Diabetes and Chromium

1. Proctor SD, Kelly SE, Stanhope KL, Havel PJ, Russell JC. Synergistic effects of conjugated linoleic acid and chromium picolinate improve vascular function and renal pathophysiology in the insulin-resistant JCR:LA-cp rat. Diabetes Obes Metab 2007 January;9(1):87-95.
   Keywords: Adiponectin/Albuminuria/Animals/Aorta/blood/Body Weight/Cardiovascular Diseases/Chromium/Diabetic Nephropathies/Dose-Response Relationship,Drug/drug effects/Drug Synergism/drug therapy/Eating/Insulin/Insulin Resistance/Kidney/Linoleic Acids,Conjugated/Male/Metabolic Syndrome X/methods/pharmacology/physiopathology/Picolinic Acids/Rats/therapeutic use/Tissue Culture Techniques/Vasoconstriction
   
   Abstract: AIMS: Conjugated linoleic acid (CLA) is a natural constituent of dairy products, specific isomers of which have recently been found to have insulin sensitizing and possible antiobesity actions. Chromium is a micronutrient which, as the picolinate (CrP), has been shown to increase insulin sensitivity in animal models, including the JCR:LA-cp rat. We tested the hypothesis that these agents may have beneficial synergistic effects on the micro- and macrovasculopathy associated with hyperinsulinaemia and early type 2 diabetes. METHODS: Insulin-resistant cp/cp rats of the JCR:LA-cp strain were treated with mixed isomers of CLA (1.5% w/w in the chow) and/or CrP at 80 microg/kg/day (expressed as Cr) from 4 weeks of age to 12 weeks of age. Plasma insulin, lipid and adiponectin levels, aortic vascular function, renal function and glomerular sclerosis were assessed. RESULTS: CLA administration reduced food intake, body weight and fasting insulin in JCR:LA-cp rats. Plasma adiponectin levels were significantly elevated in rats treated with both CLA and CrP. Aortic hypercontractility was reduced and the relaxant response to the nitric oxide-releasing agent acetylcholine (Ach) was increased in CrP-treated rats. Striking reductions were also observed in the level of urinary albumin and the severity of glomerular sclerosis in rats treated specifically with CLA. CONCLUSIONS: CLA and CrP have beneficial effects ameliorating several of the pathophysiologic features of an insulin-resistant rat model. These supplements may be useful adjuncts in the management of patients with the metabolic syndrome and warrant further study

2. Stupar J, Vrtovec M, Dolinsek F. Longitudinal hair chromium profiles of elderly subjects with normal glucose tolerance and type 2 diabetes mellitus. Metabolism 2007 January;56(1):94-104.
   Keywords: Adult/Aged/Aged,80 and over/analysis/blood/Blood Glucose/chemistry/Chromium/deficiency/Diabetes Mellitus/Diabetes Mellitus,Type 2/Female/Glucose/Hair/Hemoglobin A,Glycosylated/Humans/Insulin/Insulin Resistance/Male/metabolism/Middle Aged/Spectrophotometry,Atomic/Statistics,Nonparametric
   
   Abstract: Longitudinal hair chromium (H-Cr) profiles in a group of patients with type 2 diabetes mellitus (n = 59; age, 62 +/- 9 years) and healthy elderly (control) subjects (n = 49; age, 59 +/- 10 years) matched by age and sex were measured by solid sampling electrothermal atomic absorption spectrometry, providing data on the magnitude of variation of Cr content along the hair length. H-Cr average (H-Cr(av)) and H-Cr proximal (H-Cr(pr))(.), relating to the average Cr content of the whole hair and the proximal 3-mm hair length, respectively, were also obtained. No significant difference between the healthy and diabetic group was found in mean H-Cr(av) or H-Cr(pr) contents (248 +/- 108 vs 247 +/- 143 and 233 +/- 98 vs 278 +/- 195 ng/g, respectively. However, women in the control group had significantly lower H-Cr values (P < .01) compared with men, but this difference was absent in the diabetic population. The distribution of log H-Cr(pr) values in the control population displayed a Gaussian shape, in contrast to the substantially wider distribution, skewed toward lower H-Cr(pr) values, observed in the diabetic group. The magnitude of variation in H-Cr content in the patient group over an interval of approximately 2 to 3 months (time of growth of the hair sampled) was found to be a factor of more than 2 larger than that in the control population (+/- 58% vs +/- 26%). A strong relationship (R = 0.656; P < .01) between log H-Cr(pr) and log fasting plasma Cr was observed in the diabetic group (n = 20). The mean fasting plasma Cr value of this group was 0.41 +/- 0.10 microg Cr per liter. No correlation between H-Cr(av.) and duration of diabetes was observed. A strong positive association was observed in the control population between H-Cr(pr) and fasting plasma insulin (n = 22; R = 0.6157; P < .01), and H-Cr(pr) and fasting plasma glucose (n = 24; R = 0.4118; P < .05), which is indicative of the interrelation of these parameters. In the control population, H-Cr(av) showed a slight decrease with age (n = 54; R = 0.2691; P < .05), which is assumed to be the result of increased insulin resistance caused by various age-associated factors including Cr deficiency. None of the above relationships was significant in the diabetic group. Evidence is presented that justifies the assumption that the longitudinal H-Cr profile resembles the variation in Cr metabolic rate over the time span of growing hair, which is not appreciably affected by external contamination. This suggests that glucose intolerance (type 2 diabetes mellitus) is an important factor that disturbs Cr metabolism

3. Broadhurst CL, Domenico P. Clinical studies on chromium picolinate supplementation in diabetes mellitus--a review. Diabetes Technol Ther 2006 December;8(6):677-87.
   Keywords: blood/Blood Glucose/Body Composition/Chromium/Clinical Trials/deficiency/Diabetes Mellitus/drug effects/drug therapy/Glucose/Hemoglobin A,Glycosylated/Humans/Hyperlipidemias/Insulin/Iron Chelating Agents/Lipid Metabolism/metabolism/pharmacology/Picolinic Acids/therapeutic use
   
   Abstract: Chromium (Cr) picolinate (CrPic) is a widely used nutritional supplement for optimal insulin function. A relationship among Cr status, diabetes, and associated pathologies has been established. Virtually all trials using CrPic supplementation for subjects with diabetes have demonstrated beneficial effects. Thirteen of 15 clinical studies (including 11 randomized, controlled studies) involving a total of 1,690 subjects (1,505 in CrPic group) reported significant improvement in at least one outcome of glycemic control. All 15 studies showed salutary effects in at least one parameter of diabetes management, including dyslipidemia. Positive outcomes from CrPic supplementation included reduced blood glucose, insulin, cholesterol, and triglyceride levels and reduced requirements for hypoglycemic medication. The greater bioavailability of CrPic compared with other forms of Cr (e.g., niacin-bound Cr or CrCl(3)) may explain its comparatively superior efficacy in glycemic and lipidemic control. The pooled data from studies using CrPic supplementation for type 2 diabetes mellitus subjects show substantial reductions in hyperglycemia and hyperinsulinemia, which equate to a reduced risk for disease complications. Collectively, the data support the safety and therapeutic value of CrPic for the management of cholesterolemia and hyperglycemia in subjects with diabetes

4. Head KA. Peripheral neuropathy: pathogenic mechanisms and alternative therapies. Altern Med Rev 2006 December;11(4):294-329.
   Keywords: Acquired Immunodeficiency Syndrome/Alcoholism/Biotin/Chromium/Complementary Therapies/complications/deficiency/Diabetic Neuropathies/etiology/Humans/methods/Peripheral Nervous System Diseases/therapy
   
   Abstract: Peripheral neuropathy (PN), associated with diabetes, neurotoxic chemotherapy, human immunodeficiency virus (HIV)/antiretroviral drugs, alcoholism, nutrient deficiencies, heavy metal toxicity, and other etiologies, results in significant morbidity. Conventional pain medications primarily mask symptoms and have significant side effects and addiction profiles. However, a widening body of research indicates alternative medicine may offer significant benefit to this patient population. Alpha-lipoic acid, acetyl-L-carnitine, benfotiamine, methylcobalamin, and topical capsaicin are among the most well-researched alternative options for the treatment of PN. Other potential nutrient or botanical therapies include vitamin E, glutathione, folate, pyridoxine, biotin, myo-inositol, omega-3 and -6 fatty acids, L-arginine, L-glutamine, taurine, N-acetylcysteine, zinc, magnesium, chromium, and St. John's wort. In the realm of physical medicine, acupuncture, magnetic therapy, and yoga have been found to provide benefit. New cutting-edge conventional therapies, including dual-action peptides, may also hold promise

