The Relationship Between Chromium And Type 2 Diabetes Mellitus And Metabolic Syndrome

Diabetes and metabolic syndrome have become major national public health problems.Chromium is a putative essential micronutrient,involving in the glucose and lipid metabolism.In recent years,chromium has gained popularity as a nutritional supplement for especially diabetic and insulin-resistant subjects,but its role in the prevention and management of type 2 diabetes mellitus（T2DM）and dyslipidemia has not yet been established.Clinical trials on chromium supplements have not come to a consistent conclusion.The effect and safety of chromium need further verification.At present,the epidemiological study of chromium and diabetes,metabolic syndrome and other chronic metabolic diseases is sparse.Meanwhile,due to the low content of chromium in the human body,it is difficult to detect the accurate concentration of chromium by traditional detection methods.On the other hand,oxidative stress is closely related to diabetes and other chronic metabolic diseases,and studies have found that chromium could alleviate oxidative stress.However,there is lack of human study on chromium and oxidative stress.Thus,in this study we conducted a case-control study of large sample population,using inductively coupled plasma mass spectrometry to detect plasma chromium concentration.We aim to examine the association of plasma chromium levels with T2DM and metabolic syndrome,and further assess the dose-response relationship.We also aim to explore the role of chromium in insulin resistance,blood lipid metabolism,and oxidative stress.Furthermore,we conducted cell experiments to explore the effect of different chromium compounds on glucose uptake。This study would be helpful for the recommendation of dietary chromium intake in our country,and prevention and the adjuvant therapy for type 2 diabetes and metabolic syndrome.Section 1:The Association of Plasma Chromium and Type 2 Diabetes MellitusObjective:We aim to examine the association of plasma chromium levels with T2DM and pre-diabetes,and further assess the dose-response relationship.We also aim to explore the role of chromium in insulin resistance,lipid metabolism,and oxidative stress.Methods:We conducted a case-control study.Participants were consecutively recruited from first-time patients attending the outpatient clinics of the Department of Endocrinology,Tongji Medical College Hospital,from January 2009 to December 2015.2060 newly diagnosed T2DM,651 pre-diabetes,and 2310 healthy people were recruited.The controls were frequency-matched with T2DM by age and sex.Demographic,health status,and lifestyle data were obtained from the questionnaires.Blood samples were collected in all participants and fast plasma glucose,insulin,lipid profile,and MDA concentrations were detected.Plasma chromium was measured by inductively coupled plasma mass spectrometry.Result:Plasma chromium levels were lower in the newly diagnosed T2DM and pre-diabetes groups than in the control group（median:3.77 μg/L,3.64 μg/L,3.98 μg/L,respectively,P<0.001）.After adjustment for potential confounding factors including age,sex,BMI,current smoking status,current drinking status,family history of diabetes,hypertension,plasma magnesium,and selenium levels,the odds ratios（95%confidence intervals）for T2DM across increasing quartiles of plasma chromium levels were 1（referent）,0.91（0.75-1.11）,0.87（0.71-1.06）,0.72（0.58-0.89）,respectively（P for trend<0.001）.The corresponding odds ratios（95%confidence interval）for pre-DM were 1（referent）,0.73（0.56-0.95）,0.73（0.56-0.95）,0.61（0.44-0.83）,respectively（P for trend<0.001）.The risk of type 2 diabetes and pre-diabetes reduced by 5%and 8%with per 1μg/L increase of plasma chromium levels,respectively.A positive linear dose-response relationship for T2DM was evident in the restricted cubic spline regression model.Furthermore,Pearson correlation analysis showed a significant and inverse correlation of log-transformed chromium concentrations with fasting glucose（partial coefficient ＝-0.142）in the control group.The MDA concentrations increased first and then declined along with the chromium levels.Conclusions:Our results indicated that plasma chromium concentrations were