title: Novel Risk Factors and the Prediction of Type 2 Diabetes in the Atherosclerosis Risk in Communities (ARIC) Study The Effect of Magnesium Supplementation in Increasing Doses on the Control of Type 2 Diabetes Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Oral magnesium supplementation in insulin-requiring Type 2 diabetic patients. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Daily magnesium supplements improve glucose handling in elderly subjects. Oral magnesium supplementation decreases C-reactive protein levels in subjects with prediabetes and hypomagnesemia: a clinical randomized double-blind placebo-controlled trial. Oral magnesium supplementation improves glycaemic status in subjects with prediabetes and hypomagnesaemia: A double-blind placebo-controlled randomized trial. Effect of oral magnesium supplementation on selected cardiovascular risk factors in non-insulin-dependent diabetics. Magnesium improves the beta-cell function to compensate variation of insulin sensitivity: double-blind, randomized clinical trial. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. Effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus. Improved Insulin Response and Action by Chronic Magnesium Administration in Aged NIDDM Subjects Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type II) diabetic patients. Effects of extended-release niacin with laropiprant in high-risk patients. The effect of lowering blood pressure by magnesium supplementation in diabetic hypertensive adults with low serum magnesium levels: a randomized, double-blind, placebo-controlled clinical trial Oral magnesium supplementation in type II diabetic patients Effects of oral magnesium supplementation on insulin sensitivity and blood pressure in normo-magnesemic nondiabetic overweight Korean adults. Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial. Hypomagnesemia in Type II Diabetes: Effect of a 3-Month Replacement Therapy Magnesium and ascorbic acid supplementation in diabetes mellitus.
abstract: OBJECTIVE The objective of this study was to determine potential added value of novel risk factors in predicting the development of  type 2 diabetes  beyond that provided by st and ard clinical risk factors . RESEARCH DESIGN AND METHODS The Atherosclerosis Risk in Communities ( ARIC ) Study is a population -based prospect i ve cohort study in four U.S. communities . Novel risk factors were either measured in the full cohort or in a case-control sample nested within the cohort . We started with a basic prediction model , previously vali date d in ARIC , and evaluated 35 novel risk factors by adding them independently to the basic model . The area under the curve ( AUC ) , net reclassification index ( NRI ) , and integrated discrimination index ( IDI ) were calculated to determine if each of the novel risk factors improved risk prediction . RESULTS There were 1,457 incident cases of diabetes with a mean of > 7.6 years of follow-up among 12,277 participants at risk . None of the novel risk factors significantly improved the AUC . Forced expiratory volume in 1 s was the only novel risk factor that result ed in a significant NRI ( 0.54 % ; 95 % CI : 0.33–0.86 % ) . Adiponectin , leptin , γ-glutamyl transferase , ferritin , intercellular adhesion molecule 1 , complement C3 , white blood cell count , albumin , activated partial thromboplastin time , factor VIII , magnesium , hip circumference , heart rate , and a genetic risk score each significantly improved the IDI , but net changes were small . CONCLUSIONS Evaluation of a large panel of novel risk factors for type 2 diabetes indicated only small improvements in risk prediction , which are unlikely to meaningfully alter clinical risk reclassification or discrimination strategies OBJECTIVE Hypomagnesemia occurs in 25–38 % of patients with type 2 diabetes . Several studies have suggested an association between magnesium ( Mg ) depletion and insulin resistance and /or reduction of insulin secretion in these cases . Our purpose was to evaluate if Mg supplementation ( as magnesium oxide [ MgO ] ) would improve metabolic control in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We studied 128 patients with type 2 diabetes ( 32 men , 96 women , aged 30–69 years ) , treated by diet or diet plus oral antidiabetic drugs , in the Bahia Federal University Hospital , Brazil . Patients at risk for hypomagnesemia or with reduced renal function were excluded . This study was a clinical r and omized double-blind placebo-controlled trial . Patients received either placebo , 20.7 mmol MgO , or 41.4 mmol MgO daily(elementary Mg ) for 30 days . Mg concentrations were measured in plasma , in mononuclear cells , and in 24-h urine sample s. Fasting blood glucose , HbA1 , and fructosamine were used as parameters of metabolic control . RESULTS Of the patients , 47.7 % had low plasma Mg , and 31.1 % had low intramononuclear Mg levels . Intracellular Mg in patients with diabetes was significantly lower than in the normal population ( 62 blood donors ; 1.4 ± 0.6 vs. 1.7 ± 0.6 μg/mg of total proteins ) . No correlation was found between plasma and intracellular Mg concentrations ( r = −0.179 ; P = 0.15 ) or between Mg concentrations and glycemic control ( r = −0.165 ; P = 0.12 ) . Intracellular Mg levels were lower in patients with peripheral neuropathy than in those without ( 1.2 ± 0.5 vs. 1.5 ± 0.6 μg/mg ) . Similar findings were observed in patients with coronary disease ( 1.0 ± 0.5 vs. 1.5 ± 0.6 μg/mg ) . In the placebo and in the 20.7 mmol Mg groups , neither a change in plasma and intracellular levels nor an improvement in glycemic control were observed . Replacement with 41.4 mmol Mg tended to increase plasma , cellular , and urine Mg and caused a significant fall ( 4.1 ± 0.8 to 3.8 ± 0.7 mmol/1 ) in fructosamine ( normal , 1.87–2.87 mmol/1 ) . CONCLUSIONS Mg depletion is common in poorly controlled patients with type 2 diabetes , especially in those with neuropathy or coronary disease . More prolonged use of Mg in doses that are higher than usual is needed toestablish its routine or selective administration in patients with type 2 diabetes to improve control or prevent chronic complications Literature data on the bioavailability of various Mg forms provide scarce information on the best Mg salt to be used in animal and human supplementation . This study aim ed to investigate the bioavailability of different forms of Mg in rats using Mg stable isotopes . Eighty male Wistar rats aged 6 weeks were fed a semi-purified Mg-depleted diet for three weeks . The rats were then r and omised into ten groups and received , for two more weeks , the same diet repleted with Mg ( 550 mg Mg/kg ) as : oxide , chloride , sulphate , carbonate , acetate , pidolate , citrate , gluconate , lactate or aspartate . After 10 days of Mg-repleted diet , the rats received orally 1.8 mg of an enriched 26Mg . Faeces and urine were then collected for 4 consecutive days . Isotope ratios in faeces and urine were determined . The Mg absorption values obtained varied from 50 % to 67 % . Organic Mg salts were slightly more available than inorganic Mg salts . Mg gluconate exhibited the highest Mg bioavailability of the ten Mg salts studied . Urinary 26Mg excretion varied from 0.20 mg to 0.33 mg , and feeding with the organic pidolate , citrate , gluconate and aspartate salts result ed in higher urinary 26Mg excretion than with inorganic salts . Ultimately , 26Mg retention was higher in the rats receiving the organic salts such as gluconate , lactate and aspartate than in those receiving the inorganic salts . Taken together , these results indicate that 26Mg is sufficiently bioavailable from the ten different Mg salts studied in the present experiment , although Mg gluconate exhibited the highest bioavailability under these experimental conditions Oral magnesium ( Mg ) supplementation can improve insulin sensitivity and secretion in patients with Type 2 diabetes mellitus ( DM ) . We studied the effect of Mg supplementation on glycaemic control , blood pressure , and plasma lipids in insulin-requiring patients with Type 2 DM . Fifty moderately controlled patients were r and omized to 15 mmol Mg or placebo daily for 3 months . Plasma Mg , glucose , HbA1c , lipids , erythrocyte Mg , Mg and glucose concentrations in 24-h urine , and systolic and diastolic pressure were measured before and after 3 months treatment . Plasma Mg concentration was higher after supplementation than after placebo ( 0.82 + /- 0.07 vs 0.78 + /- 0.08 mmol l(-1 ) , p < 0.05 ) , as was Mg excretion ( 5.5 + /- 1.9 vs 3.7 + /- 1.4 mmol 24 h(-1 ) , p = 0.004 ) but erythrocyte Mg concentrations were similar . No significant differences were found in glycaemic control ( glucose : 10.7 + /- 3.8 vs 11.6 + /- 6.2 mmol l(-1 ) , p = 0.8 ; HbA1c : 8.9 + /- 1.6 vs 9.1 + /- 1.2 % , p = 0.8 ) , lipids or blood pressure . On-treatment analysis ( 34 patients : 18 on Mg , 16 on placebo ) yielded similar results . An increase in plasma Mg concentration irrespective of medication was associated