The Experts below are selected from a list of 208533 Experts worldwide ranked by ideXlab platform

R Brodows - One of the best experts on this subject based on the ideXlab platform.

  • exenAtide versus insulin glArgine in pAtients with suboptimAlly controlled type 2 diAbetes A rAndomized triAl
    Annals of Internal Medicine, 2005
    Co-Authors: Robert J Heine, Luc F Van Gaal, Don Johns, Michael J Mihm, Mario Widel, R Brodows
    Abstract:

    BAckground: PhysiciAns mAy use either insulin or exenAtide injections for pAtients with type 2 diAbetes mellitus who hAve poor glycemic control despite tAking orAl blood glucose-lowering drugs. Objective: To compAre effects of exenAtide And insulin glArgine on glycemic control in pAtients with type 2 diAbetes mellitus thAt is suboptimAlly controlled with metformin And A sulfonylureA. Design: 26-week multicenter, open-lAbel, rAndomized, controlled triAl. Setting: 82 outpAtient study centers in 13 countries. PAtients: 551 pAtients with type 2 diAbetes And inAdequAte glycemic control (defined As Hemoglobin A 1c level rAnging from 7.0% to 10.0%) despite combinAtion metformin And sulfonylureA therApy. Intervention: ExenAtide, 10 μg twice dAily, or insulin glArgine, 1 dAily dose titrAted to mAintAin fAsting blood glucose levels of less thAn 5.6 mmol/L (<100 mg/dL). MeAsurements: Hemoglobin A 1c level, fAsting plAsmA glucose level, body weight, 7-point self-monitored blood glucose, stAndArdized test-meAl chAllenge, sAfety, And tolerAbility. Results: BAseline meAn Hemoglobin A 1c level wAs 8.2% for pAtients receiving exenAtide And 8.3% for those receiving insulin glArgine. At week 26, both exenAtide And insulin glArgine reduced Hemoglobin A 1c levels by 1.11% (difference, 0.017 percentAge point [95% Cl, -0.123 to 0.157 percentAge point]). ExenAtide reduced postprAndiAl glucose excursions more thAn insulin glArgine, while insulin glArgine reduced fAsting glucose concentrAtions more thAn exenAtide. Body weight decreAsed 2.3 kg with exenAtide And increAsed 1.8 kg with insulin glArgine (difference, -4.1 kg [Cl, -4.6 to -3.5 kg]). RAtes of symptomAtic hypoglycemiA were similAr, but nocturnAl hypoglycemiA occurred less frequently with exenAtide (0.9 event/pAtient-yeAr versus 2.4 events/ pAtient-yeAr; difference, -1.6 events/pAtient-yeAr [Cl, -2.3 to -0.9 event/pAtient yeAr]). GAstrointestinAl symptoms were more common in the exenAtide group thAn in the insulin glArgine group, including nAuseA (57.1% vs. 8.6%), vomiting (17.4% vs. 3.7%) And diArrheA (8.5% vs. 3.0%). LimitAtions: The triAl wAs open-lAbel And did not Assess clinicAl complicAtions relAted to diAbetes. Of the 551 pArticipAnts, 19.4% of those receiving exenAtide And 9.7% of those receiving insulin glArgine withdrew from the study. Only 21.6% of the insulin glArgine group And 8.6% of the exenAtide group Achieved the tArget level for fAsting plAsmA glucose of less thAn 5.6 mmol/L (<100 mg/dL). Conclusions: ExenAtide And insulin glArgine Achieved similAr improvements in overAll glycemic control in pAtients with type 2 diAbetes thAt wAs suboptimAlly controlled with orAl combinAtion therApy. ExenAtide wAs AssociAted with weight reduction And hAd A higher incidence of gAstrointestinAl Adverse effects thAn insulin glArgine.

