Chromiumiii Diabetes And Insulin Response

Dietary trivalent chromium has been shown to play an important role in type 2 diabetes mellitus, gestational diabetes, steroid-induced diabetes, and glucose tolerance by providing significant beneficial effects on the insulin system, often enhancing insulin sensitivity and overcoming glucose intolerance. The relationship between Cr(III) and its effect on diabetes was determined by Davis and Vincent in 1997 in which chromium has been shown to bind to insulin receptor, thus resulting in the increase of tyrosine protein kinase activity [22].

Numerous clinical researches using dietary Cr(III) demonstrated significant beneficial effects on the insulin system. Anderson et al. in 1997 noted that chromium supplementation may prove to be a useful means to prevent or treat type 2 diabetes mellitus [23]. Several studies demonstrated that animals fed a chromium-deficient diet developed the earliest stage of diabetes, high blood insulin levels, which was reversed by adding chromium-rich foods [15, 24]. Research on epididymal fat tissue from chromium-deficient rats further suggested that chromium action was dependent on insulin. The primary function of chromium is to potentiate the effects of insulin and thereby enhance glucose, amino acid, and fat metabolism [25].

A number of trivalent chromium supplements, at different doses, administered to patients with normal glucose tolerance, diabetes, and gestational diabetes have shown effective results in glucose levels and insulin metabolism. Numerous studies on niacin-bound chromium demonstrated its efficacy on glucose and insulin sensitivity. In a randomized, double-blind, placebo-controlled trial, 15 healthy subjects (5 males, 10 females) were given ~2mg niacin-bound chromium/day for 90 days. The placebo group consisted of 11 subjects (6 males, 5 females). In subjects with relatively high fasting insulin levels at the beginning of the trial (6 subjects, 56 pmol/l), there was a decrease in fasting insulin levels after chromium supplementation (38 pmol/l at 90 days) [26].

In subjects with inadequate Cr(III), long-term glucose control by niacin-bound chromium has been demonstrated to improve altered glucose and lipid metabolism. In a double-blind, clinical investigation, two groups of volunteers received either 300 ^g elemental Cr(III) as niacin-bound chromium or a placebo daily for 3 months. Mean fasting glucose levels were lowered significantly in the niacin-bound chromium supplemented group, while glucose levels remained unchanged in the placebo group. Niacin-bound, chromium-supplemented group also experienced a decrease in mean triglycerides and glycosylated hemoglobin (Hb1Ac), a biomarker for long-term glucose control. In contrast, mean Hb1Ac increased in the placebo group [27].

Research on niacin-bound chromium in combination with exercise training resulted in a lowered insulin response to an oral glucose load. In a study conducted by Grant et al. [28], niacin-bound chromium supplementation (400 ^g elemental chromium/day) was given to young, obese women with or without exercise training. Exercise training combined with niacin-bound chromium supplementation resulted in a lowered insulin response to an oral glucose load as well as significant weight loss [28]. While under identical clinical conditions using chromium picolinate, subjects experienced significant weight gain [28].

Another study on the effects of niacin-bound chromium on GTF activity in humans was determined in a double-blind, randomized clinical fashion. Nineteen male and female volunteers received 300 ^g elemental chromium as niacin-bound chromium for 3 months. Fasting glucose values were significantly lowered in the niacin-bound chromium-supplemented volunteers, while no significant change was observed in the placebo group (Fig. 4). Mean triglyceride levels reduced from 112 to 108mg/dL in niacin-bound chromium-supplemented group. Mean Hb1Ac levels also lowered from 8.42% to 8.10%, while Hb1Ac level increased in the placebo group. No adverse effects were observed [29].

A recent study demonstrated the molecular mechanism of Cr(III) chloride supplementation which increases insulin sensitivity and glycemic control in cultured U937 monocytes. Jain et al. in 2001 demonstrated that CrCl3 inhibits the secretion of TNF-a, a cytokine known to inhibit insulin action and sensitivity. U937 monocytes were cultured in a high glucose medium and treated with and without CrCl3. CrCl3 supplementation prevented the increase in TNF-a levels as well as oxidative stress caused by the high glucose levels in cultured U937 monocytic cells. Similarly, CrCl3 prevented elevated TNF-a secretion and lipid peroxidation levels in H2O2-treated U937 cells [30].

Glucose tolerances in patients treated with niacin-bound chromium

Glucose tolerances in patients treated with niacin-bound chromium

Time (hours)

Fig. 4. Time-dependent effects of niacin-bound chromium supplementation on glucose tolerance in patients.

