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Results of RCT on the use of varying forms of chromium for glucose and insulin regulation in healthy subjects and in individuals with glucose intolerance or type 2 diabetes have produced contradictory results (Althuis et al 2002, Frauchiger et al 2004, Gunton et al 2005). Overall, it appears that positive results are more likely in persons with known glycaemic aberrations rather than in healthy subjects; however, the response to chromium is difficult to predict.

Although it is uncertain why this is the case, the varying responses of glucose and lipid regulation may be partly explained by variations in pretreatment chromium and iron status, and phenotypic characteristics of the studied individuals. Type 2 diabetes mellitus (non-insulin-dependent) Results have shown that chromium supplementation appears to be more effective in patients with type 2 diabetes than type 1 (Ravina & Slezack 1993). A 2003 review determined that 'chromium appears to be a safe supplement and may have a role as adjunctive therapy for treatment of type 2 diabetes' (Ryan et al 2003).

Patients with early-stage type 2 diabetes of less than 2 years' duration were found to have lower chromium plasma levels (33%) and increased chromium excretion (100%) compared with healthy controls. Over a period of time this may contribute to the development of the insulin resistance seen in these patients (Morris et al 1999).

The most promising RCT to date tested chromium picolinate at doses of both 200 and 1000^g/day in subjects with type 2 diabetes who were instructed to maintain their current medications, diet and lifestyle habits. HbA1cvalues (a marker of long-term glycaemic control) improved significantly in the higher treatment group after 2 months and in both groups after 4 months' treatment. Fasting glucose was lower in the 1000¡jg group after 2 and 4 months (4-month values: 7.1 ± 0.2 mmol/L vs placebo 8.8 ± 0.3 mmol/L). Two-hour glucose values were also significantly lower in the 1000¡jg group after both 2 and 4 months (4-month values: 10.5 ± 0.2 mmol/L vs placebo 12.3 ± 0.4 mmol/L). Fasting and 2-hour insulin values decreased significantly in both groups receiving supplemental chromium after 2 and 4 months. Plasma total cholesterol also decreased in the subjects receiving 1000 ¡jg chromium after 4 months (Anderson et al 1997). A double-blind, placebo-controlled crossover study using 400¡jg for 12 weeks in diabetics known to have lower serum chromium levels than the healthy controls (Ghosh et al 2002) produced positive results, but a shorter randomised, double-blind placebo-controlled study using 1000 ¡jg for only 8 weeks was not positive (Amato et al 2000). These results not only suggest that improvements are dose-related but are also affected by treatment duration and Chromium 250

possibly initial chromium status. A controlled trial of elderly patients with diabetes

(average age 73 years) reported that supplementation with chromium (200/jg twice daily) for 3 weeks improved fasting blood glucose, HbA1c, and total cholesterol levels (Rabinovitz et al 2004), suggesting lower doses may be effective in older patients.

Studies using chromium nicotinic acid have proven more promising with higher doses of nicotinic acid (100 mg/day) (Urberg & Zemel 1987) than those with low-dose nicotinic acid (1.8 mg) (Thomas & Gropper 1996), demonstrating a synergistic effect with chromium (200^g/day).

Type 1 diabetes mellitus (insulin-dependent) As chromium appears to improve insulin sensitivity rather than secretion its use in type 1 diabetes is probably limited (Edmondson 2002). One study did show reduced requirements for medication in 33.6% of patients with type 1 diabetes taking 200 fjg chromium/day (Ravina & Slezack 1993), and another showed a 30% reduction in insulin requirements in 71% of subjects at the same dose (Ravina et al 1995), but as yet it is unclear which patients might respond to treatment.

Gestational diabetes Pregnancy can be described as an increased insulin resistance state, which may result in gestational diabetes if the pancreas is unable to increase insulin levels to maintain blood glucose balance (Jovanovic & Peterson 1996). As such, the beneficial effect of chromium on insulin sensitivity provides a theoretical basis for its use in this condition. A small placebo-controlled trial using 4 or 8/jg/kg of chromium daily in gestational diabetes found a significant dose-dependent improvement in fasting insulin, 1 -hour insulin and glucose, and postprandial glucose levels after 8 weeks' supplementation (Jovanovic et al 1999).

Corticosteroid-induced diabetes mellitus Human trials have shown that corticosteroid use significantly increases urinary chromium excretion. Supplementation with chromium picolinate (equivalent to 600/jg chromium/day) in patients experiencing steroid-induced diabetes resulted in decreased fasting blood glucose values (from > 13.9 mmol/L to < 8.3 mmol/L). Furthermore, hypoglycaemic medications were also reduced by 50% in all patients within 1 week (Ravina et al 1999). Prevention of long-term diabetic complications Both QTc interval prolongation and chronic hyperinsulinaemia have been associated with atherosclerosis progression and increased cardiovascular morbidity in patients with type 2 diabetes. In a crossover trial of 60 subjects, chromium picolinate (1000 fjg/day) for 3 months was shown to reduce both QTc interval duration and plasma insulin levels (Vrtovec et al 2005), probably by reducing the adrenergic activation of the sympathetic nervous system due to hyperinsulinaemia. Benefits were most significant in obese patients with higher peripheral insulin resistance (Vrtovec et al 2005).

Animal studies have found that chromium supplementation in mice with type 2 diabetes reduces the symptoms of hyperglycaemia and improves the renal function by recovering renal chromium concentration (Mita et al 2005, Mozaffari et al 2005) which may hold promise for human trials investigating the potential role of chromium in reducing the incidence of diabetic nephropathy.

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