The Minimum Frequency of Glucose Measurements from Which Glycemic Variation Can Be Consistently Assessed The different methods of assessing glycemic variability, quality of glycemic control and glycemic risk cannot be interpreted as equivalent in clinical practice. Rationale, design, and baseline characteristics of a trial for the prevention of diabetic atherosclerosis using a DPP-4 inhibitor: the Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A). Glycemic variability in continuous glucose monitoring is inversely associated with baroreflex sensitivity in type 2 diabetes: a preliminary report Do diabetes group visits lead to lower medical care charges? Effect of once-daily insulin detemir on oral antidiabetic drug (OAD) use in patients with type 2 diabetes. The impact of initiating biphasic human insulin 30 therapy in type 2 diabetes patients after failure of oral antidiabetes drugs. Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via up-regulation of SDF-1α in type 2 diabetic patients with incipient nephropathy. Long-Term Dipeptidyl-Peptidase 4 Inhibition Reduces Atherosclerosis and Inflammation via Effects on Monocyte Recruitment and Chemotaxis Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. Effects of sitagliptin on 24-h glycemic changes in Japanese patients with type 2 diabetes assessed using continuous glucose monitoring. Baseline characteristics of the Indian cohort from the IMPROVE™ study: a multinational, observational study of biphasic insulin aspart 30 treatment for type 2 diabetes Adding biphasic insulin aspart 30 once or twice daily is more efficacious than optimizing oral antidiabetic treatment in patients with type 2 diabetes. A Very Low-Carbohydrate, Low–Saturated Fat Diet for Type 2 Diabetes Management: A Randomized Trial Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes. Effects of Concomitant Administration of a Dipeptidyl Peptidase-4 Inhibitor in Japanese Patients with Type 2 Diabetes Showing Relatively Good Glycemic Control Under Treatment with a Sodium Glucose Co-Transporter 2 Inhibitor. Therapy in type 2 diabetes: insulin glargine vs. NPH insulin both in combination with glimepiride. The Efficacy and Safety of Insulin Degludec Given in Variable Once-Daily Dosing Intervals Compared With Insulin Glargine and Insulin Degludec Dosed at the Same Time Daily A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia. The IMPROVE study--a multinational, observational study in type 2 diabetes: baseline characteristics from eight national cohorts. Adding Liraglutide to Oral Antidiabetic Drug Monotherapy: Efficacy and Weight Benefits
Aims : While there has been much debate about the clinical importance of glycemic variation ( GV ) , little attention has been directed to the properties of data sets from which it is measured . The purpose of this study is to assess the minimum frequency of glucose measurements from which GV can be consistently and meaningfully measured . Methods : Forty-eight 72 h continuous glucose monitoring traces from children with type 1 diabetes were assessed . Measures of GV included st and ard deviation ( SD ) , mean amplitude of glycemic excursion ( MAGE ) , and continuous overlapping net glycemic action ( CONGA1–4 ) . Measures of GV calculated using 5 min sampling were design ated as the 100 % or “ best estimate ” value . Calculations were then repeated for each patient using glucose values spaced at increasing intervals . For each of the specified sampling frequencies , the ratio ( % ) of the between-subject SD based on the reduced subset of data to the estimate of the SD based on the full 5 min sampling data set was calculated . Results : As the interval between observations increased , so did the variability of the estimators of GV . St and ard deviation exhibited the least systematic change at all measurement intervals , and MAGE exhibited the greatest systematic change . Conclusions : In patients with type 1 diabetes , GV as measured by SD or CONGA4 , becomes unreliable if observations are more than 2–4 h apart , and estimates of MAGE become unreliable if glucose measurements are more than 1 h apart . MAGE is more unstable and prone to r and om measurement error than either SD or CONGA . The frequency of glycemic measurements is thus pivotal when selecting a parameter for measurement of GV OBJECTIVE Several methods are available to calculate glycemic variability ( GV ) , quality of glycemic control ( QGC ) and glycemic risk ( GR ) . However , clinicians do not easily interpret these data . This study evaluates whether the results of the different methods can be interpreted as equivalent . METHODS A prospect i ve study was performed including out patients with DMT2 evaluated at the San Ignacio Hospital and the Colombian Diabetes Association in Bogotá , Colombia . From six-day continuous glucose monitoring data  , GV ( SD , CV , IQR , MODD , MAGE ) , QGC ( M-value , J-index ) and GR ( LBGI , HBGI ) were calculated . Reference values ​​were generated , classifying the patients according to GV control quartiles ( excellent , good , fair or poor ) . The concordance between the different indices was evaluated . RESULTS In total , 140 patients ( 68.9 ± 11.2 years ) were included .  