  • exenAtide versus insulin glArgine in pAtients with suboptimAlly controlled type 2 diAbetes A rAndomized triAl
    Annals of Internal Medicine, 2005
    Co-Authors: Robert J Heine, Don Johns, Michael J Mihm, Mario Widel, Luc F Van Gaal, R Brodows
    Abstract:

    BAckground: PhysiciAns mAy use either insulin or exenAtide injections for pAtients with type 2 diAbetes mellitus who hAve poor glycemic control despite tAking orAl blood glucose-lowering drugs. Objective: To compAre effects of exenAtide And insulin glArgine on glycemic control in pAtients with type 2 diAbetes mellitus thAt is suboptimAlly controlled with metformin And A sulfonylureA. Design: 26-week multicenter, open-lAbel, rAndomized, controlled triAl. Setting: 82 outpAtient study centers in 13 countries. PAtients: 551 pAtients with type 2 diAbetes And inAdequAte glycemic control (defined As Hemoglobin A 1c level rAnging from 7.0% to 10.0%) despite combinAtion metformin And sulfonylureA therApy. Intervention: ExenAtide, 10 μg twice dAily, or insulin glArgine, 1 dAily dose titrAted to mAintAin fAsting blood glucose levels of less thAn 5.6 mmol/L (<100 mg/dL). MeAsurements: Hemoglobin A 1c level, fAsting plAsmA glucose level, body weight, 7-point self-monitored blood glucose, stAndArdized test-meAl chAllenge, sAfety, And tolerAbility. Results: BAseline meAn Hemoglobin A 1c level wAs 8.2% for pAtients receiving exenAtide And 8.3% for those receiving insulin glArgine. At week 26, both exenAtide And insulin glArgine reduced Hemoglobin A 1c levels by 1.11% (difference, 0.017 percentAge point [95% Cl, -0.123 to 0.157 percentAge point]). ExenAtide reduced postprAndiAl glucose excursions more thAn insulin glArgine, while insulin glArgine reduced fAsting glucose concentrAtions more thAn exenAtide. Body weight decreAsed 2.3 kg with exenAtide And increAsed 1.8 kg with insulin glArgine (difference, -4.1 kg [Cl, -4.6 to -3.5 kg]). RAtes of symptomAtic hypoglycemiA were similAr, but nocturnAl hypoglycemiA occurred less frequently with exenAtide (0.9 event/pAtient-yeAr versus 2.4 events/ pAtient-yeAr; difference, -1.6 events/pAtient-yeAr [Cl, -2.3 to -0.9 event/pAtient yeAr]). GAstrointestinAl symptoms were more common in the exenAtide group thAn in the insulin glArgine group, including nAuseA (57.1% vs. 8.6%), vomiting (17.4% vs. 3.7%) And diArrheA (8.5% vs. 3.0%). LimitAtions: The triAl wAs open-lAbel And did not Assess clinicAl complicAtions relAted to diAbetes. Of the 551 pArticipAnts, 19.4% of those receiving exenAtide And 9.7% of those receiving insulin glArgine withdrew from the study. Only 21.6% of the insulin glArgine group And 8.6% of the exenAtide group Achieved the tArget level for fAsting plAsmA glucose of less thAn 5.6 mmol/L (<100 mg/dL). Conclusions: ExenAtide And insulin glArgine Achieved similAr improvements in overAll glycemic control in pAtients with type 2 diAbetes thAt wAs suboptimAlly controlled with orAl combinAtion therApy. ExenAtide wAs AssociAted with weight reduction And hAd A higher incidence of gAstrointestinAl Adverse effects thAn insulin glArgine.

Robert J Heine - One of the best experts on this subject based on the ideXlab platform.

  • exenAtide versus insulin glArgine in pAtients with suboptimAlly controlled type 2 diAbetes A rAndomized triAl
    Annals of Internal Medicine, 2005
    Co-Authors: Robert J Heine, Luc F Van Gaal, Don Johns, Michael J Mihm, Mario Widel, R Brodows
    Abstract:

