J Clin Endocrinol Metab. 2022 Apr 9:dgac213. doi: 10.1210/clinem/dgac213. Online ahead of print.
ABSTRACT
CONTEXT: Loss of the incretin effect (IE) in type 2 diabetes (T2D) contributes to hyperglycemia and the mechanisms underlying this impairment are unclear.
OBJECTIVE: To quantify the IE impairment in T2D and to investigate the factors associated with it using a meta-analytic approach.
DATA SOURCES: PubMed, Scopus and Web-of-Science.
STUDY SELECTION: Studies measuring IE by the gold-standard protocol employing an OGTT and an intravenous glucose infusion at matched glucose levels.
DATA EXTRACTION: We extracted IE, sex, age, BMI, HbA1c, fasting values and areas-under-curve (AUC) of glucose, insulin, C-peptide, GIP and GLP-1. In T2D subjects, we also recorded T2D duration, age at diagnosis, and the percentage of subjects taking antidiabetic medications.
DATA SYNTHESIS: The IE weighted mean difference between T2D and NGT subjects was -27.3% (CI [-36.5 -18.1]%; p<0.001; I 2 = 86.6%) and was affected by age (p<0.005). By meta-regression of combined NGT and T2D data, IE was inversely associated with glucose tolerance (lower IE in T2D), BMI, and fasting GIP (p<0.05). By meta-regression of T2D studies only, IE was associated with the OGTT glucose dose (p<0.0001). IE from insulin was larger than IE from C-peptide (weighted mean difference 11.2%, CI [9.2-13.2]%; p<0.0001; I 2=28.1%); the IE difference was inversely associated with glucose tolerance and fasting glucose.
CONCLUSIONS: The IE impairment in T2D vs NGT is consistent though considerably variable, age being a possible factor affecting the IE difference. Glucose tolerance, BMI, and fasting GIP are independently associated with IE; in T2D subjects only, the OGTT dose is a significant covariate.
PMID:35397169 | DOI:10.1210/clinem/dgac213