with a tendency to a decrease in diastolic pressure ( increased plasma Mg vs no increase : -4.0 + /- 10.1 vs + 2.5 + /- 12.0 mmHg , p = 0.059 ) . Three months ' oral Mg supplementation of insulin-requiring patients with Type 2 DM increased plasma Mg concentration and urinary Mg excretion but had no effect on glycaemic control or plasma lipid concentrations To evaluate the efficacy and safety of oral magnesium supplementation , with magnesium chloride ( MgCl2 ) , in the treatment of newly diagnosed depression in the elderly with type 2 diabetes and hypomagnesemia . Twenty-three elderly patients with type 2 diabetes and hypomagnesemia were enrolled and r and omly allocated to receive either 50 mL of MgCl2 5 % solution equivalent to 450 mg of elemental magnesium or Imipramine 50 mg daily during 12 weeks . Widowhood or divorce in the last six months , alcoholism , degenerative illnesses of the nervous central system , recent diagnosis of diabetes , previous or current treatment with antidepressants , chronic diarrhea , use of diuretics , and reduced renal function were exclusion criteria . Hypomagnesemia was defined by serum magnesium levels < 1.8 mg/dL and depression by Yasavage and Brink score > or = 11 points . The primary trial end point was the improvement of depression symptoms . At baseline , there were no differences by age ( 69 + /- 5.9 and 66.4 + /- 6.1 years , p = 0.39 ) , duration of diabetes ( 11.8 + /- 7.9 and 8.6 + /- 5.7 years , p = 0.33 ) , serum magnesium levels ( 1.3 + /- 0.04 and 1.4 + /- 0.04 mg/dL , p = 0.09 ) , and Yasavage and Brink Score ( 17.9 + /- 3.9 and 16.1 + /- 4.5 point , p = 0.34 ) in the groups with MgCl2 and imipramine , respectively . At end of follow-up , there were no significant differences in the Yasavage and Brink score ( 11.4 + /- 3.8 and 10.9 + /- 4.3 , p = 0.27 ) between the groups in study ; whereas serum magnesium levels were significantly higher in the group with MgCl2 ( 2.1 + /- 0.08 mg/dL ) than in the subjects with imipramine ( 1.5 + /- 0.07 mg/dL ) , p < 0.0005 . In conclusion , MgCl2 is as effective in the treatment of depressed elderly type 2 diabetics with hypomagnesemia as imipramine 50 mg daily We demonstrated similar plasma concentrations and urinary losses but lower erythrocyte magnesium concentrations ( 2.18 + /- 0.04 vs 1.86 + /- 0.03 mmol/L , P less than 0.01 ) in twelve aged ( 77.8 + /- 2.1 y ) vs 25 young ( 36.1 + /- 0.4 y ) , nonobese subjects . Subsequently , aged subjects were enrolled in a double-blind , r and omized , crossover study in which placebo ( for 4 wk ) and chronic magnesium administration ( CMA ) ( 4.5 g/d for 4 wk ) were provided . At the end of each treatment period an intravenous glucose tolerance test ( 0.33 g/kg body wt ) and a euglycemic glucose clamp with simultaneous [D-3H]glucose infusion and indirect calorimetry were performed . CMA vs placebo significantly increased erythrocyte magnesium concentration and improved insulin response and action . Net increase in erythrocyte magnesium significantly and positively correlated with the decrease in erythrocyte membrane microviscosity and with the net increase in both insulin secretion and action . In aged patients , correction of a low erythrocyte magnesium concentration may allow an improvement of glucose h and ling BACKGROUND AND AIMS It has been suggested that magnesium deficiency is associated with the triggering of acute phase response , which may contribute to type 2 diabetes and cardiovascular disease risk . We undertook this study to determine whether oral magnesium supplementation modifies serum levels of high-sensitivity C-reactive protein ( hsCRP ) in apparently healthy subjects with prediabetes and hypomagnesemia . METHODS A total of 62 men and non-pregnant women aged 18 - 65 year , with new diagnosis of prediabetes ( glucose 5.6 < 7.0 mmol/L and /or post-load glucose ≥7.7 < 11.1 mmol/L ) and hypomagnesemia ( serum magnesium levels < 0.74 mmol/L ) were enrolled in a clinical double-blind placebo-controlled trial and r and omly allocated to receive either magnesium chloride ( 30 mL of MgCl2 5 % solution ) or NaHCO3 0.1 % solution , once daily for 3 months . RESULTS At basal conditions , anthropometric and biochemical variables were similarly distributed in both groups . At the end of follow-up , participants who received magnesium chloride showed higher serum magnesium levels ( 0.86 ± 0.08 vs. 0.69 ± 0.16 mmol/L , p = 0.002 ) and lower hsCRP levels ( 4.8 ± 15.2 vs. 17.1 ± 21.0 nmol/L , p = 0.01 ) compared with