Role of Chromium in Human Health and in Diabetes
William T. Cefalu , MD1 and Frank B. Hu , MD, PHD2 .Division of NutritionChronic Disease, The Pennington Biomedical Research Center, Louisiana State University ، 2004.
Despite widespread use by patients with diabetes and anecdotal reports in the past regarding its efficacy, until recently, data in humans concerning chromium's effects on insulin action in vivo or on cellular aspects of insulin action were scarce. Consequently, significant controversy still exists regarding the effect of chromium supplementation on parameters assessing human health. Furthermore, elucidating the cellular and molecular mechanisms by which chromium supplements affect carbohydrate metabolism in vivo is necessary before specific recommendations can be made regarding its routine use in the management of diabetes. This review focuses on providing current information about this trace mineral's specific mechanisms of action and clinical trials in patients with diabetes.
Chromium, one of the most common elements in the earth's crust and seawater, exists in our environment in several oxidation states, principally as metallic (Cr 0 ), trivalent (+3), and hexavalent (+6) chromium. The latter is largely synthesized by the oxidation of the more common and naturally occurring trivalent chromium and is highly toxic. Trivalent chromium, found in most foods and nutrient supplements, is an essential nutrient with very low toxicity.
The interest in chromium as a nutritional enhancement to glucose metabolism can be traced back to the 1950s, when it was suggested that brewer's yeast contained a glucose tolerance factor (GTF) that prevented diabetes in experimental animals. This factor was eventually suggested to be a biologically active form of trivalent chromium that could substantially lower plasma glucose levels in diabetic mice . Interest regarding chromium administration in patients with diabetes was kindled by the observation in the 1970s that it truly was an essential nutrient required for normal carbohydrate metabolism. A patient receiving total parenteral nutrition (TPN) developed severe signs of diabetes, including weight loss and hyperglycemia that was refractory to increasing insulin dosing. Based on previous animal studies …
Chromium as adjunctive treatment for type 2 diabetes
Ryan GJ , Wanko NS , Redman AR , Cook CB . Department of Clinical and Administrative Sciences, Southern School of Pharmacy, Mercer University, Atlanta, Ann Pharmacother. 2003
OBJECTIVE: To review the chemistry, pharmacology, efficacy, and safety of trivalent chromium in the treatment of type 2 diabetes and hyperlipidemia. DATA SOURCES: The English literature was searched from 1966 through May 2002 using MEDLINE, International Pharmaceutical Abstracts, and EMBASE. The key words included chromium, glucose, lipids, and diabetes. Pertinent references from review articles and studies were used as additional sources. DATA SYNTHESIS: Trivalent chromium is an essential nutrient and has a key role in lipid and glucose metabolism. Supplementation with chromium does not appear to reduce glucose levels in euglycemia. It may, however, have some efficacy in reducing glucose levels in hyperglycemia. The effects of chromium on lipid levels are variable. Chromium in doses <1000 microg/d appears to be safe for short-term administration. Kidney function and dermatologic changes need to be monitored. CONCLUSIONS: Chromium appears to be a safe supplement and may have a role as adjunctive therapy for treatment of type 2 diabetes. Additional large-scale, long-term, randomized, double-blind studies examining the effect of various doses and forms of chromium are needed.
