Valerio Giuliana, Franzese Adriana, Salerno Mariacarolina, Muzzi Gianluca, Cecere Gaetano, Temple Karen I, Shield Julian P
Faculty of Movement Sciences, Parthenope University, Napoli, Italy.
Diabetes Care. 2004 Oct;27(10):2405-8. doi: 10.2337/diacare.27.10.2405.
To investigate beta-cell function and the long-term health of four case subjects presenting with chromosome 6-associated transient neonatal diabetes (TND).
Two unrelated case subjects presenting with paternal uniparental isodisomy of chromosome 6 (UPD6) and two siblings with a paternally inherited duplication of 6q24 were studied. Three case subjects presented with neonatal diabetes that recurred at 4-17 years, while diabetes was incidentally discovered in the other case subject at 14 years of age. beta-Cell function was investigated after diabetes relapse by means of an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and glucagon tests. The quantitative insulin sensitivity check index (QUICKI) was calculated from fasting blood samples as an estimate of insulin sensitivity.
beta-Cell function was investigated at diabetes relapse in two case subjects: the insulin response to both an OGTT and IVGTT was low, whereas the basal levels of C-peptide were normal. No evidence of insulin resistance was found. Residual beta-cell function was further explored by a glucagon test in all subjects at the age of 16-28 years and was found to be normal. Final height was within the normal percentiles, whereas one case, who had been poorly controlled since puberty, presented with diabetes-related microvascular complications.
In patients with chromosome 6-associated TND, the beta-cell is preserved and able to secrete insulin through the stimulatory G protein pathway while exhibiting a specific defect of insulin secretion after glucose stimulation. This form of diabetes can be managed with insulin or diet, although new therapeutic agents (glucagon-like synthetic analogs) may prove useful in the future. Lack of treatment leads to long-lasting hyperglycemia without the risk of ketoacidosis but associated with microangiopathy in adult life.
研究4例患有6号染色体相关短暂性新生儿糖尿病（TND）的病例受试者的β细胞功能及长期健康状况。
对2例患有6号染色体父源单亲二体（UPD6）的无关病例受试者以及2例患有父源遗传的6q24重复的同胞进行了研究。3例病例受试者出现新生儿糖尿病，在4至17岁时复发，而另一例病例受试者在14岁时偶然发现患有糖尿病。在糖尿病复发后，通过口服葡萄糖耐量试验（OGTT）、静脉葡萄糖耐量试验（IVGTT）和胰高血糖素试验研究β细胞功能。根据空腹血样计算定量胰岛素敏感性检查指数（QUICKI），作为胰岛素敏感性的估计值。
在2例病例受试者糖尿病复发时研究了β细胞功能：对OGTT和IVGTT的胰岛素反应均较低，而C肽基础水平正常。未发现胰岛素抵抗的证据。在所有受试者16至28岁时通过胰高血糖素试验进一步探索了残余β细胞功能，发现其正常。最终身高在正常百分位数范围内，然而，有1例自青春期以来血糖控制不佳，出现了糖尿病相关的微血管并发症。
在患有6号染色体相关TND的患者中，β细胞得以保留，能够通过刺激性G蛋白途径分泌胰岛素，同时在葡萄糖刺激后表现出胰岛素分泌的特定缺陷。这种形式的糖尿病可用胰岛素或饮食治疗，尽管新的治疗药物（胰高血糖素样合成类似物）未来可能证明有用。缺乏治疗会导致长期高血糖，无酮症酸中毒风险，但在成年期会伴有微血管病变。