The agreement levels ( Kappa ) between GV indices were moderate , 0.40 ( CI 95%:0.29 - 0.51 ) , 0.42 ( CI 95%:0.31 - 0.53 ) and 0.39 ( CI 95%:0.28 - 0.50 ) , for CV versus SD , IQR and CONGA respectively . The levels of agreement between GV and QGC indices were minimal ( Kappa CV vs. M-value , 0.15CI 95%:0.046 - 0.26 ) and weak between the GV and GR indices ( Kappa CVvs . LBGI 0.37CI95%:0.26 - 0.48 ) . The estimators did not improve significantly when the analysis was performed with linearly weighted or quadratic weighted Kappa . CONCLUSIONS The present study demonstrates that the concordance between the clinical interpretation of the different GV , QGC and GR indices is poor , suggesting that they can not be assumed as equivalent , so different indices evaluating different concepts , must be evaluated simultaneously to analyze adequately each patient . New studies are needed to evaluate which of the methods better predicts hypoglycemia and microvascular or macrovascular complications AIM Alogliptin , an efficacious inhibitor of DPP-4 that improves glycemic control , as well as the pancreatic beta-cell function , is now increasingly used to accomplish glycemic targets in type 2 diabetic patients . Interestingly , recent experimental studies have shown that alogliptin exerts anti-atherosclerotic effects in GLP-1-dependent and -independent manners . The aim of the present ongoing study is to investigate the preventive effects of alogliptin on the progression of atherosclerosis in type 2 diabetic subjects using the carotid intima-media thickness ( IMT ) , an established marker of cardiovascular disease . METHODS AND RESULTS The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis ( SPEAD-A ) is a prospect i ve , r and omized , open-label , blinded-endpoint , multicenter , parallel-group , comparative study . Between March 2011 and March 2012 , 341 participants were recruited at 11 clinical sites , and were r and omly allocated either to an  alogliptin treatment group ( 172 patients ) or a  conventional treatment group ( 169 patients ) . The primary outcomes are the changes in the maximum and mean IMT of the common carotid artery during a 24-month treatment period , as measured by carotid arterial echography . The secondary outcomes include the changes in glycemic control , parameters related to beta-cell function and diabetic nephropathy , the occurrence of cardiovascular events and adverse events and biochemical measurements reflecting vascular function . CONCLUSIONS This is the first study to address the effects of DPP-4 inhibitors on the progression of changes in the carotid IMT , with the patients without DPP-4 inhibitor treatment serving as a control group . The results will be available soon , and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent cardiovascular disease Background It is presently unclear whether glycemic variability ( GV ) is associated with baroreflex sensitivity ( BRS ) , which is an early indicator of cardiovascular autonomic neuropathy . The present study is the first to examine the relationships between BRS and GV measured using continuous glucose monitoring ( CGM ) . Methods This was a multicenter , prospect i ve , open-label clinical trial . A total of 102 patients with type 2 diabetes were consecutively recruited for this study . GV was assessed by measuring the st and ard deviation ( SD ) , glucose coefficient of variation ( CV ) , and the mean amplitude of glycemic excursions ( MAGE ) during CGM . The BRS was analyzed from  electrocardiogram and blood pressure recordings  using the sequence method on the first day of hospitalization . Results A total of 94 patients ( mean diabetes duration 9.7 ± 9.6 years , mean HbA1c 61.0 ± 16.8 mmol/mol [ 7.7 ± 1.5 % ] ) were analyzed . In the univariate analysis , CGM-SD ( r = − 0.375 , p = 0.000 ) , CGM-CV ( r = − 0.386 , p = 0.000 ) , and MAGE ( r = − 0.395 , p = 0.000 ) were inversely related to BRS . In addition to GV , the level of BRS correlated with the coefficient of variation in the R – R intervals ( CVR-R ) ( r = 0.520 , p = 0.000 ) , heart rate ( HR ) ( r = − 0.310 , p = 0.002 ) , cardio-ankle vascular index ( CAVI ) ( r = − 0.326 , p = 0.001 ) , age ( r = − 0.519 , p = 0.000 ) , and estimated glomerular filtration rate ( eGFR ) ( r = 0.276 , p = 0.007 ) . Multiple regression analysis showed that CGM-CV and MAGE were significantly related to a decrease in BRS . These findings remained after adjusting the BRS for age , sex , hypertension , dyslipidemia , HR , eGFR , CAVI , and CGM-mean glucose . Additionally , BRS was divided according to quartiles of the duration of diabetes ( Q1–4 ) . BRS decreased after a 2-year duration of diabetes independently of age and sex . Conclusions GV was inversely related to BRS independently of blood glucose levels in type 2 diabetic patients . Measurement of BRS may have the potential to predict CV events in consideration of GV.Trial registration UMIN Clinical Trials Registry UMIN000025964 , OBJECTIVE To evaluate whether attending diabetes group visits ( GVs ) leads to lower medical care charges for inadequately insured patients with type 2 diabetes mellitus ( DM ) . STUDY DESIGN R and omized controlled clinical trial . METHODS Data were abstract ed from financial records for 186 patients with uncontrolled type 2 DM r and omized to receive care in GVs or usual care for 12 months . Mann-Whitney tests for differences of means for outpatient visits ( primary and specialty care ) , emergency department ( ED ) visits , and inpatient stays were performed . Separate charge models were developed for primary and specialty outpatient visits . Because GV adherence is potentially dependent on unobserved patient characteristics , treatment effect models of outpatient charges and specialty care visits were estimated using maximum likelihood methods . RESULTS Mann-Whitney test results indicated that GV patients had reduced ED and total charges but more outpatient charges than usual care patients . Ordinary least squares estimations confirmed that GVs increased outpatient visit charges ; however , controlling for endogeneity by estimating a treatment effect model of outpatient visit charges showed that GVs statistically significantly reduced outpatient charges ( P < .001 ) . Estimation of a separate