Review Article

Glucagon-Like Peptide 1: A Predictor of Type 2 Diabetes?

Table 1

Overview of results.

Author and yearStudy size (n)StimulusTotal or active/intact GLP-1 and assay/detection methodGLP-1 levels: i-IFG/IFGGLP-1 levels: i-IGT/IGTGLP-1 levels: IFG/IGTBMIAgeEthnicityDiagnostic criteria (year)Ref.

Wang et al. 2016803 h OGTT (75 g)Total plasma GLP-1
ELISA, Westand Biological Technology
Not determined (ND)No change in time point GLP-1levels, ΔGLP-1, or 3 h AUC GLP-1 versus NGTNDMatchedMatchedHan ChineseWHO (‘98)[7]

Faerch et al. 201514622 h OGTT (75 g)Total GLP-1: (7–36)NH2 & (9–36)NH2
Antiserum 89390. RIA
Women:
rAUC0–30: reduced versus NGT
rAUC0–120: reduced versus NGT
iAUC120: reduced versus NGT
Women:
rAUC0–30: reduced versus NGT
rAUC0–120: reduced versus NGT
Women:
rAUC0–120: reduced versus NGT
iAUC30: reduced versus NGT
iAUC120: reduced versus NGT
Both sexes: reduced 120 min versus NGT
Not matchedNot matchedDanishWHO (‘06)[9]

Yabe et al. 20151022 h OGTT (75 g)
MTT (480 kcal)
Intact: two-site sandwich ELISA GLP-1: (7–36)NH2 & (7–37)
DPP-4 inhibitor: √
Total: GLP-1 (7–36)NH2 & (9–36)NH2
Antiserum 89390—Lab. of Holst JJ.
ND (fasting plasma glucose ≥110 mg/dl/6,1 mmol/l excluded)No change in intact or total GLP-1 in fasting or post-prandial(GLP-1 levels and 2 h AUC) versus NGT in both challengesNDIGT and NGT matchedIGT and NGT not matchedJapaneseJapanese Diabetes Society[19]

Zheng et al. 2014474OGTT (75 g)Active GLP-1: (7–36)NH2 & (7–37)
Active ELISA, Millipore
Fasting GLP-1 reduced in NGT subjects who developed prediabetes 4 year later
Prediabetes = i-IFG, i-IGT, IFG/IGT—not distinguished between subtypes
Not matched. Higher in subjects developing prediabetesNot matched. Higher in subjects developing prediabetesChineseWHO (‘98)[25]

Hussein et al. 20148030 min OGTT (75 g)Total GLP-1
ELISA (4141), DRG® (Springfield, NJ)
No difference in 30 min GLP-1 in obese IFG versus obese NGTNDNo difference in 30 min GLP-1 in obese IFG/IGT versus obese NGTNormal weight versus obese (obese groups: matched)Not matchedEgyptianADA (‘06)[27]

Fernandez-Garcia et al. 2014403 h high-fat meal (60 g)Active GLP-1: (7–36)NH2
EIA, Phoenix Pharmaceuticals
DPP-4-inhibitor: ?
No diff between 0 and 180 min GLP-1. Lower 180 min GLP-1 in IFG versus Low-Ins-Res-NGTNDNDMorbidly obese. MatchedMatchedSpanishADA (‘11)[17]

Shen et al. 2013432 h OGTT (75 g)Total GLP-1
RIA, Millipore
NDNo change in fasting GLP-1 versus NGT. GLP-1 levels at 30, 60, and 90 min and 120 min-AUCreduced versus NGTNDMatchedMatchedChineseWHO (‘99)[28]

Zhang et al. 20125312 h OGTT (75 g)Total GLP-1
ELISA, USCNLIFE™ kits
(Uscnlife Science & Technology Company)
No change: fasting GLP-1, 2 h GLP-1, and ΔGLP-1No change: fasting GLP-1 and 2 h GLP-1.
Reduced ΔGLP-1versus NGT
Reduced fasting GLP-1 versus i-IGT; reduced 2 h GLP-1 versus NGT, i-IFG, i-IGT; reduced ΔGLP-1 versus NGT, i-IFG, i-IGTMatchedMatchedHan ChineseADA (‘06)[29]

