Screening for Genetic Forms of Diabetes in Convention of Care for Children and Adolescents With Diabetes (GENEPEDIAB)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 446
- 试验地点
- 2
- 主要终点
- Genetic diagnosis of diabetes: HLA genotype
研究概览
简要总结
Background/Aims: Diabetes, which affects 420 million people worldwide with a continuously rising incidence, is defined by a state of chronic hyperglycemia; a criterion referring to a heterogeneous group of diseases with various etiologies and distinct therapeutic options. Besides the two main forms of diabetes (i.e., type 1 (T1D) and type 2 (T2D)), there are rare subtypes of the disease called monogenic diabetes (or formerly MODY) that are hardly diagnosed because of their resemblance to T1D or T2D. Since these monogenic diabetes may appear early in life, a consortium of expert pediatric clinical centers was created under a clinical research initiative (the GENEPEDIAB study) to develop tools for accurate diagnosis of rare diabetes and to propose appropriate care to these children and adolescents wrongly assigned to T1D or T2D cohorts. The GENEPEDIAB study was initiated in the context of a broader collaborative project (DiaType) with the objective to develop personalized diabetes medicine and better patient care.
Methods: For discrimination of patients with monogenic diabetes from those with classical forms of diabetes using the MODY probability calculator, patients enrolled in the GENEPEDIAB study are phenotyped and genotyped for T1D risk (anti-islet antibodies and HLA). Patients fulfilling sufficient criteria are then genotyped using the routine MODY panel, before being proposed a thorough gene analysis. More comprehensive genetic tests will be conducted in patients without anomalies found after the MODY gene-sequencing test.
Perspective: the GENEPEDIAB study will enable the investigators to adapt treatment to diabetes etiology and help to provide genetic counseling to patients and their family members. The investigators anticipate that its broad genetic analyses will provide them with important information about the genetic susceptibility of these subgroups of patients with atypical diabetes.
详细描述
BACKGROUND:
Diabetes currently affects 420 million people worldwide, a number that is expected to increase to 642 million in 2040. This disease is responsible for a high morbidity rate and an overall mortality equivalent to 5 million deaths per year. In Belgium, the prevalence of diabetes is estimated at 8% in adults over 35 years of age, the risk of diabetes being 3 to 5 times higher in populations with high consanguinity, mainly due to the susceptibility to generate recessive genetic variants, which are characteristic of atypical forms of diabetes.
Although diabetes is linearly defined by a state of chronic hyperglycaemia, this criterion refers to a heterogeneous group of diseases of various aetiologies and distinct therapeutic options. Ten to 15% of diabetic patients have insulin-dependent type 1 diabetes (T1D), attributed to autoimmune destruction of insulin-producing beta cells, while 80% of patients have type 2 diabetes (T2DM), treated - inter alia - with oral antidiabetic drugs. Despite the diagnosis of T1D is confirmed by the determination of specific antibodies, DT1 and T2D are clinically characterized by the phenotypic type and evolution of the patient, without recourse to specific etiological and/or pathognomonic criteria. Recently, subtypes of T1D and T2D have been categorized to help the clinician choose the best therapeutic interventions for the patient (i.e., dietary approach, physical activity, oral antidiabetic drugs, insulin, combined therapies).
Monogenic causes of diabetes are less common (up to 5% of all cases) and of recent discovery, their molecular basis having been established in the 1990s, under the name "maturity onset diabetes of the young" (MODY). The diagnosis of a genetic origin of diabetes has multiple consequences, primarily at therapeutic level. Despite the implications of a monogenic diabetes diagnosis, this form remains largely underdiagnosed, and it is accepted that 2 to 3% of active patients within diabetes conventions of care suffer from undetected genetic forms.
AIM:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- — 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 0 and 18 years at the age of diabetes diagnosis.
- •Patients followed and/or diagnosed within diabetes care agreements of the pediatric endocrinology departments participating in the study.
排除标准
- 未提供
结局指标
主要结局
Genetic diagnosis of diabetes: HLA genotype
时间窗: from diabetes diagnosis to study inclusion. (The study inclusion will be from 18 months after diagnosis to several years)
Presence of at risk HLA genotype
Genetic diagnosis of atypical diabetes: MODY gene-sequencing test
时间窗: at inclusion in the study
MODY gene-sequencing test (GCK, HNF1A, HNF4A, HNF1B, KCNJ11, ABCC8, and INS gene sequencing)
Diagnostic of atypical diabetes using follow-up of clinical parameters: Height
时间窗: At diabetes diagnosis
Height in meters (m)
Diagnostic of atypical diabetes using follow-up of clinical parameters: BMI
时间窗: At diabetes diagnosis
Body Mass Index (Kg/m²)
Diagnostic of atypical diabetes using follow-up of clinical parameters: Weight
时间窗: At diabetes diagnosis
Weight in kilograms (Kg)
Diagnostic of atypical diabetes using follow-up of laboratory results: HbA1c (%)
时间窗: from diabetes diagnosis to study inclusion. (The study inclusion will be from 18 months after diagnosis to several years)
Glicated hemoglobin (%)
Diagnostic of atypical diabetes using follow-up of laboratory results: HbA1c (mmol/mol)
时间窗: from diabetes diagnosis to study inclusion. (The study inclusion will be from 18 months after diagnosis to several years)
Glicated hemoglobin (mmol/mol)
Diagnostic of atypical diabetes using follow-up of laboratory results: Glycaemia
时间窗: from diabetes diagnosis to study inclusion
Glycaemia (mg/dL)
Diagnostic of atypical diabetes using follow-up of laboratory results: C-peptide
时间窗: from diabetes diagnosis to study inclusion. (The study inclusion will be from 18 months after diagnosis to several years)
C-peptide (pmol/mL)
Genetic diagnosis of diabetes: Anti-islets antibodies
时间窗: from diabetes diagnosis to study inclusion. (The study inclusion will be from 18 months after diagnosis to several years)
Presence of measurable Anti-islets antibodies
Genetic diagnosis of atypical diabetes: More comprehensive genetic tests
时间窗: After MODY gene-sequencing test, from 3 months to 1.5 year after study inclusion
More comprehensive genetic tests will be conducted in patients without anomalies found after the MODY gene-sequencing test.
次要结局
未报告次要终点