treatment effect model of specialty care visits confirmed that GV effects on outpatient visit charges occurred via a reduction in specialty care visits . CONCLUSIONS After controlling for endogeneity via estimation of a treatment effect model , GVs statistically significantly reduced outpatient visit charges . Estimation of a separate treatment effect model of specialty care visits indicated that GVs likely substitute for more expensive specialty care visits WHAT IS KNOWN AND OBJECTIVE There are acknowledged benefits to continuing metformin when initiating insulin , but there appears to be growing concern over the role of sulphonylureas and thiazolidinediones when used in combination with insulin . This analysis investigates the effects of continuing or discontinuing oral antidiabetic drugs ( OADs ) following the initiation of once-daily insulin detemir . METHODS SOLVE is a 24-week , multinational observational study of insulin detemir initiation in patients with type 2 diabetes mellitus treated with one or more OADs . RESULTS In the total cohort ( n = 17 374 ) , there were significant improvements in HbA1c ( -1·3 % , 95 % CI -1·34 ; -1·27 % ) and weight ( -0·6 kg , 95 % CI -0·65 ; -0·47 kg ) , with an increase in the incidence rate of minor hypoglycaemia ( + 0·256 events ppy , P < 0·001 ) , but not severe hypoglycaemia ( -0·038 events ppy , P < 0·001 ) . Study participants had information on OAD use either prior to ( n = 17 086 ) or during insulin initiation ( n = 16 346 ) . HbA1c reductions were significantly greater in patients continuing treatment with metformin ( -1·3 % vs. -1·1 % , P < 0·01 ) , thiazolidinediones ( -1·3 % vs. -1·0 % , P < 0·01 ) and DPP-IV inhibitors ( -1·3 % vs. -0·9 % , P < 0·001 ) . Final insulin doses were significantly greater in patients discontinuing treatment with sulphonylureas ( 0·29 vs. 0·26 IU/kg , P < 0·001 ) , glinides ( 0·28 vs. 0·26 IU/kg , P < 0·01 ) , thiazolidinediones ( 0·31 vs. 0·26 IU/kg , P < 0·001 ) and DPP-IV inhibitors ( 0·35 vs. 0·29 IU/kg , P < 0·001 ) compared with patients continuing these respective agents . All patient subgroups had a mean weight loss irrespective of OAD continuation , apart from those continuing thiazolidinediones ( + 0·2 kg ) . The largest improvements in weight were seen following the withdrawal of sulphonylureas and thiazolidinediones ( -1·1 and -1·1 kg , respectively ) . WHAT IS NEW AND CONCLUSION Discontinuation ( or switching ) of OADs at the time of insulin initiation appears to be governed principally by concerns about hypoglycaemia and weight . HbA1c improvements were smaller in patients discontinuing OADs at the time of insulin initiation and may be associated with insufficient insulin titration BACKGROUND The present study evaluated the efficacy of biphasic human insulin 30 ( BHI 30 ) in type 2 diabetes patients who had failed in therapy with two or more oral antidiabetes drugs ( OADs ) . METHODS This open-label , nonr and omized , 4-month , multicenter , clinical observational study was conducted in Shanghai , China . A total of 660 insulin-naive type 2 diabetes patients with poor glycemic control ( glycosylated hemoglobin [ HbA1c ] ≥7.5 % ) , despite treatment with two or more OADs for more than 6 months , were recruited and received BHI 30 monotherapy or BHI 30 plus OAD(s ) ( metformin only , α-glucosidase inhibitor only , or both ) . RESULTS Among the 660 subjects , 644 completed the 4-month study . At the end of the study , the median level of HbA1c decreased by 2.0 % ( from 9.1 % to 7.0 % ) in the BHI 30 monotherapy group and also 2.0 % ( from 9.5 % to 7.3 % ) in the BHI 30 plus OAD group . More patients achieved the HbA1c < 7.0 % target in the BHI 30 monotherapy group than in the BHI 30 plus OAD(s ) group ( 47.9 % vs. 35.3 % , P=0.002 ) . Compared with the expenses of the prior treatment strategy , the median daily cost decreased by 39.8 % ( 4.5 yuan , Chinese RMB ) at the end point in the BHI 30 monotherapy group but increased by 20.0 % ( 2.2 yuan ) in the BHI 30 plus OAD(s ) group ( P<0.0001 ) . Moreover , patients in the BHI 30 plus OAD(s ) group had fewer minor hypoglycemic episodes than in the BHI 30 monotherapy group ( mean of 1.06 vs. 2.77 per patient per year , P<0.0001 ) . CONCLUSIONS Short-term BHI 30 therapy can improve glycemic control in insulin-naive type 2 diabetes patients after failure of two or more OADs . With higher baseline glucose level , the BHI 30 plus OAD(s ) group had lower pharmacoeconomic efficacy than the BHI 30 monotherapy group despite having fewer hypoglycemia events Objective To compare the safety and efficacy of the dipeptidylpeptidase-4 ( DPP-4 ) inhibitors in patients with type 2 diabetes and inadequate glycemic control . Design Systematic review of r and omized controlled trials ( RCTs ) , health economic evaluation studies , systematic review s , and meta-analyses , followed by primary Bayesian mixed treatment comparison meta-analyses ( MTCs ) , and secondary frequentist direct-comparison meta-analyses using a r and om-effects model . Outcomes were reported as weighted mean change from baseline , or odds ratio ( OR ) with 95 % credible interval . Data sources MEDLINE , MEDLINE In-Process , EMBASE , and BIOSIS via Dialog ProQuest ; Cochrane Central Register of Controlled Trials and Cochrane Data base of Systematic Review s via EBSCO ; four diabetes and two technical congress abstract s ; and health technology assessment organization websites . Eligibility criteria Patients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment . Data extraction and analysis Title/ abstract s were review ed for eligibility , followed by full-text review of publications remaining after first pass . A three-person team filtered articles and an independent