease. Several lines of evidence suggest a possible, novel risk factor for type 2 diabetes S magnesium deficiency. First, several large observational studies have demonstrated strong cross-sectional associations between low serum magnesium and type 2 diabetes. Second, in vitro studies have shown an effect of magnesium on the secretion of insulin by the pancreas and on the responsiveness to insulin by peripheral tissues. Third, magnesium supplementation prevents the development of diabetes in a rat model of spontaneous type 2 diabetes. Finally, clinical intervention studies demonstrated that daily magnesium supplementation can improve short-term insulin response and glucose handling in diabetic individuals. Results from large, prospective, observational studies of the associations between serum magnesium and magnesium intake and the risk of developing type 2 diabetes will be reviewed. Although results from these studies support the notion that low serum magnesium levels and low dietary magnesium intake may be important in the development of type 2 diabetes, whether pharmacologic doses of magnesium used as dietary supplement can reduce the long-term risk for type 2 diabetes remains to be investigated.

Reference List

(1) Yajnik CS, Smith RF, Hockaday TD, Ward NI. Fasting plasma magnesium concentrations and glucose disposal in diabetes. Br Med J (Clin Res Ed) 1984; 288(6423):1032-1034.

(2) Rsnick LM, Altura BT, Gupta RK, Laragh JH, Alderman MH, Altura BM. Intracellular and extracellular magnesium depletion in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1993; 36(8):767-770.

(3) Paolisso G, Ravussin E. Intracellular magnesium and insulin resistance: results in Pima Indians and Caucasians. J Clin Endocrinol Metab 1995; 80(4):1382-1385.

(4) Paolisso G, Scheen A, D'Onofrio F, Lefebvre P. Magnesium and glucose homeostasis. Diabetologia 1990; 33(9):511-514.

(5) Levin GE, Mather HM, Pilkington TR. Tissue magnesium status in diabetes mellitus. Diabetologia 1981; 21(2):131-134.

(6) Alzaid AA, Dinneen SF, Moyer TP, Rizza RA. Effects of insulin on plasma magnesium in noninsulin-dependent diabetes mellitus: evidence for insulin resistance. J Clin Endocrinol Metab 1995; 80(4):1376-1381.

(7) McNair P, Christensen MS, Christiansen C, Madsbad S, Transbol I. Renal hypomagnesaemia in human diabetes mellitus: its relation to glucose homeostasis. Eur J Clin Invest 1982; 12(1):81-85.

(8) Mather HM, Nisbet JA, Burton GH, Poston GJ, Bland JM, Bailey PA et al. Hypomagnesaemia in diabetes. Clin Chim Acta 1979; 95(2):235-242.

(9) White JR, Jr., Campbell RK. Magnesium and diabetes: a review. Ann Pharmacother 1993; 27(6):775-780.

(10) Ma J, Folsom AR, Melnick SL, Eckfeldt JH, Sharrett AR, Nabulsi AA et al. Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study. J Clin Epidemiol 1995; 48(7):927-940.

(11) Hwang DL, Yen CF, Nadler JL. Insulin increases intracellular magnesium transport in human platelets. J Clin Endocrinol Metab 1993; 76(3):549-553.

(12) Gueux E, Rayssiguier Y. The effect of magnesium deficiency on glucose stimulated insulin secretion in rats. Horm Metab Res 1983; 15(12):594-597.

(13) Balon TW, Gu JL, Tokuyama Y, Jasman AP, Nadler JL. Magnesium supplementation reduces development of diabetes in a rat model of spontaneous NIDDM. Am J Physiol 1995; 269(4:Pt 1):Pt 1):E745-52.

(14) Paolisso G, Sgambato S, Gambardella A, Pizza G, Tesauro P, Varricchio M et al. Daily magnesium supplements improve glucose handling in elderly subjects. Am J Clin Nutr 1992; 55(6):1161-1167.

(15) Paolisso G, Sgambato S, Pizza G, Passariello N, Varricchio M, D'Onofrio F. Improved insulin response and action by chronic magnesium administration in aged NIDDM subjects. Diabetes Care 1989; 12(4):265-269.

(16) Paolisso G, Scheen A, Cozzolino D, Di Maro G, Varricchio M, D'Onofrio F et al. Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type II) diabetic patients. J Clin Endocrinol Metab 1994; 78(6):1510-1514.

