human
***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: Abstract Aims / Introduction Dipeptidyl peptidase‐4 inhibitors might have pleiotropic protective effects on cardiovascular disease ( CVD ) , in contrast to sulfonylureas . Therefore , we compared various CVD risk factors between vildagliptin and glimepiride . Material s and Methods We carried out a r and omized , prospect i ve and crossover trial . A total of 16 patients with type 2 diabetes whose glycated hemoglobin was > 7 % were r and omized to add vildagliptin or glimepiride .  After 12‐week treatment , each drug was replaced with the other for another 12 weeks . Before and after each treatment , glucose homeostasis and CVD risk factors were assessed , and the continuous glucose monitoring system was applied to calculate glycemic variability . Results The mean age of the participants was 60 years , 31 % were men , body mass index 25.5 kg/m2 and HbA1c 8.41 % .  Both vildagliptin and glimepiride significantly decreased glycated hemoglobin and glycemic variability indices . Despite the improved glucose homeostasis , favorable change of CVD markers was not prominent in both the arms , along with significant weight gain . Only plasma stromal cell‐derived factor (SDF)‐1α decreased by 30 % in the vildagliptin arm . According to regression analyses , the reduction of SDF‐1α was independently associated with vildagliptin usage and serum interleukin‐6 changes , but white blood cells were not related with the SDF‐1α changes . Conclusion Compared with glimepiride , vildagliptin arrestingly decreased plasma SDF‐1α , and its clinical implication s should be further investigated Background Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress . This study aim ed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor , vildagliptin , or a thiazolidinedione , pioglitazone , on glycemic variability and oxidative stress in patients with type 2 diabetes . Methods In this open label , r and omised , active-controlled , pilot trial , individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin ( 50 mg twice daily , n=17 )  or pioglitazone ( 15 mg once daily , n=14 ) treatment groups for 16 weeks . Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions ( MAGE ) , which was obtained from continuous glucose monitoring . Urinary 8-iso prostagl and in F2α , serum oxidised low density lipoprotein , and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation . Results Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment . Vildagliptin also significantly reduced the MAGE ( from 93.8±38.0 to 70.8±19.2 mg/dL , P=0.046 ) , and mean st and ard deviation of 24 hours glucose ( from 38±17.3 to 27.7±6.9 , P=0.026 ) ; however , pioglitazone did not , although the magnitude of decline was similar in both groups . Markers of oxidative stress or inflammation including urinary 8-iso prostagl and in F2α did not change after treatment in both groups . Conclusion In this 16-week treatment trial , vildagliptin , but not pioglitazone , reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy , although a reduction of oxidative stress markers was not observed The aim of this study was to evaluate the effect of gemigliptin vs sitagliptin or glimepiride as initial combination therapy with metformin on glycaemic variability and to assess the correlation between glycaemic variability reduction and the dipeptidyl peptidase‐4 ( DPP‐4 ) inhibition in patients with type 2 diabetes . This multicentre , r and omized , active‐controlled , open‐label exploratory study included 69 patients with HbA1c > 7.5 % . Subjects were r and omized to receive gemigliptin 50 mg ( n = 24 ) , sitagliptin 100 mg ( n = 23 ) or glimepiride 2 mg ( n = 22 ) for 12 weeks . After 12 weeks , the change in mean amplitude of glycaemic excursion ( MAGE ) compared with baseline was significantly lower in the DPP‐4 inhibitor groups compared with that in patients who received glimepiride . Furthermore , the st and ard deviation ( SD ) of glucose was significantly lower in patients who received gemigliptin than that in patients who received sitagliptin or glimepiride . The DPP‐4 inhibition was significantly correlated with changes in MAGE and SD of glucose . In conclusion , gemigliptin and sitagliptin were more effective than glimepiride in reducing glycaemic variability as initial combination therapy with metformin in patients with type 2 diabetes , and the DPP‐4 inhibition was associated with a reduction in glycaemic variability OBJECTIVE HbA(1c ) is a st and ard clinical assessment of glycemia and the basis of most data relating glycemic control to complications . It remains unclear , however , whether HbA(1c ) is affected by glycemic variation and mean glycemia . RESEARCH DESIGN AND METHODS To test this question , we analyzed the statistical relationship between HbA(1c ) levels and glycemic variability as measured by self-monitoring of blood glucose ( SMBG ) .  