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Life Extension Magazine February 2011
Abstracts

Cinsulin

The Diabetes Prevention Program is a new, 150 million dollar, NIH-sponsored study designed to determine whether non-insulin-dependent diabetes mellitus can be prevented or delayed in persons with impaired glucose tolerance. Four thousand subjects will be randomly assigned to one of four study groups and followed for 4.5 years. Study groups include intensive lifestyle intervention with diet and exercise; metformin (Glucophage) or troglitazone (an investigational drug) with standard diet and exercise; and a control group. Insulin resistance is an important pathogenic factor in impaired glucose tolerance. Trivalent chromium, a dietary supplement that potentiates the action of insulin, was not included in the program. Like metformin and troglitazone, trivalent chromium decreases insulin resistance and has an acceptable side-effect profile; furthermore, it is available at a fraction of their cost. Trivalent chromium should have been included in the Diabetes Prevention Program; it is unfortunate that it was omitted.

Med Hypotheses. 1997 Jul;49(1):47-9

The effects of inorganic chromium and brewer’s yeast supplementation on glucose tolerance, serum lipids and drug dosage in individuals with type 2 diabetes.

OBJECTIVE: To study the effects of supplementation with organic and inorganic chromium on glucose tolerance, serum lipids, and drug dosage in type 2 diabetes patients, in the hope of finding a better and more economical method of control. METHODS: Seventy eight type 2 diabetes patients were divided randomly into two groups and given Brewer’s yeast (23.3ug Cr/day), and CrCl3 (200ug Cr/day) sequentially with placebo in between, in a double blind cross-over design of four stages, each lasting 8 weeks. At the beginning and end of each stage, subjects were weighed, their dietary data and drug dosage recorded, and blood and urine samples were collected for analysis of glucose (fasting and 2 hour post 75g glucose load) fructosamine, triglycerides, total and HDL-cholesterol, and serum and urinary chromium. RESULTS: Both supplements caused a significant decrease in the means of glucose (fasting and 2 hour post glucose load), fructosamine and triglycerides. The means of HDL-cholesterol, and serum and urinary chromium were all increased. The mean drug dosage decreased slightly (and significantly in case of Glibenclamide) after both supplements and some patients no longer required insulin. No change was noted in dietary intakes or Body Mass Index. A higher percentage of subjects responded positively to Brewer’s yeast chromium, which was retained more by the body, with effects on fructosamine, triglycerides, and HDL-cholesterol maintained in some subjects when placebo followed it, and mean urinary chromium remaining significantly higher than zero time mean.CONCLUSION: Chromium supplementation gives better control of glucose and lipid variables while decreasing drug dosage in type 2 diabetes patients. A larger scale study is needed to help decide on the convenient chemical form, and dosage required to achieve optimal response.

Saudi Med J. 2000 Sep;21(9):831-7

Effect of chromium supplementation on glucose tolerance and lipid profile.

OBJECTIVES: To investigate chromium status of the adult population in the western region of Saudi Arabia and the possibility of using serum chromium status measurement as indicator of this status. METHODS: The effect of chromium supplement on glucose tolerance and lipid profile was studied in 44 normal, free living adults. 200mg chromium/day as CrCL3 or a placebo was given in a double blind cross-over study, with 8 weeks experimental periods. Fasting, 1 hour and 2 hour post glucose challenge (75 g of glucose) glucose, serum fructosamine, total cholesterol, high-density lipoprotein-cholesterol, triglycerides, chromium and dietary intakes were estimated at the beginning and the end of each stage.RESULTS: Mean serum chromium increased significantly after supplement (P<.001) indicating proper absorption of the element. Supplement did not effect the total cholesterol, however, the mean high-density lipoprotein-cholesterol level was significantly increased (P<.001), the mean triglycerides levels significantly decreased (P<.001), and the mean fructosamine level significantly decreased (P<.05). In addition, chromium supplement effected 1 hour and 2 hour post glucose challenge glucose levels in subgroups of subjects with 2 hour glucose level > 10% above or below fasting level and significantly differing to it (P<.05 in both cases), by decreasing or increasing them significantly (P<.05 in all cases) so that the 2 hour mean became not significantly different to the fasting mean. Since no significant changes in weight, dietary intake or habits were found, and placebo had no effect, all noted biochemical changes were attributed to chromium. CONCLUSION: Improved glucose control, and lipid profile following chromium supplement suggests the presence of low chromium status in the studied population. However, serum chromium could not be recommended for use as an indicator of chromium status as subjects with widely varying levels responded favorably to the chromium supplement.

Saudi Med J. 2000 Jan;21(1):45-50

Quest for the molecular mechanism of chromium action and its relationship to diabetes.

