[Chromium: physiologic role and implications in human pathology]
[Article in French]
Laboratoire de Biochimie B,
Reported values for total body stores of chromium vary between 0.4 mg and 6 mg. Chromium stores may be higher in neonates than in adults, relative to body size, whereas tissular chromium may be depleted in the elderly. The recommended daily allowance for chromium is 50 to 200 micrograms/day but actual needs are poorly known. Digestive absorption is better for organic chromium, which is part of the "glucose tolerance factor" (GTF), than for inorganic chromium. Furthermore, chromium (VI) is better absorbed than chromium (III). In the body, chromium (VI) is rapidly reduced to chromium (III) by a number of metabolic pathways. Absorbed chromium binds to proteins, mainly to transferrin which exhibits a high affinity for chromium (III). Most absorbed chromium is eliminated through the kidneys. Renal excretion occurs according to a two or more-compartment model. Current methods used to assay chromium, i.e., atomic absorption spectrometry using a graphite furnace or neutron activation, are sufficiently sensitive and specific to evaluate chromium levels in blood, urine or hair. However, none of these levels accurately reflects chromium body stores. Chromium is part of the GTF molecule. This factor has no effect per se but may facilitate binding of insulin to insulin receptors and amplify the effects of insulin on carbohydrate and lipid metabolism. Chromium deficiency may play a role in a development of some forms of adult diabetes mellitus and of arteriosclerosis. Partial chromium deficiencies seem to be common, especially in individuals with high intakes of refined foods. Acute chromium poisoning is usually due to an excess of chromium (VI) and is sometimes seen in the chromium industry.(ABSTRACT TRUNCATED AT 250 WORDS)
The therapeutic potential of glucose tolerance factor.
Glucose Tolerance Factor (GTF) is synthesized in vivo from absorbed dietary chromium, and acts as a physiological enhancer of insulin activity, binding to insulin and potentiating its action about three-fold. Since GTF is well absorbed orally, the development of sufficiently concentrated and stable supplementary sources of this agent may enable convenient and physiologically appropriate pharmacological modulation of insulin activity. A review of the numerous physiological actions of insulin suggests a number of therapeutic applications for GTF, in such diverse ailments as diabetes mellitus, hyperlipidemia, reactive hypoglycemia, obesity, cancer, protein malnutrition or malabsorption, endogenous depression, Parkinsonism, hypertension and cardiac arrhythmias. GTF supplementation may also have value in preventive medicine.
Magnesium Intake and Risk of Type 2 Diabetes in Men and Women.
Lopez-Ridaura R, Willett WC, Rimm EB, Liu S, Stampfer MJ, Manson JE, Hu FB.
Department of Nutrition, Harvard
OBJECTIVE:-To examine the association between magnesium intake and risk of type 2 diabetes. RESEARCH DESIGN AND METHODS-We followed 85,060 women and 42,872 men who had no history of diabetes, cardiovascular disease, or cancer at baseline. Magnesium intake was evaluated using a validated food frequency questionnaire every 2-4 years. After 18 years of follow-up in women and 12 years in men, we documented 4,085 and 1,333 incident cases of type 2 diabetes, respectively. RESULTS:-After adjusting for age, BMI, physical activity, family history of diabetes, smoking, alcohol consumption, and history of hypertension and hypercholesterolemia at baseline, the relative risk (RR) of type 2 diabetes was 0.66 (95% CI 0.60-0.73; P for trend <0.001) in women and 0.67 (0.56-0.80; P for trend <0.001) in men, comparing the highest with the lowest quintile of total magnesium intake. The RRs remained significant after additional adjustment for dietary variables, including glycemic load, polyunsaturated fat, trans fat, cereal fiber, and processed meat in the multivariate models. The inverse association persisted in subgroup analyses according to BMI, physical activity, and family history of diabetes. CONCLUSIONS:-Our findings suggest a significant inverse association between magnesium intake and diabetes risk. This study supports the dietary recommendation to increase consumption of major food sources of magnesium, such as whole grains, nuts, and green leafy vegetables.
Dietary Magnesium Intake in Relation to Plasma Insulin Levels and Risk of Type 2 Diabetes in Women.
Song Y, Manson JE, Buring JE, Liu S.