The records of 256 subjects were studied .  SMBG data for the preceding 3 months were downloaded , and HbA(1c ) was measured by ion-exchange high-performance liquid chromatography . Simple- and r and om-effects linear regression models were used to assess the independent contributions of mean blood glucose ( BG ) and SD of BG to HbA(1c ) , after adjusting for the mean BG . RESULTS Mean + /- SD for HbA(1c ) was 7.66 + /- 1.11 % and for BG was 8.5 + /- 1.9 mmol/l ( 153.3 + /- 34.9 mg/dl ) ; SD of BG for individual subjects was 3.5 mmol/l ( 63.3 mg/dl ) , varying from 0.4 mmol/l ( 8.1 mg/dl ; very stable glycemia ) to 8.4 mmol/l ( 152.5 mg/dl ; very unstable glycemia ) . A close correlation between mean BG and HbA(1c ) was demonstrated ( r = 0.62 ) . Also , within-subject SD of BG correlated with HbA(1c ) ( r = 0.375 ) , indicating that people with poorer glycemic control had higher BG variance . After adjusting for mean BG in a linear regression model , however , the effect of the within-subject SD of BG on the HbA(1c ) was insignificant . Several further analyses confirmed the strength of the observation . CONCLUSIONS HbA(1c ) reflects mean glycemia and is not meaningfully affected by glycemic instability after adjusting for mean BG Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Aims Type 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease . CD34 + endothelial Progenitor Cells ( EPCs ) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker . This study investigated whether the addition of saxagliptin , a DPP-IV inhibitor , to metformin , may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients . Methods In 12 week , double-blind , r and omized placebo-controlled trial , 42 subjects already taking metformin 1–2 grams/day were r and omized to placebo or saxagliptin 5 mg . Subjects aged 40–70 years with diabetes for < 10 years , with no known cardiovascular disease , BMI 25–39.9 , HbA1C 6–9 % were included . We evaluated EPCs number , function , surface markers and gene expression , in addition to arterial stiffness , blood biochemistries , resting energy expenditure , and body composition parameters . A mixed model regression to examine saxagliptin vs placebo , accounting for within-subject autocorrelation , was done with SAS ( p < 0.05 ) . Results Although there was no significant increase in CD34 + cell number , CD31 + cells percentage increased . Saxagliptin  increased migration ( in response to SDF1α ) with a trend of higher colony formation count . MNCs cytometry showed higher percentage of CXCR4 double positivity for both CD34 and CD31 positive cells , indicating a functional improvement . Gene expression analysis showed an upregulation in CD34 + cells for antioxidant SOD1 ( p < 0.05 ) and a downregulation in CD34− cells for IL-6 ( p < 0.01 ) . For arterial stiffness , both augmentation index and systolic blood pressure measures went down in saxagliptin subjects ( p < 0.05 ) . ConclusionS axagliptin , in combination with metformin , can help improve endothelial dysfunction in early diabetes before macrovascular complications appear . Trial registration Trial is registered under clinical trials.gov , The objective of this study was to investigate the characteristics of blood glycemic excursion , incretins and pancreatic hormone secretion in elderly people with newly diagnosed type 2 diabetes mellitus ( T2DM ) and to study the effects of sitagliptin on glycemic excursion in these subjects . A total of 129 newly diagnosed T2DM patients were enrolled in the study from March 2012 to August 2013 .  Clinical data , serum incretin , pancreatic hormone and continuous glucose monitoring data were collected . Among these subjects , elderly patients ( NEDM ) r and omly received metformin combined with sitagliptin phosphate or glimepiride for 24 weeks . The blood glucose , glycosylated hemoglobin A1c ( GHbA1c ) , serum incretins and pancreatic hormone levels were determined . During the oral glucose tolerance test ( OGTT ) , 30 min insulin and C-peptide levels , 120 min insulin levels and ratio of the increases of insulin and blood glucose levels after 30 min of sugar loading ( ∆Ins30/∆Glu30 ) were significantly lower in elderly patients than in middle-aged patients ( P<0.05 ) . In addition , the glucagon