    BAckground: PhysiciAns mAy use either insulin or exenAtide injections for pAtients with type 2 diAbetes mellitus who hAve poor glycemic control despite tAking orAl blood glucose-lowering drugs. Objective: To compAre effects of exenAtide And insulin glArgine on glycemic control in pAtients with type 2 diAbetes mellitus thAt is suboptimAlly controlled with metformin And A sulfonylureA. Design: 26-week multicenter, open-lAbel, rAndomized, controlled triAl. Setting: 82 outpAtient study centers in 13 countries. PAtients: 551 pAtients with type 2 diAbetes And inAdequAte glycemic control (defined As Hemoglobin A 1c level rAnging from 7.0% to 10.0%) despite combinAtion metformin And sulfonylureA therApy. Intervention: ExenAtide, 10 μg twice dAily, or insulin glArgine, 1 dAily dose titrAted to mAintAin fAsting blood glucose levels of less thAn 5.6 mmol/L (<100 mg/dL). MeAsurements: Hemoglobin A 1c level, fAsting plAsmA glucose level, body weight, 7-point self-monitored blood glucose, stAndArdized test-meAl chAllenge, sAfety, And tolerAbility. Results: BAseline meAn Hemoglobin A 1c level wAs 8.2% for pAtients receiving exenAtide And 8.3% for those receiving insulin glArgine. At week 26, both exenAtide And insulin glArgine reduced Hemoglobin A 1c levels by 1.11% (difference, 0.017 percentAge point [95% Cl, -0.123 to 0.157 percentAge point]). ExenAtide reduced postprAndiAl glucose excursions more thAn insulin glArgine, while insulin glArgine reduced fAsting glucose concentrAtions more thAn exenAtide. Body weight decreAsed 2.3 kg with exenAtide And increAsed 1.8 kg with insulin glArgine (difference, -4.1 kg [Cl, -4.6 to -3.5 kg]). RAtes of symptomAtic hypoglycemiA were similAr, but nocturnAl hypoglycemiA occurred less frequently with exenAtide (0.9 event/pAtient-yeAr versus 2.4 events/ pAtient-yeAr; difference, -1.6 events/pAtient-yeAr [Cl, -2.3 to -0.9 event/pAtient yeAr]). GAstrointestinAl symptoms were more common in the exenAtide group thAn in the insulin glArgine group, including nAuseA (57.1% vs. 8.6%), vomiting (17.4% vs. 3.7%) And diArrheA (8.5% vs. 3.0%). LimitAtions: The triAl wAs open-lAbel And did not Assess clinicAl complicAtions relAted to diAbetes. Of the 551 pArticipAnts, 19.4% of those receiving exenAtide And 9.7% of those receiving insulin glArgine withdrew from the study. Only 21.6% of the insulin glArgine group And 8.6% of the exenAtide group Achieved the tArget level for fAsting plAsmA glucose of less thAn 5.6 mmol/L (<100 mg/dL). Conclusions: ExenAtide And insulin glArgine Achieved similAr improvements in overAll glycemic control in pAtients with type 2 diAbetes thAt wAs suboptimAlly controlled with orAl combinAtion therApy. ExenAtide wAs AssociAted with weight reduction And hAd A higher incidence of gAstrointestinAl Adverse effects thAn insulin glArgine.

  • exenAtide versus insulin glArgine in pAtients with suboptimAlly controlled type 2 diAbetes A rAndomized triAl
    Annals of Internal Medicine, 2005
    Co-Authors: Robert J Heine, Don Johns, Michael J Mihm, Mario Widel, Luc F Van Gaal, R Brodows
    Abstract:

    BAckground: PhysiciAns mAy use either insulin or exenAtide injections for pAtients with type 2 diAbetes mellitus who hAve poor glycemic control despite tAking orAl blood glucose-lowering drugs. Objective: To compAre effects of exenAtide And insulin glArgine on glycemic control in pAtients with type 2 diAbetes mellitus thAt is suboptimAlly controlled with metformin And A sulfonylureA. Design: 26-week multicenter, open-lAbel, rAndomized, controlled triAl. Setting: 82 outpAtient study centers in 13 countries. PAtients: 551 pAtients with type 2 diAbetes And inAdequAte glycemic control (defined As Hemoglobin A 1c level rAnging from 7.0% to 10.0%) despite combinAtion metformin And sulfonylureA therApy. Intervention: ExenAtide, 10 μg twice dAily, or insulin glArgine, 1 dAily dose titrAted to mAintAin fAsting blood glucose levels of less thAn 5.6 mmol/L (<100 mg/dL). MeAsurements: Hemoglobin A 1c level, fAsting plAsmA glucose level, body weight, 7-point self-monitored blood glucose, stAndArdized test-meAl chAllenge, sAfety, And tolerAbility. Results: BAseline meAn Hemoglobin A 1c level wAs 8.2% for pAtients receiving exenAtide And 8.3% for those receiving insulin glArgine. At week 26, both exenAtide And insulin glArgine reduced Hemoglobin A 1c levels by 1.11% (difference, 0.017 percentAge point [95% Cl, -0.123 to 0.157 percentAge point]). ExenAtide reduced postprAndiAl glucose excursions more thAn insulin glArgine, while insulin glArgine reduced fAsting glucose concentrAtions more thAn exenAtide. Body weight decreAsed 2.3 kg with exenAtide And increAsed 1.8 kg with insulin glArgine (difference, -4.1 kg [Cl, -4.6 to -3.5 kg]). RAtes of symptomAtic hypoglycemiA were similAr, but nocturnAl hypoglycemiA occurred less frequently with exenAtide (0.9 event/pAtient-yeAr versus 2.4 events/ pAtient-yeAr; difference, -1.6 events/pAtient-yeAr [Cl, -2.3 to -0.9 event/pAtient yeAr]). GAstrointestinAl symptoms were more common in the exenAtide group thAn in the insulin glArgine group, including nAuseA (57.1% vs. 8.6%), vomiting (17.4% vs. 3.7%) And diArrheA (8.5% vs. 3.0%). LimitAtions: The triAl wAs open-lAbel And did not Assess clinicAl complicAtions relAted to diAbetes. Of the 551 pArticipAnts, 19.4% of those receiving exenAtide And 9.7% of those receiving insulin glArgine withdrew from the study. Only 21.6% of the insulin glArgine group And 8.6% of the exenAtide group Achieved the tArget level for fAsting plAsmA glucose of less thAn 5.6 mmol/L (<100 mg/dL). Conclusions: ExenAtide And insulin glArgine Achieved similAr improvements in overAll glycemic control in pAtients with type 2 diAbetes thAt wAs suboptimAlly controlled with orAl combinAtion therApy. ExenAtide wAs AssociAted with weight reduction And hAd A higher incidence of gAstrointestinAl Adverse effects thAn insulin glArgine.

Ele Ferrannini - One of the best experts on this subject based on the ideXlab platform.

  • metAbolic effects of viscerAl fAt AccumulAtion in type 2 diAbetes
    The Journal of Clinical Endocrinology and Metabolism, 2002
    Co-Authors: Amalia Gastaldelli, Yoshinori Miyazaki, Maura Pettiti, Masafumi Matsuda, Srihanth Mahankali, Eleonora Santini, Ralph A Defronzo, Ele Ferrannini
    Abstract:

    ViscerAl fAt (VF) excess hAs been AssociAted with decreAsed peripherAl insulin sensitivity And hAs been suggested to contribute to hepAtic insulin resistAnce. However, the mechAnisms by which VF impActs on hepAtic glucose metAbolism And the quAntitAtive role of VF in glycemic control hAve not been investigAted. In the present study 63 type 2 diAbetic subjects (Age, 55 +/- 1 yr; fAsting plAsmA glucose, 5.5-14.4 mmol/liter; Hemoglobin A(1c), 6.1-11.7%) underwent meAsurement of 1) fAt-free mAss ((3)H(2)O technique), 2) sc And viscerAl AbdominAl fAt AreA (mAgnetic resonAnce imAging), 3) insulin sensitivity (euglycemic insulin clAmp), 4) endogenous glucose output ([(3)H]glucose infusion technique), And 5) gluconeogenesis ((2)H(2)O method). After Adjustment for sex, Age, body mAss index, diAbetes durAtion, ethnicity, And sc fAt AreA, VF AreA wAs positively relAted to fAsting hyperglycemiA (pArtiAl r = 0.46; P = 0.001) As well As to Hemoglobin A(1c) (pArtiAl r = 0.50; P = 0.0003). Insulin sensitivity wAs reciprocAlly relAted to VF independently of body mAss index (pArtiAl r = 0.33; P = 0.01). In contrAst, the relAtion of bAsAl endogenous glucose output to VF wAs not stAtisticAlly significAnt. This lAck of AssociAtion wAs explAined by the fAct thAt VF wAs positively AssociAted with gluconeogenesis flux (confounder-Adjusted, pArtiAl r = 0.45; P = 0.003), but wAs reciprocAlly AssociAted with glycogenolysis (pArtiAl r = 0.31; P < 0.05). We conclude thAt in pAtients with estAblished type 2 diAbetes, VF AccumulAtion hAs A significAnt negAtive impAct on glycemic control through A decreAse in peripherAl insulin sensitivity And An enhAncement of gluconeogenesis.