5. Khanam R, Pillai KK. Effect of chromium picolinate on modified forced swimming test in diabetic rats: involvement of serotonergic pathways and potassium channels. Basic Clin Pharmacol Toxicol 2006 February;98(2):155-9.
   Keywords: analysis/Animals/Antidepressive Agents/Behavior,Animal/blood/Blood Glucose/chemically induced/Chromium/Diabetes Mellitus/Diabetes Mellitus,Experimental/drug effects/drug therapy/Female/Glucose/Glyburide/Insulin/Male/metabolism/pharmacology/ph ysiopathology/Picolinic Acids/Potassium Channel Blockers/Potassium Channels/Rats/Rats,Wistar/Serotonin/Streptozocin/Swimming/Water
   
   Abstract: Depression occurs frequently in patients with diabetes mellitus. Chromium picolinate, an essential trace element is recommended for diabetes and also has been reported to benefit depression, but its mechanism is still debated. To investigate the mechanism, we studied its effects on serum insulin, serum glucose and on modified forced swimming test, a behavioural paradigm for depression in rats. The study involving co-administration of sub-active doses of glimepiride, a K(+) channel blocker and chromium picolinate on blood glucose levels and modified forced swimming test was also performed to probe any role of K(+) channels in its antidiabetic and antidepressants effects. Streptozotocin (55 mg/kg, intraperitoneally) was injected in rats to induce diabetes (Type 1). After a week, chromium picolinate (8 microg/ml in drinking water) was administered for 4 weeks. Normal rats received similar drug treatment. The sub-active doses of chromium picolinate (4 microg/ml in drinking water) and glimeperide (2.5 mg/kg, orally) were co-administered and their effects on modified forced swimming test and on glucose levels were measured. Chromium picolinate (8 microg/ml in drinking water) produced hypoglycaemia in diabetic and normal rats. It had no effects on the streptozotocin-induced reduction in insulin levels. Chromium picolinate (8 microg/ml in drinking water) increased swimming with subsequent decrease in immobility. The sub-active doses of chromium picolinate and glimeperide showed significant additive effects in modified forced swimming test and reduction in serum glucose concentrations, though statistically insignificant. In conclusion chromium picolinate shows antidepressant action on modified forced swimming test affecting only swimming that suggests serotonergic pathways involvement. The additive effects on swimming in modified forced swimming test and reduction in serum glucose levels shows involvement of K(+) channels in antidiabetic and antidepressant actions of chromium picolinate

6. Machalinski B, Walczak M, Syrenicz A et al. Hypoglycemic potency of novel trivalent chromium in hyperglycemic insulin-deficient rats. J Trace Elem Med Biol 2006;20(1):33-9.
   Keywords: Alanine Transaminase/analysis/Animals/Aspartate Aminotransferases/blood/Blood Glucose/Body Weight/Cell Line/chemically induced/Chromium/Creatine Kinase/deficiency/Diabetes Mellitus,Experimental/Disease Models,Animal/Dose-Response Relationship,Drug/drug effects/drug therapy/Eating/Glucose/Insulin/Male/Picolinic Acids/Rats/Rats,Sprague-Dawley/Streptozocin/therapeutic use/Treatment Outcome
   
   Abstract: Two sources of chromium III, "chromium 454" and "chromium picolinate," were tested in insulin-deficient Streptozocin-treated diabetic rats. This model was selected in order to evaluate the possibility of any hypoglycemic potency of chromium in a relative absence of blood insulin concentration. Three weeks of the treatment with CRC454 and CrP resulted in a 38% and 11% reduction of blood glucose levels, respectively. Body weight gains were equally improved by both treatments. Blood levels of CK, ALT and AST were significantly reduced by CRC454 and CrP. These results might suggest that any hypoglycemic effect of trivalent chromium under insulin-deficient conditions could be largely dependent upon the type of chromium agent and associated characteristics such as solubility and bioavalibility. In contrast, improvement of body weight gains and blood levels of CK, AST and ALT seems to be less dependent on the type of chromium compound under these experimental conditions. In conclusion, CRC454 showed significant reduction of hyperglycemia under insulin-deficient conditions

7. Martin J, Wang ZQ, Zhang XH et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 2006 August;29(8):1826-32.
   Keywords: Adipose Tissue/Adult/Aged/Body Composition/Body Weight/Chromium/Diabetes Mellitus,Type 2/drug effects/drug therapy/Drug Therapy,Combination/Female/Glucose/Humans/Insulin/Male/metabolism/method s/Middle Aged/pharmacology/Phenotype/physiopathology/Picolinic Acids/therapeutic use/Weight Gain
   
   Abstract: OBJECTIVE: Chromium picolinate (CrPic) supplementation has been suggested to improve glycemia, but there are conflicting reports on efficacy. We sought to determine the effect of CrPic on insulin sensitivity, glycemic control, and body composition in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty-seven subjects with type 2 diabetes were evaluated. After baseline, subjects were placed on a sulfonylurea (glipizide gastrointestinal therapeutic system 5 mg/day) with placebo for 3 months. Subjects were then randomized in a double-blind fashion to receive either the sulfonylurea plus placebo (n = 12) or the sulfonylurea plus 1,000 microg Cr as CrPic (n = 17) for 6 months. Body composition, insulin sensitivity, and glycemic control were determined at baseline, end of the 3-month single-blind placebo phase, and end of study. RESULTS: Subjects randomized to sulfonylurea/placebo, as opposed to those randomized to sulfonylurea/CrPic, had a significant increase in body weight (2.2 kg, P < 0.001 vs. 0.9 kg, P = 0.11), percent body fat (1.17%, P < 0.001 vs. 0.12%, P = 0.7), and total abdominal fat (32.5 cm(2), P < 0.05 vs. 12.2 cm(2), P < 0.10) from baseline. Subjects randomized to sulfonylurea/CrPic had significant improvements in insulin sensitivity corrected for fat-free mass (28.8, P < 0.05 vs. 15.9, P = 0.4), GHb (-1.16%, P < 0.005 vs. -0.4%, P = 0.3), and free fatty acids (-0.2 mmol/l, P < 0.001 vs. -0.12 mmol/l, P < 0.03) as opposed to sulfonylurea/placebo. CONCLUSIONS: This study demonstrates that CrPic supplementation in subjects with type 2 diabetes who are taking sulfonylurea agents significantly improves insulin sensitivity and glucose control. Further, CrPic supplementation significantly attenuated body weight gain and visceral fat accumulation compared with the placebo group

8. Ou SJ, Chen G, Lin ZH, Bai ZP, Duan CY, Mao CP. Chromium(III) complexes of D-glucosaminic acid and their effect on decreasing blood sugar in vivo. Arch Pharm (Weinheim) 2006 September;339(9):527-30.
   Keywords: Alloxan/analogs & derivatives/Animals/blood/Blood Glucose/chemical synthesis/chemically induced/chemistry/Chromium/Chromium Compounds/Diabetes Mellitus,Experimental/Disease Models,Animal/drug therapy/Glucosamine/Glucose/Male/metabolism/pharmacology/Picolinic Acids/Rats/toxicity
   
   Abstract: Two chromium(III) complexes of glucosaminic acid were synthesized by neutralization and exchange reaction. The formation of 1 : 1 and 2 : 3 (Cr : glucosaminate) complexes was confirmed by elemental analyses and spectroscopic studies. The effect of the complexes on decreasing blood sugar was investigated on type-2 diabetes model rats induced by tetraoxypyrimidine. The results indicated that the effect on decreasing blood sugar was comparable to that of picolinate chromium complex (Cr(pic)(3)) currently used world wide

9. Pattar GR, Tackett L, Liu P, Elmendorf JS. Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions. Mutat Res 2006 November 7;610(1-2):93-100.
   Keywords: 3T3-L1 Cells/Adipocytes/Animals/ATP-Binding Cassette Transporters/chemistry/Cholesterol/Chromium/Chromium Compounds/Culture Media/cytology/Diabetes Mellitus/drug effects/Electrophoresis/Glucose/Glucose Transport Proteins,Facilitative/Glucose Transporter Type 4/Homeostasis/Immunoblotting/metabolism/methods/Mice/pharmacology/physio logy/Picolinic Acids/Sterol Regulatory Element Binding Protein 1/therapy
   
