Association of glycemia with insulin sensitivity and β-cell function in adults with early type 2 diabetes on metformin alone.

Publisher: Elsevier Science Pub. Co Country of Publication: United States NLM ID: 9204583 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-460X (Electronic) Linking ISSN: 10568727 NLM ISO Abbreviation: J Diabetes Complications Subsets: MEDLINE

Original Publication: New York, NY : Elsevier Science Pub. Co., c1992-

Blood Glucose* ; Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/drug therapy ; Insulin Resistance* ; Metformin*/therapeutic use; Insulin-Secreting Cells/*physiology; C-Peptide ; Cross-Sectional Studies ; Glycated Hemoglobin ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulin/blood ; Randomized Controlled Trials as Topic

Aims: Evaluate the relationship between measures of glycemia with β-cell function and insulin sensitivity in adults with early type 2 diabetes mellitus (T2DM).
Methods: This cross-sectional analysis evaluated baseline data from 3108 adults with T2DM <10 years treated with metformin alone enrolled in the Glycemia Reduction Approaches in Diabetes. A Comparative Effectiveness (GRADE) Study. Insulin and C-peptide responses and insulin sensitivity were calculated from 2-h oral glucose tolerance tests. Regression models evaluated the relationships between glycemic measures (HbA1c, fasting and 2-h glucose), measures of β-cell function and insulin sensitivity.
Results: Insulin and C-peptide responses were inversely associated with insulin sensitivity. Glycemic measures were inversely associated with insulin and C-peptide responses adjusted for insulin sensitivity. HbA1c demonstrated modest associations with β-cell function (range: r - 0.22 to -0.35). Fasting and 2-h glucose were associated with early insulin and C-peptide responses (range: r - 0.37 to -0.40) as well as late insulin and total insulin and C-peptide responses (range: r - 0.50 to -0.60).
Conclusion: Glycemia is strongly associated with β-cell dysfunction in adults with early T2DM treated with metformin alone. Efforts to improve glycemia should focus on interventions aimed at improving β-cell function. This Trial is registered in Clinicaltrials.gov as NCT01794143.
Competing Interests: Declaration of competing interest The writing group reports the following as relevant conflicts of interest: KMU reports support from Medtronics, personal fees from Novo Nordisk, outside the submitted work; NR reports grants and other support from Novo Nordisk, outside the submitted work; RMC reports grants from National Institutes of Health during the conduct of the study; other support from Bristol Myers Squibb and Pfizer, outside the submitted work; DJW reports grants from an NIDDK funded trial during the conduct of the study; and other support from Novo Nordisk, outside the submitted work. SEK reports grants from NIH during the conduct of the study; personal fees from Boehringer Ingelheim, Eli Lilly, Intarcia, Janssen, Merck, Novo Nordisk, and Pfizer, outside the submitted work. KJM reports grants from National Institutes of Health during the conduct of the study; and at the time of publication. KJM is an employee of Eli Lilly and Company. Data collection, analysis, and preparation of the manuscript occurred prior to this employment and were independent of Eli Lilly and Company. NY, JB, MAB, EVG, FIB, JML, and PR have nothing to disclose. KMU and SEK are supported by funding from the United States Department of Veterans Affairs.
(Published by Elsevier Inc.)

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UL1 TR000445 United States TR NCATS NIH HHS; UL1 TR002529 United States TR NCATS NIH HHS; UL1 TR000439 United States TR NCATS NIH HHS; P30 DK020541 United States DK NIDDK NIH HHS; UL1 TR002378 United States TR NCATS NIH HHS; P30 DK020572 United States DK NIDDK NIH HHS; UL1 TR002345 United States TR NCATS NIH HHS; P30 DK017047 United States DK NIDDK NIH HHS; UL1 TR002548 United States TR NCATS NIH HHS; U34 DK088043 United States DK NIDDK NIH HHS; UL1 TR002537 United States TR NCATS NIH HHS; P30 DK092926 United States DK NIDDK NIH HHS; UL1 TR002535 United States TR NCATS NIH HHS; P30 DK072476 United States DK NIDDK NIH HHS; P30 DK079626 United States DK NIDDK NIH HHS; UL1 TR001409 United States TR NCATS NIH HHS; U01 DK098246 United States DK NIDDK NIH HHS; UL1 TR001449 United States TR NCATS NIH HHS; UL1 TR002489 United States TR NCATS NIH HHS; U54 GM104940 United States GM NIGMS NIH HHS; UL1 TR001108 United States TR NCATS NIH HHS; UL1 TR002243 United States TR NCATS NIH HHS; I01 BX005831 United States BX BLRD VA

Keywords: Beta-cell function; Glucose tolerance; Glycemic control; Insulin sensitivity; Type 2 diabetes

ClinicalTrials.gov NCT01794143

0 (Blood Glucose)
0 (C-Peptide)
0 (Glycated Hemoglobin A)
0 (Hypoglycemic Agents)
0 (Insulin)
9100L32L2N (Metformin)

Date Created: 20210323 Date Completed: 20220113 Latest Revision: 20230610

20230610

PMC8048071

10.1016/j.jdiacomp.2021.107912

33752962