Division of Preventive Medicine, Brigham and Women's Hospital,
OBJECTIVE:-Higher intake of magnesium appears to improve glucose and insulin homeostasis; however, there are sparse prospective data on the association between magnesium intake and incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS-In the Women's Health Study, a cohort of 39,345 U.S. women aged >/==" BORDER="0">45 years with no previous history of cardiovascular disease, cancer, or type 2 diabetes completed validated semiquantitative food frequency questionnaires in 1993 and were followed for an average of 6 years. We used Cox proportional hazard models to estimate multivariate relative risks (RRs) of type 2 diabetes across quintiles of magnesium intake compared with the lowest quintile. In a sample of 349 apparently healthy women from this study, we measured plasma fasting insulin levels to examine their relation to magnesium intake. RESULTS:-During 222,523 person-years of follow-up, we documented 918 confirmed incident cases of type 2 diabetes. There was a significant inverse association between magnesium intake and risk of type 2 diabetes, independent of age and BMI (P = 0.007 for trend). After further adjustment for physical activity, alcohol intake, smoking, family history of diabetes, and total calorie intake, the multivariate-adjusted RRs of diabetes from the lowest to highest quintiles of magnesium intake were attenuated at 1.0, 1.06, 0.81, 0.86, and 0.89 (P = 0.05 for trend). Among women with BMI >/==" BORDER="0">25 kg/m(2), the inverse trend was significant; multivariate-adjusted RRs were 1.0, 0.96, 0.76, 0.84, and 0.78 (P = 0.02 for trend). Multivariate-adjusted geometric mean insulin levels for overweight women in the lowest quartile of magnesium intake was 53.5 compared with 41.5 pmol/l among those at the highest quartile (P = 0.03 for trend). CONCLUSIONS:-These findings support a protective role of higher intake of magnesium in reducing the risk of developing type 2 diabetes, especially in overweight women.
Low plasma magnesium in type 2 diabetes.
Walti MK, Zimmermann MB,
Laboratory for Human Nutrition,
QUESTIONS UNDER STUDY/PRINCIPLES: Magnesium depletion has a negative impact on glucose homeostasis and insulin sensitivity in type 2 diabetic patients. Low plasma magnesium concentration is a highly specific indicator of poor magnesium status. In the
Magnesium, the second most abundant intracellular divalent cation, is a cofactor of many enzymes involved in glucose metabolism. Magnesium has an important role in insulin action, and insulin stimulates magnesium uptake in insulin-sensitive tissues. Impaired biological responses to insulin is referred to as insulin resistance. This review was designed to reach a better understanding of the mechanism involved in the correlation between magnesium and insulin resistance. Intracellular magnesium concentration is low in type 2 diabetes mellitus and in hypertensive patients. In patients with type 2 diabetes an inverse association exists between the plasma magnesium and insulin resistance due to intracellular changes. The suppressed intracellular magnesium concentration may result in defective tyrosine kinase activity and modify insulin sensitivity by influencing receptor activity after binding or by influencing intracellular signaling and processing. Intracellular magnesium deficiency may affect the development of insulin resistance and alter the glucose entry into the cell. CONCLUSIONS: Magnesium is required for both proper glucose utilization and insulin signaling. Metabolic alterations in cellular magnesium, which may play the role of a second messenger for insulin action, contribute to insulin resistance.
Magnesium (Mg) is one of the most abundant ions present in living cells and its plasma concentration is remarkably constant in healthy subjects. Plasma and intracellular Mg concentrations are tightly regulated by several factors. Among them, insulin seems to be one of the most important. In vitro and in vivo studies have demonstrated that insulin may modulate the shift of Mg from extracellular to intracellular space. Intracellular Mg concentration has also been shown to be effective in modulating insulin action (mainly oxidative glucose metabolism), offset calcium-related excitation-contraction coupling, and decrease smooth cell responsiveness to depolarizing stimuli. A poor intracellular Mg concentration, as found in noninsulin-dependent diabetes mellitus (NIDDM) and in hypertensive patients, may result in a defective tyrosine-kinase activity at the insulin receptor level and exaggerated intracellular calcium concentration. Both events are responsible for the impairment in insulin action and a worsening of insulin resistance in noninsulin-dependent diabetic and hypertensive patients. By contrast, in NIDDM patients daily Mg administration, restoring a more appropriate intracellular Mg concentration, contributes to improve insulin-mediated glucose uptake. The benefits deriving- from daily Mg supplementation in NIDDM patients are further supported by epidemiological studies showing that high daily Mg intake are predictive of a lower incidence of NIDDM. In conclusion, a growing body of studies suggest that intracellular Mg may play a key role in modulating insulin-mediated glucose uptake and vascular tone. We further suggest that a reduced intracellular Mg concentration might be the missing link helping to explain the epidemiological association between NIDDM and hypertension.
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