   Abstract: Since trivalent chromium (Cr(3+)) enhances glucose metabolism, interest in the use of Cr(3+)as a therapy for type 2 diabetes has grown in the mainstream medical community. Moreover, accumulating evidence suggests that Cr(3+) may also benefit cardiovascular disease (CVD) and atypical depression. We have found that cholesterol, a lipid implicated in both CVD and neurodegenerative disorders, also influences cellular glucose uptake. A recent study in our laboratory shows that exposure of 3T3-L1 adipocytes to chromium picolinate (CrPic, 10 nM) induces a loss of plasma membrane cholesterol. Concomitantly, accumulation of intracellularly sequestered glucose transporter GLUT4 at the plasma membrane was dependent on the CrPic-induced cholesterol loss. Since CrPic supplementation has the greatest benefit on glucose metabolism in hyperglycemic insulin-resistant individuals, we asked here if the CrPic effect on cells was glucose-dependent. We found that GLUT4 redistribution in cells treated with CrPic occurs only in cells cultured under high glucose (25 mM) conditions that resemble the diabetic-state, and not in cells cultured under non-diabetic (5.5 mM glucose) conditions. Examination of the effect of CrPic on proteins involved in cholesterol homeostasis revealed that the activity of sterol regulatory element-binding protein (SREBP), a membrane-bound transcription factor ultimately responsible for controlling cellular cholesterol balance, was upregulated by CrPic. In addition, ABCA1, a major player in mediating cholesterol efflux was decreased, consistent with SREBP transcriptional repression of the ABCA1 gene. Although the exact mechanism of Cr(3+)-induced cholesterol loss remains to be determined, these cellular responses highlight a novel and significant effect of chromium on cholesterol homeostasis. Furthermore, these findings provide an important clue to our understanding of how chromium supplementation might benefit hypercholesterolemia-associated disorders

10. Pei D, Hsieh CH, Hung YJ, Li JC, Lee CH, Kuo SW. The influence of chromium chloride-containing milk to glycemic control of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Metabolism 2006 July;55(7):923-7.
    Keywords: administration & dosage/Aged/analysis/Animals/blood/Blood Glucose/Chlorides/Cholesterol/Chromium/Chromium Compounds/Diabetes Mellitus/Diabetes Mellitus,Type 2/Dietary Supplements/Double-Blind Method/drug therapy/Female/Food Contamination/Glucose/Glucose Tolerance Test/Homeostasis/Humans/Insulin/Insulin Resistance/Male/metabolism/Middle Aged/Milk/Prospective Studies
    
    Abstract: The aim of this study is to evaluate the effect and safety of chromium-containing milk powder in patients with type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial was conducted in Taiwan. A total of 60 patients with type 2 diabetes mellitus, aged 30 to 75 years, and on a dose of gliclazide sulfonylurea agent (< or =160 mg/d) for at least 3 months were enrolled. Their glycosylated hemoglobin ranged from 7.5% to 12%, fasting plasma glucose (FPG) from 140 to 250 mg/dL, and body mass index from 20 to 35 kg/m(2). The subjects were divided into 2 groups, one group to receive chromium-containing milk powder (chromium 200 microg/20 g milk powder) and the other to receive placebo twice a day for 16 weeks. Frequently sampled intravenous glucose tolerance test (IVGTT) was performed before and after treatment. The chromium group demonstrated a lower FPG and fasting insulin (-38.1 +/- 9.2 vs 63 +/- 8. 5 mg/dL and -1.7 +/- 0.2 vs 1.9 +/- 0.3 microU/mL, respectively; P < .05), especially in male patients (-41 +/- 9.2 vs 85 +/- 11.7 mg/dL and -2.7 +/- 0.2 vs 3.1 +/- 0.3 microU/mL, respectively; P < .01), at the end of the study. Lower glycosylated hemoglobin was observed in chromium-treated male patients (-1.1 +/- 0. 5 vs 0.7 +/- 0. 2; P < .05). However, there were no significant changes in other metabolic parameters (lipid profiles including total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), except improvement of insulin resistance (homeostasis model assessment for insulin resistance and insulin sensitivity index from frequently sampled intravenous glucose tolerance test) observed in male patients (-2.1 +/- 1.1 vs -0.41 +/- 1.12 and 0.18 +/- 0.11 vs -0.15 +/- 0. 2, respectively; P < .05). There were no adverse events in both groups, except for mild complaints in the chromium group on constipation (5%) and flatulence (5%). Intake of milk powder containing 400 microg/d of chromium for 16 weeks in subjects with type 2 diabetes mellitus resulted in lowering of FPG, fasting insulin, and improvement of metabolic control in male patients

11. Racek J, Trefil L, Rajdl D, Mudrova V, Hunter D, Senft V. Influence of chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markers of oxidative stress in subjects with type 2 diabetes mellitus. Biol Trace Elem Res 2006 March;109(3):215-30.
    Keywords: administration & dosage/Aged/Biological Markers/blood/Blood Glucose/Body Mass Index/Chromium/Diabetes Mellitus/Diabetes Mellitus,Type 2/drug effects/Female/Glucose/Glutathione Peroxidase/Hemoglobin A,Glycosylated/Humans/Insulin/Lipids/Male/metabolism/Middle Aged/Oxidative Stress/pharmacology/Superoxide Dismutase/Yeast,Dried
    
    Abstract: The aim of this study was to determine the effect of chromium (Cr)- enriched yeast on blood glucose and insulin variables, blood lipids, and blood markers of oxidative stress in persons with type 2 diabetes mellitus (median duration: 3.0 yr). Thirty-six subjects (9 men, 27 women; mean age: 61.3 yr; mean body mass index: 34.33 kg/m2) were supplemented with 400 microg Cr/d as Cr-enriched yeast (n = 19) or placebo (n = 17) for 12 wk in a randomized, double-blind study. The most interesting results were obtained by comparison of the change in the placebo group to the change in the Cr group. The Cr group showed a significantly greater increase in serum Cr compared to the placebo group (p < 0.05). Supplementation with Cr-enriched yeast was associated with a significant decrease in fasting serum glucose compared to placebo (p < 0.01). Blood markers of oxidative stress glutathione peroxidase activity and levels of reduced glutathione were essentially unchanged in the Cr group after 12 wk, but decreased significantly in the placebo group (p < 0.05, p < 0.01, respectively). Serum HbA1c and glycated protein (fructosamine) were essentially unchanged in the Cr group, whereas HbA1c tended to increase in the placebo group (from 6.94% to 7.11%). Fasting serum insulin decreased in both groups, with a greater tendency in the Cr group (-16.5% vs -9.5%). These data suggest that supplementation of well-controlled type 2 diabetics with Cr-enriched yeast is safe and can result in improvements in blood glucose variables and oxidative stress

12. Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther 2006 December;8(6):636-43.
    Keywords: Adult/adverse effects/Antilipemic Agents/Biotin/blood/Blood Glucose/Cholesterol/Chromium/Diabetes Mellitus/Diabetes Mellitus,Type 2/Double-Blind Method/Drug Combinations/drug effects/drug therapy/Female/Glucose/Glucose Tolerance Test/Humans/Hypoglycemic Agents/Iron Chelating Agents/Lipid Metabolism/Lipids/Male/metabolism/methods/Middle Aged/pharmacology/Picolinic Acids/Pilot Projects/therapeutic use/therapy/Triglycerides/Vitamin B Complex
    
    Abstract: BACKGROUND: Preclinical studies have shown that the combination of chromium picolinate and biotin significantly enhances glucose uptake in skeletal muscle cells and enhances glucose disposal. The present pilot study was conducted to determine if supplementation with chromium picolinate and biotin can improve glycemic control in patients with type 2 diabetes mellitus with suboptimal glycemic control despite use of oral antihyperglycemic agents. METHODS: Forty-three subjects with impaired glycemic control (2-h glucose >200 mg/dL; glycated hemoglobin >or=7%), despite treatments with oral antihyperglycemic agents, were randomized to receive 600 microg of chromium as chromium picolinate and biotin (2 mg/day) (Diachrome(, Nutrition 21, Inc., Purchase, NY) in addition to their prestudy oral antihyperglycemic agent therapy. Measurements of glycemic control and blood lipids were taken at baseline and after 4 weeks. RESULTS: After 4 weeks, there was a significantly greater reduction in the total area under the curve for glucose during the 2-h oral glucose tolerance test for the treatment group (mean change -9.7%) compared with the placebo group (mean change +5.1%, P < 0.03). Significantly greater reductions were also seen in fructosamine (P < 0.03), triglycerides (P < 0.02), and triglycerides/ high-density lipoprotein cholesterol ratio (P < 0.05) in the treatment group. No significant adverse events were attributed to chromium picolinate and biotin supplementation. CONCLUSIONS: This pilot study demonstrates that supplementation with a combination of chromium picolinate and biotin in poorly controlled patients with diabetes receiving antidiabetic therapy improved glucose management and several lipid measurements. Chromium picolinate/ biotin supplementation may represent an effective adjunctive nutritional therapy to people with poorly controlled diabetes with the potential for improving lipid metabolism

13. Trumbo PR, Ellwood KC. Chromium picolinate intake and risk of type 2 diabetes: an evidence-based review by the United States Food and Drug Administration. Nutr Rev 2006 August;64(8):357-63.
    Keywords: blood/Blood Glucose/Chromium/Diabetes Mellitus,Type 2/Dietary Supplements/drug effects/epidemiology/Evidence-Based Medicine/Food Labeling/Glucose/Humans/Insulin/Insulin Resistance/Picolinic Acids/prevention & control/Risk Factors/therapeutic use/United States/United States Food and Drug Administration
    