participants in the control group . CONCLUSIONS Oral magnesium supplementation decreases hsCRP levels in apparently healthy subjects with prediabetes and hypomagnesemia AIM This study evaluated the efficacy of oral magnesium supplementation in the reduction of plasma glucose levels in adults with prediabetes and hypomagnesaemia . METHODS A total of 116 men and non-pregnant women , aged 30 to 65 years with hypomagnesaemia and newly diagnosed with prediabetes , were enrolled into a r and omized double-blind placebo-controlled trial to receive either 30 mL of MgCl2 5 % solution ( equivalent to 382 mg of magnesium ) or an inert placebo solution once daily for four months . The primary trial endpoint was the efficacy of magnesium supplementation in reducing plasma glucose levels . RESULTS At baseline , there were no significant statistical differences in terms of anthropometric and biochemical variables between individuals in the supplement and placebo groups . At the end of follow-up , fasting ( 86.9 ± 7.9 and 98.3 ± 4.6 mg/dL , respectively ; P = 0.004 ) and post-load glucose ( 124.7 ± 33.4 and 136.7 ± 23.9 mg/dL , respectively ; P = 0.03 ) levels , HOMA-IR indices ( 2.85 ± 1.0 and 4.1 ± 2.7 , respectively ; P = 0.04 ) and triglycerides ( 166.4 ± 90.6 and 227.0 ± 89.7 , respectively ; P = 0.009 ) were significantly decreased , whereas HDL cholesterol ( 45.6 ± 10.9 and 46.8 ± 9.2 mg/dL , respectively ; P = 0.04 ) and serum magnesium ( 1.96 ± 0.27 and 1.60 ± 0.26 mg/dL , respectively ; P = 0.005 ) levels were significantly increased in those taking MgCl2 compared with the controls . A total of 34 ( 29.4 % ) people improved their glucose status ( 50.8 % and 7.0 % in the magnesium and placebo groups , respectively ; P < 0.0005 ) . CONCLUSION Our results show that magnesium supplementation reduces plasma glucose levels , and improves the glycaemic status of adults with prediabetes and hypomagnesaemia OBJECTIVE To evaluate the impact of oral magnesium supplementation on risk factors for end-organ disease in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . DESIGN A 16-week r and omized , double-blind , placebo-controlled crossover trial . SETTING Outpatient center of an academic family medicine residency program . PATIENTS Twenty-eight patients ( age range , 28 to 84 years ; 57.1 % black ; 85.7 % women ) with NIDDM controlled by diet and /or an oral hypoglycemic , with a serum cholesterol levels over 5.20 mmol/L ( 200 mg/dL ) . INTERVENTION Following a 2-week placebo run-in period , each patient was r and omized to receive either sustained-release magnesium chloride ( Slo-Mag ) , 384 mg/d , or an identical-appearing placebo for 6 weeks . After a 2-week interim washout period , each patient was then treated with the alternative regimen for an additional 6-week period . MAIN OUTCOME MEASURES The systolic and diastolic blood pressure and levels of serum glucose , low-density and high-density lipoprotein and total cholesterol , triglycerides , and serum and total erythrocyte magnesium were measured at the beginning , midpoint , and end of each 6-week treatment phase . RESULTS Systolic blood pressure fell an average of 7.4 mm Hg ( P < .05 ) with treatment . There was no significant change in diastolic blood pressure or levels of serum glucose , low-density and high-density lipoprotein and total cholesterol , triglycerides , or serum and erythrocyte magnesium . CONCLUSIONS Oral magnesium supplementation in the doses and duration studied is modestly effective in reducing systolic blood pressure in patients with NIDDM but has little impact on other important biochemical parameters related to diabetes-associated end-organ disease BACKGROUND Given that role of magnesium in insulin secretion is uncertain , our objective was to determine whether oral supplementation with magnesium chloride ( MgCl(2 ) ) improves the ability of beta-cells to compensate for variations in insulin sensitivity in non-diabetic individuals with significant hypomagnesaemia . MATERIAL S AND METHODS Eligible individuals were non-diabetic , normo-tensive men and non-diabetic , normo-tensive , non-pregnant women with serum magnesium levels ≤0·70 mM/L ; they were enrolled in a r and omized double-blind clinical trial to receive either 50 mL of 5 % MgCl(2 ) solution or 50 mL of inactive solution daily for 3 months . The primary trial end point was a change in the AUC of the hyperbolic model of beta-cell function ( HMbCF ) derived from the fasting state . Individuals , caregivers and personnel who assessed the