(17) Paolisso G, Passariello N, Pizza G, Marrazzo G, Giunta R, Sgambato S et al. Dietary magnesium supplements improve B-cell response to glucose and arginine in elderly non-insulin dependent diabetic subjects. Acta Endocrinol (Copenh) 1989; 121(1):16-20.

(18) Paolisso G, Sgambato S, Giugliano D, Torella R, Varricchio M, Scheen AJ et al. Impaired insulin-induced erythrocyte magnesium accumulation is correlated to impaired insulin-mediated glucose disposal in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1988; 31(12):910-915.

(19) Colditz GA, Manson JE, Stampfer MJ, Rosner B, Willett WC, Speizer FE. Diet and risk of clinical diabetes in women. Am J Clin Nutr 1992; 55(5):1018-1023.

(20) Meyer KA, Kushi LH, Jacobs DR, Jr., Slavin J, Sellers TA, Folsom AR. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr 2000; 71(4):921-930.

(21) Kao WH, Folsom AR, Nieto FJ, Mo JP, Watson RL, Brancati FL. Serum and dietary magnesium and the risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. Arch Intern Med 1999; 159(18):2151-2159.


Vitamin Interventions to Prevent the Onset or Complications of Diabetes

John J. Cunningham, Ph.D., FACN

 

ABSTRACT

Hyperglycemia resulting from pancreatic beta cell destruction (insulin-dependent , IDDM) or defective insulin receptor function (non insulin-dependent, NIDDM) causes the degenerative complications of diabetes mellitus. Intervention strategies include primary prevention and alterations of glucose metabolism. Tight" (euglycemic) glucose control is accomplished by customizing the insulin regimen, diet and lifestyle and is well documented to be effective in delaying the onset of complications. Niacinamide has been tested at a pharmacologic dose in at-risk siblings of IDDMS, such as in the CanENDIT and DENIS trials. The results to date will be reviewed. Vitamin C is an ëaldose reductase inhibitor" in the sorbitol pathway with a potential for efficacy. Vitamins C and E offer protection against the oxidatative glycation of proteins that may also contribute to the delay of clinical complications.

References

The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin dependent diabetes mellitus. N Engl J Med 329:977-986, 1993.

Cunningham JJ. Micronutrients as nutriceutical interventions in diabetes mellitus.

Journal of the American College of Nutrition8;17:7-10, 1998.

Niacinamide

Pozzilli P, Brown PD, Kolb H: Meta-analysis of nicotinamide treatment in patients with recent onset insulin dependent diabetes. Diabetes Care 19:1357-1363, 1996

Manna R, Migliore A, Martini LS, Ponte E, Marietti G, Scuderi F, Cristiano G, Ghirlanda G, Gambassi G: Nicotinamide treatment in subjects at high risk of developing IDDM improves insulin secretion.Br J Clin Pract 46:177-179, 1997

Elliot RB, Pilcher C, Stewart A: The use of nicotinamade in the prevention of type I diabetes. Ann NY Acad Sci 696:333-341, 1993.

Elliot RB, Pilcher C, Fergusson DM, Stewart AW: A population based strategy to prevent insulin-dependent diabetes using nicotinimide. J Pediatr Endocr Met 9:501-509, 1996

Gale EAM, Bingley PJ: Can we prevent IDDM? Diabetes Care 17:339-344, 1994

Sharma A, Kharb S, Chugh SN, Kakkar R, Singh G. Effect of glycemic control and vitamin E supplementation on total glutathione content in non-insulin-dependent diabetes mellitus. Ann Nutr Metab 44:11-13, 2000

Vitamin E

Bursell S-E, Clermont A, Aiello LP, Aiello L, et al. High-dose vitami E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Diabetes Care 22:1245- 1251, 1999.

Jain SK, McVie R, Jaramillo JJ, Palmer M, Smith T: Effect of modest vitamin E supplementation on glycated hemoglobin and triglyceride levels and red cell indices in type I diabetic patients. J Am Coll Nutr 15:458-461, 1996.

Vitamin C

Cunningham JJ, Mearkle PL, Brown RG: Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus. J Am Coll Nutr 13:344-350, 1994.

