Marilyn M. Polansky

Elevated Intakes of Supplemental Chromium Improve Glucose and Insulin Variables in Individuals With Type 2 Diabetes

Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism. The chromium requirement is postulated to increase with increased glucose intolerance and diabetes. The objective of this study was to test the hypothesis that the elevated intake of supplemental chromium is involved in the control of type 2 diabetes. Individuals being treated for type 2 diabetes (180 men and women) were divided randomly into three groups and supplemented with: 1) placebo, 2) 1.92 μmol (100 μg) Cr as chromium picolinate two times per day, or 3) 9.6 μmol (500 μg) Cr two times per day. Subjects continued to take their normal medications and were instructed not to change their normal eating and living habits. HbA1c values improved significantly after 2 months in the group receiving 19.2 pmol (1,000 pg) Cr per day and was lower in both chromium groups after 4 months (placebo, 8.5 ± 0.2%; 3.85 pmol Cr, 7.5 ± 0.2%; 19.2 pmol Cr, 6.6 ± 0.1%). Fasting glucose was lower in the 19.2-μmol group after 2 and 4 months (4-month values: placebo, 8.8 ± 0.3 mmol/1; 19.2 μmol Cr, 7.1 ± 0.2 mmol/1). Two-hour glucose values were also significantly lower for the subjects consuming 19.2 μmol supplemental Cr after both 2 and 4 months (4-month values: placebo, 12.3 ± 0.4 mmol/1; 19.2 μmol Cr, 10.5 ± 0.2 mmol/1). Fasting and 2-h insulin values decreased significantly in both groups receiving supplemental chromium after 2 and 4 months. Plasma total cholesterol also decreased after 4 months in the subjects receiving 19.2 μmol/day Cr. These data demonstrate that supplemental chromium had significant beneficial effects on HbA1c, glucose, insulin, and cholesterol variables in subjects with type 2 diabetes. The beneficial effects of chromium in individuals with diabetes were observed at levels higher than the upper limit of the Estimated Safe and Adequate Daily Dietary Intake.

Regulation of PTP-1 and Insulin Receptor Kinase by Fractions from Cinnamon: Implications for Cinnamon Regulation of Insulin Signalling

Bioactive compound(s) extracted from cinnamon potentiate insulin activity, as measured by glucose oxidation in the rat epididymal fat cell assay. Wortmannin, a potent PI 3′-kinase inhibitor, decreases the biological response to insulin and bioactive compound(s) from cinnamon similarly, indicating that cinnamon is affecting an element(s) upstream of PI 3′-kinase. Enzyme studies done in vitro show that the bioactive compound(s) can stimulate autophosphorylation of a truncated form of the insulin receptor and can inhibit PTP-1, a rat homolog of a tyrosine phosphatase (PTP-1B) that inactivates the insulin receptor. No inhibition was found with alkaline phosphate or calcineurin suggesting that the active material is not a general phosphatase inhibitor. It is suggested, then, that a cinnamon compound(s), like insulin, affects protein phosphorylation-dephosphorylation reactions in the intact adipocyte. Bioactive cinnamon compounds may find further use in studies of insulin resistance in adult-onset diabetes.

Lack of toxicity of chromium chloride and chromium picolinate in rats.

OBJECTIVE To evaluate the safety of chromium (Cr) as a nutrient supplement. Several recent studies have reported beneficial effects of supplemental Cr at levels higher than the upper limit of the suggested intake for Cr. Trivalent Cr is considered relatively nontoxic but some recent unconfirmed studies have questioned its toxicity. We evaluated the toxicity of Cr chloride and a more bioavailable form of trivalent Cr, Cr tripicolinate. METHODS Harlan Sprague Dawley rats (4 weeks of age) were fed a stock diet to which was added 0, 5, 25, 50 or 100 mg of Cr per kg of diet as chloride or picolinate. Fasting blood samples were taken at 11 and 17 weeks and animals sacrificed at 24 weeks of age. Lack of toxicity was demonstrated by blood and histological measurements. Chromium incorporation into tissues was determined by graphite furnace atomic absorption. RESULTS There were no statistically significant differences in body weight, organ weights or blood variables among all the groups tested at 11, 17 and 24 weeks. Blood variables measured were glucose, cholesterol, triglycerides, blood urea nitrogen, lactic acid dehydrogenase, transaminases, total protein and creatinine. Histological evaluation of the liver and kidney of control and animals fed 100 mg/kg Cr as Cr chloride or picolinate also did not show any detectable differences. Liver and kidney Cr concentrations increased linearly for both the Cr chloride and picolinate fed animals. CONCLUSIONS These data demonstrate a lack of toxicity of trivalent Cr, at levels that are on a per kg basis, several thousand times the upper limit of the estimated safe and adequate daily dietary intake for humans. Animals consuming the picolinate supplemented diets had several-fold higher Cr concentrations in both the liver and kidney than those fed Cr chloride.