Melvin B Weiss - One of the best experts on this subject based on the ideXlab platform.

Juliette T. J. Lecomte - One of the best experts on this subject based on the ideXlab platform.

  • histidine lysine AxiAl ligAnd switching in A Hemoglobin A role for heme propionAtes
    Biochemistry, 2018
    Co-Authors: Dillon B Nye, Matthew R. Preimesberger, Ananya Majumdar, Juliette T. J. Lecomte
    Abstract:

    The Hemoglobin of Synechococcus sp. PCC 7002, GlbN, is A monomeric group I truncAted protein (TrHb1) thAt coordinAtes the heme iron with two histidine ligAnds At neutrAl pH. One of these is the distAl histidine (His46), A residue thAt cAn be displAced by dioxygen And other smAll molecules. Here, we show with mutAgenesis, electronic Absorption spectroscopy, And nucleAr mAgnetic resonAnce (NMR) spectroscopy thAt At high pH And exclusively in the ferrous stAte, Lys42 competes with His46 for the iron coordinAtion site. When b heme is originAlly present, the populAtion of the lysine-bound species remAins too smAll for detAiled chArActerizAtion; however, the populAtion cAn be increAsed significAntly by using dimethyl-esterified heme. Electronic Absorption And NMR spectroscopies showed thAt the reversible ligAnd switching process occurs with An AppArent pKA of 9.3 And A Lys-ligAted populAtion of ∼60% At the bAsic pH limit in the modified holoprotein. The switching rAte, which is slow on the chemicAl shift time s...

  • Histidine–Lysine AxiAl LigAnd Switching in A Hemoglobin: A Role for Heme PropionAtes
    2017
    Co-Authors: Dillon B. Nye, Matthew R. Preimesberger, Ananya Majumdar, Juliette T. J. Lecomte
    Abstract:

    The Hemoglobin of Synechococcus sp. PCC 7002, GlbN, is A monomeric group I truncAted protein (TrHb1) thAt coordinAtes the heme iron with two histidine ligAnds At neutrAl pH. One of these is the distAl histidine (His46), A residue thAt cAn be displAced by dioxygen And other smAll molecules. Here, we show with mutAgenesis, electronic Absorption spectroscopy, And nucleAr mAgnetic resonAnce (NMR) spectroscopy thAt At high pH And exclusively in the ferrous stAte, Lys42 competes with His46 for the iron coordinAtion site. When b heme is originAlly present, the populAtion of the lysine-bound species remAins too smAll for detAiled chArActerizAtion; however, the populAtion cAn be increAsed significAntly by using dimethyl-esterified heme. Electronic Absorption And NMR spectroscopies showed thAt the reversible ligAnd switching process occurs with An AppArent pKA of 9.3 And A Lys-ligAted populAtion of ∼60% At the bAsic pH limit in the modified holoprotein. The switching rAte, which is slow on the chemicAl shift time scAle, wAs estimAted to be 20–30 s–1 by NMR exchAnge spectroscopy. Lys42–His46 competition And AttendAnt conformAtionAl reArrAngement AppeAred to be relAted to weAkened bis-histidine ligAtion And enhAnced bAckbone dynAmics in the ferrous protein. The pH- And redox-dependent ligAnd exchAnge process observed in GlbN illustrAtes the structurAl plAsticity Allowed by the TrHb1 fold And demonstrAtes the importAnce of electrostAtic interActions At the heme periphery for Achieving AxiAl ligAnd selection. An AnAlogy is drAwn to the AlkAline trAnsition of cytochrome c, in which Lys–Met competition is detected At AlkAline pH, but, in contrAst to GlbN, in the ferric stAte only