Despite forty years of research on the potential role of chromium in carbohydrate and lipid metabolism, significant progress has only recently been made regarding the mode of action of chromium at a molecular level. The oligopeptide low-molecular-weight chromium-binding substance (LMWCr) may function as part of a novel insulin-signaling autoamplification mechanism. The proposed mechanism of action also sheds some light on the potential of chromium-containing compounds as nutritional supplements or in the treatment of adult-onset diabetes and other conditions. The potential relationship between the results of recent studies on diabetic patients and the proposed mode of action of LMWCr are discussed.

Nutr Rev. 2000 Mar;58(3 Pt 1):67-72

Glycemic control in patients with type 2 diabetes mellitus with a disease-specific enteral formula: stage II of a randomized, controlled multicenter trial.

BACKGROUND: Stage I of a preplanned 2-stage study has provided good evidence for improved glycemic control with a disease-specific enteral formula low in carbohydrates and high in monounsaturated fatty acids (MUFAs), fish oil, chromium, and antioxidants in insulin-treated type 2 diabetes. The study was continued with stage II to give confirmatory proof of these beneficial effects.

METHODS: 105 patients with HbA1C>or=7.0% and/or fasting blood glucose (FG)>6.7 mmol/L (>120 mg/dL) requiring enteral tube feeding due to neurological dysphagia received 113 kJ (27 kcal)/kg body weight of either test formula (Diben) or an isoenergetic, isonitrogenous standard formula (control) for up to 84 days. Total insulin (TI) requirements, FG, and afternoon blood glucose (AG) were assessed daily. HbA1C and safety criteria were evaluated on days 1, 28, 56, and 84. RESULTS: 55 patients completed the study; on day 84, median changes from baseline (data as available, test vs control) were the following: TI, -8.0 vs +2.0 IU; FG, -2.17 vs -0.67 mmol/L (-39.0 vs -12.1 mg/dL); HbA(1C), -1.30% vs -1.20%; AG, -2.36 vs -0.49 mmol/L (-42.5 vs -8.9 mg/dL). The number of relevant hypoglycemic episodes (FG<3.33 mmol/L<60 mg/dL) was 1 vs 5. Feeding tolerance was comparable in both groups.CONCLUSIONS: Long-term tube feeding with a disease-specific enteral formula was safe and well tolerated in type 2 diabetic patients with neurological disorders. When compared with a standard diet, TI requirement decreased significantly with less hypoglycemia whereas FG and AG were significantly lowered, resulting in improved glycemic control.

JPEN J Parenter Enteral Nutr. 2009 Jan-Feb;33(1):37-49

Chromium as adjunctive treatment for type 2 diabetes.

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.

Ann Pharmacother. 2003 Jun;37(6):876-85

Characterization of the metabolic and physiologic response to chromium supplementation in subjects with type 2 diabetes mellitus.

The objective of the study was to provide a comprehensive evaluation of chromium (Cr) supplementation on metabolic parameters in a cohort of type 2 diabetes mellitus subjects representing a wide phenotype range and to evaluate changes in “responders” and “nonresponders.” After preintervention testing to assess glycemia, insulin sensitivity (assessed by euglycemic clamps), Cr status, and body composition, subjects were randomized in a double-blind fashion to placebo or 1000 microg Cr. A substudy was performed to evaluate 24-hour energy balance/substrate oxidation and myocellular/intrahepatic lipid content. There was not a consistent effect of Cr supplementation to improve insulin action across all phenotypes. Insulin sensitivity was negatively correlated to soleus and tibialis muscle intramyocellular lipids and intrahepatic lipid content. Myocellular lipids were significantly lower in subjects randomized to Cr. At preintervention, responders, defined as insulin sensitivity change from baseline of at least 10% or greater, had significantly lower insulin sensitivity and higher fasting glucose and A(1c) when compared with placebo and nonresponders, that is, insulin sensitivity change from baseline of less than 10%. Clinical response was significantly correlated (P < .001) to the baseline insulin sensitivity, fasting glucose, and A(1c). There was no difference in Cr status between responder and nonresponders. Clinical response to Cr is more likely in insulin-resistant subjects who have more elevated fasting glucose and A(1c) levels. Chromium may reduce myocellular lipids and enhance insulin sensitivity in subjects with type 2 diabetes mellitus who do respond clinically independent of effects on weight or hepatic glucose production. Thus, modulation of lipid metabolism by Cr in peripheral tissues may represent a novel mechanism of action.

Metabolism. 2010 May;59(5):755-62

Effects of acute chromium supplementation on postprandial metabolism in healthy young men.