Cunningham JJ: The glucose/insulin system and vitamin C: implications in insulin-dependent diabetes mellitus. J Am Coll Nutr 17:105-108, 1998.


Lessons From Micronutrient Studies In Patients With Glucose Intolerance and Diabetes Mellitus: Chromium and Vanadium

Henry C. Lukaski, Ph.D.

ABSTRACT

Public interest in the use of supplemental vanadium and chromium to ameliorate the symptoms of diabetes is burgeoning because of their putative action as insulin potentiating agents. Since 1980, evidence has accumulated to show that vanadium salts, vanadyl and vanadate, mimic insulin action in isolated cell systems and produce glucose-lowering effects when given to animals with diabetes. Supplementation of diabetic patients with vanadium salts in doses ranging from 25 to 100 mg of elemental vanadium daily for up to six weeks elicits partial normalization of glucose metabolic irregularities. Also, chromium supplements, specifically chromium picolinate, in amounts of 400 to 1000 mcg/d ameliorate glucose metabolic abnormalities in some patients with insulin resistance or type 2 diabetes. The doses of supplemental vanadium far exceed the apparent human vanadium requirement (10 mcg/d) whereas the levels of chromium supplementation surpass the safe and adequate intake level for chromium (50 to 200 mcg/d). Adverse effects of ingestion of these mineral supplements at these doses have been reported. Thus, doses of these minerals that elicit beneficial effects are pharmacologic and not nutritional.

References

Chromium

Anderson RA. Nutritional factors influencing the glucose/insulin system: chromium. J Am Coll Nutr 16: 404-410, 1997.

Anderson RA, N Cheng, NA Bryden, MM Polansky, N Cheng, J Chi, J Feng. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 46: 1786-1791, 1997.

Cefalu WT, AD Bell-Farrow, J Stenger, ZQ Wang, T King, T Morgan, JG Terry. Effect of chromium picolinate on insulin sensitivity in vivo. J Trace Elem Exp Med 12: 71-83, 1999.

Cheng N, X Zhu, H Shi, W Wu, J Chi, J Cheng, RA Anderson. Follow-up survey of people in China with type 2 diabetes consuming supplemental chromium. J Trace Elem Exp Med 12: 55-60, 1999.

Davis CM, JB Vincent. Chromium oligopeptide activates insulin receptor kinase activity. Biochemistry 36: 4382-4385, 1997.

Davis CM, JB Vincent. Isolation and characterization of a biologically active chromium oligopeptide from bovine liver. Arch Biochem Biophys 339: 335-343, 1997.

Jovanovic L, M Guttierrez, CM Peterson. Chromium supplementation for women with gestational diabetes. J Trace Elem Exp Med 12: 91-97, 1999.

Lukaski HC. Chromium as a supplement. Ann Rev Nutr 19: 279-302, 1999.

Mertz W. Chromium in human nutrition: a review. J Nutr 123: 626-633, 1993.

Ravina A, L Slezak, N Mirsky, RA Anderson. Control of steroid-induced diabetes with supplemental chromium. J Trace Elem Exp Med 12: 375-378, 1999.

Speetjens JK, RA Collins, JB Vincent, SA Wolski. The nutritional supplement chromium(III) tris(picolinate) cleaves DNA. Chem Res Toxicol 12: 483-487, 1999.

Stearns, DM. Is chromium a trace essential metal? Biofactors 11: 149-162, 2000.

Vincent JB. Mechanisms of chromium action: low-molecular weight-chromium-binding substance. J Am Coll Nutr 18: 6-12, 1999.

Vincent JB. The biochemistry of chromium. J Nutr 130: 715-718, 2000.

 

Vanadium

Cohen N, M Halberstram, P Shilmovich, CJ Chang, H Sharnoon, L Rossetti. Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin dependent diabetes mellitus. J Clin Invest 95: 2501-2509, 1995.

Goldfine AB, DC Simonson, F Folli, ME Patti, CR Kahn. Metabolic effects of vanadyl sulfate in humans with insulin-dependent and non insulin-dependent diabetes mellitus in vivo and in vitro studies. J Clin Endocrinol Metab 80: 3311-3320, 1995.

Goldfine AB, DC Simonson, F Folli, ME Patti, CR Kahn. In vivo and in vitro studies of vanadate in human and rodent diabetes mellitus. Mol Cell Biochem 153: 217-231, 1995.

