. 2020 Jun 9;69(9):1989–2002. doi: 10.2337/db20-0074

Table 3.

Glucose, C-peptide, C-peptide/glucose, and glucagon

Intervention	PLA+NaCl	PLA+GIP	PLA+GLP-1	SU+NaCl	SU+GIP	SU+GLP-1	Interaction P value
Plasma glucose
HNF1A mutation carriers
Baseline (mmol/L)	8.6 ± 1.1	8.9 ± 1.0	8.6 ± 1.0	8.9 ± 1.0	8.9 ± 1.1	8.7 ± 1.1
AUC_0–120 min (mol/L × min)	1.28 ± 0.15	1.33 ± 0.15	1.28 ± 0.15	1.34 ± 0.16	1.31 ± 0.16	1.28 ± 0.16
PG/FPG AUC_0–120 (min⁻¹)	150 ± 1	149 ± 1	149 ± 1	149 ± 1	147 ± 1	147 ± 1
Control subjects without diabetes
Baseline (mmol/L)	4.8 ±0.1	5.0 ± 0.1	4.9 ± 0.1	5.0 ± 0.1	5.0 ± 0.1	5.0 ± 0.1
AUC_{0–120 min} (mol/L × min)	0.72 ± 0.02	0.75 ± 0.02	0.73 ± 0.02	0.75 ± 0.02	0.73 ± 0.01	0.74 ± 0.01
PG/FPG AUC_{0–120 min} (min)	149 ± 1	149 ± 1	149 ± 1	150 ± 1	148 ± 1	148 ± 1
Glucose infused
HNF1A mutation carriers
Time 0–60 min (g)	3.6 ± 1.0	5.7 ± 1.4	6.2 ± 1.0	6.5 ± 1.3	9.7 ± 1.8^*	9.3 ± 1.5^*	0.6745
Time 60–120 min (g)	14 ± 1.0	16 ± 2.0	18 ± 1.6	19 ± 1.3	28 ± 2.7^*^†^‡^§	24 ± 2.2^*^‡^§	0.0144
Time 0–120 min (g)	18 ± 1.7	22 ± 3.2	24 ± 2.3	26 ± 2.1	37 ± 4.2^*^†^‡^§	33 ± 3.3^*^‡^§	0.0472
Control subjects without diabetes
Time 0–60 min (g)	0.8 ± 0.6	4.6 ± 0.9^*	4.9 ± 0.8^*	3.7 ± 0.9	6.1 ± 1.3^*	9.3 ± 1.2^*^†^‡^§^‖	0.1237
Time 60–120 min (g)	9.7 ± 1.9	20 ± 3.6	20 ± 4.4	17 ± 2.6	30 ± 5.3^*^†	39 ± 5.8^*^†^‡^§	0.0180
Time 0–120 min (g)	11 ± 2.3	25 ± 4.3	25 ± 5.0	21 ± 3.2	36 ± 6.3^*^†	48 ± 6.7^*^†^‡^§	0.0205
C-peptide
HNF1A mutation carriers
Baseline (pmol/L)	302 ± 14	299 ± 21	314 ± 23	299 ± 24	314 ± 18	310 ± 19
bsAUC_{0–60 min} (nmol/L × min)	0.7 ± 0.9	7.5 ± 1.7	5.8 ± 1.4	8.0 ± 2.4	19 ± 3.8^*^†^‡^§	18 ± 3.4^*^†^‡^§	0.1617
bsAUC_{60–120 min} (nmol/L × min)	9.6 ± 1.6	20 ± 3.3	26 ± 3.1^*	21 ± 4.3	45 ± 6.5^*^†^‡	46 ± 5.6^*^†^‡^§	0.0190
bsAUC_{0–120 min} (nmol/L × min)	10 ± 2.1	28 ± 4.7^*	32 ± 4.0^*	29 ± 6.5	64 ± 10^*^†^‡^§	63 ± 8.6^*^†^‡^§	0.0294
Control subjects without diabetes
Baseline (pmol/L)	358 ± 42	415 ± 35	370 ± 27	394 ± 50	372 ± 34	426 ± 39
bsAUC_{0–60 min} (nmol/L × min)	−2.7 ± 2.4	5.5 ± 2.2	5.1 ± 2.4	3.9 ± 1.8	12 ± 2.9^*	24 ± 3.9^*^†^‡^§^‖	0.0233
bsAUC_{60–120 min} (nmol/L × min)	17 ± 5.8	48 ± 6.7	60 ± 11^*	40 ± 7.7	80 ± 14^*^†	131 ± 17^*^†^‡^§^‖	0.0097
