Arslanian Silva A, Bacha Fida, Saad Rola, Gungor Neslihan
Division of Pediatric Endocrinology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Diabetes Care. 2005 Jan;28(1):115-9. doi: 10.2337/diacare.28.1.115.
Family history of type 2 diabetes is a major risk factor for type 2 diabetes in youth, which is increasing. This investigation aimed to evaluate the impact of family history of type 2 diabetes on insulin secretion relative to insulin sensitivity in healthy children. beta-Cell compensation for insulin sensitivity was calculated as the product of insulin sensitivity x first-phase insulin secretion, termed glucose disposition index (GDI).
A total of 28 healthy white children (12 boys and 16 girls; 12.1 +/- 0.5 years of age) with a positive family history of type 2 diabetes and 26 healthy white children (13 boys and 13 girls; 11.5 +/- 0.4 years of age) with a negative family history of type 2 diabetes underwent a 3-h 40 mU.m(-2).min(-1) hyperinsulinemic-euglycemic clamp to assess insulin sensitivity and clearance and a 2-h hyperglycemic clamp to assess insulin secretion. Body composition and visceral adiposity were evaluated with dual-energy X-ray absorptiometry and computed tomography at the L4-L5 intervertebral space.
Insulin sensitivity was lower in children with a family history of type 2 diabetes versus children without a family history (8.8 +/- 0.9 vs. 12.2 +/- 1.1 micromol.kg(-1).min(-1) per pmol/l, P = 0.02). Similarly, insulin clearance was lower. First- and second-phase insulin levels were not different between groups with and without a positive family history. The GDI was lower in youth with versus youth without a positive family history (4.1 +/- 0.3 vs. 5.2 +/- 0.5 mmol.kg(-1).min(-1), P = 0.039). IGF binding protein-1 (IGFBP-1) was 60% lower in youth with versus youth without the positive family history.
These results demonstrate that family history of type 2 diabetes in white children is associated with decreased insulin sensitivity and clearance, decreased IGFBP-1, and an impaired relationship between insulin action and beta-cell compensation. Detection of these alterations in hormonal and metabolic parameters in children with a positive family history suggests that at least some of the determinants of GDI are genetic/heritable.
2型糖尿病家族史是青少年2型糖尿病的主要危险因素，且该危险因素呈上升趋势。本研究旨在评估2型糖尿病家族史对健康儿童胰岛素分泌相对于胰岛素敏感性的影响。β细胞对胰岛素敏感性的代偿通过胰岛素敏感性×第一相胰岛素分泌的乘积来计算，称为葡萄糖处置指数（GDI）。
共有28名2型糖尿病家族史阳性的健康白人儿童（12名男孩和16名女孩；12.1±0.5岁）和26名2型糖尿病家族史阴性的健康白人儿童（13名男孩和13名女孩；11.5±0.4岁）接受了3小时40 mU·m⁻²·min⁻¹的高胰岛素-正常血糖钳夹试验以评估胰岛素敏感性和清除率，以及2小时的高血糖钳夹试验以评估胰岛素分泌。采用双能X线吸收法和L4-L5椎间隙计算机断层扫描评估身体成分和内脏脂肪。
有2型糖尿病家族史的儿童胰岛素敏感性低于无家族史的儿童（8.8±0.9 vs. 12.2±1.1 μmol·kg⁻¹·min⁻¹ per pmol/l，P = 0.02）。同样，胰岛素清除率也较低。有和无阳性家族史的两组之间第一相和第二相胰岛素水平无差异。有阳性家族史的青少年的GDI低于无阳性家族史的青少年（4.1±0.3 vs. 5.2±0.5 mmol·kg⁻¹·min⁻¹，P = 0.039）。有阳性家族史的青少年的胰岛素样生长因子结合蛋白-1（IGFBP-1）比无阳性家族史的青少年低60%。
这些结果表明，白人儿童的2型糖尿病家族史与胰岛素敏感性和清除率降低、IGFBP-1降低以及胰岛素作用与β细胞代偿之间的关系受损有关。在有阳性家族史的儿童中检测到这些激素和代谢参数的改变表明，至少GDI的一些决定因素是遗传/可遗传的。
