Prevalence of microvascular and macrovascular disease in the Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) Study cohort

the GRADE Research Group

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Abstract

Aims: The Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) trial is a randomized clinical trial comparing glycemic effects of four diabetes medications added to metformin in type 2 diabetes (T2D). Microvascular and macrovascular diseases are secondary outcomes. We evaluated the prevalence and risk factor relationships for microvascular and macrovascular complications in the GRADE cohort at study entry. Methods: Complication prevalence and risk factors were analyzed based on data from screening in all consenting participants meeting GRADE eligibility. Logistic regression and Z-statistics were used to assess risk factor relationships with complications. Results: We enrolled 5047 T2D participants [mean age 57 years; 36% female; mean known T2D duration 4 years (all < 10 years); mean HbA1c 8.0% (∼64 mmol/mol) at screening]. Urinary albumin/creatinine ratio (ACR) ≥ 30 mg/gram was present in 15.9% participants; peripheral neuropathy (by Michigan Neuropathy Screening Instrument) in 21.5%; cardiovascular autonomic neuropathy by electrocardiography-derived indices in 9.7%; self-reported retinopathy in 1.0%. Myocardial infarction ascertained by self-report or electrocardiogram was present in 7.3%, and self-reported history of stroke in 2.0%. Conclusions: In the GRADE cohort with < 10 years of T2D and a mean HbA1c of 8.0%, diabetes complications were present in a substantial fraction of participants, more so than might otherwise have been expected.

Original languageEnglish (US)
Article number108235
JournalDiabetes Research and Clinical Practice
Volume165
DOIs
StatePublished - Jul 2020

Bibliographical note

Funding Information:
RMC reports grants from National Institutes of Health, during the conduct of the study; “other” conflicts from Bristol Myers Squibb, “other” conflicts from Pfizer, outside the submitted work. CD reports grants and personal fees from Novo Nordisk, personal fees from Astra Zeneca, grants from Sanofi, grants from the Department of Defense, outside the submitted work. JBG reports grants from NIDDK, during the conduct of the study; grants and personal fees from Boehringer Ingelheim, grants from Sanofi, grants from GlaxoSmithKline, grants from Intarcia Therapeutics, grants and personal fees from AstraZeneca, personal fees from Daiichi, personal fees from NovoNordisk, grants from Merck, personal fees from PriMedCME, personal fees from Horizon CME, personal fees from Potomac Center for Medical Education, personal fees from Guthrie Clinic, personal fees from University of Kentucky, personal fees from Bioscientifica, personals fees from The Endocrine Society, outside the submitted work. MSK reports grants from Novo Nordisk, grants from Theracos, grants from Bayer, outside the submitted work. ERS reports grants and personal fees from Eli Lilly, personal fees from Sanofi, personal fees from Zucara, personal fees from MannKind, outside the submitted work. DJW reports other from NovoNordisk, outside the submitted work. RPB reports grants from National Institute of Diabetes and Digestive and Kidney Diseases, NIH (U34 DK088043 and U01 DK098246, from National Heart, Lung, and Blood Institute, from Centers for Disease Control and Prevention, and from The American Diabetes Association during the conduct of the study; grants from Astra Zeneca, personal fees from Novo Nordisk, outside the submitted work. KJM, IB, CB, JPC, HKS, MEL, JP, EZS, and EBS have nothing to disclose.