    Abstract: The labeling of both health claims that meet significant scientific agreement (SSA) and qualified health claims on conventional foods and dietary supplements requires pre-market approval by the US Food and Drug Administration (FDA). Approval by the FDA involves, in part, a thorough review of the scientific evidence to support an SSA or a qualified health claim. This article discusses FDA's evidence-based review of the scientific evidence on the role of chromium picolinate supplements in reducing the risk of type 2 diabetes. Based on this evidence-based review, FDA issued a letter of enforcement discretion for one qualified health claim on chromium picolinate and risk of insulin resistance, a surrogate endpoint for type 2 diabetes. The agency concluded that the relationship between chromium picolinate intake and insulin resistance is highly uncertain

14. Wang ZQ, Zhang XH, Russell JC, Hulver M, Cefalu WT. Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR:LA-cp rats. J Nutr 2006 February;136(2):415-20.
    Keywords: 1-Phosphatidylinositol 3-Kinase/Animals/drug effects/Glucose/Insulin/Insulin Resistance/Male/metabolism/Muscle,Skeletal/Obesity/pharmacology/Phosphop roteins/Phosphorylation/Picolinic Acids/Rats/Signal Transduction/Water
    
    Abstract: Chromium is one of the few trace minerals for which a specific cellular mechanism of action has not been identified. Recent in vitro studies suggest that chromium supplementation may improve insulin sensitivity by enhancing insulin receptor signaling, but this has not been demonstrated in vivo. We investigated the effect of chromium supplementation on insulin receptor signaling in an insulin-resistant rat model, the JCR:LA-corpulent rat. Male JCR:LA-cp rats (4 mo of age) were randomly assigned to receive chromium picolinate (CrPic) (obese n=6, lean n=5) or vehicle (obese n=5, lean n=5) for 3 mo. The CrPic was provided in the water, and based on calculated water intake, rats randomized to CrPic received 80 microg/(kg.d). At the end of the study, skeletal muscle (vastus lateralis) biopsies were obtained at baseline and at 5, 15, and 30 min postinsulin stimulation to assess insulin signaling. Obese rats treated with CrPic had significantly improved glucose disposal rates and demonstrated a significant increase in insulin-stimulated phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI)-3 kinase activity in skeletal muscle compared with obese controls. The increase in cellular signaling was not associated with increased protein levels of the IRS proteins, PI-3 kinase or Akt. However, protein tyrosine phosphatase 1B (PTP1B) levels were significantly lower in obese rats administered CrPic than obese controls. When corrected for protein content, PTP1B activity was also significantly lower in obese rats administered CrPic than obese controls. Our data suggest that chromium supplementation of obese, insulin-resistant rats may improve insulin action by enhancing intracellular signaling

15. Fuhr JP, Jr., He H, Goldfarb N, Nash DB. Use of chromium picolinate and biotin in the management of type 2 diabetes: an economic analysis. Dis Manag 2005 August;8(4):265-75.
    Keywords: administration & dosage/analysis/Biotin/blood/Chromium/Cost Savings/Diabetes Mellitus,Type 2/Drug Combinations/drug therapy/economics/Health Care Costs/Hemoglobin A,Glycosylated/Humans/Hypoglycemic Agents/Iron Chelating Agents/metabolism/Models,Economic/Picolinic Acids/therapeutic use/therapy/Vitamin B Complex
    
    Abstract: This paper addresses the potential economic benefits of chromium picolinate plus biotin (Diachrome) use in people with Type 2 diabetes (T2DM). The economic model was developed to estimate the impact on health care systems' costs by improved HbA1C levels with chromium picolinate plus biotin (Diachrome). Lifetimes cost savings were estimated by adjusting a benchmark from the literature, using a price index to adjust for inflation. The cost of diabetes is highly dependent on the HbA1C level with higher initial levels and higher annual increments increasing the cost. Improvement in glycemic control has proven to be cost-effective in delaying the onset and progression of T2DM, reducing the risk for diabetes-associated complications and lowering utilization and cost of care. Chromium picolinate plus biotin (Diachrome) showed greater improvement of glycemic control in poorly controlled T2DM patients (HbA(1C) > or = 10%) compared to their better controlled counterparts (HbA(1C) < 10%). This improvement was additive to that achieved by oral hypoglycemic medications and correlates to calculated levels of cost savings. Average 3-year cost savings for chromium picolinate plus biotin (Diachrome) use could range from 1,636 dollars for a poorly controlled patient with diabetes without heart diseases or hypertension, to 5,435 dollars for a poorly controlled patient with diabetes, heart disease, and hypertension. Average 3-year cost savings was estimated to be between 3.9 billion dollars and 52.9 billion dollars for the 16.3 million existing patients with diabetes. Chromium picolinate plus biotin (Diachrome) use among the 1.17 million newly diagnosed patients with T2DM each year could deliver lifetime cost savings of 42 billion dollars, or 36,000 dollars per T2DM patient. Affordable, safe, and convenient, chromium picolinate plus biotin (Diachrome) could prove to be a cost-effective complement to existing pharmacological therapies for controlling T2DM

16. McCarty MF. Nutraceutical resources for diabetes prevention--an update. Med Hypotheses 2005;64(1):151-8.
    Keywords: administration & dosage/Animals/Biotin/Chromium/classification/Clinical Trials/Diabetes Mellitus/Dietary Supplements/Glucose/Health Food/Humans/Hypoglycemic Agents/Insulin/methods/Nutrition Physiology/prevention & control/Risk Assessment/Risk Factors
    
    Abstract: There is considerable need for safe agents that can reduce risk for diabetes in at-risk subjects. Although certain drugs--including metformin, acarbose, and orlistat--have shown diabetes-preventive activity in large randomized studies, nutraceuticals have potential in this regard as well. Natural agents which slow carbohydrate absorption may mimic the protective effect of acarbose; these include: soluble fiber--most notably glucomannan; chlorogenic acid--likely responsible for reduction in diabetes risk associated with heavy coffee intake; and legume-derived alpha-amylase inhibitors. There does not appear to be a natural lipase inhibitor functionally equivalent to orlistat, although there are poorly documented claims for Cassia nomame extracts. Metformin's efficacy reflects activation of AMP-activated kinase; there is preliminary evidence that certain compounds in barley malt have similar activity, without the side effects associated with metformin. In supraphysiological concentrations, biotin directly activates soluble guanylate cyclase; this implies that, at some sufficient intake, biotin should exert effects on beta cells, the liver, and skeletal muscle that favor good glucose tolerance and maintenance of effective beta cell function. Good magnesium status is associated with reduced diabetes risk and superior insulin sensitivity in recent epidemiology; ample intakes of chromium picolinate appear to promote insulin sensitivity in many individuals and improve glycemic control in some diabetics; calcium/vitamin D may help preserve insulin sensitivity by preventing secondary hyperparathyroidism. Although conjugated linoleic acid--like thiazolidinediones, a PPAR-gamma agonist--has not aided insulin sensitivity in clinical trials, the natural rexinoid phytanic acid exerts thiazolidinedione-like effect in animals and cell cultures, and merits clinical examination. Other natural agents with the potential to treat and possibly prevent diabetes include extracts of bitter melon and of cinnamon. Nutraceuticals featuring meaningful doses of combinations of these agents would likely have substantial diabetes-preventive efficacy, and presumably could be marketed legally as aids to good glucose tolerance and insulin sensitivity

17. Mita Y, Ishihara K, Fukuchi Y, Fukuya Y, Yasumoto K. Supplementation with chromium picolinate recovers renal Cr concentration and improves carbohydrate metabolism and renal function in type 2 diabetic mice. Biol Trace Elem Res 2005;105(1-3):229-48.
    Keywords: analysis/Animals/blood/Blood Glucose/Body Weight/Carbohydrate Metabolism/Chromium/Creatinine/Diabetes Mellitus,Experimental/Diabetes Mellitus,Type 2/Diabetic Neuropathies/Diet/Dietary Supplements/drug therapy/Glucose/Glucose Tolerance Test/Insulin/Iron Chelating Agents/Kidney/Male/metabolism/Mice/Mice,Inbred C57BL/pharmacology/Picolinic Acids/prevention & control/Time Factors
    