Dietary Chromium Intake Freely Chosen Diets, Institutional Diets, and Individual Foods

Chromium content of 22 daily diets, designed by nutritionists to be well-balanced, ranged from 8.4 to 23.7 μg/1000 cal with a mean ±SEM chromium content of 13.4±1.1 μg/1000 cal. Most dairy products are low in chromium and provide <0.6μg/serving. Meats, poultry, and fish are also low in chromium, providing 2 μg of chromium or less per serving. Chromium contents of grain products, fruits, and vegetables vary widely, with some foods providing >20 μg/serving. In summary, chromium content of individual foods varies, and is dependent upon chromium introduced in the growing, transport, processing, and fortification of the food. Even well-balanced diets may contain suboptimal levels of dietary chromium.

Dietary chromium effects on tissue chromium concentrations and chromium absorption in rats

Chromium (Cr) absorption is low (<1%) and there is a need to find Cr compounds that are absorbed better than inorganic Cr salts. Therefore, the incorporation of nine different chromium (Cr) compounds on tissue Cr concentration of 6-week male Wistar rats was investigated. Chromium compounds tested were Cr chloride (Cr chloride), Cr acetate (Cr acetate), Cr potassium sulfate (CrAlum), Cr trihistidine (Cr histidine), Cr triglycine (Cr glycine), Cr trinicotinic acid (CrNA), Cr dinicotinic acid dihistidine (CrNA-HIS), Cr tripicolinic acid (Cr picolinate), and Cr dinicotinic acid diglycine cysteine glutamic acid (CrNA-AA). Complexes were fed to weanling rats for 3 weeks at 5,000 ng of Cr/g of diet. Basal control diet was a cornstarch-based diet containing 30 ng Cr/g. Chromium incorporation into the kidney was greatest for CrNA-AA complex (850 ng/g dry wt) followed by CrAlum (407 ng/g), Cr acetate (397), CrNA-HIS (394), Cr picolinate (368), Cr glycine (343), Cr nicotinate (166), Cr chloride (74), CrHIS (49), and control (23 ng/g). Chromium concentration of the liver was greatest for the Cr picolinate compound (50 ng/g) followed by CrNA-AA and Cr acetate. Liver Cr concentrations of remaining complexes were not significantly different from those of the control animals that received no added Cr. Chromium concentrations were significantly greater in the kidney than those for the liver, spleen, heart, lungs, and gastrocnemius muscle. Supplemental Cr did not affect tissue zinc and copper but did alter tissue iron concentrations. Absorption of radioactive forms of Cr did not explain the differences in tissue Cr concentrations. Chromium absorption after 4 hours and retention after 24 hours were not significantly different for the forms of Cr tested. These data demonstrate that Cr concentrations are greatest in the kidney and that the form of dietary Cr significantly affects tissue Cr concentrations. Absorption of Cr does not correlate with tissue Cr concentrations and blood Cr is not in equilibrium with tissue Cr stores.