bsAUC_{0–120 min} (nmol/L × min)	14 ± 7.8	53 ± 8.2	65 ± 13	43 ± 8.9	93 ± 16^*^†	156 ± 20^*^†^‡^§^‖	0.0078
C-peptide/glucose
HNF1A mutation carriers
Baseline (pmol/L)	41 ± 6.4	40 ± 7.3	42 ± 6.3	36 ± 5.1	39 ± 6.1	42 ± 6.5
bsAUC_{0–60 min} (nmol/L × min)	−0.0 ± 0.12	0.8 ± 0.2^*	0.7 ± 0.2^*	0.9 ± 0.3	2.5 ± 0.4^*^†^‡^§	2.2 ± 0.4^*^†^‡^§	0.0398
bsAUC_{60–120 min} (nmol/L × min)	0.1 ± 0.1	1.0 ± 0.3	1.6 ± 0.3^*	1.0 ± 0.3	3.1 ± 0.5^*^†^‡	3.3 ± 0.5^*^†^‡^§	0.0042
bsAUC_{0–120 min} (nmol/L × min)	0.1 ± 0.2	1.8 ± 0.4^*	2.3 ± 0.5^*	2.0 ± 0.5	5.6 ± 0.9^*^†^‡^§	5.5 ± 0.8^*^†^‡^§	0.0077
Control subjects without diabetes
Baseline (pmol/L)	75 ± 9.2	83 ± 6.8	75 ± 5.9	78 ± 8.5	75 ± 7.3	75 ± 7.0
bsAUC_{0–60 min} (nmol/L × min)	−0.7 ± 0.52	1.2 ± 0.5	1.1 ± 0.5	0.8 ± 0.4	2.6 ± 0.6^*	5.0 ± 0.9^*^†^‡^§^‖	0.0260
bsAUC_{60–120 min} (nmol/L × min)	0.8 ± 0.9	4.7 ± 0.9	6.6 ± 1.6	3.5 ± 1.0	9.3 ± 1.9^*^†	16 ± 2.4^*^†^‡^§^‖	0.0166
bsAUC_{0–120 min} (nmol/L × min)	0.2 ± 0.1	5.8 ± 1.3	7.7 ± 2.1	4.4 ± 1.3	12 ± 2.4^*^†	21 ± 3.2^*^†^‡^§^‖	0.0148
Glucagon
HNF1A mutation carriers
Baseline (pmol/L)	13 ± 1	12 ± 1	11 ± 1	11 ± 2	13 ± 1	12 ± 2
bsAUC_{0–60 min} (pmol/L × min)	−306 ± 59	−182 ± 59	−381 ± 59	−186 ± 59	−152 ± 59	−255 ± 59	0.5167
bsAUC_{60–120 min} (pmol/L × min)	−463 ± 57	−435 ± 57	−488 ± 57	−351 ± 60	−353 ± 57	−420 ± 57	0.9094
bsAUC_{0–120 min} (pmol/L × min)	−770 ± 106	−618 ± 106	−869 ± 106	−560 ± 111	−505 ± 106	−675 ± 106	0.8320
Control subjects without diabetes
Baseline (pmol/L)	8 ± 2	9 ± 2	9 ± 2	10 ± 2	8 ± 2	13 ± 2
bsAUC_{0–60 min} (nmol/L × min)	−93 ± 76	−163 ± 76	−248 ± 76	−148 ± 76	−52.7 ± 76	−321 ± 81	0.2472
bsAUC_{60–120 min} (nmol/L × min)	−325 ± 100	−388 ± 100	−408 ± 100	−374 ± 100	−274 ± 100	−538 ± 105	0.2707
bsAUC_{0–120 min} (nmol/L × min)	−419 ± 171	−605 ± 177	−655 ± 171	−523 ± 171	−325 ± 171	−857 ± 179	0.1979

Data are mean ± SEM. A significant interaction describes a supra-additive of combining SU+GIP and/or SU+GLP-1.

FPG, fasting plasma glucose; PG, plasma glucose; PLA, placebo.

Symbols show significant differences (P < 0.05) between interventions:

significantly greater than PLA+NaCl;

^†

significantly greater SU+NaCl;

^‡

significantly greater than PLA+GIP;

^§

significantly greater than PLA+GLP-1;

^‖

significantly greater than SU+GIP.