Loss-of-Function Mutations in ABCA1 and Enhanced β-Cell Secretory Capacity in Young Adults
Article Figures & Tables
Figures
- Figure 1
Plasma glucose (A and B) and insulin (C and D) levels during the 75-g OGTT in ABCA1 homozygous (n = 3), ABCA1 heterozygous (n = 8), and matched normal control (n = 8) subjects (A and C) and in isolated low HDL-C (n = 9) and matched normal control (n = 9) subjects (B and D). The incremental area under the curve (AUC) for glucose was 1,255 ± 1,543, 4,369 ± 1,115, and 5,565 ± 914 mg/dL ⋅ min for ABCA1 homozygous, heterozygous, and control subjects, respectively (P < 0.05 for ABCA1 homozygous vs. control subjects), and 4,060 ± 1,154 and 3,686 ± 1,205 mg/dL ⋅ min for the isolated low HDL-C subjects and their control subjects. The AUC for insulin was 7,786 ± 1,951 and 5,811 ± 763 μU/mL ⋅ min for the ABCA1 heterozygous subjects and their control subjects and 7,062 ± 1,221 and 5,195 ± 629 μU/mL ⋅ min for the isolated low HDL-C subjects and their control subjects. Not shown are the insulin levels of one ABCA1 homozygous subject whose samples were affected by gross hemolysis that invalidated the insulin assay.
- Figure 2
Plasma insulin (A, C, and E) and C-peptide (B, D, and F) levels in response to bolus injections of arginine (arrows) administered under fasting, ∼230 mg/dL hyperglycemic clamp, and ∼340 mg/dL hyperglycemic clamp conditions in ABCA1 homozygous (n = 3) (A and B), ABCA1 heterozygous (n = 8) (C and D), and matched normal control (n = 8) subjects and in isolated low HDL-C (n = 9) and matched normal control (n = 9) subjects (E and F).
Tables
- Table 1
Subject characteristics
ABCA1 Low HDL-C Homozygous Heterozygous Control subjects Case subjects Control subjects Sex (n) Male 2 5 5 7 7 Female 1 3 3 2 2 Race (n) Caucasian 3 7 7 7 7 African American 0 1 1 2 2 Age (years) 25 ± 11 28 ± 7 28 ± 6 26 ± 6 26 ± 4 BMI (kg/m2) 25 ± 4 25 ± 4 25 ± 3 25 ± 2 25 ± 2 Glucose (mg/dL) 95 ± 9 86 ± 10 89 ± 9 89 ± 4 88 ± 7 Insulin (µU/mL) 13.8 ± 1.2* 10.3 ± 4.7 8.4 ± 3.5 9.1 ± 6.7 7.1 ± 2.2 Total cholesterol (mg/dL) 74 ± 21† 157 ± 24 181 ± 27 158 ± 36 175 ± 27 Triglyceride (mg/dL) 127 ± 59 115 ± 59 75 ± 32 134 ± 44* 84 ± 45 HDL-C (mg/dL) 2 ± 0† 27 ± 7‡ 65 ± 17 30 ± 4‡ 65 ± 10 LDL-C (mg/dL) 57 ± 26* 105 ± 22 97 ± 20 97 ± 24 94 ± 21 VLDL-C (mg/dL) 16 ± 6 24 ± 22 19 ± 8 30 ± 17 17 ± 10 ApoA-I (mg/dL) 8 ± 3‡ 83 ± 12† 159 ± 38 100 ± 13† 155 ± 20 ApoB (mg/dL) 76 ± 14 86 ± 16 68 ± 15 83 ± 20 66 ± 19 Data are means ± SD.
ApoA-I, apoprotein A-I; ApoB, apoprotein B.
*P < 0.05 case vs. control subjects.
†P < 0.001 case vs. control subjects.
‡P < 0.0001 case vs. control subjects.
- Table 2
GPA test parameters
ABCA1 Low HDL-C Homozygous Heterozygous Control subjects Case subjects Control subjects n = 3 n = 8 n = 8 n = 9 n = 9 AIRarg (μU/mL) 62 ± 32a 33 ± 8 28 ± 7 58 ± 10* 27 ± 6 AIRpot (µU/mL) 350 ± 228a 195 ± 33* 122 ± 20 278 ± 45† 134 ± 14 AIRmax (µU/mL) 426 ± 153* 219 ± 30* 173 ± 34 304 ± 66† 143 ± 20 ACRarg (ng/mL) 3.47 ± 0.86* 2.03 ± 0.36* 1.43 ± 0.26 3.07 ± 0.29* 1.64 ± 0.25 ACRpot (ng/mL) 14.17 ± 6.24a 8.31 ± 1.70* 6.30 ± 0.97 9.70 ± 1.06† 5.24 ± 0.52 ACRmax (ng/mL) 14.08 ± 6.01* 8.39 ± 1.16* 5.77 ± 0.55 10.45 ± 1.66* 5.60 ± 0.65 M (mg/kg/min) 9.8 ± 0.1 9.6 ± 0.5 9.4 ± 0.7 8.7 ± 0.4 10.3 ± 1.0 I (µU/mL) 52 ± 25 45 ± 11 28 ± 4 50 ± 10 34 ± 6 M/I (mg/kg per min/µU/mL) 0.30 ± 0.12 0.29 ± 0.05 0.36 ± 0.03 0.22 ± 0.03† 0.37 ± 0.06 DI (mg/kg/min) 11.0 ± 1.8 9.0 ± 2.6 9.7 ± 2.3 11.0 ± 1.5 10.4 ± 3.6 Data are means ± SE.
ACRarg, acute C-peptide response to arginine under fasting conditions; ACRmax, acute C-peptide response to arginine under ∼340 mg/dL glucose clamp conditions; ACRpot, acute C-peptide response to arginine under ∼230 mg/dL glucose clamp conditions.
aP ≤ 0.1 case subjects vs. control subjects.
*P < 0.05 case subjects vs. control subjects.
†P < 0.01 case subjects vs. control subjects.
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