Glucose Homeostasis in Pseudohypoparathyroidism
キーワード
概要
説明
Pseudohypoparathyroidism type 1A (PHP1A) is a rare, genetic disorder caused by impaired stimulatory G-protein signaling due to heterozygous mutations in the gene, GNAS. The most severe form of the disease, PHP1A occurs when a GNAS mutation is inherited on the preferentially expressed maternal allele. A less severe form of the disease, pseudopseudohypoparathyroidism (PPHP), occurs when a GNAS mutation is inherited on the paternal allele. Clinically, PHP1A is characterized by multi-hormone resistance, cognitive impairment and early-onset obesity while PPHP has a mild phenotype without multi-hormone resistance. It is increasingly recognized that PHP1A is associated with an increased risk of type 2 diabetes but the mechanism is unknown. Glucose homeostasis and diabetes risk has not been studied in PPHP. As part of the parent K23 award, we investigated glucose tolerance in children with PHP1A. In contrast to the adult literature, we found that children with PHP1A had greater insulin sensitivity than matched controls. When challenged with an oral glucose load, however, children with PHP1A had persistent hyperglycemia and 25% met criteria for impaired glucose tolerance. The goal of this proposal is to quantify β-cell function in PHP1A. It is plausible that these individuals have a) impaired β-cell function, b) differences in insulin sensitivity, and c) impaired incretin function. Thus, in this pilot study we will definitively assess one of these, β-cell function, using the frequently sampled intravenous glucose tolerance test in patients with PHP1A and PPHP (aim 1). We will also assess oral glucose tolerance over time by bringing back children and young adults with PHP1A from our original cohort for repeat glucose tolerance testing (aim 2). The ultimate goal is to rigorously define glucose homeostasis defects in PHP1A in order to design and conduct an intervention study for glucose intolerance and type 2 diabetes in PHP1A.
日付
最終確認済み: | 03/31/2020 |
最初に提出された: | 11/28/2018 |
提出された推定登録数: | 11/28/2018 |
最初の投稿: | 12/02/2018 |
最終更新が送信されました: | 04/07/2020 |
最終更新日: | 04/08/2020 |
実際の研究開始日: | 06/18/2019 |
一次完了予定日: | 02/28/2021 |
研究完了予定日: | 02/28/2021 |
状態または病気
段階
アームグループ
腕 | 介入/治療 |
---|---|
Pseudphypoparathyroidism type 1A (PHP1A) Case | |
Pseudopseudohypoparathyroidism (PPHP) Case | |
Controls Matched control group |
適格基準
研究の対象となる年齢 | 6 Years に 6 Years |
研究に適格な性別 | All |
サンプリング方法 | Non-Probability Sample |
健康なボランティアを受け入れる | 番号 |
基準 | Inclusion Criteria: 1. Diagnosis of PHP1A/PPHP 2. Age between 6 and 50 years old Controls will be matched based on: 1. Gender 2. Race 3. Age (±2 years if <25 years old or ±5 years if ≥25 years old) 4. BMI (±2 kg/m2) 5. Diabetes status Exclusion Criteria: 1. Treatment with appetite-altering drug or initiation of a new weight loss program in the past 3 months 2. Type 1 diabetes 3. Type 2 diabetes treated with insulin or GLP-1 receptor agonists or A1c >9%at their most recent clinic visit 4. Pregnant or lactating women |
結果
主な結果の測定
1. Insulin sensitivity (Si) [baseline]