Insulin potentiating factor and chromium content of selected foods and spices

An unidentified factor that potentiates the action of insulin in glucose metabolism was investigated in selected foods and spices. Chromium content of these foods and spices was also determined. Foods and spices were extracted with 0.1N NH4OH (1∶20, w/v) and the supernatants assayed for insulin potentiation activity in the rat epididymal fat cell assay (see ref.6). Among the selected foods, tuna fish, peanut butter, and vanilla ice cream had some insulin potentiating activity. Among the spices, apple pie spice, cinnamon, cloves, bay leaves, and turmeric potentiated insulin activity more than three-fold. Chromium concentration of foods ranged from 1 to 145 ng/g, and spices ranged from 4 to 1818 ng/g. Insulin potentiating activity of foods and spices did not correlate with total chromium. Spices are generally used for flavor and taste in food preparations, but cinnamon, cloves, bay leaves, and turmeric may have an additional role in glucose metabolism.

Chromium supplementation of human subjects: effects on glucose, insulin, and lipid variables

Seventy-six normal, free-living subjects were given supplements of 200 micrograms chromium (Cr) in the form of chromic chloride or a placebo in a double-blind crossover study with 3-month experimental periods. Twenty of the 76 subjects had serum glucose concentrations greater than or equal to 100 mg/dL 90 minutes after a glucose challenge (1 g glucose per kilogram of body weight). Chromium supplementation significantly decreased (P less than 0.05) the 90-minute glucose concentration of these subjects from 135 +/- 9 to 116 +/- 11 mg/dL; fasting glucose concentrations also decreased significantly. The 90-minute serum glucose levels of the 35 subjects with glucose concentrations less than the fasting serum glucose level were increased significantly by Cr supplementation, from 71 +/- 1 to 81 +/- 4 mg/dL. Fasting and 90-minute serum glucose concentrations of the remaining subjects who displayed 90-minute glucose concentrations greater than fasting levels but less than 100 mg/dL were not affected by Cr supplementation. In this study, immunoreactive serum insulin concentration, body weight, lipids, and other selected clinical variables did not change significantly during Cr supplementation. These data demonstrate that Cr supplementation decreases the serum glucose levels of subjects with 90-minute glucose concentrations greater than or equal to 100 mg/dL following a glucose challenge, increases serum glucose levels of subjects with 90-minute glucose concentrations less than fasting levels, and has no effect on the serum glucose levels of subjects with 90-minute glucose values similar to but greater than fasting levels.

Chromium intake and urinary chromium excretion of trauma patients

Glucose metabolism is altered after trauma and those factors that affect glucose metabolism often affect chromium (Cr) metabolism and excretion. To ascertain whether urinary Cr excretion is affected by the elevated serum glucose and other factors associated with trauma, the serum glucose and urinary Cr and Creatinine (Cre) excretion of seven severely traumatized patients were determined. The Cr concentration of intravenous (IV) fluids administered was determined and approximate Cr intake calculated. For all patients, urinary Cr concentration was high in the initial sample collected within 24 h of admission (10.3 ± 2.5 ng/mL, mean ± SEM) and decreased significantly (P < 0.05) by 42 h (2.0 ±0.6 ng/mL). The mean urinary Cr concentration 42 h following admission was 10 times greater than the urinary Cr concentration of normal, healthy subjects (0.2 ± 0.02 ng/mL). There was no significant change in urinary Cre concentration within 42 h of admission, therefore the ratio of urinary Cr to Cre (ng Cr:mg Cre) also decreased. Serum glucose concentration was elevated at admission (170 ± 18 mg/dL, mean ± SD) and decreased to 145 ± 10 mg/dL by 48 h post-admission. The intravenous fluids, dextrose and NaCl, were the lowest in Cr of the samples tested, range 0.02 to 0.20 ng/mL; lactated Ringer’s solution, with or without dextrose, contained 10-20 times more Cr and plasma protein fraction contained approximately 32 ng/mL. The mean calculated Cr intake for the first 24 h postadmission was 37.1 µg/d, significantly greater (P < 0.01) than intake from 24 to 48 h (0.12 µg/d) and 48-72 h (1.63 µg/d). The IV intake of Cr varied for trauma patients depending on fluids required during treatment, but for all patients the relatively high IV Cr intake was rapidly excreted in the urine. These data demonstrate that urinary Cr concentration is elevated several-fold within 24 h of trauma and that Cr contents of intravenous fluids administered in the days immediately following injury vary dramatically. The effects of trauma alone on Cr excretion are difficult to assess because of the variable intake of Cr from IV fluids.

