Magnesium: Diabetes by rudenski Blog entry

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Magnesium: Diabetes

: Med Hypotheses. 1996 Feb;46(2):89-100. Related Articles, Links

Complementary vascular-protective actions of magnesium and taurine: a rationale for magnesium taurate.

McCarty MF.

Nutrition 21, San Diego, CA 92109, USA.

By a variety of mechanisms, magnesium functions both intracellularly and extracellularly to minimize the cytoplasmic free calcium level, [Ca2+]i. This may be the chief reason why correction of magnesium deficiency, or induction of hypermagnesemia by parenteral infusion, exerts antihypertensive, anti-atherosclerotic, anti-arrhythmic and antithrombotic effects. Although the amino acid taurine can increase systolic calcium transients in cardiac cells (and thus has positive inotropic activity), it has other actions which tend to reduce [Ca2+]i. Indeed, in animal or clinical studies, taurine lowers elevated blood pressure, retards cholesterol-induced atherogenesis, prevents arrhythmias and stabilizes platelets--effects parallel to those of magnesium. The com

Date: 8/9/2006 2:04:54 PM ( 18 y ) ... viewed 4463 times

DIABETES NUTRITIONAL RESEARCH

Complementary vascular-protective actions of magnesium and taurine: a rationale for magnesium taurate.
Magnesium and ascorbic acid supplementation in diabetes mellitus.
Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells.
alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes.
Insufficient glycemic control increases nuclear factor-kappa B binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes.
Exploiting complementary therapeutic strategies for the treatment of type II diabetes and prevention of its complications.
Pharmacological doses of vitamin E and insulin action in elderly subjects.
Relation between insulin resistance and plasma concentrations of lipid hydroperoxides, carotenoids, and tocopherols.

2: Ann Nutr Metab. 1995;39(4):217-23. Related Articles, Links

Magnesium and ascorbic acid supplementation in diabetes mellitus.

Eriksson J, Kohvakka A.

Malmi Municipal Hospital, Helsinki, Finland.

The effect of magnesium (Mg) and ascorbic acid (AA) supplementation on metabolic control was assessed in 56 outpatient diabetics. A 90-day run-in period was followed by two 90-day treatment periods, during which Mg (600 mg/day) and AA (2 g/day) were administered in a randomized double-blind cross-over fashion. A decrease in systolic and diastolic blood pressure (132 +/- 3 vs. 138 +/- 4 and 77 +/- 2 vs. 82 +/- 2 mm Hg; p < 0.05) was observed in insulin-dependent diabetes mellitus subjects during Mg supplementation. No beneficial effect of Mg supplementation was observed on glycemic control, lipids or blood pressure in non-insulin-dependent diabetes mellitus (NIDDM) subjects. AA supplementation improved glycemic control among NIDDM subjects and both fasting blood glucose (9.1 +/- 0.5 vs. 10.1 +/- 0.6 mmol/l; p < 0.05) and HbA1c (8.5 +/- 0.3 vs. 9.3 +/- 0.3%; p < 0.05) improved. Beneficial effects of AA supplementation on cholesterol (5.9 +/- 0.2 vs. 6.2 +/- 0.2 mmol/l; p < 0.05) and triglycerides (2.2 +/- 0.2 vs. 2.5 +/- 0.2; p < 0.05) were also observed in NIDDM subjects. The results suggest that high-dose AA supplementation may have a beneficial effect in NIDDM subjects on both glycemic control and blood lipids.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 8546437 [PubMed - indexed for MEDLINE]

3: Diabetes. 1997 Sep;46(9):1481-90. Related Articles, Links

Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells.

Bierhaus A, Chevion S, Chevion M, Hofmann M, Quehenberger P, Illmer T, Luther T, Berentshtein E, Tritschler H, Muller M, Wahl P, Ziegler R, Nawroth PP.

Department of Internal Medicine, University of Heidelberg, Germany.

Depletion of cellular antioxidant defense mechanisms and the generation of oxygen free radicals by advanced glycation end products (AGEs) have been proposed to play a major role in the pathogenesis of diabetic vascular complications. Here we demonstrate that incubation of cultured bovine aortic endothelial cells (BAECs) with AGE albumin (500 nmol/l) resulted in the impairment of reduced glutathione (GSH) and ascorbic acid levels. As a consequence, increased cellular oxidative stress led to the activation of the transcription factor NF-kappaB and thus promoted the upregulation of various NF-kappaB-controlled genes, including endothelial tissue factor. Supplementation of the cellular antioxidative defense with the natural occurring antioxidant alpha-lipoic acid before AGE albumin induction completely prevented the AGE albumin-dependent depletion of reduced glutathione and ascorbic acid. Electrophoretic mobility shift assays (EMSAs) revealed that AGE albumin-mediated NF-kappaB activation was also reduced in a time- and dose-dependent manner as long as alpha-lipoic acid was added at least 30 min before AGE albumin stimulation. Inhibition was not due to physical interactions with protein DNA binding, since alpha-lipoic acid, directly included into the binding reaction, did not prevent binding activity of recombinant NF-kappaB. Western blots further demonstrated that alpha-lipoic acid inhibited the release and translocation of NF-kappaB from the cytoplasm into the nucleus. As a consequence, alpha-lipoic acid reduced AGE albumin-induced NF-kappaB mediated transcription and expression of endothelial genes relevant in diabetes, such as tissue factor and endothelin-1. Thus, supplementation of cellular antioxidative defense mechanisms by extracellularly administered alpha-lipoic acid reduces AGE albumin-induced endothelial dysfunction in vitro.