outcomes were all blinded to the group assignments . RESULTS A total of 54 and 52 individuals were assigned to the MgCl(2 ) and placebo groups , respectively ; five individuals in the MgCl(2 ) group and four in the placebo group dropped out . There were no serious adverse events or side effects because of MgCl(2 ) or placebo . At the beginning of the study , the AUC of the HMbCF was similar in both groups ( AUC = 7·591 and 7·895 cm(2 ) ) ; at the end of follow-up , the curve of the MgCl(2 ) group showed a hyperbolic distribution ( AUC = 18·855 cm(2 ) ) , whereas in the placebo group , there were no changes ( AUC = 7·631 cm(2 ) ) . CONCLUSIONS MgCl(2 ) 2·5 g daily improves the ability of beta-cells to compensate for variations in insulin sensitivity in non-diabetic individuals with significant hypomagnesaemia BACKGROUND In patients with established cardiovascular disease , residual cardiovascular risk persists despite the achievement of target low-density lipoprotein ( LDL ) cholesterol levels with statin therapy . It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein ( HDL ) cholesterol is superior to simvastatin alone in reducing such residual risk . METHODS We r and omly assigned eligible patients to receive extended-release niacin , 1500 to 2000 mg per day , or matching placebo . All patients received simvastatin , 40 to 80 mg per day , plus ezetimibe , 10 mg per day , if needed , to maintain an LDL cholesterol level of 40 to 80 mg per deciliter ( 1.03 to 2.07 mmol per liter ) . The primary end point was the first event of the composite of death from coronary heart disease , nonfatal myocardial infa rct ion , ischemic stroke , hospitalization for an acute coronary syndrome , or symptom-driven coronary or cerebral revascularization . RESULTS A total of 3414 patients were r and omly assigned to receive niacin ( 1718 ) or placebo ( 1696 ) . The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy . At 2 years , niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter ( 0.91 mmol per liter ) to 42 mg per deciliter ( 1.08 mmol per liter ) , lowered the triglyceride level from 164 mg per deciliter ( 1.85 mmol per liter ) to 122 mg per deciliter ( 1.38 mmol per liter ) , and lowered the LDL cholesterol level from 74 mg per deciliter ( 1.91 mmol per liter ) to 62 mg per deciliter ( 1.60 mmol per liter ) . The primary end point occurred in 282 patients in the niacin group ( 16.4 % ) and in 274 patients in the placebo group ( 16.2 % ) ( hazard ratio , 1.02 ; 95 % confidence interval , 0.87 to 1.21 ; P=0.79 by the log-rank test ) . CONCLUSIONS Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter ( 1.81 mmol per liter ) , there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period , despite significant improvements in HDL cholesterol and triglyceride levels . ( Funded by the National Heart , Lung , and Blood Institute and Abbott Laboratories ; AIM -HIGH Clinical Trials.gov number , NCT00120289 . ) We evaluated the effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus . Twenty-six persons with non-insulin-dependent diabetes mellitus received 4.5 g magnesium pidolate/d for one month , and 17 persons received placebo . Before and at the end of the treatment period cholesterol concentration , triglycerides , LDL cholesterol , HDL cholesterol , and plasma and erythrocyte magnesium were evaluated . Chronic magnesium supplementation produced a significant reduction of plasma cholesterol and LDL cholesterol , and an increase of HDL cholesterol . These results suggest that oral supplementation of magnesium may be useful in the treatment of hyperlipidaemia in patients with non-insulin-dependent diabetes mellitus In eight aged non-insulin-dependent diabetes mellitus ( NIDDM ) subjects , insulin response and action were studied before and after chronic magnesium supplementation ( 2 g/day ) to diet . Chronic magnesium supplementation to diet versus placebo produced 7 ) a significant increase in plasma ( 0.83 ± 0.05 vs. 0.78 ± 0.06 mM , P < .05 ) and erythrocyte ( 2.03 ± 0.06 vs. 1.88 ± 0.09 mM , P < .01 ) magnesium levels , 2 ) an increase in acute insulin response ( AIR ) ( 4.0 ± 0.6 vs. - 1 .6 ± 0.6 mU/L , P < .05 ) to glucose pulse , and 3 ) an increase in glucose infusion rate ( GIR ) ( 3.6 ± 0.6 vs. 2.9 ± 0.5 mg kg∼1 min−1 P < .025 ) calculated in the last 60 min of a euglycemic-hyperinsulinemic ( 100U m2 · min−1 during 180 min ) glucose clamp . Net increase in AIR , glucose disappearance rate after glucose pulse , and GIR were significantly and positively