β-Cell Function Across the Spectrum of Glucose Tolerance in Obese Youth
Article Figures & Tables
Figures
- FIG. 1.
Glucose, insulin, and C-peptide during the hyperglycemic clamp. ♦, NGT; ▪, IGT; ▴, type 2 diabetes (T2DM). A: *P < 0.05 and **P < 0.01 for type 2 diabetes vs. IGT. B: †P = 0.01 for 4, 6, and 8 min; *P < 0.05 and **P < 0.01 for diabetes vs. IGT. C: †P < 0.05 for IGT vs. NGT for 6 and 8 min and P < 0.01 for type 2 diabetes vs. IGT for 4 and 6 min; *P < 0.05 and **P < 0.01 for type 2 diabetes vs. IGT.
- FIG. 2.
Glucose sensitivity of the first- and second-phase insulin response in NGT, IGT, and diabetic subjects. A: Glucose sensitivity of β-cell first-phase secretion in adolescents with NGT (blue), IGT (yellow), and type 2 diabetes (T2DM) (red). B: Glucose sensitivity of β-cell second-phase secretion in adolescents with NGT (blue), IGT (yellow), and type 2 diabetes (red). P < 0.01 for IGT vs. NGT; P < 0.02 for type 2 diabetes vs. IGT.
- FIG. 3.
Relation of fasting plasma glucose and the β-cell glucose sensitivity of second-phase insulin secretion in subjects with NGT (A) and IGT (B). Scatterplot of glucose sensitivity of β-cell second-phase secretion (y axis) vs. fasting plasma glucose in adolescents with NGT (A), IGT (B).
- FIG. 4.
Relation of insulin sensitivity and the β-cell glucose sensitivity of second-phase secretion. Scatterplot of glucose sensitivity of β-cell second-phase secretion (σ2nd; y axis) vs. insulin sensitivity (Si; x axis) in adolescents with NGT (♦), IGT (▪), and type 2 diabetes (T2DM) (▴). The two curves are generated by the following equation found by nonlinear regression analysis, as described in research design and methods: σ2nd = A× (1 + ds × C) × ISB, where ds = 0 in NGT and IGT subjects and ds = 1 in type 2 diabetes subjects, IS = insulin sensitivity, A = 36.7 (95% CI 26.3–66.1), B = −0.37 (−0.49 to −0.10), and C = −0.40 (−0.57 to −0.25).
- FIG. 5.
The proinsulin-to-insulin ratio during acute-phase insulin secretion. Proinsulin-to-insulin ratio during the hyperglycemic clamp. P < 0.001 and P = 0.01 for 4 min, P = 0.001 and P = 0.04 for 6 min for type 2 diabetes (red) vs. NGT (blue) and IGT (yellow).
Tables
- TABLE 1
Demographic and anthropometric features of the study subjects
NGT IGT Type 2 diabetes P value n (M/F) 30 (12/18) 22 (10/12) 10 (4/6) 0.92 Ethnicity (AA/C/H) 6/8/16 7/9/6 5/3/2 0.144 Age (years) 13.8 ± 0.5 13.1 ± 0.6 15.0 ± 0.8 <0.05 Height (cm) 160 ± 2 159 ± 2 166 ± 4 0.25 Weight (kg) 99.6 ± 4 95 ± 6 106 ± 6 0.47 BMI (kg/m2) 38.0 ± 1.1 37.2 ± 1.6 38.3 ± 1.3 0.78 Percent body fat 41.3 ± 1.1 41.3 ± 1.4 38.7 ± 1.9 0.27 Data are means ± SE. AA, African American; C, Caucasian; H, Hispanic.
- TABLE 2
Fasting biochemical values
NGT IGT Type 2 diabetes P value Glucose (mmol/l) 5.27 ± 0.09 5.32 ± 0.09 5.71 ± 0.21 0.07 Insulin (mU/l) 33.2 ± 2.4 40.0 ± 3.5 36.8 ± 3.6 0.36 C-peptide (nmol/l) 1.12 ± 0.07 1.33 ± 0.08 1.11 ± 0.02 0.23 HbA1c (%) 5.2 ± 0.3 5.4 ± 0.4 7.1 ± 1.6* P <0.001 Proinsulin (pmol/l) 26 ± 2 34 ± 5 33 ± 7 0.22 Proinsulin-to-insulin ratio 0.80 ± 0.31 0.78 ± 0.30 1.07 ± 0.64 0.17 Triglicerides (mg/dl) 98 ± 8 119 ± 13 128 ± 27 0.25 Free fatty acids 545 ± 222 528 ± 125 480 ± 111 0.62 Data are means ± SE.
- TABLE 3
Weighted residuals (i.e., difference between measured and model predicted C-peptide concentration divided by the SD of C-peptide measurement) of model fit to plasma C-peptide experimental data of the hyperglycemic clamps performed in NGT, IGT, and type 2 diabetic adolescents
Time C-peptide weighted residuals NGT (n = 30) IGT (n = 22) DM2 (n = 10) 2 −0.34 ± 0.36 −0.06 ± 0.44 −0.08 ± 0.11 4 0.41 ± 0.38 0.31 ± 0.38 0.28 ± 0.58 6 0.18 ± 0.47 −0.04 ± 0.34 0.14 ± 0.55 8 −0.37 ± 0.52 −0.41 ± 0.33 −0.45 ± 0.34 10 −0.16 ± 0.63 −0.07 ± 0.39 0.10 ± 0.57 20 0.50 ± 0.61 0.58 ± 0.61 0.32 ± 0.37 40 0.15 ± 0.75 −0.39 ± 0.75 −0.18 ± 0.65 60 −0.30 ± 0.59 −0.05 ± 0.66 −0.21 ± 0.50 80 −0.20 ± 0.70 0.04 ± 0.66 −0.10 ± 0.83 100 −0.02 ± 0.65 0.19 ± 0.57 0.34 ± 0.42 120 0.58 ± 0.80 0.19 ± 0.65 0.23 ± 0.77 Data are means ± SD. The weighted residuals are a quantitative assessment of the goodness-of-fit of the models to the data: a theorically perfect fit should generate weighted residuals with mean of 0 and SD of 1.
- TABLE 4
Correlation matrix in the whole dataset (n = 62)
Fasting glucose Fasting insulin Fasting C-peptide Si First-phase glucose sensitivity Fasting glucose 1 Fasting insulin 0.32* 1 Fasting C-peptide 0.28† 0.70‡ 1 Si −0.14 −0.67‡ −0.59‡ 1 First-phase glucose sensitivity −0.31† 0.04 0.04 −0.19 1 Second-phase glucose sensitivity 0.07 0.30† 0.33* −0.53‡ 0.39* - *
* P < 0.01;
- †
† P < 0.05;
- ‡
‡ P < 0.001.
- *
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