PMID: 9287050 [PubMed - indexed for MEDLINE]

4: Diabetes Care. 1999 Feb;22(2):280-7. Related Articles, Links

alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes.

Konrad T, Vicini P, Kusterer K, Hoflich A, Assadkhani A, Bohles HJ, Sewell A, Tritschler HJ, Cobelli C, Usadel KH.

Department of Internal Medicine, J.W. Goethe-University, Frankfurt, Germany.

OBJECTIVE: We examined the effect of lipoic acid (LA), a cofactor of the pyruvate dehydrogenase complex (PDH), on insulin sensitivity (SI) and glucose effectiveness (SG) and on serum lactate and pyruvate levels after oral glucose tolerance tests (OGTTs) and modified frequently sampled intravenous glucose tolerance tests (FSIGTTs) in lean (n = 10) and obese (n = 10) patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: FSIGTT data were analyzed by minimal modeling technique to determine SI and SG before and after oral treatment (600 mg, twice a day, for 4 weeks). Serum lactate and pyruvate levels of diabetic patients after glucose loading were compared with those of lean (n = 10) and obese (n = 10) healthy control subjects in which SI and SG were also determined from FSIGTT data. RESULTS: Fasting lactate and pyruvate levels were significantly increased in patients with type 2 diabetes. These metabolites did not exceed elevated fasting concentrations after glucose loading in lean patients with type 2 diabetes. However, a twofold increase of lactate and pyruvate levels was measured in obese diabetic patients. LA treatment was associated with increased SG in both diabetic groups (lean 1.28 +/- 0.14 to 1.93 +/- 0.13; obese 1.07 +/- 0.11 to 1.53 +/- 0.08 x 10(-2) min-1, P < 0.05). Higher SI and lower fasting glucose were measured in lean diabetic patients only (P < 0.05). Lactate and pyruvate before and after glucose loading were approximately 45% lower in lean and obese diabetic patients after LA treatment. CONCLUSIONS: Treatment of lean and obese diabetic patients with LA prevents hyperglycemia-induced increments of serum lactate and pyruvate levels and increases SG.

PMID: 10333946 [PubMed - indexed for MEDLINE]

5: Diabetes Care. 1998 Aug;21(8):1310-6. Related Articles, Links

Insufficient glycemic control increases nuclear factor-kappa B binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes.

Hofmann MA, Schiekofer S, Kanitz M, Klevesath MS, Joswig M, Lee V, Morcos M, Tritschler H, Ziegler R, Wahl P, Bierhaus A, Nawroth PP.

Department of Medicine, University of Heidelberg, Germany.

OBJECTIVE: The redox-sensitive transcription factor nuclear factor-kappa B (NF-kappa B) is believed to contribute to late diabetic complications. It is unknown whether NF-kappa B is influenced by glycemic control. RESEARCH DESIGN AND METHODS: To determine whether NF-kappa B is activated in patients with insufficient glycemic control (HbA1c > 10%), we developed a tissue culture-independent electrophoretic mobility shift assay (EMSA)-based semiquantitative detection system that allowed us to determine NF-kappa B activation in ex vivo-isolated peripheral blood mononuclear cells (PBMCs). We included 43 patients with type 1 diabetes in this cross-sectional study. 10 of those received the antioxidant thioctic acid (600 mg/day p.o.) for 2 weeks. RESULTS: Monocytes of patients with HbA1c levels > 10% demonstrated significantly higher NF-kappa B binding activity in an EMSA and a stronger NF-kappa B staining in immunohistochemistry than monocytes of patients with HbA1c levels of 6-8%. The increase in NF-kappa B activation correlated with an increase in plasmatic markers of lipid peroxidation. Treatment with the antioxidant thioctic acid decreased NF-kappa B binding activity. CONCLUSIONS: Hyperglycemia induces activation of the transcription factor NF-kappa B in ex vivo-isolated PBMCs of patients with type 1 diabetes. NF-kappa B activation is at least partially dependent on oxidative stress, since the antioxidant thioctic acid [ALPHA LIPOIC ACID] significantly lowered the extent of NF-kappa B binding activity.