Goldfine AB, ME Patti, L Zuberi, BJ Goldstein, R LeBlanc, EJ Landaker, ZY Jiang, GR Willsky, CR Kahn. Metabolic effects of vanadyl sulfate in humans with non-insulin dependent diabetes mellitus: in vivo and in vitro studies. Metabolism 49: 400-410, 2000.

Hamel FG, WC Duckworth. The relationship between insulin and vanadium metabolism in insulin target tissues. Mol Cell Biochem 153: 95-102, 1995.

Thompson KH. Vanadium and diabetes. BioFactors 10: 43-51, 1999.

Thompson KH, JH McNeill, C Orvig. Vanadium compounds as insulin mimetics. Chem Rev 99: 2561-2571, 1999.

Verna S, MC Cam, JH McNeill. Nutritional factors that can favorably influence the glucose/insulin system: vanadium. J Am Coll Nutr 17: 11-18, 1998.


Is There a Role for Taurine Supplementation

in the Management of Diabetes?

Katherine Chauncey, PhD, RD, CDE

 

ABSTRACT

Taurine is a small sulfur-containing amino acid and is one of the most abundant free amino acids in humans. Its real importance has been recognized only within the past 25 years. Once considered non-essential, taurine is now considered "conditionally essential." In pre-term and term infants, taurine insufficiency results in impaired fat absorption, bile acid secretion, retinal function, and hepatic function, all of which can be reversed by taurine supplementation. An increasing body of data demonstrates that taurine at pharmacological concentrations alters carbohydrate metabolism. People with diabetes have lower than average blood levels of taurine, but whether this means they should take extra taurine is unclear. This presentation will describe the steps involved in designing and implementing a clinical trial to study taurine supplementation in patients with type 2 diabetes mellitus.

References

Ackerman, D., Heinsen, H.A. (1935) Uber die physiologische wirkung des asterubins and anderer, zum tiel neu dargestellter, schwefelhaltiger guanidinderivate. Z. Physiol. Chem. 235: 115-121.

Elizarova, E.P., Nedosugova, L.V. (1996) First Experiments in Taurine Administrationfor Diabetes Mellitus. Adv. Exp. Med. Biol. 403: 583-587.

Franconi, F., Miceli, M., Fazzini, A., Sehgieri, G., Dileo, M., Lepore, D., Ghirlanda, G. (1996) Taurine and Diabetes. Adv. Exp. Med. Biol. 403: 579-582.

Gaull, G.E., Rassin, D.K. (1980) Taurine in development and nutrition, in: Proceedings of the 72nd Ciba Foundation Symposium on Sulfur in Biology. Excerpta Med. Amsterdam. pp. 271.

Gaull, G.E., Rassin, D.K., Räihä, N.C.R., Sturman, J.A., (1977) Milk protein quantity and quality in low-birthweight infants. III. Effects on sulfur amino acids in plasma and urine. J. Pediatr. 90: 348-355.

Geggel, H., Ament, M., Heckenlively, J. (1985) Nutritional requirement for taurine in patients receiving long-term, parenteral nutrition. N. Engl. J. Med. 312: 142.

Geggel, H.S., Heckenlively, J.R., Martin, D.A. (1982) Human retinal dysfunction and taurine deficiency. Dox. Opthamol. Proc. Ser. 31: 199.

Helms, R., Storm, M., Christensen, M., Hak, E., Chesnew, R. (1999) Cysteine supplementation results in normalization of plasma taurine concentrations in children receiving home parenteral nutrition. J. Pediatr 134: 358-361.

Kulakowski, E.C., Maturo, J. (1984) Hypoglycemic properties of taurine: not mediated by enhanced insulin release. Biochem. Pharmacol. 33: 2835-2838.

Laidlaw, S., Schultz, T., Cecchino, J., Kopple, J., (1988) Plasma and urine taurine levels in vegans. Am. J. Clin. Nutr. 47: 660-663.

Lampson, W.G., Kramer, J.H., Schaffer, S.W. (1983) Potentiation of insulin by sulfones. Can. Chem. Process. 26: 669.

Rassin, D.K., Sturman, J.A., Gaull, G.E. (1977) Taurine in milk: Species variation. Pediatr. Res. 11: 463A.


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