correlated to the net increase in erythrocyte magnesium content calculated after chronic magnesium supplementation to diet . In conclusion , our data suggest that NIDDM subjects may benefit from therapeutic chronic administration of magnesium salts The aim of the present study was to investigate the effects of magnesium supplementation on glucose uptake and substrate oxidation in noninsulin-dependent ( type II ) diabetic patients . Nine elderly non-obese noninsulin-dependent ( type II ) diabetic patients , treated by diet only , participated in the study , which was design ed as r and omized , double blind , and cross-over . Each patient was followed up for a pre study period of 3 weeks before inviting him/her to receive placebo or magnesium supplementation ( 15.8 mmol/day ) for 4 weeks . At the end of each treatment period , a euglycemic hyperinsulinemic glucose clamp with simultaneous D-[3 - 3H]glucose infusion and indirect calorimetry was performed . Magnesium supplementation result ed in significantly increased plasma and erythrocyte magnesium levels , whereas body weight and fasting plasma glucose did not change . In the last 60 min of the glucose clamp , insulin-mediated glucose disappearance , total body glucose disposal ( 24.5 + /- 0.4 vs. 28.2 + /- 0.7 mumol/kg.min ; P < 0.005 ) , and glucose oxidation ( 13.0 + /- 0.4 vs. 16.3 + /- 0.8 mumol/kg.min ; P < 0.01 ) were increased after chronic magnesium supplementation . Endogenous glucose production , nonoxidative glucose disposal , lipid and protein oxidation , and insulin MCR were not affected . In conclusion , a 4-week magnesium supplementation improves insulin sensitivity and glucose oxidation in the course of a euglycemic-hyperinsulinemic glucose clamp in noninsulin-dependent diabetic patients . Long term studies are needed to determine whether magnesium supplementation is useful in the management of type II diabetes BACKGROUND Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein ( LDL ) cholesterol level . Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein ( HDL ) cholesterol level , but its clinical efficacy and safety are uncertain . METHODS After a prer and omization run-in phase to st and ardize the background statin-based LDL cholesterol-lowering therapy and to establish participants ' ability to take extended-release niacin without clinical ly significant adverse effects , we r and omly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily . The primary outcome was the first major vascular event ( nonfatal myocardial infa rct ion , death from coronary causes , stroke , or arterial revascularization ) . RESULTS During a median follow-up period of 3.9 years , participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter ( 0.25 mmol per liter as measured in the central laboratory ) lower and an HDL cholesterol level that was an average of 6 mg per deciliter ( 0.16 mmol per liter ) higher than the levels in those assigned to placebo . Assignment to niacin-laropiprant , as compared with assignment to placebo , had no significant effect on the incidence of major vascular events ( 13.2 % and 13.7 % of participants with an event , respectively ; rate ratio , 0.96 ; 95 % confidence interval [ CI ] , 0.90 to 1.03 ; P=0.29 ) . Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious ( absolute excess as compared with placebo , 3.7 percentage points ; P<0.001 ) and with an increased incidence of diabetes diagnoses ( absolute excess , 1.3 percentage points ; P<0.001 ) , as well as increases in serious adverse events associated with the gastrointestinal system ( absolute excess , 1.0 percentage point ; P<0.001 ) , musculoskeletal system ( absolute excess , 0.7 percentage points ; P<0.001 ) , skin ( absolute excess , 0.3 percentage points ; P=0.003 ) , and unexpectedly , infection ( absolute excess , 1.4 percentage points ; P<0.001 ) and bleeding ( absolute excess , 0.7 percentage points ; P<0.001 ) . CONCLUSIONS Among participants with atherosclerotic vascular disease , the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events . ( Funded by Merck and others ; HPS2-THRIVE Clinical Trials.gov number , NCT00461630 . ) To test the blood pressure (BP)-lowering effect of oral magnesium supplementation ( that is , magnesium chloride ( MgCl2 ) solution ) in diabetic hypertensive adults with hypomagnesaemia not on diuretic treatment but receiving concurrent captopril  , we conducted a double-blind , placebo-controlled trial . Eighty-two subjects between 40 and 75 years of age were r and omly