Effect of chromium supplementation on glucose metabolism and lipids
Balk EM , Tatsioni A , Lichtenstein AH , Lau J , Pittas AG . Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Boston, Diabetes Care. 2007
OBJECTIVE: A systematic review of the effect of chromium supplementation on glucose metabolism and lipid levels. RESEARCH DESIGN AND METHODS: A literature search was conducted in MEDLINE and the Commonwealth Agricultural Bureau. Eligible studies were English language randomized controlled trials of chromium supplement intake > or = 3 weeks, with > or = 10 participants receiving chromium. All trials with glucose metabolism outcomes and trials of individuals with diabetes or glucose intolerance for lipid outcomes were included. Meta-analyses were performed as appropriate. RESULTS: Forty-one studies met criteria, almost half of which were of poor quality. Among participants with type 2 diabetes, chromium supplementation improved glycosylated hemoglobin levels by -0.6% (95% CI -0.9 to -0.2) and fasting glucose by -1.0 mmol/l (-1.4 to -0.5) but not lipids. There was no benefit in individuals without diabetes. There were some indications of dose effect and differences among chromium formulations. Larger effects were more commonly observed in poor-quality studies. The evidence was limited by poor study quality, heterogeneity in methodology and results, and a lack of consensus on assessment of chromium status. CONCLUSIONS: No significant effect of chromium on lipid or glucose metabolism was found in people without diabetes. Chromium supplementation significantly improved glycemia among patients with diabetes. However, future studies that address the limitations in the current evidence are needed before definitive claims can be made about the effect of chromium supplementation.
Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring
Zimmermann MB . Human Nutrition Laboratory, Swiss Federal Institute of Technology Zentrum, Zürich, Switzerland Am J Clin Nutr. 2009
The World Health Organization (WHO) recently increased their recommended iodine intake during pregnancy from 200 to 250 microg/d and suggested that a median urinary iodine (UI) concentration of 150-249 microg/L indicates adequate iodine intake in pregnant women. Thyrotropin concentrations in blood collected from newborns 3-4 d after birth may be a sensitive indicator of even mild iodine deficiency during late pregnancy; a <3% frequency of thyrotropin values >5 mU/L indicates iodine sufficiency. New reference data and a simple collection system may facilitate use of the median UI concentration as an indicator of iodine status in newborns. In areas of severe iodine deficiency, maternal and fetal hypothyroxinemia can cause cretinism and adversely affect cognitive development in children; to prevent fetal damage, iodine should be given before or early in pregnancy. Whether mild-to-moderate maternal iodine deficiency produces more subtle changes in cognitive function in offspring is unclear; no controlled intervention studies have measured long-term clinical outcomes. Cross-sectional studies have, with few exceptions, reported impaired intellectual function and motor skills in children from iodine-deficient areas, but many of these studies were likely confounded by other factors that affect child development. In countries or regions where <90% of households are using iodized salt and the median UI concentration in school-age children is <100 microg/L, the WHO recommends iodine supplementation in pregnancy and infancy.
Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer
Zhang SM , Willett WC , Selhub J , Hunter DJ , Giovannucci EL , Holmes MD , Colditz GA , Hankinson SE . Department of Epidemiology, Harvard School of Public Health, Division of Preventive Medicine, Boston, USA. J Natl Cancer Inst. 2003
BACKGROUND: In several epidemiologic investigations, folate intake has appeared to reduce the elevated risk of breast cancer associated with moderate alcohol consumption. However, data relating plasma folate levels to breast cancer risk are sparse. We investigated the association between plasma folate and other vitamins with breast cancer in a prospective, nested case-control study. METHODS: Blood samples were obtained during 1989 and 1990 from 32 826 women in the Nurses' Health Study who were followed through 1996 for the development of breast cancer. We identified 712 breast cancer case patients and selected 712 individually matched control subjects. Dietary information was obtained using food frequency questionnaires given in 1980, 1984, 1986, and 1990. Logistic regression was used to estimate the relative risks (RRs) of breast cancer (after adjustment for potential risk factors), and a generalized linear model was used to calculate the Pearson correlation coefficients between plasma estimates of folate, vitamin B(6), vitamin B(12), and homocysteine, and intakes of folate, vitamin B(6), and vitamin B(12). All statistical tests were two-sided. RESULTS: The multivariable RR comparing women in the highest quintile of plasma folate with those in the lowest was 0.73 (95% confidence interval [CI] = 0.50 to 1.07; P(trend) =.06). The inverse association between plasma folate and breast cancer risk was highly statistically significant among women consuming at least 15 g/day (i.e., approximately 1 drink/day) of alcohol (multivariable RR = 0.11, 95% CI = 0.02 to 0.59 for highest versus lowest quintile) in contrast with that of women consuming less than 15 g/day (multivariable RR = 0.72, 95% CI = 0.49 to 1.05). The multivariable RR comparing women in the highest quintile of plasma vitamin B(6) levels with those in the lowest quintile was 0.70 (95% CI = 0.48 to 1.02; P(trend) =.09). Plasma vitamin B(12) levels were inversely associated with breast cancer risk among premenopausal women (multivariable RR = 0.36, 95% CI = 0.15 to 0.86 for highest versus lowest quintile) but not among postmenopausal women. Plasma homocysteine was not associated with breast cancer risk. CONCLUSIONS: Higher plasma levels of folate and possibly vitamin B(6) may reduce the risk of developing breast cancer. Achieving adequate circulating levels of folate may be particularly important for women at higher risk of developing breast cancer because of higher alcohol consumption.