Smushkin et al. 20121652 h OGTT (75 g)Active GLP-1: N-terminusepitope + epitope in middle of peptide
Inactive GLP-1: N-terminus epitope + epitope in middle of peptide
Total: active + inactive
DPP-4 inhibitor: √
Theranos System: fully automated, Chemiluminescence ELISA
No change in either active or total GLP-1 in fasting or postprandial response (max, 2 h AUC, 2 h AAB) versus NFG/NGTNo change in fasting active or total GLP-1. Increased integrated incremental concentrations (AAB) of total (2 h) GLP-1 versus NFG/NGT. Otherwise, no change in active or total postprandial GLP-1 response versus NFG/NGTNo change in either active or total GLP-1 in fasting or postprandial response (max, 2 h AUC, 2 h AAB) versus NFG/NGTNot matchedNot matchedAmericanADA (‘03≤)[14]

Pala et al. 2010562 h OGTT (75 g)Active GLP-1: (7–36)NH2 & (7–37)
ELISA, Linco—N-terminal specific
DPP-4 inhibitor: √
NDDecreased 30 min GLP-1 and 2 h AUC GLP-1 in IGT versus NGTNDMatchedMatchedNot reportedWHO (‘98)[26]

Nathanson et al. 2010509 men60 min OGTT (75 g)Total GLP-1: (7–36)NH2 & (9–36)
RIA, C-terminal specific (7–36)NH2
NDNo change in fasting and 60 min GLP-1 versus NGT. Reduced ΔGLP-1 versus NGTNDNot reportedMatchedSwedishWHO (‘99)[30]

Lee et al. 2010402 h OGTT (75 g)
MTT(480 kcal)
Active GLP-1
ELISA, Linco
DPP-4 inhibitor: √
NDNo change in peak GLP-1 or 2 h–iAUC in IGT versus NGT in both challengesNDNot matchedMatchedJapaneseWHO[20]

Faerch et al. 2008663 h OGTT (75 g)
(IVGTT)
(Clamp)
Total GLP-1: (7–36)NH2 & (9–36)NH2
Antiserum number 89390
Department of Biomedical Sciences—University of Copenhagen
Fasting GLP-1: no change versus NGT.
Significantly higher 3 h AUC versus NGT
Fasting and 3 h AUC GLP-1: no change versus NGTNDSignificant higher in i-IFG, i-IGT versus NGTMatchedEuropidWHO (‘99)[21]

Muscelli et al. 2008513 h OGTT (75 g)
(Isoglycaemic IV test)
Total GLP-1: 7-36NH2 & 9-36NH2
Antiserum number 89390. RIA
NDNo change in either GLP-1 levels or 3 h AUC GLP-1 versus NGTNDMatchedMatchedNot reportedADA (‘97)[22]

Laakso et al. 2008278: GLP-1 (874)2 h OGTT (75 g)
(IVGTT)
(Clamp)
Total GLP-1: (7–36)NH2 & (9–36)NH2
Antiserum number 89390
Reduced 15, 90, and 120 min GLP-1 versus NGT.
Reduced AUC0–240 versus NGT
Reduced 15, 90, and 120 min GLP-1 versus NGT.
Reduced AUC0–240 versus NGT
Reduced 15, 90, and 120 min GLP-1 versus NGT.
Reduced AUC0–240 versus NGT
DanishADA (‘03)[23]

Vollmer et al. 2008484 h OGTT (75 g)
Mixed meal (820 kcal)
Total GLP-1: (7–36)NH2 & (9–36)NH2
Antiserum number 89390. RIA
NDNo change in GLP-1levels in both challenges versus NGTNDMatchedMatchedNot reportedWHO[24]

Rask et al. 200430 women3 h OGTT (75 g)Total GLP-1: (7–36)NH2 & (9–36)NH2 RIANDNo change in fasting GLP-1, GLP-1 levels, 30-minAUC, 60 min AUC GLP-1 versus NGT. Reduced first 30 min [GLP-1] increase versus NGTNDMatchedMatchedCaucasianNot reported (Fulfil WHO & ADA)[31]

Toft-Nielsen et al. 20011024 h mixed meal (2250 kJ)Total GLP-1: (7–36)NH2 & (9–36)NH2
Antiserum number 89390. RIA
NDNo change in fasting GLP-1 or 4 h AUC GLP-1 versus NGTNDNot matchedMatchedDanishWHO (‘85)[18]

Ahrén et al. 199713 women2 h OGTT (75 g)Total GLP-1: (7–36)NH2 & (9–36)NH2
Antiserum number 89390. RIA
NDNo change in fasting GLP-1, GLP-1 increase (AUC0–60) or GLP-1 decrease versus NGTNDMatchedMatchedNot reportedWHO (‘85)[32]