    Abstract: To study the preventive effect of supplemented chromium picolinate (CrPic) on the development of diabetic nephropathy in mice, we analyzed the effects of CrPic supplementation on renal function and concentrations of serum glucose and tissue chromium (Cr). In experiment 1, male KK-Ay obese diabetic mice were fed either a control diet (control) or a diet supplemented with 2 mg/kg diet (Cr2) or 10 mg/kg diet (Cr10) of Cr for 12 wk. Cr10 significantly ameliorated hyperglycemia after a glucose load, creatinine clearance rates, and urinary microalbumin levels (p<0.05). In experiment 2, the Cr10 diet was fed to male KK-Ay obese diabetic mice and C57BL nondiabetic mice for 4 wk. The CrPic diet reduced urinary albumin excretion in the diabetic mice (p<0.05). Inductively coupled plasma-mass spectrometry analysis revealed that the renal Cr content and the recovery of renal Cr concentration after Cr supplementation were significantly lower in the diabetic mice than in the nondiabetic mice (p<0.01). These observations suggest that Cr supplementation of type 2 diabetic mice reduces the symptoms of hyperglycemia and improves the renal function by recovering renal Cr concentration

18. Vladeva SV, Terzieva DD, Arabadjiiska DT. Effect of chromium on the insulin resistance in patients with type II diabetes mellitus. Folia Med (Plovdiv ) 2005;47(3-4):59-62.
    Keywords: administration & dosage/Adult/Aged/blood/Chromium/deficiency/Diabetes Mellitus/Diabetes Mellitus,Type 2/Female/Humans/Insulin/Insulin Resistance/Male/methods/Middle Aged/Overweight/therapy/Treatment Outcome
    
    Abstract: INTRODUCTION: Chromium deficiency in diabetic patients is a debatable problem. The prevailing opinion suggests the presence of low serum concentrations in such patients and therefore an early, long-term addition of chromium to the standard therapy is recommended. PURPOSE: The aim of the present study was to evaluate the effect of chromium on the insulin resistance in diabetic patients with type II diabetes mellitus. MATERIAL AND METHODS: We have studied a total of 34 overweight patients with type II diabetes mellitus, who were distributed in two study sub-groups--patients with very good metabolic control and patients with bad control. For sixty days the patients of both groups received 30 microg of chromium picolinate as food additive. We measured the serum concentration of chromium (using atom-absorption methods), immune-reactive insulin and the insulin resistance index at baseline and at the end of the two-month period. RESULTS: The serum concentrations of chromium was significantly lower in diabetic patients than in the healthy individuals used as controls (2.18 +/- 0.87 nmol/l versus 4.03 +/- 0.96 nmol/l; p < 0.001). We found a significant decrease of the immune-reactive insulin and the insulin resistance index after a two-month application of chromium 30 microg daily (1 tablet of chrome picolinate). The effects of this trace element are analysed in the light of an improved first phase of secretion of insulin or facilitated post-receptor insulin sensibility as a way of potentiating the insulin action. CONCLUSION: Chromium included early in the complex therapy of diabetes is beneficial in the reduction of the degree of insulin resistance

19. Vrtovec M, Vrtovec B, Briski A, Kocijancic A, Anderson RA, Radovancevic B. Chromium supplementation shortens QTc interval duration in patients with type 2 diabetes mellitus. Am Heart J 2005 April;149(4):632-6.
    Keywords: Body Mass Index/Chromium/Cross-Over Studies/Diabetes Mellitus/Diabetes Mellitus,Type 1/Dietary Supplements/Double-Blind Method/drug effects/drug therapy/Electrocardiography/Heart Conduction System/Humans/methods/pharmacology/physiopathology/Picolinic Acids/therapeutic use/urine
    
    Abstract: BACKGROUND: We investigated the potential effects of chromium supplementation on QTc interval duration in type 2 diabetic patients. METHODS: Of 60 patients with type 2 diabetes mellitus, 30 were randomly assigned to group A, and 30 to group B. Group A received 1000 microg of chromium picolinate (CrPic) daily for 3 months, followed by placebo in the next 3 months; group B was treated with placebo for the first 3 months and CrPic in the next 3 months. At each visit, QT interval was measured on a standard electrocardiogram by averaging 3 consecutive beats in leads II and V4 and corrected for heart rate with Bazett formula. RESULTS: Although baseline QTc interval was similar in both groups (422 +/- 34 milliseconds in group A vs 425 +/- 24 milliseconds in group B, P = .77), QTc interval at 3 months was shorter in group A (406 +/- 35 milliseconds) than in group B (431 +/- 26 milliseconds, P = .01). In the following 3 months, QTc interval shortened in group B but not in group A, which resulted in a comparable QTc interval duration of both groups at the end of the study (414 +/- 28 milliseconds in group A vs 409 +/- 22 milliseconds in group B, P = .50). Apart from body mass index (31.4 +/- 4.2 kg/m2 in patients with QTc shortening vs 28.7 +/- 4.2 kg/m2 in patients without QTc shortening, P = .03), none of the clinical and laboratory variables predicted QTc interval shortening in our patient cohort. CONCLUSIONS: Short-term chromium supplementation shortens QTc interval in patients with type 2 diabetes mellitus

20. Wang H, Kruszewski A, Brautigan DL. Cellular chromium enhances activation of insulin receptor kinase. Biochemistry 2005 June 7;44(22):8167-75.
    Keywords: Amino Acid Sequence/Animals/antagonists & inhibitors/Cell Membrane/chemistry/Cho Cells/Chromium/Cricetinae/drug effects/Enzyme Activation/Enzyme Inhibitors/enzymology/genetics/Glucose/Glutathione Transferase/Humans/Insulin/Insulin Resistance/metabolism/Molecular Sequence Data/Oxidation-Reduction/pharmacology/Phosphorylation/physiology/Protein Structure,Tertiary/Protein-Tyrosine-Phosphatase/Receptor,Insulin/Recombi nant Fusion Proteins/Tyrosine
    
    Abstract: Chromium has been recognized for decades as a nutritional factor that improves glucose tolerance by enhancing in vivo insulin action, but the molecular mechanism is unknown. Here we report pretreatment of CHO-IR cells with chromium enhances tyrosine phosphorylation of the insulin receptor. Different chromium(III) compounds were effective at enhancing insulin receptor phosphorylation in intact cells, but did not directly activate recombinant insulin receptor kinase. The level of insulin receptor phosphorylation in cells can be increased by inhibition of the opposing protein tyrosine phosphatase (PTP1B), a target for drug development. However, chromium did not inhibit recombinant human PTP1B using either p-nitrophenyl phosphate or the tyrosine-phosphorylated insulin receptor as the substrate. Chromium also did not alter reversible redox regulation of PTP1B. Purified plasma membranes exhibited insulin-dependent kinase activity in assays using substrate peptides mimicking sites of Tyr phosphorylation in the endogenous substrate IRS-1. Plasma membranes prepared from chromium-treated cells had higher specific activity of insulin-dependent kinase relative to controls. We conclude that cellular chromium potentiates insulin signaling by increasing insulin receptor kinase activity, separate from inhibition of PTPase. Our results suggest that nutritional and pharmacological therapies may complement one another to combat insulin resistance, a hallmark of type 2 diabetes

21. A scientific review: the role of chromium in insulin resistance. Diabetes Educ 2004;Suppl:2-14.
    Keywords: Animals/Cardiovascular Diseases/Chromium/deficiency/Diabetes Mellitus,Type 2/drug therapy/Glucose/Humans/Insulin/Insulin Resistance/Metabolic Syndrome X/metabolism/physiology/physiopathology/Risk Factors/therapeutic use
    
    Abstract: Chromium is an essential mineral that appears to have a beneficial role in the regulation of insulin action and its effects on carbohydrate, protein and lipid metabolism. Chromium is an important factor for enhancing insulin activity. Studies show that people with type 2 diabetes have lower blood levels of chromium than those without the disease. Insulin resistance is the common denominator in a cluster of cardiovascular disease risk factors. One out of every five Americans has metabolic syndrome. It affects 40% of people in their 60s and 70s. Insulin resistance, with or without the presence of metabolic syndrome, significantly increases the risk of cardiovascular disease. Insulin resistance is present in two serious health problems in women; polycystic ovarian syndrome (PCOS) and gestational diabetes. Several studies have now demonstrated that chromium supplements enhance the metabolic action of insulin and lower some of the risk factors for cardiovascular disease, particularly in overweight individuals. Chromium picolinate, specifically, has been shown to reduce insulin resistance and to help reduce the risk of cardiovascular disease and type 2 diabetes. Dietary chromium is poorly absorbed. Chromium levels decrease with age. Supplements containing 200-1,000 mcg chromium as chromium picolinate a day have been found to improve blood glucose control. Chromium picolinate is the most efficacious form of chromium supplementation. Numerous animal studies and human clinical trials have demonstrated that chromium picolinate supplements are safe