Serum selenium concentrations and diabetes in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004
Laclaustra M , Navas-Acien A , Stranges S , Ordovas JM , Guallar E . Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain Environ Health Perspect. 2009
BACKGROUND: Increasing evidence suggests that high selenium levels are associated with diabetes and other cardiometabolic risk factors. OBJECTIVES: We evaluated the association of serum selenium concentrations with fasting plasma glucose, glycosylated hemoglobin levels, and diabetes in the most recently available representative sample of the U.S. population. METHODS: We used a cross-sectional analysis of 917 adults > or = 40 years of age who had a fasting morning blood sample in the National Health and Nutrition Examination Survey 2003-2004. We evaluated the association of serum selenium, measured by inductively coupled plasma-dynamic reaction cell-mass spectrometry, and diabetes, defined as a self-report of current use of hypoglycemic agents or insulin or as fasting plasma glucose > or = 126 mg/dL. RESULTS: Mean serum selenium was 137.1 microg/L. The multivariable adjusted odds ratio [95% confidence interval (CI)] for diabetes comparing the highest quartile of serum selenium (> or = 147 microg/L) with the lowest (< 124 microg/L) was 7.64 (3.34-17.46). The corresponding average differences (95% CI) in fasting plasma glucose and glycosylated hemoglobin were 9.5 mg/dL (3.4-15.6 mg/dL) and 0.30% (0.14-0.46%), respectively. In spline regression models, the prevalence of diabetes as well as glucose and glycosylated hemoglobin levels increased with increasing selenium concentrations up to 160 microg/L. CONCLUSIONS: In U.S. adults, high serum selenium concentrations were associated with higher prevalence of diabetes and higher fasting plasma glucose and glycosylated hemoglobin levels. Given high selenium intake in the U.S. population, further research is needed to determine the role of excess selenium levels in the development or the progression of diabetes.
Nutritional supplementation for type 2 diabetes: a systematic review
Bartlett HE , Eperjesi F . Ophthalmic Research Group, School of Life and Health Sciences, Aston University, Birmingham , UK .Ophthalmic Physiol Opt. 2008
The role of nutritional supplementation is of increasing interest with regard to ocular disease. Randomised controlled trials have demonstrated the effectiveness of supplementation for age-related macular degeneration, and formulations are now being developed for use by people with diabetes and diabetic retinopathy. The aim of this review was to synthesise the evidence for use of nutritional supplementation in type 2 diabetes. MEDLINE and EMBASE databases were searched using a systematic approach. Only double-masked randomised controlled trials were selected. A total of 50 trials were identified as suitable for inclusion. The potential role of alpha-lipoic acid, chromium, folic acid, isoflavones, magnesium, Pycnogenol, selenium, vitamin C, vitamin E, and zinc in the treatment of type 2 diabetes is discussed. The review of trials identifies positive effects of these nutrients on various outcome measures relating to insulin resistance and cardiovascular factors. Chromium was the most studied supplement, accounting for 16 of the 50 trials. A majority of the trials found a positive effect of chromium on fasting plasma glucose. Isoflavones were found to have a positive effect on insulin resistance and cardiovascular outcome measures, but only when combined with soy proteins. Vitamin E is reported to reduce oxidative stress at levels of 200 mg day(-1) or more.