Chromium improves insulin response to glucose in rats

The effects of chromium (Cr) supplementation on insulin secretion and glucose clearance (KG) during intravenous glucose tolerance tests (IVGTTS) were assessed in rats with impaired glucose tolerance due to dietary Cr deficiency. Male Wistar rats were maintained after weaning on a basal low-Cr diet containing 55% sucrose, 15% lard, 25% casein. American Institute of Nutrition (AIN)-recommended levels of vitamins, no added Cr, and an altered mineral content as required to produce Cr deficiency and impaired glucose tolerance. The Cr-supplemented group ([+Cr] n = 6) were provided with 5 ppm Cr as CrCl3 in the drinking water, and the Cr-deficient group ([-Cr]n = 5) received purified drinking water. At 12 weeks on the diet, both groups of rats were hyperinsulinemic (+Cr, 103 +/- 13; -Cr, 59 +/- 12 microU/mL) and normoglycemic (+Cr, 127 +/- 7; -Cr, 130 +/- 4 mg/dL), indicating insulin resistance. After 24 weeks, insulin levels were normal (+Cr, 19 +/- 5; -Cr, 21 +/- 3 microU/mL) and all rats remained normoglycemic (+Cr, 124 +/- 8; -Cr, 131 +/- 6 mg/dL). KG values during IVGTTS were lower in -Cr rats (KG = 3.58%/min) than in +Cr rats (KG = 5.29%/min), correlating with significantly greater 40-minute glucose areas in the -Cr group (P < .01). Comparisons of 40-minute insulin areas indicated marked insulin hyperresponsiveness in the -Cr group, with insulin-secretory responses increased nearly twofold in -Cr animals (P < .05). Chromium deficiency also led to significant decreases in cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (PDE) activity in spleen and testis (P < .01). In these studies, Cr deficiency was characterized by both beta-cell hypersecretion of insulin and tissue insulin resistance that were associated with decreased tissue levels of cAMP PDE activity.

Green tea polyphenols improve cardiac muscle mRNA and protein levels of signal pathways related to insulin and lipid metabolism and inflammation in insulin-resistant rats

Epidemiological studies indicate that the consumption of green tea polyphenols (GTP) may reduce the risk of coronary artery disease. To explore the underlying mechanisms of action at the molecular level, we examined the effects of GTP on the cardiac mRNA and protein levels of genes involved in insulin and lipid metabolism and inflammation. In rats fed a high-fructose diet, supplementation with GTP (200 mg/kg BW daily dissolved in distilled water) for 6 wk, reduced systemic blood glucose, plasma insulin, retinol-binding protein 4, soluble CD36, cholesterol, triglycerides, free fatty acids and LDL-C levels, as well as the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and IL-6. GTP did not affect food intake, bodyweight and heart weight. In the myocardium, GTP also increased the insulin receptor (Ir), insulin receptor substrate 1 and 2 (Irs1 and Irs2), phosphoinositide-3-kinase (Pi3k), v-akt murine thymoma viral oncogene homolog 1 (Akt1), glucose transporter 1 and 4 (Glut1 and Glut4) and glycogen synthase 1 (Gys1) expression but inhibited phosphatase and tensin homolog deleted on chromosome ten (Pten) expression and decreased glycogen synthase kinase 3beta (Gsk3beta) mRNA expression. The sterol regulatory element-binding protein-1c (Srebp1c) mRNA, microsomal triglyceride transfer protein (Mttp) mRNA and protein, Cd36 mRNA and cluster of differentiation 36 protein levels were decreased and peroxisome proliferator-activated receptor (Ppar)gamma mRNA levels were increased. GTP also decreased the inflammatory factors: Tnf, Il1b and Il6 mRNA levels, and enhanced the anti-inflammatory protein, zinc-finger protein, protein and mRNA expression. In summary, consumption of GTP ameliorated the detrimental effects of high-fructose diet on insulin signaling, lipid metabolism and inflammation in the cardiac muscle of rats.