22. Bonnefont-Rousselot D. The role of antioxidant micronutrients in the prevention of diabetic complications. Treat Endocrinol 2004;3(1):41-52.
    Keywords: administration & dosage/Antioxidants/Ascorbic Acid/Chromium/deficiency/Diabetes Complications/Diet/Flavonoids/Humans/Metals/Micronutrients/Niacinamide/p revention & control/Riboflavin/Thioctic Acid/Tocopherols/Ubiquinone/Vitamins
    
    Abstract: Diabetes mellitus is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This leads to oxidative stress, which is partly responsible for diabetic complications. Tight glycemic control is the most effective way of preventing or decreasing these complications. Nevertheless, antioxidant micronutrients can be proposed as adjunctive therapy in patients with diabetes. Indeed, some minerals and vitamins are able to indirectly participate in the reduction of oxidative stress in diabetic patients by improving glycemic control and/or are able to exert antioxidant activity. This article reviews the use of minerals (vanadium, chromium, magnesium, zinc, selenium, copper) and vitamins or cofactors (tocopherol [vitamin E], ascorbic acid [vitamin C], ubidecarenone [ubiquinone; coenzyme Q], nicotinamide, riboflavin, thioctic acid [lipoic acid], flavonoids) in diabetes, with a particular focus on the prevention of diabetic complications. Results show that dietary supplementation with micronutrients may be a complement to classical therapies for preventing and treating diabetic complications. Supplementation is expected to be more effective when a deficiency in these micronutrients exists. Nevertheless, many clinical studies have reported beneficial effects in individuals without deficiencies, although several of these studies were short term and had small sample sizes. However, a randomized, double-blind, placebo-controlled, multicenter trial showed that thioctic acid at an oral dosage of 800 mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2 diabetic patients. Above all, individuals with diabetes should be educated about the importance of consuming adequate amounts of vitamins and minerals from natural food sources, within the constraints of recommended sugar and carbohydrate intake

23. Cheng HH, Lai MH, Hou WC, Huang CL. Antioxidant effects of chromium supplementation with type 2 diabetes mellitus and euglycemic subjects. J Agric Food Chem 2004 March 10;52(5):1385-9.
    Keywords: administration & dosage/Adult/analysis/Antioxidants/blood/Catalase/Chromium/Diabetes Mellitus/Diabetes Mellitus,Type 2/Dietary Supplements/Double-Blind Method/drug therapy/Female/Hemoglobin A,Glycosylated/Humans/Male/Middle Aged/Oxidative Stress/Placebos/Thiobarbituric Acid Reactive Substances/urine
    
    Abstract: To determine the effects of chromium (Cr) supplementations on oxidative stress of type 2 diabetes and euglycemic (EU) subjects, adult having HbA(1C) values of <6.0% (EU), 6.8-8.5% (mildly hyperglycemic, MH), and >8.5% (severely hyperglycemic, SH) were supplemented for 6 months with 1000 microg/day of Cr (as Cr yeast) or with a placebo. In the beginning, the levels of the plasma Cr in the MH and SH groups were 25-30% lower than those of the EU subjects. The values of thiobarbituric acid reactive substances (TBARS) and total antioxidative status (TAS) of the MH and SH groups were significantly higher than those of the EU ones. Following supplementations, the levels of plasma TBARS in the Cr groups of MH and SH groups were significantly decreased (the inverse was found in the EU) and showed no significant changes in the placebo group. The levels of plasma TAS in the Cr groups of EU and MH were significantly decreased (the inverse was found in the SH) and showed no significant changes in the placebo group. No significant difference was found in the antioxidant enzyme (superoxide dismutase, glutathione peroxidase, catalase) activities during supplementations. These data suggest that Cr supplementation was an effective treatment strategy to minimize increased oxidative stress in type 2 diabetes mellitus patients whose HbA(1C) level was >8.5%, and the Cr in EU groups might act as a prooxidant

24. Cicero AF, Derosa G, Gaddi A. What do herbalists suggest to diabetic patients in order to improve glycemic control? Evaluation of scientific evidence and potential risks. Acta Diabetol 2004 September;41(3):91-8.
    Keywords: adverse effects/blood/Blood Glucose/Chromium/Diabetes Mellitus/Dietary Supplements/Glucose/Humans/Italy/Medicine,Herbal/metabolism/Phytotherapy /therapy/Vitamins
    
    Abstract: In the course of 12 continuing education seminars given in different regions of Italy in 2001, we distributed a questionnaire to all the attending herbalists asking information about the herbal remedy and dietary supplement they mainly recommended to subjects who required a "natural" treatment to control glycemia. We distributed 720 questionnaires and we received 685 completed ones. We have compiled a short review on the efficacy and safety of the 10 most frequently advised products for each category. The 10 more frequently suggested herbal remedies were gymnema, psyllium, fenugreek, bilberry, garlic, Chinese ginseng, dandelion, burdock, prickly pear cactus, and bitter melon. The 10 most frequently recommended dietary supplements were biotin, vanadium, chromium, vitamin B6, vitamin C, vitamin E, zinc, selenium, alpha-lipoic acid, and fructooligosaccharides. The majority of the products recommended by Italian herbalists may be efficacious in reducing glycemia. If a diabetic patient is already assuming products that even slightly reduce glycemia, we risk to underestimate the level of glucose intolerance, while if the patient stops the complementary treatment after initiating pharmaceutical therapy, in the subsequent visit we may underestimate the effect of our prescription. Therefore, if doctors are to have a role in gate-keeping or advising patients about complementary and alternative medicine, they need to be familiar with this type of medicine. If they choose otherwise, then the provision of complementary and alternative medicine will continue to be patchy and largely outside the conventional care framework, perhaps through a growing network of parallel care providers involving a large number of non-medically qualified practitioners, who patients will continue to access directly

25. Kim DS, Kim TW, Kang JS. Chromium picolinate supplementation improves insulin sensitivity in Goto-Kakizaki diabetic rats. J Trace Elem Med Biol 2004;17(4):243-7.
    Keywords: administration & dosage/Animals/blood/Blood Glucose/Body Weight/Carbohydrate Metabolism/Chromium/Diabetes Mellitus/Diabetes Mellitus,Experimental/Dietary Supplements/drug therapy/Glucose/Glucose Tolerance Test/Humans/Insulin/Insulin Resistance/Iron Chelating Agents/Male/metabolism/pharmacology/physiology/Picolinic Acids/Rats/Rats,Inbred Strains/Rats,Sprague-Dawley/therapy
    
    Abstract: Chromium picolinate (CrP) supplementation has been studied as a potential therapy of insulin resistance and lipid abnormalities. There have been some reports involving chromium supplementation in patients with diabetes, but the results are varied. The present study was conducted to assess the effects of CrP on insulin sensitivity and body weight in Goto-Kakizaki (GK) diabetic rats. We supplemented normal Sprague-Dawley (SD) rats and GK diabetic rats with supplemental CrP, 100 mg/kg/day once a day for 4 weeks. In the normal SD rats, the mean body weight of the control group increased by 50.5%, whereas that of the CrP-treated group increased by 65.9% (P < 0.05 vs control). Similarly, in the diabetic GK rats, CrP supplementation showed increased weight gain compared to the control group (133.4% vs 119.6% of the baseline weight, P < 0.01). Glucose tolerance tests (GTT) [ip injection of glucose; 2 g/kg] and insulin sensitivity tests [SQ injection of insulin (5 U/kg) plus ip injection of glucose (30 min after insulin injection)] were conducted. During insulin sensitivity tests at the end of treatment, the glucose levels were significantly lower in CrP-treated rats compared with the control rats (AUC0-->120; 113.1 +/- 32.0 vs 170.5 +/- 49.0 mg-min/mL, P < 0.05). During GTTs, the glucose levels and insulin concentrations in the CrP-treated rats were not different from those in the control rats. The results of these studies suggest that CrP supplementation in GK diabetic rats leads to increase of weight gain and improvement of insulin sensitivity. This raises the possibility that CrP supplementation can be considered to improve carbohydrate metabolism in patients with type 2 diabetes mellitus

26. Kleefstra N, Bilo HJ, Bakker SJ, Houweling ST. [Chromium and insulin resistance]. Ned Tijdschr Geneeskd 2004 January 31;148(5):217-20.
    Keywords: adverse effects/analysis/blood/Blood Glucose/Body Weight/chemically induced/Chromium/deficiency/Diabetes Mellitus/Diabetes Mellitus,Type 2/Diet/Dietary Supplements/drug therapy/Glucose/Hemoglobin A,Glycosylated/Humans/Hypoglycemia/Insulin/Insulin Resistance/metabolism/therapeutic use
    
