Lowest Glucose Variability and Hypoglycemia Are Observed With the Combination of a GLP-1 Receptor Agonist and Basal Insulin (VARIATION Study)

被引:54
作者
Bajaj, Harpreet S. [1 ,2 ]
Venn, Karri [3 ]
Ye, Chenglin [4 ]
Patrick, Avril [3 ]
Kalra, Shivani [5 ]
Khandwala, Hasnain [6 ]
Aslam, Nadeem [6 ]
Twum-Barima, David [7 ]
Aronson, Ronnie [3 ]
机构
[1] LMC Diabet & Endocrinol, Brampton, ON, Canada
[2] Mt Sinai Hosp, Leadership Sinai Ctr Diabet, Toronto, ON, Canada
[3] LMC Diabet & Endocrinol, Toronto, ON, Canada
[4] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada
[5] Royal Coll Surg, Dublin, Ireland
[6] LMC Diabet & Endocrinol, Etobicoke, ON, Canada
[7] LMC Diabet & Endocrinol, Oakville, ON, Canada
关键词
GLUCAGON-LIKE PEPTIDE-1; OXIDATIVE STRESS; MICROVASCULAR COMPLICATIONS; ENDOTHELIAL FUNCTION; HORMONE RESPONSES; TYPE-2; HYPERGLYCEMIA; RISK; INFLAMMATION; LIRAGLUTIDE;
D O I
10.2337/dc16-1582
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE There is a dearth of published literature comparing glucose variability (GV) between different insulin regimens in type 2 diabetes. This cohort study compares GV using continuous glucose monitoring (CGM) in patients with well-controlled type 2 diabetes using four common insulin regimens: basal insulin + oral drugs (BO), basal insulin + glucagon-like peptide 1 receptor agonist (GLP-1 RA) (BGLP), premixed insulin ( PM), and basal-bolus insulin (BB). RESEARCH DESIGN AND METHODS Consecutive patients from three endocrinology clinics who met study criteria-type 2 diabetes, age 18 to 80 years, BMI <= 45 kg/m(2), stable insulin regimen for aminimum of 6 months, and stable A1C value <= 7.5% ( 58 mmol/mol) before study enrollment-underwent 6-day masked CGM. Hypoglycemia was defined as a sensor glucose concentration < 70 mg/dL on CGM. RESULTS A total of 160 patients with comparable baseline characteristics formed four equal insulin regimen cohorts. The daily glucose SD (the primary outcome) was significantly lower in the BGLP cohort versus the BO, PM, and BB cohorts (P = 0.03, P = 0.01, and P < 0.01, respectively), and remained so after adjusting for age, BMI, type 2 diabetes duration, and A1C. Similarly, daily hypoglycemia outcomes on CGM were least for the BGLP cohort. CONCLUSIONS The lowest GV and lowest hypoglycemia were observed in patients using the combination of basal insulin with a GLP-1 RA, supporting the complementary glycemic action of these agents in type 2 diabetes. These observed benefits in GV and hypoglycemia may contribute to the cardiovascular outcome reduction seen with GLP-1 RA therapy and should be investigated further.
引用
收藏
页码:194 / 200
页数:7
相关论文
共 35 条
[1]   Emerging role of insulin with incretin therapies for management of type 2 diabetes [J].
Ahluwalia R. ;
Vora J. .
Diabetes Therapy, 2011, 2 (3) :146-161
[2]   Further Improvement in Postprandial Glucose Control With Addition of Exenatide or Sitagliptin to Combination Therapy With Insulin Glargine and Metformin A proof-of-concept study [J].
Arnolds, Sabine ;
Dellweg, Sibylle ;
Clair, Janina ;
Dain, Marie-Paule ;
Nauck, Michael A. ;
Rave, Klaus ;
Kapitza, Christoph .
DIABETES CARE, 2010, 33 (07) :1509-1515
[3]   Recommendations for Standardizing Glucose Reporting and Analysis to Optimize Clinical Decision Making in Diabetes: The Ambulatory Glucose Profile (AGP) [J].