Funding Information:
The GRADE Study is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health under Award Number U01DK098246. The planning of GRADE was supported by a U34 planning grant from the NIDDK (U34-DK-088043). The American Diabetes Association supported the initial planning meeting for the U34 proposal. The National Heart, Lung, and Blood Institute and the Centers for Disease Control and Prevention also provided funding support. The Department of Veterans Affairs provided resources and facilities. Additional support was provided by grant numbers P30 DK017047, P30 DK020541-44, P30 DK020572, P30 DK072476, P30 DK079626, P30 DK092926, U54 GM104940, UL1 TR000439, UL1 TR000445, UL1 TR001108, UL1 TR001409, UL1 TR001449, UL1 TR002243, UL1 TR002345, UL1 TR002378, UL1 TR002489, UL1 TR002489, UL1 TR002529, UL1 TR002535, UL1 TR002537, and UL1 TR002548. Educational materials have been provided by the National Diabetes Education Program. Material support in the form of donated medications and supplies has been provided by BD, Bristol-Myers Squibb, Merck, NovoNordisk, Roche Diagnostics, and Sanofi. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. RMC reports grants from National Institutes of Health, during the conduct of the study; ?other? conflicts from Bristol Myers Squibb, ?other? conflicts from Pfizer, outside the submitted work. CD reports grants and personal fees from Novo Nordisk, personal fees from Astra Zeneca, grants from Sanofi, grants from the Department of Defense, outside the submitted work. JBG reports grants from NIDDK, during the conduct of the study; grants and personal fees from Boehringer Ingelheim, grants from Sanofi, grants from GlaxoSmithKline, grants from Intarcia Therapeutics, grants and personal fees from AstraZeneca, personal fees from Daiichi, personal fees from NovoNordisk, grants from Merck, personal fees from PriMedCME, personal fees from Horizon CME, personal fees from Potomac Center for Medical Education, personal fees from Guthrie Clinic, personal fees from University of Kentucky, personal fees from Bioscientifica, personals fees from The Endocrine Society, outside the submitted work. MSK reports grants from Novo Nordisk, grants from Theracos, grants from Bayer, outside the submitted work. ERS reports grants and personal fees from Eli Lilly, personal fees from Sanofi, personal fees from Zucara, personal fees from MannKind, outside the submitted work. DJW reports other from NovoNordisk, outside the submitted work. RPB reports grants from National Institute of Diabetes and Digestive and Kidney Diseases, NIH (U34 DK088043 and U01 DK098246, from National Heart, Lung, and Blood Institute, from Centers for Disease Control and Prevention, and from The American Diabetes Association during the conduct of the study; grants from Astra Zeneca, personal fees from Novo Nordisk, outside the submitted work. KJM, IB, CB, JPC, HKS, MEL, JP, EZS, and EBS have nothing to disclose. All authors affirm that authorship is merited based on the ICMJE authorship criteria. IB, JPC, CD, JBG, HKS, MEL, KJM, RP-B, EBS, and DJW contributed to the conception and design of this manuscript. IB, JPS, CD, JBG, HKS, KJM, JP, ERS, RP-B and EZS contributed to the acquisition of data for this manuscript. IB contributed to the statistical analysis of data for this manuscript. CB, IB, RMC, JPC, CD, JBG, MSK, HKS, KJM, RP-B, ERS, EBS, EZS, and DJW contributed to the interpretation of data and results for this manuscript. CD, KJM, RP-B, and ERS contributed to the supervision and management of research for this manuscript. IB, CD, HKS, HKS, MEL, KJM, and RP-B contributed to the drafting of this manuscript. CB, IB, RMC, JPC, CD, JBG, MSK, HKS, KJM, JP, RP-B, ERS, EBS, EZS, and DJS contributed to the critical review of this manuscript. IB, KJM and RP-B are guarantors of this work, and as such, had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.

Funding Information:
The GRADE Study is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health under Award Number U01DK098246. The planning of GRADE was supported by a U34 planning grant from the NIDDK ( U34-DK-088043 ). The American Diabetes Association supported the initial planning meeting for the U34 proposal. The National Heart, Lung, and Blood Institute and the Centers for Disease Control and Prevention also provided funding support. The Department of Veterans Affairs provided resources and facilities. Additional support was provided by grant numbers P30 DK017047, P30 DK020541-44, P30 DK020572, P30 DK072476, P30 DK079626, P30 DK092926, U54 GM104940, UL1 TR000439, UL1 TR000445, UL1 TR001108, UL1 TR001409, UL1 TR001449, UL1 TR002243, UL1 TR002345, UL1 TR002378, UL1 TR002489, UL1 TR002489, UL1 TR002529, UL1 TR002535, UL1 TR002537, and UL1 TR002548. Educational materials have been provided by the National Diabetes Education Program. Material support in the form of donated medications and supplies has been provided by BD, Bristol-Myers Squibb, Merck, NovoNordisk, Roche Diagnostics, and Sanofi. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2020 Elsevier B.V.

Keywords

  • Comparative effectiveness
  • Complications
  • Diabetes
  • Pragmatic
  • Prevalence
  • Treatment

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