Diabetes and osteoporosis
Saller A , Maggi S , Romanato G , Tonin P , Crepaldi G . Aging Section, CNR Institute of Neuroscience, Padova, Italy. Aging Clin Exp Res. 2008
Care of patients with diabetes should include assessment of bone health. The extension of the average life expectancy of people with diabetes, which has accompanied improvements in medical care, has also increased the significance of osteoporosis. In addition to the usual causes of osteoporosis associated with aging, bone health is also compromised by diabetes. Studies on bone involvement in patients with diabetes mellitus have generated conflicting results, largely because of the pathogenetic complexity of the condition. It is now clear that patients with type 1 diabetes have lower bone mineral density (BMD) and a higher risk of fractures. Evidence is emerging that patients with type 2 diabetes who have complications are also at increased risk of certain types of osteoporotic fractures, despite having a higher BMD when compared to patients with type 1 diabetes. Although many factors, including number and type of falls, visual impairment, neuropathy, and reduced muscle strength, influence the probability of fractures, the most significant factor seems to be the strength of the bone itself. Thus, sarcopenia, a reduction in muscle mass and muscle strength, is considered one of the main determinants of bone fragility. The aim of this review is to examine the occurrence of osteoporosis in type 1 and type 2 diabetes.
Magnesium, the metabolic syndrome, insulin resistance, and type 2 diabetes mellitus
Volpe SL . Division of Biobehavioral and Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia,USA Crit Rev Food Sci Nutr. 2008
Magnesium is an essential mineral and has been established as a cofactor for over 300 metabolic reactions in the body. Some research has indicated that lower intakes of magnesium and lower serum magnesium concentrations may lead to and are associated with the metabolic syndrome, insulin resistance, and/or type 2 diabetes mellitus. The goal of this review is to examine the research conducted on: 1) magnesium status, metabolic syndrome, insulin resistance, and type 2 diabetes mellitus, and 2) the effects of magnesium intake and/or supplementation on metabolic syndrome, insulin resistance, and type 2 diabetes mellitus. To make this review as current as possible, the majority of research articles reviewed were from 2000 to the present.
High prevalence of vitamin D deficiency in type 1 diabetes mellitus and healthy children
Bener A , Alsaied A , Al-Ali M , Al-Kubaisi A , Basha B , Abraham A , Guiter G , Mian M . Department of Medical Statistics and Epidemiology, Hamad General Hospital, Hamad Medical Corporation, Weill Cornell Medical College Qatar, Doha, Qatar .Acta Diabetol. 2009
Epidemiological studies suggest a link between vitamin D deficiency in early life and the later onset of type 1 diabetes. The aim of this matched case-control study was to find the association between vitamin D and T1DM then to study the difference in the level of vitamin D in T1DM and healthy subjects, and to determine the associated environmental risk factors in young Qatari population. The study was carried out among T1DM children and healthy subjects below 16 years at the pediatric endocrinology outpatient clinics of the Hamad General Hospital and the Primary Health care Clinics (PHCs). The survey was conducted over a period from 6 August to 25 December 2007. The subjects were Qatari nationals male and female aged below 16 years. The study is based on matching by age, gender and ethnicity of 170 cases with those of 170 controls. Face-to-face interviews were based on a questionnaire that included variables such as socio-demographic information, assessment of non-dietary covariates, assessment of dietary intake, vitamin D intake, type of feeding, clinical manifestations and laboratory investigations. Their health status was assessed by medical conditions, family history, BMI, past or present clinical manifestations, 25 (OH)D, Calcium, alkaline phosphatase, phosphorus, HbA1C, PTH, Mg and creatinine analysis. The study revealed that vitamin D deficiency was considerably higher in T1DM children (90.6%) compared to non-diabetic children (85.3%). There was a significant difference found in the mean value of vitamin D between T1DM and non-diabetic children (P = 0.009). There were statistically significant differences between type 1 diabetic and healthy subjects with respect to the occupation of parents (P < 0.001) and consanguinity rate (P < 0.047). Family history of vitamin D deficiency was considerably higher among T1DM children (35.3%) with a significant difference between diabetic and non-diabetic children (22.9) (P < 0.012). Vitamin D supplement with breast milk was very poor in diabetic children (37.4%) compared to non-diabetic children (47.7%). Majority of the studied subjects were breast-fed children (95.1% of diabetic children and 97.2% of healthy children). Multivariate logistic regression analysis revealed that fathers and mothers occupation, family history of DM, physical activity, low duration of time under sun light, breast feeding less than 6 months and low vitamin D level were considered as the main factors associated with the T1DM. In conclusion, the present study revealed that vitamin D deficiency was higher in T1DM children compared to non-diabetic. Moreover, vitamin D deficiency was common in Qatari young population. Vitamin D intake was very poor in children and it shows that supplementing infants with vitamin D might be a safe and effective strategy for reducing the risk of T1DM.