enrolled . Over 4 months , subjects in the intervention group received 2.5 g of MgCl2 ( 50 ml of a solution containing 50 g of MgCl2 per 1000 ml of solution ) equivalent to 450 mg of elemental magnesium , and control subjects inert placebo . The primary trial end point was a reduction in systolic ( SBP ) and diastolic ( DBP ) blood pressure . Complete follow-up was achieved for 79 of the 82 r and omized subjects . SBP ( −20.4±15.9 versus −4.7 ± 12.7 mm Hg , P=0.03 ) and DBP ( −8.7±16.3 versus −1.2±12.6 mm Hg , P=0.02 ) showed significant decreases , and high-density lipoprotein-cholesterol ( 0.1±0.6 versus −0.1±0.7 mmol l−1 , P=0.04 ) a significant increase in the magnesium group compared to the placebo group . The adjusted odds ratio between serum magnesium and BP was 2.8 ( 95%CI : 1.4–6.9 ) . Oral magnesium supplementation with MgCl2 significantly reduces SBP and DBP in diabetic hypertensive adults with hypomagnesaemia Background : Magnesium is the second most abundant intracellular cation . It plays an important role in insulin homeostasis and glucose metabolism through multiple enzymatic reactions . With increasing data on magnesium deficiency in diabetic patients and epidemiological studies demonstrating magnesium deficiency as a risk factor for diabetes , it is logical to search for its possible beneficial effects on diabetes control and prevention . We aim ed to determine whether oral magnesium supplementation improves metabolic control , lipid profile and blood pressure in patients with type II diabetes . Methods : Fifty four patients with type II diabetes were included in a r and omized double blind placebocontrolled clinical trial . Patients received either placebo or 300 mg elemental magnesium ( as magnesium sulfate -MgSo4- ) daily , for 3 months . Metabolic control , lipid profile , blood pressure , magnesium status , hepatic enzymes , hemoglobin concentration , and anthropometric indices were determined in the beginning and at the end of the study . Results : Daily administration of 300 mg elemental magnesium for 3 months , significantly improved fasting blood glucose ( 183.9±15.43 to 125.8±6.52 vs. 196.5±28.12 to 136.5±7.94 , p < 0.0001 ) , 2-hour post pr and ial glucose ( 239.1±74.75 to 189.1±60mg/dl vs. 246.4±97.37 to 247.8±86.74mg/dl , p < 0.01 ) , lipid profile , blood pressure and hepatic enzymes . Conclusion : Oral magnesium supplementation with proper dosage has beneficial effects on blood glucose , lipid profile , and blood pressure in patients with type II diabetes BACKGROUND AND AIM Little is known about the effect of magnesium on insulin sensitivity and BP in healthy individuals . Therefore , we investigated whether magnesium could improve insulin sensitivity and blood pressure ( BP ) in normo-magnesemic nondiabetic overweight adults . METHODS AND RESULTS In a double-blinded , placebo-controlled , r and omized trial , a total of 155 participants ( BMI > or = 23 kg/m(2 ) ) received either 12.3 mmol ( 300 mg ) of elemental magnesium in the form of magnesium oxide ( n=75 ) or placebo ( n=80 ) each day for 12 weeks , constituting the intent-to-treat population . A repeated- measures ANOVA was used to evaluate the between-group changes in variables during the study . The baseline characteristics between the intervention and control groups were similar . There were no significant differences between the groups in the pattern of change of the homeostasis model assessment insulin resistance index , BP over time during the 12-week study . In subgroup analysis , magnesium supplementation ( n=8 , 27 , and 24 , respectively ) lowered BP much more than placebo ( n=16 , 29 , and 25 , respectively ) in those subjects whose systolic BP > or = 140 mmHg , diastolic BP 80 - 90 mmHg , and diastolic BP > or = 90 mmHg at the start of the study ( P=0.016 , 0.043 , and 0.023 , respectively ) ; in comparison , those subjects whose initial BP reading was low at baseline did not show a change in BP . No significant adverse events related to magnesium supplementation were recorded . CONCLUSIONS These results suggested that magnesium supplementation does not reduce BP and enhance insulin sensitivity in normo-magnesemic nondiabetic overweight people . However , it appears that magnesium supplementation may lower BP in healthy adults with higher BP OBJECTIVE Although hypomagnesemia reduces insulin sensitivity , benefits of magnesium supplementation to non-diabetic insulin resistant subjects has not been established . Our purpose was to determine whether oral magnesium