Reduced Insulinotropic Effect of Gastric Inhibitory Polypeptide in First-Degree Relatives of Patients With Type 2 Diabetes
Article Figures & Tables
Figures
- FIG. 1.
Plasma concentrations of glucose (capillary measurement; A) and immunoreactive GIP (B) in 21 first-degree relatives of patients with type 2 diabetes (⧫), 10 patients with type 2 diabetes (○), and 10 healthy control subjects (•) participating in hyperglycemic clamp experiments with intravenous infusions of GIP (2 pmol · kg−1 · min−1). Mean ± SE P values were calculated using repeated measures by ANOVA for the interaction of group assignment and time. Significant difference (P < 0.05) at individual time points: *to patients with type 2 diabetes; †to normal subjects (Duncan’s post hoc test).
- FIG. 2.
Plasma concentrations of insulin (A) and C-peptide (B) in 21 first-degree relatives of patients with type 2 diabetes (⧫), 10 patients with type 2 diabetes (○), and 10 healthy control subjects (•) participating in hyperglycemic clamp experiments with intravenous infusions of GIP (2 pmol · kg−1 · min−1). Mean ± SE P values were calculated using repeated measures by ANOVA for the interaction of group assignment and time. Significant difference (P < 0.05) at individual time points: *to patients with type 2 diabetes; †to normal subjects (Duncan’s post hoc test).
- FIG. 3.
Differences (Δ) between the values at 30 min (hyperglycemia) and 90 min (hyperglycemia plus exogenous GIP) for insulin (A) and C-peptide (B) concentrations in 21 first-degree relatives of patients with type 2 diabetes (⧫), 10 patients with type 2 diabetes (○), and 10 healthy control subjects (•). P values: ANOVA (overall comparison) and Duncan’s post hoc test (comparison of individual groups).
- FIG. 4.
Individual plasma concentrations (thin lines) of insulin (A) and C-peptide (B) in 21 first-degree relatives shown in relation to the upper and lower 95% CI for normal subjects (thick dashed lines).
Tables
- TABLE 1
Characteristics of the participants in hyperglycemic clamp experiments with GIP infusion
Parameter Healthy control subjects First-degree relatives of type 2 diabetic patients Type 2 diabetic patients Significance (P value)* Sex (female/male) 4/6 15/6 3/7 0.059 Age (years) 49 ± 17 49 ± 12 52 ± 9 0.83 BMI (kg/m2) 25.7 ± 3.6 26.0 ± 4.2 28.6 ± 5.1 0.23 Waist-to-hip ratio (cm/cm) 0.89 ± 0.1 0.84 ± 0.1§ 0.93 ± 0.07 0.028 Participants with first-degree relatives (type 2 diabetes) 0/10§ 21/21§ 4/10‡ <0.0001 Father — 8 2 Mother — 15 2 Siblings — 3 3 HbA1c (%)† 5.0 ± 0.5§ 5.1 ± 0.3§ 6.2 ± 0.7‡ <0.0001 Oral glucose tolerance Fasting plasma glucose (mg/dl) 94 ± 7§ 88 ± 8§ 117 ± 15‡ <0.0001 120-min plasma glucose (mg/dl) 101 ± 16 112 ± 15 NE 0.81 Blood pressure Systolic (mmHg) 128 ± 9 130 ± 18 131 ± 14 0.93 Diastolic (mmHg) 81 ± 4 80 ± 9 77 ± 5 0.36 Triglycerides (mg/dl) 113 ± 65 117 ± 75 189 ± 107 0.06 HDL cholesterol (mg/dl) 60 ± 26 71 ± 24§ 43 ± 19 0.013 LDL cholesterol (mg/dl) 140 ± 30 120 ± 35 146 ± 25 0.70 Creatinine (mg/dl) 1.1 ± 0.1§ 1.0 ± 0.1§ 1.0 ± 0.1‡ 0.017 -
Data are n and means ± SE. NE, not examined.
- *
* ANOVA or χ2 tests;
- †
† normal range, 4.0–6.2%;
- ‡
‡ significant difference (P < 0.05) versus healthy control subjects (Duncan’s post hoc test);
- §
§ significant difference (P < 0.05) versus patients with type 2 diabetes (Duncan’s post hoc test).
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- TABLE 2
Glucose infusion rates (mg · kg−1 · min−1) during hyperglycemic clamp experiments with the exogenous administration of GIP (30–90 min: 2 pmol · kg−1 · min−1)
Experimental period Healthy control subjects First-degree relatives of type 2 diabetic patients Type 2 diabetic patients Significance (P value, ANOVA) 0–15 min 4.0 ± 0.4 3.9 ± 0.3 1.3 ± 0.4* <0.0001 15–30 min 4.4 ± 0.6 4.0 ± 0.4 1.7 ± 0.7* 0.0025 30–45 min 4.2 ± 0.6 4.4 ± 0.4 1.3 ± 0.5* 0.0004 45–60 min 4.5 ± 0.5 5.3 ± 0.5 1.2 ± 0.5* <0.0001 60–75 min 6.9 ± 0.9 6.9 ± 0.8 1.5 ± 0.5* <0.0001 75–90 min 8.2 ± 1.0 7.8 ± 0.6 2.3 ± 0.6* <0.0001 90–105 min 8.5 ± 1.5 8.2 ± 0.8 2.3 ± 0.6* 0.0003 105–120 min 8.2 ± 1.3 8.4 ± 0.9 1.7 ± 0.5* <0.0001 -
Data are means ± SE. P values were calculated by ANOVA with Duncan’s post hoc test to describe differences between the three groups of patients.
- *
* Significant difference (P < 0.05) versus healthy control subjects.
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- TABLE 3
Insulin sensitivity and B-cell function according to various models of calculation
Parameter [reference] Healthy control subjects First-degree relatives of type 2 diabetic patients Type 2 diabetic patients Significance (P value, ANOVA) Reference B-cell function HOMA B-cell function index (% of normal) 67 ± 7 49 ± 5 63 ± 15 0.27 42 Insulin/glucose [basal] ([mU/l]/[mg/dl]) 0.06 ± 0.01 0.05 ± 0.0 0.09 ± 0.01 0.19 55 Insulin/glucose [hyperglycemia‡] ([mU/l]/[mg/dl]) 0.09 ± 0.01 0.07 ± 0.01 0.10 ± 0.02 0.34 no reference Insulin sensitivity HOMA insulin resistance index (fold normal) 1.31 ± 0.95* 1.03 ± 0.12* 3.56 ± 1.01† 0.0002 42 Glucose infusion/insulin ([mg · kg−1 · min−1]/ [mU/l])§ 0.43 ± 0.09 0.46 ± 0.05 0.25 ± 0.13 0.19 no reference Fasting Belfiore index ([l/mU] · [dl/mg]) 0.078 ± 0.008 0.107 ± 0.012* 0.045 ± 0.014† 0.0006 56 FIRI ([l/mU] · [dl/mg]) 1.11 ± 0.2* 0.88 ± 0.1* 3.55 ± 0.98† 0.0003 57 -
Data are means ± SE. P values were calculated by ANOVA with Duncan’s post hoc test to describe differences among the three groups of patients.
- *
* Significant difference (P < 0.05) versus type 2 diabetic patients;
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† significant difference (P < 0.05) versus healthy control subjects;
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‡ hyperglycemia refers to the time point 30 min (see Fig. 1), i.e., before start of the GIP infusion;
- §
§ glucose infusion was calculated for the period 15–30 min (see Fig. 1) and related to the mean insulin concentrations at 15 and 30 min.
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