    Abstract: Since as early as the 50s of the last century, it has been known that chromium is essential for normal glucose metabolism. Too little chromium in the diet may lead to insulin resistance. However, there is still no standard against which chromium deficiency can be established. Nevertheless, chromium supplements are becoming increasingly popular. Various systematic reviews have been unable to demonstrate any effects of chromium on glycaemic regulation (possibly due partly to the low dosages used), but there is a slight reduction in body weight averaging 1 kg. In a double-blind randomised placebo-controlled trial in a Chinese population with type-2 diabetes mellitus, supplementation with 1000 micrograms of chromium led to a fall in the glycosylated haemoglobin level (HbA1c) by 2%. Toxic effects of chromium are seldom seen; recently, however, the safety of one of the dosage forms of chromium, chromium picolinate, has been questioned. One should be aware that individual patients with type-2 diabetes mellitus may have an increased risk of hypoglycaemic episodes when taking chromium supplements as self-medication

27. Rabinovitz H, Friedensohn A, Leibovitz A, Gabay G, Rocas C, Habot B. Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. Int J Vitam Nutr Res 2004 May;74(3):178-82.
    Keywords: administration & dosage/Aged/Aged,80 and over/analysis/blood/Blood Glucose/Cholesterol/Cholesterol,HDL/Cholesterol,LDL/Chromium/Diabetes Mellitus/Diabetes Mellitus,Type 2/Diet/Dietary Supplements/drug therapy/Female/Glucose/Humans/Insulin/Lipids/Male/Middle Aged/Triglycerides
    
    Abstract: Intervention trials have shown the beneficial effects of chromium supplementation in type 2 diabetes (non-insulin-dependent diabetes mellitus). This study investigated the effects of chromium picolinate on elderly diabetic patients within a rehabilitation program. Thirty-nine diabetic subjects, average age 73 years (18 males and 21 females), undergoing rehabilitation following stroke or hip fracture, were recruited to participate in this study. An additional 39 diabetic patients constituted the control group. Along with standard treatment for diabetes, the study group received 200 microg of chromium twice a day for a three-week period. Blood samples, dietary intake, and anthropometric data were collected prior to and post-intervention. Throughout the study period, participants received a diet of approximately 1500 kcal/day. Significant differences in the fasting blood level of glucose compared to the baseline (190 mg/dL vs 150 mg/dL, p < 0.001) were found at the end of the study. HbA1c also improved from 8.2% to 7.6% (p < 0.01). Total cholesterol was also reduced from 235 mg/dL to 213 mg/dL (p < 0.02). A trend towards lowered triglyceride levels was also observed (152 mg/dL vs 136 mg/dL). We conclude that, in this population of elderly, diabetic patients undergoing rehabilitation, dietary supplementation with chromium is beneficial in moderating glucose intolerance. In addition, chromium intake appears to lower plasma lipid levels

28. Rajpathak S, Rimm EB, Li T et al. Lower toenail chromium in men with diabetes and cardiovascular disease compared with healthy men. Diabetes Care 2004 September;27(9):2211-6.
    Keywords: Adult/Aged/analysis/Cardiovascular Diseases/Case-Control Studies/chemistry/Chromium/Clinical Trials/Cross-Sectional Studies/Diabetes Mellitus/Follow-Up Studies/Humans/Insulin/Male/metabolism/methods/Middle Aged/Nails/Reference Values/Retrospective Studies/Toes
    
    Abstract: OBJECTIVE: Chromium may improve insulin sensitivity, which can modify the risk of diabetes and cardiovascular disease (CVD). Therefore, we evaluated the association between toenail chromium and CVD in diabetic men. RESEARCH DESIGN AND METHODS: We performed cross-sectional and nested case-control analyses among men aged 40-75 years within the Health Professionals Follow-up Study. The cross-sectional analysis compared men with diabetes only (n = 688), diabetes with prevalent CVD (n = 198), and healthy control subjects (n = 361). The nested case-control study included 202 men with baseline diabetes who developed incident CVD and 361 matched control subjects. RESULTS: Mean toenail chromium (microg/g) was 0.71 in healthy control subjects, 0.61 in diabetes-only subjects, and 0.52 in diabetic subjects with prevalent CVD (P for trend = 0.003). In the cross-sectional analysis, the multivariate odds ratio (OR) between extreme quartiles was 0.74 (95% CI 0.49-1.11; P for trend = 0.18), comparing diabetes only with healthy control subjects. A similar comparison between diabetic subjects with prevalent CVD and healthy control subjects yielded an OR of 0.45 (0.24-0.84; P for trend = 0.003). In the nested case-control study, comparing diabetic men with incident CVD with healthy control subjects, the multivariate OR was 0.65 (0.36-1.17; P for trend = 0.16) between extreme quartiles. When we combined prevalent and incident CVD cases among diabetic men and compared them with healthy control subjects, the OR was 0.62 (0.39-1.01; P for trend = 0.02) between extreme quartiles. CONCLUSIONS: Our results suggest that diabetic men with CVD have lower toenail chromium than healthy control subjects. However, this study could not distinguish between the effects of chromium on diabetes and those on CVD. Long-term clinical trials are needed to determine whether chromium supplementation is beneficial for preventing CVD among diabetic patients

29. Sharafetdinov K, Meshcheriakova VA, Plotnikova OA, Mazo VK, Gmoshinskii IV, Nechaeva SV. [Effect of food diet supplements with chromium on the clinical and metabolic parameters in type 2 diabetic patients]. Vopr Pitan 2004;73(5):17-20.
    Keywords: administration & dosage/blood/Blood Pressure/Body Weight/Cholesterol/Chromium/Diabetes Mellitus,Type 2/Diabetic Diet/Diet/diet therapy/Dietary Supplements/drug effects/Female/Humans/Male/Middle Aged/Triglycerides
    
    Abstract: It was investigated the influence of food diet supplements with chromium on dynamic of glycaemia, lipid profile, blood pressure and weight in type 2 diabetic patients. Traditional hypocaloric diet was supplemented with chromium-spirulina (50 mcg chromium per day). The results investigations indicated that a chromium-enriched diet has beneficial effects on basal and postprandial glycaemia, the content of cholesterol and triglycerides in serum in compared with a traditional hypocaloric diet

30. Shindea UA, Sharma G, Xu YJ, Dhalla NS, Goyal RK. Insulin sensitising action of chromium picolinate in various experimental models of diabetes mellitus. J Trace Elem Med Biol 2004;18(1):23-32.
    Keywords: 3T3 Cells/Adipocytes/Adipose Tissue/Adult/Animals/Animals,Newborn/Area Under Curve/blood/Cell Differentiation/chemically induced/Cholesterol/Chromium/cytology/Diabetes Mellitus/Diabetes Mellitus,Experimental/drug therapy/Glucose/Glucose Tolerance Test/Humans/Insulin/Insulin Resistance/Iron Chelating Agents/Lipid Metabolism/Male/metabolism/Mice/Myoblasts/pharmacology/physiology/Picoli nic Acids/Random Allocation/Rats/Rats,Wistar/therapeutic use/Triglycerides/Water
    
    Abstract: Although chromium is an essential element for carbohydrate and lipid metabolism, its effects in diabetic patients are still debated. We have studied the effect of 6 week treatment with chromium picolinate (8 microg/ml in drinking water) in streptozotocin (STZ)-induced type 1 and type 2 diabetic rat models. The mechanism of anti-diabetic action of chromium picolinate was studied using C2C12 myoblasts and 3T3-L1 adipocytes. Chromium picolinate significantly decreased the area under the curve over 120 min for glucose of both STZ-induced type 1 (40mg/kg, i.v. in adult rats) and type 2 (90 mg/kg, i.p. in 2 day old rat neonates) diabetic rats without any significant change in area under the curve over 120 min for insulin as compared to controls. The composite insulin sensitivity index and insulin sensitivity index (KITT) values of both type 1 and type 2 diabetic rats were increased significantly by chromium picolinate. Treatment with chromium picolinate produced a significant decrease in elevated cholesterol and triglyceride levels in both types of diabetic rats. In 3T3-L1 adipocytes, chromium picolinate (0-10 micromol) per se did not produce any effect, however, when co-incubated with insulin it significantly increased the intracellular triglyceride synthesis (EC50 = 363.7nmol/1). Similarly in C2C12 myoblasts, chromium picolinate alone did not produce any effect, however, it significantly increased insulin-induced transport of 14C-glucose. In conclusion, chromium picolinate significantly improves deranged carbohydrate and lipid metabolism of experimental chemically induced diabetes in rats. The mechanism of in vivo anti-diabetic action appears to be peripheral (skeletal muscle and adipose tissue) insulin enhancing action of chromium

31. Terpilowska S, Zaporowska H. [The role of chromium in cell biology and medicine]. Przegl Lek 2004;61 Suppl 3:51-4.
    Keywords: Animals/Antioxidants/blood/Cholesterol/Cholesterol,HDL/Cholesterol,LDL/C hromium/deficiency/Diabetes Mellitus/drug effects/Energy Metabolism/Glucose/Humans/Hypoglycemia/Lipid Metabolism/metabolism/Oxidation-Reduction/Oxidative Stress/pharmacology/Trace Elements/Triglycerides
    