elevation at 30 min was higher and the glucagon-like peptide-1 ( GLP-1 ) at 30 min was lower in the elderly patients ( P<0.05 ) . Glucose excursion indices , including the st and ard deviation of the average blood glucose , intraday mean average glucose excursions ( MAGE ) , and mean of daily differences ( MODD ) , were significantly higher in the elderly patients ( P<0.05 ) . During the OGTT , insulin , C-peptide and ∆Ins30/∆Glu30 results at 30 min and GLP-1 levels at 120 min in NEDM subjects were significantly increased ( P<0.05 ) and glucagon levels at 30 min was significantly lower after sitagliptin treatment ( P<0.05 ) compared with glimepiride . Moreover , MAGE and MODD were significantly lower in the sitagliptin group after treatment compared to those in the glimepiride group ( P<0.05 ) . No severe hypoglycemia or cardiovascular diseases were observed . Strong blood glucose excursions occur in elderly patients with newly diagnosed T2DM . Sitagliptin phosphate combined with metformin effectively and safely improves glycemic excursion and carbohydrate metabolism in NEDM patients by promoting the first phase of insulin and incretin secretion and inhibiting glucagon secretion of BACKGROUND In patients with type 2 diabetes , intensive blood-glucose control with insulin or sulphonylurea therapy decreases progression of microvascular disease and may also reduce the risk of heart attacks . This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage . METHODS Of 4075 patients recruited to UKPDS in 15 centres , 1704 overweight ( > 120 % ideal bodyweight ) patients with newly diagnosed type 2 diabetes , mean age 53 years , had raised fasting plasma glucose ( FPG ; 6.1 - 15.0 mmol/L ) without hyperglycaemic symptoms after 3 months ' initial diet . 753 were included in a r and omised controlled trial , median duration 10.7 years , of conventional policy , primarily with diet alone ( n=411 ) versus intensive blood-glucose control policy with metformin , aim ing for FPG below 6 mmol/L ( n=342 ) . A secondary analysis compared the 342 patients allocated metformin with 951 overweight patients allocated  
    Output:
    
agent
Initial combination therapy with DPP-IV inhibitors more effectively reduced MAGE than stepwise add-on therapies ( p = 0.006 ) , although no differences in MAGE were found based on HbA1c values .
These findings indicate that DPP-IV inhibitors are promising alternatives for reducing GV in type 2 diabetes patients .
***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: Abstract Aims / Introduction Dipeptidyl peptidase‐4 inhibitors might have pleiotropic protective effects on cardiovascular disease ( CVD ) , in contrast to sulfonylureas . Therefore , we compared various CVD risk factors between vildagliptin and glimepiride . Material s and Methods We carried out a r and omized , prospect i ve and crossover trial . A total of 16 patients with type 2 diabetes whose glycated hemoglobin was > 7 % were r and omized to add vildagliptin or glimepiride .  After 12‐week treatment , each drug was replaced with the other for another 12 weeks . Before and after each treatment , glucose homeostasis and CVD risk factors were assessed , and the continuous glucose monitoring system was applied to calculate glycemic variability . Results The mean age of the participants was 60 years , 31 % were men , body mass index 25.5 kg/m2 and HbA1c 8.41 % .  Both vildagliptin and glimepiride significantly decreased glycated hemoglobin and glycemic variability indices . Despite the improved glucose homeostasis , favorable change of CVD markers was not prominent in both the arms , along with significant weight gain . Only plasma stromal cell‐derived factor (SDF)‐1α decreased by 30 % in the vildagliptin arm . According to regression analyses , the reduction of SDF‐1α was independently associated with vildagliptin usage and serum interleukin‐6 changes , but white blood cells were not related with the SDF‐1α changes . Conclusion Compared with glimepiride , vildagliptin arrestingly decreased plasma SDF‐1α , and its clinical implication s should be further investigated Background Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress . This study aim ed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor , vildagliptin , or a thiazolidinedione , pioglitazone , on glycemic variability and oxidative stress in patients with type 2 diabetes . Methods In this open label , r and omised , active-controlled , pilot trial , individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin ( 50 mg twice daily , n=17 )  or pioglitazone ( 15 mg once daily , n=14 ) treatment groups for 16 weeks . Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions ( MAGE ) , which was obtained from continuous glucose monitoring . Urinary 8-iso prostagl and in F2α , serum oxidised low density lipoprotein , and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation . Results Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment . Vildagliptin also significantly reduced the MAGE ( from 93.8±38.0 to 70.8±19.2 mg/dL , P=0.046 ) , and mean st and ard deviation of 24 hours glucose ( from 38±17.3 to 27.7±6.9 , P=0.026 ) ; however , pioglitazone did not , although the magnitude of decline was similar in both groups . Markers of oxidative stress or inflammation including urinary 8-iso prostagl and in F2α did not change after treatment in both groups . Conclusion In this 16-week treatment trial , vildagliptin , but not pioglitazone , reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy , although a reduction of oxidative stress markers was not observed The aim of this study was to evaluate the effect of gemigliptin vs sitagliptin or glimepiride as initial combination therapy with metformin on glycaemic variability and to assess the correlation between glycaemic variability reduction and the dipeptidyl peptidase‐4 ( DPP‐4 ) inhibition in patients with type 2 diabetes . This multicentre , r and omized , active‐controlled , open‐label exploratory study included 69 patients with HbA1c > 7.5 % . Subjects were r and omized to receive gemigliptin 50 mg ( n = 24 ) , sitagliptin 100 mg ( n = 23 ) or glimepiride 2 mg ( n = 22 ) for 12 weeks . After 12 weeks , the change in mean amplitude of glycaemic excursion ( MAGE ) compared with baseline was significantly lower in the DPP‐4 inhibitor groups compared with that in patients who received glimepiride . Furthermore , the st and ard deviation ( SD ) of glucose was significantly lower in patients who received gemigliptin than that in patients who received sitagliptin or glimepiride . The DPP‐4 inhibition was significantly correlated with changes in MAGE and SD of glucose . In conclusion , gemigliptin and sitagliptin were more effective than glimepiride in reducing glycaemic variability as initial combination therapy with metformin in patients with type 2 diabetes , and the DPP‐4 inhibition was associated with a reduction in glycaemic variability OBJECTIVE HbA(1c ) is a st and ard clinical assessment of glycemia and the basis of most data relating glycemic control to complications . It remains unclear , however , whether HbA(1c ) is affected by glycemic variation and mean glycemia . RESEARCH DESIGN AND METHODS To test this question , we analyzed the statistical relationship between HbA(1c ) levels and glycemic variability as measured by self-monitoring of blood glucose ( SMBG ) .  The records of 256 subjects were studied .  SMBG data for the preceding 3 months were downloaded , and HbA(1c ) was measured by ion-exchange high-performance liquid chromatography . Simple- and r and om-effects linear regression models were used to assess the independent contributions of mean blood glucose ( BG ) and SD of BG to HbA(1c ) , after adjusting for the mean BG . RESULTS Mean + /- SD for HbA(1c ) was 7.66 + /- 1.11 % and for BG was 8.5 + /- 1.9 mmol/l ( 153.3 + /- 34.9 mg/dl ) ; SD of BG for individual subjects was 3.5 mmol/l ( 63.3 mg/dl ) , varying from 0.4 mmol/l ( 8.1 mg/dl ; very stable glycemia ) to 8.4 mmol/l ( 152.5 mg/dl ; very unstable glycemia ) . A close correlation between mean BG and HbA(1c ) was demonstrated ( r = 0.62 ) . Also , within-subject SD of BG correlated with HbA(1c ) ( r = 0.375 ) , indicating that people with poorer glycemic control had higher BG variance . After adjusting for mean BG in a linear regression model , however , the effect of the within-subject SD of BG on the HbA(1c ) was insignificant . Several further analyses confirmed the strength of the observation . CONCLUSIONS HbA(1c ) reflects mean glycemia and is not meaningfully affected by glycemic instability after adjusting for mean BG Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Aims Type 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease . CD34 + endothelial Progenitor Cells ( EPCs ) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker . This study investigated whether the addition of saxagliptin , a DPP-IV inhibitor , to metformin , may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients . Methods In 12 week , double-blind , r and omized placebo-controlled trial , 42 subjects already taking metformin 1–2 grams/day were r and omized to placebo or saxagliptin 5 mg . Subjects