inversely associated with T2DM and pre-diabetes in Chinese adults.Section 2:The Association of Plasma Chromium and Metabolic SyndromeObjective:We aim to investigate the association of plasma chromium levels with metabolic syndrome,and association of plasma chromium levels with central obesity,dyslipidemia and hypertension.Methods:We conducted a case-control study.The participants were consecutively recruited from patients attending the outpatient clinics of the Department of Endocrinology,Tongji Medical College Hospital,from January 2009 to December 2015.783 individuals with metabolic syndrome and 1347 healthy people were recruited.The controls were frequency-matched with T2DM by age and sex.Demographic,health status,and lifestyle data were obtained from the questionnaires.Anthropometric data including height,mass,waistline,hipline and blood pressure were measured.Blood samples were collected in all participants and fast plasma glucose,insulin,lipid profile,and MDA concentrations were detected.Plasma chromium was measured by inductively coupled plasma mass spectrometry.Result:Plasma chromium levels in individuals with metabolic syndrome and the control group were 3.66（2.89-4.56）μg/L and 3.76（2.72-4.71）μg/L,with no significant difference.The plasma chromium levels in central obesity,dyslipidemia and hypertension population with controls were not significant different.After adjustment for potential confounding factors including age,sex,BMI,current smoking status,current drinking status,family history of diabetes,and physical activity,the odds ratios（95%confidence intervals）for T2DM across increasing thirtiles of plasma chromium levels were 1（referent）,1.04（0.81-1.33）,0.86（0.66-1.11）,respectively.After sensitivity analysis excluding type 2 diabetes population,the results were consistant.The odds ratios（95%confidence intervals）for central obesity across increasing thirtiles of plasma chromium levels were 1（referent）,0.90（0.71-1.14）,0.84（0.66-1.07）,respectively.The odds ratios（95%confidence intervals）for dyslipidemia across increasing thirtiles of plasma chromium levels were 1（referent）,1.02（0.80-1.31）,0.97（0.76-1.24）,respectively.The odds ratios（95%confidence intervals）for hypertension across increasing thirtiles of plasma chromium levels were 1（referent）,1.07（0.91-1.27）,1.18（0.99-1.42）respectively.Conclusions:Our results indicated that there was no association between plasma chromium and metabolic syndrome,and there was no association between plasma chromium and central obesity,dyslipidemia and hypertension.Section 3:Effects of Different Forms of Chromium Compounds on Glucose Uptake in C2C12 Skeletal Muscle CellsObjective:To explore the effect of different forms of chromium compounds on glucose uptake in skeletal muscle cells,and to explore the effect on oxidative stress in cells.Methods:We use C2C12 skeletal muscle cells.Different concentrations of chromium chloride（CrCl3）,chromium picolinate（CrPic）and sodium chromate（NaaCrO4）were used for 4h,8h,12h,24h and 48h,then cell viability was measured using CCK-8 kit.The ’cells were treated with CrC13,CrPic and Na₂CrO₄ at appropriate concentration and intervention time,and insulin-stimulated glucose uptake experiments were performed using fluorescently labeled glucose analog 2-NBDG.In addition,the effects of chromium compounds on the levels of MDA,SOD and GSH were measured.Result:When intervened at 100 nM 12 h,50 nM 8 h,50 nM 24 h,respectively,with CrCl3,CrPic and Na₂CrO₄,the highest cell viability was observed.Insulin-stimulated glucose uptake was significantly increased,compared to the control group.Both CrCl3 and CrPic can promote insulin-stimulated glucose uptake,while the promotion effect of CrPic is stronger.Na₂CrO₄ was observed not promoting insulin-stimulated glucose uptake.CrCl3 and Na₂CrO₄ increased the contents of MDA and GSH,and SOD activity.CrPic increased the content of GSH,but there was no significant increase in MDA and SOD.Conclusions:CrCl3 and CrPic can promote insulin-stimulated glucose uptake,while Na₂CrO₄ cannot.CrCl3 and Na₂CrO₄ can increase the level of lipid peroxidation,but may also enhance the antioxidant capacity.CrPic may enhance the antioxidant capacity,while not cause increased oxidative stress levels.