    Abstract: Chromium (Cr3+) is an essential trace element for animals and humans. Its deficiency in organisms causes e.g. disturbances of carbohydrate and lipid metabolism, hypoglycemia, impaired glucose tolerance, elevated cholesterol and triglycerides in blood, but a decrease in HDL-cholesterol. It plays an important role in insulin-receptor activation. In the literature, antioxidative and anti-diabetic effects of chromium were also described. An excess of trivalent chromium can act as a prooxidant

32. Keszthelyi Z, Past T, Koltai K, Szabo L, Mozsik G. [Chromium (III)-ion enhances the utilization of glucose in type-2 diabetes mellitus]. Orv Hetil 2003 October 19;144(42):2073-6.
    Keywords: administration & dosage/Adult/blood/Blood Glucose/Cholesterol/Chromium/deficiency/Diabetes Mellitus/Diabetes Mellitus,Type 2/drug therapy/Female/Glucose/Hemoglobin A,Glycosylated/Humans/Hypoglycemic Agents/Insulin/Insulin Resistance/Lipid Metabolism/Male/metabolism/methods/Middle Aged/pharmacology/Picolinic Acids/therapy
    
    Abstract: INTRODUCTION: The prevalence of the type 2 diabetes mellitus is still growing. Although the occurrence of insulin resistance is quite frequent in the whole population, diabetes not always develops because for a time the compensating mechanism avoids it. In a frequent variation of type-2 diabetes the disease is not the result of an alteration in the insulin receptor or the glucose transporter, but a genetically determined defect of the postreceptorial intracellular signaling mechanism plays a role in its occurrence. There have been investigations for decades to find out more about the role of chromium (III) ions in glucose metabolism and in the prevention of type-2 diabetes. It has also been investigated if chromium substitution can prevent or treat those forms of diabetes where chromium deficiency is suspected to be in the background of the disorder. AIM: The aim of our present investigation is to test the role of chromium (III) compounds in glucose metabolism that are known from literature. The authors examined the effect of oral chromium supplementation on antidiabetic treatment. Chromium supplementation was applied for 6 months. METHODS: Before, through and after the investigation changes in the patient's carbohydrate and lipid metabolism were followed by laboratory tests. RESULTS: At the end of our examination the cholesterin level significantly, the HbA1c level close to the significant value decreased. Due to their results the authors presume that chromium (III) compounds may be effective in the treatment of patients' with decreased glucose tolerance or type-2 diabetes mellitus as a supplement to their therapy

33. Ryan GJ, Wanko NS, Redman AR, Cook CB. Chromium as adjunctive treatment for type 2 diabetes. Ann Pharmacother 2003 June;37(6):876-85.
    Keywords: Animals/blood/chemistry/Chromium/Clinical Trials/Diabetes Mellitus,Type 2/drug therapy/Glucose/Humans/Kidney/Lipids/metabolism/pharmacology/statistics & numerical data/therapeutic use/therapy
    
    Abstract: 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

34. Bahijri SM, Mufti AM. Beneficial effects of chromium in people with type 2 diabetes, and urinary chromium response to glucose load as a possible indicator of status. Biol Trace Elem Res 2002 February;85(2):97-109.
    Keywords: administration & dosage/Adult/Aged/analysis/blood/Blood Glucose/Chromium/Diabetes Mellitus,Type 2/drug therapy/Female/Glucose/Humans/Male/Middle Aged/therapeutic use/urine
    
    Abstract: No reliable method for the estimation of chromium (Cr) status is available yet. The aim of this study is to investigate the possibility of using urinary Cr response to glucose load as an indicator of Cr status. Seventy-eight non-insulin-dependent diabetes mellitus patients, were divided randomly into two groups and given Cr supplements as brewer's yeast and CrCl3 sequentially with placebo in between, in a double-blind, crossover design of four stages, each lasting 8 wk. At the beginning and end of each stage, subjects were weighed, their dietary data and drug dosage recorded, and blood and urine samples collected for analysis of glucose and urinary chromium (fasting and 2 h post-75-g glucose load) and fructosamine. The mean urinary Cr after the glucose load was significantly higher than the fasting mean at zero time (p<0.01). However, only 52 of the patients showed an obvious increase; the others showed a slight decrease or no change. Both supplements caused a significant increase in the means of urinary Cr and a significant decrease in the means of glucose and fructosamine. Only those subjects responding to Cr supplement by improved glucose control showed an increase in post-glucose-load urinary Cr over fasting level, after the supplement but not at zero time. Therefore, it was concluded that urinary Cr response to glucose load could be used as an indicator of Cr status

35. Cefalu WT, Wang ZQ, Zhang XH, Baldor LC, Russell JC. Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats. J Nutr 2002 June;132(6):1107-14.
    Keywords: administration & dosage/Administration,Oral/Animals/Area Under Curve/blood/Blood Glucose/Carbohydrate Metabolism/Chromium/Diabetes Mellitus,Type 2/Disease Models,Animal/drug effects/drug therapy/Glucose/Glucose Tolerance Test/Glucose Transporter Type 4/Hyperinsulinism/Insulin/Insulin Resistance/Iron Chelating Agents/Lipid Metabolism/Male/Metabolic Syndrome X/metabolism/Monosaccharide Transport Proteins/Muscle Proteins/Muscle,Skeletal/Obesity/pharmacology/physiology/Picolinic Acids/Random Allocation/Rats/Water
    
    Abstract: Human studies suggest that chromium picolinate (CrPic) decreases insulin levels and improves glucose disposal in obese and type 2 diabetic populations. To evaluate whether CrPic may aid in treatment of the insulin resistance syndrome, we assessed its effects in JCR:LA-corpulent rats, a model of this syndrome. Male lean and obese hyperinsulinemic rats were randomly assigned to receive oral CrPic [80 microg/(kg. d); n = 5 or 6, respectively) in water or to control conditions (water, n = 5). After 3 mo, a 120-min intraperitoneal glucose tolerance test (IPGTT) and a 30-min insulin tolerance test were performed. Obese rats administered CrPic had significantly lower fasting insulin levels (1848 +/- 102 vs. 2688 +/- 234 pmol/L; P < 0.001; mean +/- SEM) and significantly improved glucose disappearance (P < 0.001) compared with obese controls. Glucose and insulin areas under the curve for IPGTT were significantly less for obese CrPic-treated rats than in obese controls (P < 0.001). Obese CrPic-treated rats had lower plasma total cholesterol (3.57 +/- 0.28 vs. 4.11 +/- 0.47 mmol/L, P < 0.05) and higher HDL cholesterol levels (1.92 +/- 0.09 vs. 1.37 +/- 0.36 mmol/L, P < 0.01) than obese controls. CrPic did not alter plasma glucose or cholesterol levels in lean rats. Total skeletal muscle glucose transporter (Glut)-4 did not differ among groups; however, CrPic significantly enhanced membrane-associated Glut-4 in obese rats after insulin stimulation. Thus, CrPic supplementation enhances insulin sensitivity and glucose disappearance, and improves lipids in male obese hyperinsulinemic JCR:LA-corpulent rats

36. Lamson DS, Plaza SM. The safety and efficacy of high-dose chromium. Altern Med Rev 2002 June;7(3):218-35.
    Keywords: administration & dosage/Adult/adverse effects/blood/Blood Glucose/Chromium/Chromium Compounds/Diabetes Mellitus,Type 2/Dietary Supplements/Dose-Response Relationship,Drug/drug effects/drug therapy/Female/Glucose/Humans/Insulin/Insulin Resistance/Male/metabolism/Middle Aged/Nutritional Requirements/pharmacology/Randomized Controlled Trials
    
    Abstract: The data on the standards for chromium requirements and the safety of various chromium compounds and doses are reviewed. The 350-fold difference between the acceptable daily intake and the calculated reference dose for humans of 70 mg per day seems without precedent with respect to other nutritional minerals. Previous claims of mutagenic effects of chromium are of questionable relevance. While studies have found DNA fragmentation (clastogenic effects) by chromium picolinate, anecdotal reports of high-dose chromium picolinate toxicity are few and ambiguous. The beneficial effects of chromium on serum glucose and lipids and insulin resistance occur even in the healthy. Serum glucose can be improved by chromium supplementation in both types 1 and 2 diabetes, and the effect appears dose dependent. Relative absorption of various chromium compounds is summarized and the mechanism of low molecular weight chromium binding substance (LMWCr) in up-regulating the insulin effect eight-fold is discussed. There is evidence of hormonal effects of supplemental chromium besides the effect on insulin. Chromium supplementation does result in tissue retention, especially in the kidney, although no pathogenic effect has been demonstrated despite considerable study