aged 40–70 years with diabetes for < 10 years , with no known cardiovascular disease , BMI 25–39.9 , HbA1C 6–9 % were included . We evaluated EPCs number , function , surface markers and gene expression , in addition to arterial stiffness , blood biochemistries , resting energy expenditure , and body composition parameters . A mixed model regression to examine saxagliptin vs placebo , accounting for within-subject autocorrelation , was done with SAS ( p < 0.05 ) . Results Although there was no significant increase in CD34 + cell number , CD31 + cells percentage increased . Saxagliptin  increased migration ( in response to SDF1α ) with a trend of higher colony formation count . MNCs cytometry showed higher percentage of CXCR4 double positivity for both CD34 and CD31 positive cells , indicating a functional improvement . Gene expression analysis showed an upregulation in CD34 + cells for antioxidant SOD1 ( p < 0.05 ) and a downregulation in CD34− cells for IL-6 ( p < 0.01 ) . For arterial stiffness , both augmentation index and systolic blood pressure measures went down in saxagliptin subjects ( p < 0.05 ) . ConclusionS axagliptin , in combination with metformin , can help improve endothelial dysfunction in early diabetes before macrovascular complications appear . Trial registration Trial is registered under clinical trials.gov , The objective of this study was to investigate the characteristics of blood glycemic excursion , incretins and pancreatic hormone secretion in elderly people with newly diagnosed type 2 diabetes mellitus ( T2DM ) and to study the effects of sitagliptin on glycemic excursion in these subjects . A total of 129 newly diagnosed T2DM patients were enrolled in the study from March 2012 to August 2013 .  Clinical data , serum incretin , pancreatic hormone and continuous glucose monitoring data were collected . Among these subjects , elderly patients ( NEDM ) r and omly received metformin combined with sitagliptin phosphate or glimepiride for 24 weeks . The blood glucose , glycosylated hemoglobin A1c ( GHbA1c ) , serum incretins and pancreatic hormone levels were determined . During the oral glucose tolerance test ( OGTT ) , 30 min insulin and C-peptide levels , 120 min insulin levels and ratio of the increases of insulin and blood glucose levels after 30 min of sugar loading ( ∆Ins30/∆Glu30 ) were significantly lower in elderly patients than in middle-aged patients ( P<0.05 ) . In addition , the glucagon elevation at 30 min was higher and the glucagon-like peptide-1 ( GLP-1 ) at 30 min was lower in the elderly patients ( P<0.05 ) . Glucose excursion indices , including the st and ard deviation of the average blood glucose , intraday mean average glucose excursions ( MAGE ) , and mean of daily differences ( MODD ) , were significantly higher in the elderly patients ( P<0.05 ) . During the OGTT , insulin , C-peptide and ∆Ins30/∆Glu30 results at 30 min and GLP-1 levels at 120 min in NEDM subjects were significantly increased ( P<0.05 ) and glucagon levels at 30 min was significantly lower after sitagliptin treatment ( P<0.05 ) compared with glimepiride . Moreover , MAGE and MODD were significantly lower in the sitagliptin group after treatment compared to those in the glimepiride group ( P<0.05 ) . No severe hypoglycemia or cardiovascular diseases were observed . Strong blood glucose excursions occur in elderly patients with newly diagnosed T2DM . Sitagliptin phosphate combined with metformin effectively and safely improves glycemic excursion and carbohydrate metabolism in NEDM patients by promoting the first phase of insulin and incretin secretion and inhibiting glucagon secretion of BACKGROUND In patients with type 2 diabetes , intensive blood-glucose control with insulin or sulphonylurea therapy decreases progression of microvascular disease and may also reduce the risk of heart attacks . This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage . METHODS Of 4075 patients recruited to UKPDS in 15 centres , 1704 overweight ( > 120 % ideal bodyweight ) patients with newly diagnosed type 2 diabetes , mean age 53 years , had raised fasting plasma glucose ( FPG ; 6.1 - 15.0 mmol/L ) without hyperglycaemic symptoms after 3 months ' initial diet . 753 were included in a r and omised controlled trial , median duration 10.7 years , of conventional policy , primarily with diet alone ( n=411 ) versus intensive blood-glucose control policy with metformin , aim ing for FPG below 6 mmol/L ( n=342 ) . A secondary analysis compared the 342 patients allocated metformin with 951 overweight patients allocated  
    Output:
    