review er checked a r and om selection ( 10 % ) of filtered articles . Data extraction and quality assessment of studies were also independently review ed . Five DPP-4 inhibitors ( alogliptin , linagliptin , saxagliptin , sitagliptin , and vildagliptin ) were compared via meta- analysis ( where data were available ) as monotherapy , dual therapy ( plus metformin , sulfonylurea , pioglitazone , or insulin ) , and triple therapy ( plus metformin/sulfonylurea ) . Results The review identified 6,601 articles ; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis . MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin ( HbA1c ) or body weight , or the proportions of patients achieving HbA1c < 7 % or experiencing a hypoglycemic event , apart from in patients on alogliptin plus metformin , who achieved HbA1c < 7 % more frequently than those treated with saxagliptin plus metformin [ OR 6.41 ( 95 % CI 3.15–11.98 ) versus 2.17 ( 95 % CI 1.56–2.95 ) ] . Conclusions This systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes , either as monotherapy or combination therapy Dipeptidyl peptidase-4 ( DPP-4 ) inhibitor is a new class of anti-diabetic drug which exerts its glucose-lowering action by suppressing the degradation of a gut incretin hormone glucagon-like peptide-1 ( GLP-1 ) . To eluci date whether treatment with stronger DPP-4 inhibitor on top of angiotensin II type 1 receptor blocker ( ARB ) provides greater renal protective effects , we performed a crossover study with two DPP-4 inhibitors , sitagliptin and alogliptin , in twelve type 2 diabetic patients with incipient nephropathy taking ARBs .  This study consisted of three treatment periods : sitagliptin 50 mg/day for 4 weeks ( first period ) , alogliptin 25 mg/day for 4 weeks ( second period ) , and sitagliptin 50 mg/day for 4 weeks ( third period ) . Significant changes in body mass index , blood pressure , serum lipids , serum creatinine , estimated glomerular filtration rate , and HbA1c were not observed among the three treatment periods . Reduced urinary levels of albumin and an oxidative stress marker 8-hydroxy-2'-deoxyguanosine ( 8-OHdG ) , increased urinary cAMP levels , and elevated plasma levels of stromal cell-derived factor-1α ( SDF-1α ) which is a physiological substrate of DPP-4 were observed after the switch from sitagliptin to a stronger DPP-4 inhibitor alogliptin . Given a large body of evidence indicating anti-oxidative action of cAMP and up-regulation of cellular cAMP production by SDF-1α , the present results suggest that more powerful DPP-4 inhibition on top of angiotensin II type 1 receptor blockade would offer additional protection against early-stage diabetic nephropathy beyond that attributed to glycemic control , via reduction of renal oxidative stress by SDF-1α-cAMP pathway activation Background — Dipeptidyl-peptidase 4 ( DPP-4 ) inhibitors are increasingly used to accomplish glycemic targets in patients with type II diabetes mellitus . Because DPP-4 is expressed in inflammatory cells , we hypothesized that its inhibition will exert favorable effects in atherosclerosis . Methods and Results — Male LDLR−/− mice ( 6 weeks ) were fed a high-fat diet or normal chow diet for 4 weeks and then r and omized to vehicle or alogliptin , a high-affinity DPP-4 inhibitor ( 40 mg · kg−1 · d−1 ) , for 12 weeks . Metabolic parameters , blood pressure , vascular function , atherosclerosis burden , and indexes of inflammation were obtained in target tissues , including the vasculature , adipose , and bone marrow , with assessment of global and cell-specific inflammatory pathways . In vitro and in vivo assays of DPP-4 inhibition ( DPP-4i ) on monocyte activation/migration were conducted in both human and murine cells and in a short-term ApoE−/− mouse model .  DPP-4i improved markers of insulin resistance and reduced blood pressure . DPP-4i reduced visceral adipose tissue macrophage content ( adipose tissue macrophages ; CD11b+ , CD11c+ , Ly6Chi ) concomitant with upregulation of CD163 . DPP-4 was highly expressed in bone marrow – derived CD11b+ cells , with DPP-4i downregulating proinflammatory genes in these cells . DPP-4i  decreased aortic plaque with a striking reduction in plaque macrophages .  DPP-4i  prevented monocyte migration and actin polymerization in in vitro assays via Rac-dependent mechanisms and prevented in vivo migration of labeled monocytes to the aorta in response to exogenous tumor necrosis factor-&agr ; and DPP-4 . Conclusion — DPP-4i exerts antiatherosclerotic effects and reduces inflammation via inhibition of monocyte activation/chemotaxis . These findings have important implication s for the use of this class of drugs in atherosclerosis CONTEXT In response to a meal , glucagon-like peptide-1 ( GLP-1 ) and glucose-dependent insulinotropic peptide ( GIP ) are released and modulate glycemic control . Normally these incretins are rapidly de grade d by dipeptidyl peptidase-4 ( DPP-4 ) . DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes . The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test ( OGTT ) were evaluated . OBJECTIVE The objective of the study was to examine the pharmacodynamics , pharmacokinetics , and tolerability of sitagliptin . DESIGN This was a r and omized , double-blind , placebo-controlled , three-period , single-dose crossover study . SETTING The study was conducted at six investigational sites . PATIENTS The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents . INTERVENTIONS Interventions included sitagliptin 25 mg , sitagliptin 200 mg , or placebo . MAIN OUTCOME MEASURES Measurements included plasma DPP-4 activity ; post-OGTT glucose excursion ; active and total incretin GIP levels ; insulin , C-peptide , and glucagon concentrations ; and