PMID: 9702439 [PubMed - indexed for MEDLINE]

6: Med Hypotheses. 1997 Aug;49(2):143-52. Related Articles, Links

Exploiting complementary therapeutic strategies for the treatment of type II diabetes and prevention of its complications.

McCarty MF.

Nutrition 21, San Diego, CA 92109, USA.

Impaired glycemic control in type II diabetes results from peripheral insulin resistance, hepatic insulin resistance, and a relative failure of beta cell function. Nutritional and pharmaceutical measures are now available for addressing each of these defects, presumably enabling a rational and highly effective clinical management of non-insulin-dependent diabetes mellitus. Peripheral insulin resistance, which usually responds to a very-low-fat diet, aerobic exercise training, and appropriate weight loss, can also treated with high-dose chromium picolinate, high-dose vitamin E, magnesium, soluble fiber, and possibly taurine; these measures appear likely to correct the diabetes-associated metabolic derangements of vascular smooth muscle, and thus lessen risk for macrovascular disease. Metformin's clinical efficacy is primarily reflective of reduced hepatic glucose output; this action should complement the benefits of peripheral insulin sensitizers. When these measures are not sufficient for optimal control, beta cell function can be boosted with second-generation sulfonylureas.

PMID: 9278926 [PubMed - indexed for MEDLINE]

7: Am J Clin Nutr. 1994 Jun;59(6):1291-6. Related Articles, Links

Pharmacological doses of vitamin E and insulin action in elderly subjects.

Paolisso G, Di Maro G, Galzerano D, Cacciapuoti F, Varricchio G, Varricchio M, D'Onofrio F.

Department of Geriatric Medicine and Metabolic Diseases, II University of Naples, Italy.

Twenty elderly (77 +/- 0.4 y), nonobese [body mass index (in kg/m2) 26.4 +/- 0.5] subjects with normal glucose tolerance were submitted to a euglycemic hyperinsulinemic (3.5 pmol.min/kg) glucose clamp in a double-blind, crossover, randomized procedure after 4 mo treatment with either vitamin E (900 mg d-alpha-tocopherol/d, Ephynal; Roche, Milan, Italy) or placebo. Body mass index was practically unchanged throughout the study. After the glucose clamp, insulin-mediated stimulation 2 of whole-body glucose disposal (18.4 +/- 0.5 vs 26.1 +/- 0.6 mumol.min/kg lean body mass P < 0.02) was significantly potentiated by vitamin E rather than placebo administration. Furthermore, net changes in plasma vitamin E concentrations correlated with net changes in insulin-stimulated whole-body glucose disposal (r = 0.60 P < 0.003). Plasma vitamin E concentrations seem to play an important role in the modulation of insulin action in elderly people.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 8198053 [PubMed - indexed for MEDLINE]

8: Am J Clin Nutr. 2000 Sep;72(3):776-9. Related Articles, Links

Relation between insulin resistance and plasma concentrations of lipid hydroperoxides, carotenoids, and tocopherols.

Facchini FS, Humphreys MH, DoNascimento CA, Abbasi F, Reaven GM.

Department of Medicine, Division of Nephrology, San Francisco General Hospital, CA 94110, USA. fste2000@yahoo.com

BACKGROUND: It is not known whether total circulating lipid hydroperoxides are increased in insulin-resistant individuals and whether this correlates with depletion of liposoluble antioxidant vitamins that are consumed during lipid peroxidation. OBJECTIVE: The goal of this study was to define the relation between resistance to insulin-mediated glucose disposal and plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins in healthy volunteers. DESIGN: Insulin-mediated glucose disposal was determined in 36 healthy, nondiabetic volunteers by measuring their steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a 180-min constant infusion of octreotide, insulin, and glucose. In addition, fasting plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins were determined by using the FOX 2 assay and liquid chromatography. RESULTS: Statistically significant direct relations were observed between SSPG and mean arterial blood pressure (r = 0.44, P: = 0.008) and plasma lipid hydroperoxide concentrations (r = 0.42, P: = 0.01), whereas significant inverse correlations were found between SSPG and alpha-carotene (r = -0.58, P: = 0.0002), beta-carotene (r = -0.49, P: = 0.004), lutein (r = -0.35, P: = 0.04), alpha-tocopherol (r = -0. 36, P: = 0.04), and delta-tocopherol (r = -0.45, P: = 0.007). CONCLUSIONS: Variations in insulin-mediated glucose disposal in healthy individuals are significantly related to plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins. These findings suggest that total plasma lipid peroxidation is increased in insulin-resistant individuals at an early, preclinical stage, ie, well before the development of glucose intolerance and type 2 diabetes.

PMID: 10966898 [PubMed - indexed for MEDLINE]