supplementation with magnesium chloride ( MgCl2 ) 2.5 g daily modify insulin sensitivity in non-diabetic subjects . MATERIAL AND METHODS This study was a 3 months r and omized double-blind placebo-controlled trial . Apparently healthy subjects were eligible to participate if they had insulin resistance ( HOMA-IR index equal or greater than 3.0 ) and hypomagnesemia ( Serum magnesium levels equal or lower than 0.74 mmol/l ) . Subjects were r and omized to receive either , MgCl2 2.5 g daily or placebo by 3-months . RESULTS At baseline there were not significant anthropometric or laboratory differences between both groups . At ending of the study , magnesium-supplemented subjects significantly increased their serum magnesium levels ( 0.61 + /- 0.08 to 0.81 + /- 0.08 mmol/l , p<0.0001 ) and reduced HOMA-IR index ( 4.6 + /- 2.8 to 2.6 + /- 1.1 , p<0.0001 ) , whereas control subjects did not ( 0.62 + /- 0.08 to 0.61 + /- 0.08 mmol/l , p=0.063 and 5.2 + /- 1.9 to 5.3 + /- 2.9 , p=0.087 ) . CONCLUSIONS Oral magnesium supplementation improves insulin sensitivity in hypomagnesemic non-diabetic subjects . Clinical implication s of this finding have to be established OBJECTIVE To investigate the effects of long-term high-dose oral magnesium ( Mg ) therapy ( 30 mmol/day ) in patients with type II diabetes . Low plasma magnesium levels have been reported in type II diabetes and are associated with insulin resistance and diabetic late complications . RESEARCH DESIGN AND METHODS Forty patients with type II diabetes and hypomagnesemia were observed in a r and omized double-blind placebo-controlled trial for 3 months ( body mass index : 28 ± 4 kg/m2 ; HbA1c : 7.4 ± 0.8 % ) . Plasma and urine magnesium and metabolic control parameters were determined , and side effects were considered , especially with regard to patients ' compliance . RESULTS A significant increase in plasma magnesium levels was observed after 3 months of treatment ( Mg : 0.73 ± 0.8 vs. 0.81 ±0.1 mmol/1 ) , reaching magnesium levels of the control group ( 0.88 ± 0.8 mmol/1 ; NS ) ; metabolic control , however , was not altered ( HbA1c : 7.2 ± 0.7 vs. 7.4 ± 0.9 % ) . Six months after the end of the trial , plasma magnesium declined to pretreatment levels ( Mg : 0.73 ± 0.07 mmol/1 ) . The prevalence of side effects was high at the beginning and was reduced significantly during treatment . CONCLUSIONS We conclude that oral magnesium replacement therapy corrects hypomagnesemia after a minimum treatment period of 3 months . These observations might be important for the prevention of diabetic late complications The effect of magnesium ( Mg ) and ascorbic acid ( AA ) supplementation on metabolic control was assessed in 56 outpatient diabetics . A 90-day run-in period was followed by two 90-day treatment periods , during which Mg ( 600 mg/day ) and AA ( 2 g/day ) were administered in a r and omized double-blind cross-over fashion . A decrease in systolic and diastolic blood pressure ( 132 + /- 3 vs. 138 + /- 4 and 77 + /- 2 vs. 82 + /- 2 mm Hg ; p < 0.05 ) was observed in insulin-dependent diabetes mellitus subjects during Mg supplementation . No beneficial effect of Mg supplementation was observed on glycemic control , lipids or blood pressure in non-insulin-dependent diabetes mellitus ( NIDDM ) subjects . AA supplementation improved glycemic control among NIDDM subjects and both fasting blood glucose ( 9.1 + /- 0.5 vs. 10.1 + /- 0.6 mmol/l ; p < 0.05 ) and HbA1c ( 8.5 + /- 0.3 vs. 9.3 + /- 0.3 % ; p < 0.05 ) improved . Beneficial effects of AA supplementation on cholesterol ( 5.9 + /- 0.2 vs. 6.2 + /- 0.2 mmol/l ; p < 0.05 ) and triglycerides ( 2.2 + /- 0.2 vs. 2.5 + /- 0.2 ; p < 0.05 ) were also observed in NIDDM subjects . The results suggest that high-dose AA supplementation may have a beneficial effect in NIDDM subjects on both glycemic control and blood lipids
target: During subgroup analysis , a more beneficial effect of magnesium supplementation was observed in diabetic subjects with hypomagnesaemia .
  CONCLUSIONS Magnesium supplementation can produce a favourable effect on FPG , HDL , LDL , TG and SBP .
background: BACKGROUND Cardiovascular disorders remain the leading cause of death in type 2 diabetic patients .
  In the present study , a systematic review and a meta- analysis of r and omised controlled trials ( RCTs ) were conducted aim ing to evaluate the effect of magnesium supplementation on  type 2 diabetes ( T2D ) associated cardiovascular risk factors in both diabetic and nondiabetic individuals .