***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Glycemic control and prevention of secondary complications are the most important goals of using pharmacologic treatment of diabetes mellitus ( DM ) . The inadequate responses to oral hypoglycemic agents may be attributed to inadequate postreceptor events even when insulin levels are quite sufficient , and associated with oxidative stress induced by long-term hyperglycemia . The administration of antioxidants such as melatonin and zinc may improve tissue responses to insulin and increase the efficacy of drugs , e.g. metformin , which act through this pathway . This project was design ed to evaluate the effects of melatonin and zinc on the lipid profile and renal function in type 2 DM patients poorly controlled with metformin .  A placebo-controlled , double-blind clinical trial was performed in which 46 type 2 diabetic patients were selected and allocated into three groups . These groups were treated with single daily oral doses of both 10 mg of melatonin and 50 mg of zinc acetate alone : 10 mg of melatonin and 50 mg of zinc acetate in addition to the regularly used metformin or placebo , given at bedtime for 90 days . Fasting lipid profiles and microalbuminuria ( MAU ) were measured before initiating the treatments ( zero time ) and after 30 and 90 days of treatment . Daily administration of melatonin and zinc improved the impaired lipid profile and decreased the level of MAU ; the addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent . In conclusion , the combination of melatonin and zinc acetate , when used alone or in combination with metformin , improves DM-related complications such as the impaired lipid profile and MAU in type 2 DM patients OBJECTIVE The present study was design ed to assess the effect of magnesium plus zinc , vitamins C plus E , and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients . RESEARCH DESIGN AND METHODS In a r and omized , double-blind , placebo-controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for 3 months : group M ( n = 16 ) , 200 mg Mg and 30 mg Zn ; group V ( n = 18 ) , 200 mg vitamin C and 100 IU vitamin E ; group MV ( n = 17 ) , minerals plus vitamins ; and group P ( n = 18 ) , placebo .  Urinary albumin excretion and N-acetyl-beta-d-glucosaminidase activity ( NAG ) in urine were determined at the beginning and at the end of the trial . Treatment effects were analyzed by general linear modeling . RESULTS Results indicate that after 3 months of supplementation , levels of urinary albumin excretion decreased in the V and MV groups ( P = 0.034 and P = 0.005 , respectively ) . Urinary NAG activity did not significantly change in any treatment groups . Levels of systolic , diastolic , and mean blood pressure significantly decreased in the MV group ( P = 0.008 , P = 0.017 , and P = 0.009 , respectively ) . Also , combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose ( P = 0.035 ) and malondialdehyde concentrations ( P = 0.004 ) and in increasing HDL cholesterol and apolipoprotein A1 levels ( P = 0.019 ) . There was no significant change in the levels of these parameters in the other three groups . CONCLUSIONS In conclusion , the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium , zinc , and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients BACKGROUND Oxidative stress is an important pathogenic factor in the development of diabetic vascular complications . AIMS To study the effect of vitamin E supplementation on microalbuminuria , plasma levels of malondialdehyde ( MLD ) and metabolites of prostagl and ins TXA2 ( TXB2 ) and PGI2 ( 6-keto-PGF1alpha ) and to evaluate the relation between plasma MLD and thromboxane B2 ( TXB2 ) in diabetic patients . PATIENTS AND METHODS Diabetic microalbuminuric patients were supplemented with vitamin E 1200 IU daily ( EVIT , Rodisma , Germany ) and measurements of microalbuminuria , MLD , TXB2 and 6-ketoPGF1alpha were repeated after 4 months of treatment . RESULTS Vitamin E supplementation lowered microalbuminuria ( 93.8 + /- 45.6 vs 67.95 + /- 28.4 microg/min , p < 0.05 ) , MLD ( 0.55 + /- 0.26 vs 0.32 + /- 0.16 micromol/l , p < 0.001 ) and also TXB2 level ( 115.14 + /- 22.7 vs 15.32 + /- 14.7 ng/l , p < 0.001 ) in diabetic microalbuminuric patients . The changes of 6-keto-PGF1alpha after treatment were not significant . CONCLUSIONS Our results did not show any significant relationship between levels of MLD and TXB2 .  Vitamin E supplementation significantly lowered microalbuminuria , MLD and TXB2 . ( Tab . 2 , Fig. 2 , Ref . 35 ) The object of the study was to test whether high dose ascorbic acid ( AA ) could normalize glomerular hyperfiltration in insulin-dependent diabetes mellitus ( IDDM ) patients . A prospect i ve , double-blind , r and omized , placebo ( tartaric acid , TA ) controlled study design was used , with parallel treatment lasting 4 weeks . Measurements were made before and after treatment , on 24 normoalbuminuric , normotensive male IDDM patients , who were r and omized to ascorbic acid ( n = 12 , age 35 years ( 18 - 39 ) , diabetes duration 12 years ( 2 - 12 ) , BP 128/82 mmHg ( SD 14/6 ) ) , or to placebo ( TA ) ( n = 12 , age 30 years ( 19 - 36 ) , diabetes duration 8 years ( 2 - 17 ) , BP 119/75 mmHg ( SD 9/7 ) . The intervention consisted of 6 enterosoluble tablets of 500 mg AA or 213 mg TA , twice a day , being daily doses of 6 g AA or 2.55 g TA . No significant differences in any of the parameters measured were seen , when comparing results