sitagliptin pharmacokinetics . RESULTS Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h , enhanced active GLP-1 and GIP levels , increased insulin/C-peptide , decreased glucagon , and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin . Sitagliptin was generally well tolerated , with no hypoglycemic events . CONCLUSIONS In this study in patients with type 2 diabetes , near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80 % or greater , corresponding to a plasma sitagliptin concentration of 100 nm or greater , and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT BACKGROUND This study was performed to examine the efficacy of sitagliptin , a dipeptidyl peptidase-4 inhibitor , in Japanese patients with type 2 diabetes using continuous glucose monitoring ( CGM ) of 24-h glycemic changes . SUBJECTS AND METHODS The study was a prospect i ve open-label pilot study in patients with type 2 diabetes who were admitted to our hospital and treated with sitagliptin alone or concomitantly with another oral hypoglycemic drug .  CGM was performed for 2 days before sitagliptin administration and for another 2 days after administration . The average 24-h blood glucose level , SD of the 24-h blood glucose level , 24-h glycemic fluctuation range , mean amplitude of glycemic excursions ( MAGE ) , and hyperglycemic and hypoglycemic time periods were compared before and after administration . RESULTS Sitagliptin administration alone and with a concomitant drug decreased the average 24-h blood glucose level , SD of the 24-h blood glucose level , 24-h glycemic fluctuation range , MAGE , and hyperglycemic time , compared with these parameters before administration . There were significant correlations between the average 24-h blood glucose level before administration and the decrease in the average 24-h blood glucose level after administration and between MAGE before administration and the decrease in MAGE after administration . CONCLUSIONS Sitagliptin decreased the average glycemic level and also improved 24-h glycemic fluctuation , including postpr and ial hyperglycemia Introduction The IMPROVE ™ study is an openlabel , nonr and omized , observational study aim ed at determining the safety and efficacy of biphasic insulin aspart 30 ( BIAsp 30 ) treatment in subjects with type 2 diabetes from 11 countries . Here , we report the baseline data of the Indian cohort . Methods All subjects with type 2 diabetes requiring insulin and considered suitable for BIAsp 30 therapy based on their physician ’s clinical judgment were eligible to enter the study . The data recorded at baseline included demographic characteristics , detailed medical histories , physician-cited reasons for starting BIAsp 30 treatment , and the chosen dosage regimens . Results The Indian cohort included 17,995 subjects with diabetes . Poor glycemic control ( glycated hemoglobin [ HbA1c ] , 8.7%–9.6 % ) was observed at baseline in all four geographical zones ( North , South , East , and West ) and pre study treatment groups ( no therapy , only oral antidiabetic drug [ OAD ] , OAD ± insulin , and OAD ± insulin ± BIAsp 30 )  . Prevalence of both micro- and macrovascular complications was high , also reflecting poor glycemic control . Improving HbA1c and fasting and postpr and ial blood glucose levels were the most common reasons for starting BIAsp 30 therapy . The subjects were prescribed a mean BIAsp 30 dose of approximately 24 IU , and a twice-daily regimen was employed in almost 80 % of subjects . Conclusion The baseline results of the IMPROVE study Indian cohort confirm the poor glycemic control and the delayed initiation and /or inadequacy of treatment in subjects with type 2 diabetes . These results also highlight the need for timely and appropriately intensive insulin-based therapy AIM To evaluate the efficacy and safety of adding biphasic insulin aspart 30 ( BIAsp30 ; NovoMix 30 ) to existing oral antidiabetic agents ( OADs ) vs. optimizing OADs in a subgroup of Western Pacific patients with type 2 diabetes inadequately controlled on oral monotherapy or oral combination therapy . METHODS This 26-week , multi-centre , open-labelled , r and omized , two-arm parallel trial consisted of a 2-week screening period , followed by 24 weeks of treatment . Subjects r and omized to BIAsp30 treatment ( n = 129 ) received BIAsp30 once daily ( o.d . ) at dinnertime between Week 2 and Week 14 , and those not reaching treatment targets were switched to twice daily ( b.i.d . ) BIAsp30 at Week 14 ( n = 50 ) . Subjects r and omized to the OAD-only arm ( n = 63 ) continued with their previous OAD treatment and , in an attempt to reach treatment goals , the dose was optimized ( but OAD unchanged ) in accordance to local treatment practice and labelling . RESULTS Significantly greater reductions in HbA(1c ) over Weeks 0 - 13 with BIAsp30 ( o.d . ) vs. OAD-only treatment ( 1.16 vs. 0.58 % ; p < 0.001 ) , and over Weeks 0 - 26 , with BIAsp30 ( o.d . ) and BIAsp30 ( b.i.d . ) treatments vs. OAD-only treatment ( 1.24 vs. 1.34 vs. 0.67 % ; p < 0.01 ) . Hypoglycaemic episodes were reported in 54 % of the patients in BIAsp30 ( o.d . and b.i.d . pooled ) and 30 % of the patients in OAD-only group . All episodes were minor or symptomatic , except for one in each treatment group , which was major . CONCLUSIONS Initiating BIAsp30 treatment is a safe and more effective way to improve glycaemic control in Western Pacific patients with type 2 diabetes inadequately controlled with oral monotherapy or oral combination therapy compared with optimizing oral combination therapy alone . In patients not reaching treatment target on BIAsp30 ( o.d . ) , treatment with BIAsp30 ( b.i.d . ) should be considered OBJECTIVE To comprehensively compare the