Time (hours)

Fig. 4. Time-dependent effects of niacin-bound chromium supplementation on glucose tolerance in patients.

In a double-blind, 12-week study, 23 healthy adult men aged 31-60 years received either 200 ^g elemental chromium as CrCl3 in 5 mL water or 5 mL plain water daily 5 days each week. Half the subjects volunteered for glucose tolerance tests with insulin levels. Decreases in insulin and glucose were found in those subjects having normal glucose levels together with elevated insulin levels at baseline. Results suggested that CrCl3 improved insulin sensitivity in subjects with evidence of insulin resistance but normal glucose tolerance [31].

In a similar study, CrCl3 was shown to exhibit significant anti-diabetic potential in chemically induced diabetes in rats thus leading to improved peripheral insulin sensitivity. The effect of 6-week oral administration of CrCl3 on the glucose and lipid metabolism was also studied in streptozotocin diabetic and neonatal-streptozotocin diabetic rats. Treatment with CrCl3 significantly improved the impaired glucose tolerance and insulin sensitivity of both streptozotocin diabetic and neonatal-streptozotocin diabetic rats without any change in basal or glucose-stimulated insulin response indicating insulin-sensitizing action of chromium. CrCl3 treatment also significantly improved deranged lipid metabolism [32].

Various researches on chromium picolinate and its effects on insulin sensitivity and mechanisms of anti-diabetic action were evaluated in various experimental models of diabetes mellitus. Chromium picolinate was shown to significantly decrease glucose of both type 1 and type 2 diabetic rats without any significant change as compared to controls. A significant increase in the composite insulin sensitivity index values of both type 1 and type 2 diabetic rats were also determined. Results demonstrated that chromium picolinate significantly improves deranged carbohydrate and lipid metabolism of experimental, chemically induced diabetes in rats. According to Shindea et al. in 2004, the mechanism of in vivo anti-diabetic action appears to be the peripheral insulin enhancing action of chromium [33].

Cefalu et al. in 1999 indicated that chromium picolinate supplementation can improve insulin sensitivity in clinically obese and pre-diabetic individuals [34]. In a double-blind, placebo-controlled, clinical trial, 29 subjects at risk of developing type 2 diabetes were given either 1000 ^g chromium picolinate per day or placebo for 8 months. The patients who received the chromium picolinate supplements showed a significant increase in insulin sensitivity at 4 and 8 months. Results were seen in the absence of significant changes in body fat distribution, demonstrating that chromium picolinate can beneficially affect insulin sensitivity independent of changes in weight or body fat percentage, therefore yielding a direct influence on muscle insulin action [34]. In a similar study conducted by Anderson et al. in 1997, 180 people being treated for type 2 diabetes supplemented with 200 or 1000 ^g of chromium picolinate or placebo a day. Supplemental chromium demonstrated dramatic effects on glucose and insulin variables in individuals with type 2 diabetes. Significant and sustained reductions in diabetic symptoms were observed in subjects who received 1000 ^g of chromium picolinate a day for 4 months [35]. A similar study by Evans, in 1989, in adult non-insulin-dependent diabetic patients demonstrated an average decrease of 32mg/dL (or 18%) in blood sugar levels and 8mg/dL or 8% decrease in low-density lipoprotein (LDL) following a daily administration of 200 ^g of elemental chromium as chromium picolinate [36].

In another study on elderly diabetic patients, the effects of chromium picolinate on 39 patients within a rehabilitation program were investigated. Along with standard treatment for diabetes, the study group received 200 ^g of elemental chromium twice a day for a 3-week period. Results demonstrated that dietary supplementation with chromium is beneficial in moderating glucose intolerance in elderly, diabetic patients undergoing rehabilitation [37].

Low-molecular-weight organic chromium complexes, such as chromium with phenylalanine, Cr(pa)3, have shown to improve insulin responsiveness and reduce whole body glucose tolerance. This newly synthesized complex of Cr(III) chelated with D-phenylalanine ligand has shown to augment insulin-stimulated glucose-uptake in mouse 3T3-adipocytes. At the molecular level, Cr(pa)3 was shown to enhance insulin-stimulated phosphorylation of Akt in a time- and concentration-dependent manner without altering the phosphorylation of insulin receptor. Oral treatment with Cr(pa)3 (150 ^g elemental Cr/kg body weight/day, for 6 weeks) in ob/ob+/+ obese mice significantly alleviated glucose tolerance compared with untreated obese mice [38].

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