Bergenstal, Richard M. ;
Ahmann, Andrew J. ;
Bailey, Timothy ;
Beck, Roy W. ;
Bissen, Joan ;
Buckingham, Bruce ;
Deeb, Larry ;
Dolin, Robert H. ;
Garg, Satish K. ;
Goland, Robin ;
Hirsch, Irl B. ;
Klonoff, David C. ;
Kruger, Davida F. ;
Matfin, Glenn ;
Mazze, Roger S. ;
Olson, Beth A. ;
Parkin, Christopher ;
Peters, Anne ;
Powers, Margaret A. ;
Rodriguez, Henry ;
Southerland, Phil ;
Strock, Ellie S. ;
Tamborlane, William ;
Wesley, David M. .
DIABETES TECHNOLOGY & THERAPEUTICS, 2013, 15 (03) :198-211
[4]   The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study [J].
Bonds, Denise E. ;
Miller, Michael E. ;
Bergenstal, Richard M. ;
Buse, John B. ;
Byington, Robert P. ;
Cutler, Jeff A. ;
Dudl, R. James ;
Ismail-Beigi, Faramarz ;
Kimel, Angela R. ;
Hoogwerf, Byron ;
Horowitz, Karen R. ;
Savage, Peter J. ;
Seaquist, Elizabeth R. ;
Simmons, Debra L. ;
Sivitz, William I. ;
Speril-Hillen, Joann M. ;
Sweeney, Mary Ellen .
BMJ-BRITISH MEDICAL JOURNAL, 2010, 340 :137
[5]   Can glycaemic variability, as calculated from blood glucose self-monitoring, predict the development of complications in type 1 diabetes over a decade? [J].
Bragd, J. ;
Adamson, U. ;
Backlund, L. B. ;
Lins, P. E. ;
Moberg, E. ;
Oskarsson, P. .
DIABETES & METABOLISM, 2008, 34 (06) :612-616
[6]   Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients [J].
Ceriello, Antonio ;
Esposito, Katherine ;
Piconi, Ludovica ;
Ihnat, Michael A. ;
Thorpe, Jessica E. ;
Testa, Roberto ;
Boemi, Massimo ;
Giugliano, Dario .
DIABETES, 2008, 57 (05) :1349-1354
[7]   Simultaneous GLP-1 and Insulin Administration Acutely Enhances Their Vasodilatory, Antiinflammatory, and Antioxidant Action in Type 2 Diabetes [J].
Ceriello, Antonio ;
Novials, Anna ;
Canivell, Silvia ;
La Sala, Lucia ;
Pujadas, Gemma ;
Esposito, Katherine ;
Testa, Roberto ;
Bucciarelli, Loredana ;
Rondinelli, Maurizio ;
Genovese, Stefano .
DIABETES CARE, 2014, 37 (07) :1938-1943
[8]   Glucagon-Like Peptide 1 Reduces Endothelial Dysfunction, Inflammation, and Oxidative Stress Induced by Both Hyperglycemia and Hypoglycemia in Type 1 Diabetes [J].
Ceriello, Antonio ;
Novials, Anna ;
Ortega, Emilio ;
Canivell, Silvia ;
La Sala, Lucia ;
Pujadas, Gemma ;
Esposito, Katherine ;
Giugliano, Dario ;
Genovese, Stefano .
DIABETES CARE, 2013, 36 (08) :2346-2350
[9]   Evidence That Hyperglycemia After Recovery From Hypoglycemia Worsens Endothelial Function and Increases Oxidative Stress and Inflammation in Healthy Control Subjects and Subjects With Type 1 Diabetes [J].
Ceriello, Antonio ;
Novials, Anna ;
Ortega, Emilio ;
La Sala, Lucia ;
Pujadas, Gemma ;
Testa, Roberto ;
Bonfigli, Anna Rita ;
Esposito, Katherine ;
Giugliano, Dario .
DIABETES, 2012, 61 (11) :2993-2997
[10]   Hyperglycaemia and the vessel wall: the pathophysiological aspects on the atherosclerotic burden in patients with diabetes [J].
Ceriello, Antonio .
EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION, 2010, 17 :S15-S19