Dietary calcium and magnesium intakes and the risk of type 2 diabetes: the Shanghai Women's Health Study
Villegas R , Gao YT , Dai Q , Yang G , Cai H , Li H , Zheng W , Shu XO . Vanderbilt Epidemiology Center, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, USA .Am J Clin Nutr. 2009
BACKGROUND: Diet plays a key role in the development of type 2 diabetes (T2D), but little is known about the contributions of specific nutrients in populations in which dietary patterns differ from Western populations. OBJECTIVE: We examined associations between calcium and magnesium intakes and the risk of T2D in a Chinese population. DESIGN: We used data from a population-based, prospective study of 64,191 women who were free of T2D or other chronic diseases at study recruitment and were living in urban Shanghai, China. Dietary intake, physical activity, and anthropometric measurements were assessed through in-person interviews. A Cox regression model was used to evaluate the association of the exposures under study with the risk of T2D. RESULTS: An inverse association between calcium and magnesium intakes and T2D risk was observed. The relative risks for the lowest to the highest quintiles of calcium intake were 1.00, 0.82, 0.73, 0.67, and 0.74 (P for trend < 0.001), and for magnesium they were 1.00, 0.84, 0.84, 0.79, and 0.86 (P for trend < 0.001). Milk intake was also inversely associated with the risk of T2D. CONCLUSION: Our data suggest that calcium and magnesium intakes may protect against the development of T2D in this population.
Role of dietary magnesium in cardiovascular disease prevention, insulin sensitivity and diabetes
Bo S , Pisu E . Department of Internal Medicine, University of Turin, Italy Curr Opin Lipidol. 2008
PURPOSE OF REVIEW: This review summarizes the evidence for benefits of magnesium on metabolic abnormalities, inflammatory parameters, and cardiovascular risk factors and related-potential mechanisms. Controversy due to contrasting results in the literature is also discussed. RECENT FINDINGS: Increased dietary magnesium intake confers protection against the incidence of diabetes, metabolic syndrome, hypertension, and cardiovascular disease. It ameliorates insulin resistance, serum lipid profiles, and lowers inflammation, endothelial dysfunction, oxidative stress, and platelet aggregability. Magnesium acts as a mild calcium antagonist on vascular smooth muscle tone, and on postreceptor insulin signaling; it is critically involved in energy metabolism, fatty acid synthesis, glucose utilization, ATPase functions, release of neurotransmitters, and endothelial cell function and secretion. Prospective studies, however, have found only a modest effect for dietary magnesium on incident pathologies. Furthermore, magnesium supplementation on glucose metabolism, blood lipid levels, and ischemic heart disease has given inconsistent results. SUMMARY: There is strong biological plausibility for the direct impact of magnesium intake on metabolic and cardiovascular risk factors, but in-vivo magnesium deficiency might play only a modest role. Reverse causality, the strong association between magnesium and other beneficial nutrients, or the possibility that people who choose magnesium-rich foods are more health-conscious may be confounding factors.