BACKGROUND: Chromium (Cr) potentiates the action of insulin in the cell and improves glucose tolerance after long-term supplementation. OBJECTIVE: We hypothesized that Cr may also have acute effects and might be beneficial in lowering the glycemic index of a meal. METHODS: We studied the effects of short-term Cr supplementation using a randomized crossover design. Thirteen apparently healthy, non-smoking young men of normal body mass index performed three trials each separated by one week. Test meals, providing 75 g of available carbohydrates, consisted of white bread with added Cr (400 or 800 microg as Cr picolinate) or placebo. RESULTS: After addition of 400 and 800 microg Cr incremental area under the curve (AUC) for capillary glucose was 23% (p = 0.053) and 20% (p = 0.054), respectively, lower than after the white bread meal. These differences reached significance if the subjects were divided into responders (n = 10) and non-responders (n = 3). For the responders AUC after 400 and 800 microg Cr was reduced by 36% and 30%, respectively (Placebo 175 +/- 22, Cr400 111 +/- 14 (p < 0.01), Cr800 122 +/- 15 mmol. min/L (p < 0.01)). Glycemia was unchanged after addition of Cr in the non-responders. Responders and non-responders differed significantly in their nutrient intake and eating pattern, and total serum iron concentration tended to be lower in the responder group (p = 0.07).CONCLUSIONS: Acute chromium supplementation showed an effect on postprandial glucose metabolism in most but not all subjects. The response to Cr may be influenced by dietary patterns.

J Am Coll Nutr. 2004 Aug;23(4):351-7

Trivalent chromium inhibits protein glycosylation and lipid peroxidation in high glucose-treated erythrocytes.

Epidemiological studies have shown lower levels of chromium among men with diabetes and cardiovascular disease (CVD) compared with healthy control subjects. The mechanism by which chromium may decrease the incidence of CVD and insulin resistance is not known. Using erythrocytes as a model, this study demonstrates that chromium inhibits the glycosylation of proteins and oxidative stress, both risk factors in the development of CVD. Erythrocytes were treated with high levels of glucose (mimicking diabetes) in the presence or absence of chromium chloride in the medium at 37 degrees C for 24 hours. Chromium supplementation prevented the increases in protein glycosylation and oxidative stress caused by the high levels of glucose in erythrocytes. This study demonstrates for the first time that chromium supplementation inhibits protein glycosylation in erythrocytes exposed to high glucose medium, which appears to be mediated by its antioxidative effect. This provides evidence for a novel mechanism by which chromium supplementation may decrease incidence of CVD in diabetic patients.

Antioxid Redox Signal. 2006 Jan-Feb;

8(1-2):238-41

Chromium (III)-ion enhances the utilization of glucose in type-2 diabetes mellitus.

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.

Orv Hetil. 2003 Oct 19;144(42):2073-6

Cinnamon and health.

Cinnamon has been used as a spice and as traditional herbal medicine for centuries. The available in vitro and animal in vivo evidence suggests that cinnamon has anti-inflammatory, antimicrobial, antioxidant, antitumor, cardiovascular, cholesterol-lowering, and immunomodulatory effects. In vitro studies have demonstrated that cinnamon may act as an insulin mimetic, to potentiate insulin activity or to stimulate cellular glucose metabolism. Furthermore, animal studies have demonstrated strong hypoglycemic properties. However, there are only very few well-controlled clinical studies, a fact that limits the conclusions that can be made about the potential health benefits of cinnamon for free-living humans. The use of cinnamon as an adjunct to the treatment of type 2 diabetes mellitus is the most promising area, but further research is needed before definitive recommendations can be made.

Crit Rev Food Sci Nutr. 2010 Oct;50(9):822-34

Cinnamon extract regulates plasma levels of adipose-derived factors and expression of multiple genes related to carbohydrate metabolism and lipogenesis in adipose tissue of fructose-fed rats.

We reported earlier that dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we have examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molecular mechanisms of CE in epididymal adipose tissue (EAT). In Wistar rats fed a high-fructose diet (HFD) to induce insulin resistance, supplementation with a CE (Cinnulin PF, 50 mg/kg daily) for 8 weeks reduced blood glucose, plasma insulin, triglycerides, total cholesterol, chylomicron-apoB48, VLDL-apoB100, and soluble CD36. CE also inhibited plasma retinol binding protein 4 (RBP4) and fatty acid binding protein 4 (FABP4) levels. CE-induced increases in plasma adiponectin were not significant. CE did not affect food intake, bodyweight, and EAT weight. In EAT, there were increases in the insulin receptor ( IR) and IR substrate 2 ( IRS2) mRNA, but CE-induced increases in mRNA expression of IRS1, phosphoinositide-3-kinase, AKT1, glucose transporters 1 and 4 , and glycogen synthase 1 expression and decreased trends in mRNA expression of glycogen synthase kinase 3beta were not statistically significant. CE also enhanced the mRNA levels of ADIPOQ, and inhibited sterol regulatory element binding protein-1c mRNA levels. mRNA and protein levels of fatty acid synthase and FABP4 were inhibited by CE and RBP4, and CD36 protein levels were also decreased by CE. These results suggest that CE effectively ameliorates circulating levels of adipokines partially mediated via regulation of the expression of multiple genes involved in insulin sensitivity and lipogenesis in the EAT.

Horm Metab Res. 2010 Mar;42(3):187-93