effects of a very low-carbohydrate , high – unsaturated/low – saturated fat diet ( LC ) with those of a high – unrefined carbohydrate , low-fat diet ( HC ) on glycemic control and cardiovascular disease ( CVD ) risk factors in type 2 diabetes ( T2DM ) . RESEARCH DESIGN AND METHODS Obese adults ( n = 115 , BMI 34.4 ± 4.2 kg/m2 , age 58 ± 7 years ) with T2DM were r and omized to a hypocaloric LC diet ( 14 % carbohydrate [ < 50 g/day ] , 28 % protein , and 58 % fat [ < 10 % saturated fat ] ) or an energy-matched HC diet ( 53 % carbohydrate , 17 % protein , and 30 % fat [ < 10 % saturated fat ] ) combined with structured exercise for 24 weeks . The outcomes measured were as follows : glycosylated hemoglobin ( HbA1c ) , glycemic variability ( GV ; assessed by 48-h continuous glucose monitoring ) , antiglycemic medication changes ( antiglycemic medication effects score [ MES ] ) , and blood lipids and pressure . RESULTS A total of 93 participants completed 24 weeks . Both groups achieved similar completion rates ( LC 79 % , HC 82 % ) and weight loss ( LC −12.0 ± 6.3 kg , HC −11.5 ± 5.5 kg ) ; P ≥ 0.50 . Blood pressure ( −9.8/−7.3 ± 11.6/6.8 mmHg ) , fasting blood glucose ( −1.4 ± 2.3 mmol/L ) , and LDL cholesterol ( −0.3 ± 0.6 mmol/L ) decreased , with no diet effect ( P ≥ 0.10 ) . LC achieved greater reductions in triglycerides ( −0.5 ± 0.5 vs. −0.1 ± 0.5 mmol/L ) , MES ( −0.5 ± 0.5 vs. −0.2 ± 0.5 ) , and GV indices ; P  ≤ 0.03 . LC induced greater HbA1c reductions ( −2.6 ± 1.0 % [ −28.4 ± 10.9 mmol/mol ] vs. −1.9 ± 1.2 % [ −20.8 ± 13.1 mmol/mol ] ; P = 0.002 ) and HDL cholesterol ( HDL-C ) increases ( 0.2 ± 0.3 vs. 0.05 ± 0.2 mmol/L ; P = 0.007 ) in participants with the respective baseline values HbA1c > 7.8 % ( 62 mmol/mol ) and HDL-C < 1.29 mmol/L. CONCLUSIONS Both diets achieved substantial improvements for several clinical glycemic control and CVD risk markers . These improvements and reductions in GV and antiglycemic medication requirements were greatest with the LC compared with HC . This suggests an LC diet with low saturated fat may be an effective dietary approach for T2DM management if effects are sustained beyond 24 weeks CONTEXT Dipeptidyl peptidase 4 ( DPP-4 ) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus ( T2DM ) by prolonging the activity of the circulating incretins , glucose-dependent insulinotropic polypeptide ( GIP ) and glucagon-like peptide 1 ( GLP-1 ) . Consistent with this mechanism of action , DPP-4 inhibitors improve glucose tolerance after meals by increasing insulin and reducing glucagon levels in the plasma . However , DPP-4 inhibitors also reduce fasting blood glucose , an unexpected effect because circulating levels of active GIP and GLP-1 are low in the postabsorptive state . OBJECTIVE The objective of the study was to examine the effects of DPP-4 inhibition on fasting islet function . DESIGN We conducted a r and omized , double-blind , placebo-controlled trial . SETTING The study was performed in General Clinical Research Centers at two University Hospitals . SUBJECTS Forty-one subjects with T2DM were treated with metformin or diet , having good glycemic control with glycosylated hemoglobin values of 6.2 - 7.5 % . INTERVENTION Subjects were treated with vildagliptin ( 50 mg twice daily ) or placebo for 3 months , followed by a 2-wk washout . Major Outcome Measure : We measured insulin secretion in response to iv glucose and arginine before and after treatment and after drug washout . RESULTS There were small and comparable reductions in glycosylated hemoglobin in both groups over 3 months . Vildagliptin increased fasting GLP-1 levels in subjects taking metformin , but not those managed with diet , and raised active GIP levels slightly . DPP-4 inhibitor treatment improved the acute insulin and C-peptide responses to glucose ( 50 and 100 % respectively ; P < 0.05 ) and increased the slope of the C-peptide response to glucose ( 33 % ; P = 0.023 ) . CONCLUSION Vildagliptin improves islet function in T2DM under fasting conditions . This suggests that DPP-4 inhibition has metabolic benefits in addition to enhancing meal-induced GLP-1 and GIP activity We conducted this study to determine whether additional administration of a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor might provide further improvement of the glycemic control in Japanese type 2 diabetes patients showing relatively good glycemic control under treatment with a sodium glucose co-transporter 2 ( SGLT2 ) inhibitor . Five SGLT2 inhibitor ( luseogliflozin , dapagliflozin , tofogliflozin , empagliflozin and canagliflozin ) preparations and five DPP-4 inhibitor ( sitagliptin , vildagliptin , alogliptin , anagliptin and linagliptin ) preparations were used . The results showed that monotherapy with SGLT2 inhibitor produced significant decreases of the body weight and BMI , hemoglobin A1c ( HbA1c ) also decreased , but not to a significant extent . However , decreases of the serum aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , γ-glutamyltransferase ( γ-GTP ) and uric acid were observed in this group . On the other h and , in type 2 diabetes patients treated concomitantly with a DPP-4 inhibitor and SGLT2 inhibitor , significant decrease of the HbA1c was observed , indicating the favorable effect of the concomitant therapy . The body weight and BMI decreased . As for the serum lipid profile , elevation of the serum HDL-cholesterol ( HDL-C ) was observed . Furthermore , AST , ALT , γ-GTP and uric acid decreased in the combined treatment group . Then , the therapeutic responses to concurrent administration with SGLT2 inhibitor of each of the 5 individual DPP-4 inhibitors used in this study were analyzed . The results showed that concomitant administration of sitagliptin , a DPP-4 inhibitor , with the SGLT2 inhibitor yielded the best results in terms of the lowering of the HbA1c and improvement of the serum lipid profile BACKGROUND Type 2 diabetes ( T2DM ) patients often fail to achieve adequate glycemic control with oral antidiabetic drugs ( OADs ) . Insulin has been shown to improve glycemic control in these patients but with increased risk of hypoglycemia . This study compared the efficacy and safety of insulin glargine and NPH insulin , both in combination with a once-daily fixed dose of glimepiride , in terms of glycemic control and incidence of hypoglycemia . METHODS In this open-label , 24-week r and omized trial in ten Latin American countries , T2DM patients poorly controlled on OADs ( HbA1c > or = 7.5 and < or = 10.5 % ) received glimepiride plus insulin glargine ( n = 231 ) or NPH insulin ( n = 250 ) using a forced titration algorithm . The primary endpoint was the equivalence of 24-week mean changes in HbA1c . RESULTS Insulin glargine and NPH insulin achieved similar HbA1c reductions ( adjusted mean difference -0.047 ; 90 % CI -0.232 , 0.138 ; per- protocol analysis ) . Confirmed nocturnal hypoglycemia was significantly lower with insulin glargine vs. NPH insulin ( 16.9 vs. 30.0 % ; p < 0.01 ; safety analysis ) . Patients receiving insulin glargine were significantly more likely to achieve HbA1c levels < 7.0 % without hypoglycemia ( 27 vs. 17 % ; p = 0.014 ; per- protocol analysis ) . There was a more pronounced treatment satisfaction improvement with insulin glargine vs. NPH insulin ( p < 0.02 ; full analysis ) . The proportion of patients who lost time from work or normal activities due to diabetes was lower with insulin glargine vs. NPH ( 1.8 vs. 3.3 % ; full analysis ) . CONCLUSIONS In patients with T2DM , inadequately controlled on OADs , once-daily insulin glargine plus glimepiride is effective in improving metabolic control with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin OBJECTIVE The requirement to inject current basal insulin analogs at a fixed time each day may complicate adherence and compromise glycemic control . This trial evaluated the efficacy and safety of varying the daily injection time of insulin degludec ( IDeg ) , an ultra-long-acting basal insulin . RESEARCH DESIGN AND METHODS This 26-week , open-label , treat-to-target trial enrolled adults ( ≥18 years ) with type 2 diabetes who were either insulin naïve and receiving oral antidiabetic drugs ( OADs ) ( HbA1c = 7–11 % ) or previously on basal insulin ± OAD(s ) ( HbA1c = 7–10 % ) . Participants were r and omized to 1 ) once-daily ( OD ) IDeg in a prespecified dosing schedule , creating 8–40-h intervals between injections ( IDeg OD Flex ; n = 229 ) ; 2 ) once-daily IDeg at the main evening meal ( IDeg OD ; n = 228 ) ; or 3 ) once-daily insulin glargine at the same time each day ( IGlar OD ; n = 230 ) . The primary outcome was noninferiority of IDeg OD Flex to IGlar OD in HbA1c reduction after 26 weeks . RESULTS After 26 weeks , IDeg OD Flex , IDeg OD , and IGlar OD improved HbA1c by 1.28 , 1.07 , and 1.26 % points , respectively ( estimated treatment difference [ IDeg OD Flex − IGlar OD ] : 0.04 % points [ –0.12 to 0.20 ] , confirming noninferiority ) . No statistically significant differences in overall or nocturnal hypoglycemia were found between IDeg OD Flex and IGlar OD . Comparable glycemic control and rates of hypoglycemia were seen with IDeg OD Flex and IDeg OD . Adverse event profiles were similar across groups . CONCLUSIONS The use of extreme dosing intervals of 8–40 h demonstrates that the daily injection time of IDeg can be varied without compromising glycemic control or safety Background New-onset diabetes mellitus after transplantation ( NODAT ) , a frequent and serious complication after transplantation , is associated with decreased graft and patient survival . Currently , it is diagnosed and treated primarily according to existing guidelines for type II diabetes . To date , only a few trials have studied antidiabetic drugs in patients with NODAT .  Vildagliptin is a novel dipeptidyl peptidase-4 ( DPP-4 ) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose . Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants . Therefore , the therapy of NODAT with this class of compounds seems attractive . At present , vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs , since that it efficiently decreases glycated hemoglobin ( HbA1c ) values . Additionally , vildagliptin has been shown to be safe in patients with moderately impaired kidney function . This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT . Methods / Design This study is a r and omized , placebo-controlled , double-blind , prospect i ve phase II trial . Using the results of routinely performed oral glucose tolerance tests ( OGTT ) in stable renal transplant patients at our center , we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl ( 11.1 mmol/l ) . They are r and omized to receive either 50 mg vildagliptin or placebo once daily . A total of 32 patients with newly diagnosed NODAT will be included . The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start , compared between the vildagliptin- and the placebo-group . Secondary endpoints include changes in HbA1c and fasting plasma glucose ( FPG ) . The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes ( glucose < 72 mg/dl or 4 mmol/l ) , the number of adverse events , and possible medication-associated side-effects . Discussion NODAT is a severe complication after kidney transplantation . Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients . The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.Trial Registration Clinical Trials.gov BACKGROUND & AIMS The aim was to assess relative contributions of gastric volumes ( GV ) and  gastric emptying ( GE ) to meal size and postpr and ial symptoms in patients with functional dyspepsia . METHODS Patients with chronic upper gastrointestinal symptoms were prospect ively evaluated . GV during fasting and after 300 mL Ensure was measured with 99 m Tc-single-photon emission computed tomography imaging and solid GE ( 99 m Tc-egg ) by scintigraphy .  Maximum tolerated volume ( MTV ) and symptoms were measured after Ensure challenge . RESULTS Of 57 adult patients evaluated , 39 ( 23 women , 16 men ) met Rome II criteria for functional dyspepsia and had no other diagnosis to account for dyspepsia . The most frequent symptoms were abdominal pain ( 90 % ) , pain predominantly after meals ( 76 % ) , nausea ( 85 % ) , and early fullness after meals ( 79 % ) . Relative to established laboratory normal values , MTV was abnormal in 82 % , aggregate symptom score > 209 in 72 % , GE ( at 1 hour ) accelerated in 41 % , GE ( at 4 hours ) delayed in 41 % , and postmeal GV reduced in 52 % . Lower body mass was associated with lower MTV and higher postchallenge symptoms . Lower fasting ( not postpr and ial ) GV and faster GE were independent predictors of lower MTV , explaining 18 % of the variance after adjusting for body weight ( 32 % of variance ) . GE was an independent predictor of postchallenge symptoms ( 10 % of variance ) after adjusting for volume ingested ( 10 % ) , age ( 20 % ) , and weight ( 10 % ) . CONCLUSIONS In adults with functional dyspepsia seen in a tertiary referral practice , decreased meal size and postmeal symptoms are associated with low fasting GV and faster GE . These data provide physiologic targets for ameliorating symptoms of functional dyspepsia AIMS The IMPROVE study is a multinational , open-label , non-r and omised , 26-week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 ( BIAsp 30 ) treatment in type 2 diabetes in routine clinical practice . The principal aims of this report were to characterise the baseline population and physicians ' treatment decisions . METHODS Patients with type 2 diabetes who required insulin and whose physician had decided to initiate BIAsp 30 were eligible . At baseline , demographic data and detailed medical histories were collected and physicians recorded their reasons for starting BIAsp 30 , the glycaemic targets set and the regimens chosen . RESULTS Data from 51,286 patients were included in analyses . Baseline glycaemic control was poor in all eight countries in the present analysis and in all pre study treatment groups [ no therapy , oral antidiabetic drugs ( OADs ) only , insulin with or without OADs ] , and the rates of vascular complications were high . Although the management of each of the three main measures of glycaemic control were key reasons for starting BIAsp 30 , target- setting for postpr and ial glucose levels was variable . A twice-daily regimen was used to start BIAsp 30 therapy for 80 % or more of patients . CONCLUSIONS The IMPROVE baseline data reaffirm the global nature of poor glycaemic control in type 2 diabetes and echo the concerns that initiation of therapy , particularly insulin , is commonly delayed in clinical practice . Although postpr and ial glucose control was a key driver for physicians ' choice of BIAsp 30 , this was not consistently reflected in the targets set Abstract Aim : To examine the options for add-on therapy in patients with type 2 diabetes whose disease is no longer adequately controlled by lifestyle interventions and oral antidiabetic drug ( OAD ) monotherapy .  Methods : This analysis included a subset of patients receiving prior OAD monotherapy from 2 phase 3 , 26-week , r and omized , double-blind , double-dummy , active-control , parallel-group , multicenter , multinational trials . Prior to r and omization , patients not already receiving either metformin or glimepiride  were switched to monotherapy with one of these drugs , and the dose was titrated to defined targets . Patients were then r and omized to liraglutide ( 1.8 mg , 1.2 mg , or 0.6 mg once daily ) , placebo ( OAD monotherapy plus placebo ) , or active comparator ( rosiglitazone or glimepiride ) . For this analysis , only the liraglutide 1.8-mg dose was included . The primary outcome measure was change in glycosylated hemoglobin ( HbA1c ) from baseline . Secondary endpoints included in this analysis are percentage of patients achieving HbA1c < 7 % , change in fasting plasma glucose , systolic blood pressure , body weight , β-cell function , hypoglycemic episodes , and nausea . Results : There was a significant reduction in HbA1c in patients previously treated with OAD monotherapy ( P < 0.0001 ) and significantly more patients achieved HbA1c < 7 % ( P = 0.0005 ) with the addition of liraglutide than with rosiglitazone . In addition , rosiglitazone plus glimepiride was associated with significantly more weight gain ( P < 0.0001 ) than liraglutide plus glimepiride ( P = 0.04 ) . For patients on metformin monotherapy , the addition of liraglutide or glimepiride result ed in similar levels of glycemic control ; however , patients receiving glimepiride had significantly greater weight gain ( P < 0.0001 ) and higher rates of minor hyperglycemia . Conclusion : Given the combination of effective glycemic control and weight benefits , liraglutide is a good option for early add-on therapy for patients on OAD monotherapy
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 .
Glycemic variability ( GV ) has been an emerging target for preventing complications related to type 2 diabetes .
For reducing GV , DPP-IV inhibitors have shown effectiveness compared to other oral anti-hyperglycemic drugs ( OADs ) , but systematic evaluation has yet to be existed .