following AA or placebo treatment . The glomerular filtration rate ( GFR , clearance of 125I-iothalamate ) was unchanged while effective renal plasma flow ( ERPF , clearance of 131I-hippuran ) tended to decline in both groups . The GFRs before and after treatment in the AA-treated group were 141 ( SD 15 ) and 134 ( SD 12 ) ml min-1 1.73 m-2 ; NS ( 2p = 0.09 ) . In the TA-treated group they were 142 ( SD 19 ) and 137 ( SD 16 ) ml min-1 1.73 m-2 ; NS ( 2p = 0.20 ) . The ERPFs in the AA group were 584 ( SD 93 ) and 545 ( SD 47 ) ml min-1 1.73 m-2 ; ( 2p = 0.06 ) . In the TA group they were 618 ( SD 108 ) and 574 ( SD 98 ) ml min-1 1.73 m-2 ( 2p = 0.03 ) . The filtration fractions ( FFs ) in the AA group were 0.244 and 0.246 NS . ( ABSTRACT TRUNCATED AT 250 WORDS Background : Tocotrienols ( T3 ) were neglected in the past ; today , get attentions due to their antioxidant and none-antioxidant activity . The objective of this study was to evaluate the effects of the daily intake of 200 mg T3 added in canola oil over 8 weeks on microalbuminuria , inflammation , and nitrosative stress in type 2 diabetic patients . Methods : This study was a double-blinded , placebo-controlled , r and omized trial . A total of 50 patients with T2DM and FBS > 126 mg/dl treated by non-insulin hypoglycemic drugs  were r and omly assigned to receive either 15 ml T3-enriched canola oil ( 200 mg/day T3 ) or pure canola oil for 8 weeks . Urine microalbumin , volume and creatinine levels , serum hs-CRP , and nitric oxide ( NO ) levels were measured before and after intervention . Results : From 50 patients participated in this study , 44 completed the study . There were no significant differences in baseline characteristics , dietary intake , and physical activity between groups . Urine microalbumin and serum hs-CRP were declined significantly in T3-treated group . At the end of the study , patients who treated with T3 had lower urine microalbumin ( 11 ( 9 , 25 ) vs. 22 ( 15 , 39.75 ) nmol/dl , P = 0.003 ) and hs-CRP changes ( −10.91 ± 15.5 vs. −9.88 ± 27.5 Pg/ml , P = 0.048 ) than control group . A non-significant decrease was also observed in serum NO level in T3-treated group with no changes in urine volume and creatinine levels . Conclusions : These findings indicate that T3 leads to ameliorate proteinuria and can protect the kidney against inflammation ( hs-CRP ) and nitrosative stress ( NO ) This study was design ed to investigate the effects of combined administration of lipoic acid and pyridoxine on albuminuria , oxidative stress , blood pressure , serum advanced glycation end-products , nitric oxide ( NO ) , and endothelin-1 in patients with diabetic nephropathy . Thirty-four patients were r and omly assigned to either a supplement group or a placebo group . The patients in the supplement group received 800 mg lipoic acid and 80 mg pyridoxine daily for 12 weeks , whereas the placebo group received corresponding placebos .  Urinary albumin , serum malondialdehyde ( MDA ) , and systolic blood pressure decreased significantly in the supplement group compared to the placebo group ( p < 0.05 ) . Serum NO increased in the supplement group compared to the placebo group ( p < 0.05 ) . Serum pentosidine and carboxymethyl lysine decreased significantly in the supplement group at the end of week 12 compared to baseline ( p < 0.05 ) . No statistically significant differences were observed between the two groups in mean changes of serum endothelin-1 , glucose , and diastolic blood pressure . The present study indicates that combined administration of lipoic acid and pyridoxine improves albuminuria in patients with diabetic nephropathy by reducing oxidative stress , advanced glycation end-products , and systolic blood pressure . The reduction in microalbuminuria may be of benefit in retarding the progression of diabetic nephropathy OBJECTIVES Oxidative stress can contribute to microvascular complications in diabetes . A decisive event associated with this condition may be the decrease in the synthesis of zinc-containing antioxidant enzymes such as superoxide dismutase and glutathione peroxidase . This consideration led us to investigate the effect of zinc supplementation versus placebo on microalbuminuria in diabetic patients in a r and omized double blind clinical trial . METHODS Fifty diabetic patients with microalbuminuria were enrolled .  Fasting plasma glucose , HbA1c , lipid profiles , plasma zinc levels and r and om urine for albumin and creatinine were measured . Patients r and omly received 30 mg elemental zinc ( group 1 ) or placebo ( group 2 ) for 3 months . After a 4 week wash-out period , the groups were crossed over ( i.e. the zinc group were given placebo , and the placebo group were given zinc ) and the protocol was repeated . RESULTS From an initial number of 50 selected patients ( 25 in each of two groups ) , 39 patients ( 21 in group 1 and 18 in group 2 ) completed the study . In group 1 , after zinc supplementation , urinary albumin excretion decreased significantly from 86.5 + /- 57 to 75 + /- 71 mg/g ( p = 0.01 ) . After placebo , patients in group 1 showed no significant reduction in microalbuminuria ( 85 + /- 72 mg/g to 83 + /- 63 mg/g creatinine ) . In group 2 , no change in albumin excretion was observed after placebo treatment ( 90.5 + /- 63 mg/g to 90 + /- 60 mg/g creatinine ) . After zinc supplementation , a significant reduction was observed in 
    Output:
    
CONCLUSIONS In DKD patients , antioxidants may improve early renal damage .