Genetic Risk Score of Type 1 Diabetes Mellitus for Progression to Insulin in Diabetic Patients Lack of Predictive Value: a Multicenter Nested Case-control Study

The goal of this observational study is to evaluate the predictive value of the genetic risk score for type 1 diabetes in the progression to insulin deficiency in diabetic patients. The main question it aims to answer is:

1. To investigate the predictive efficacy of the genetic risk score for T1DM in determining whether diabetic patients will progress to insulin deficiency;
2. To compare the differences in genetic characteristics between the insulin-deficient cohort and the non-insulin-deficient cohort.

This study is a nested case-control study, in which a case group and a control group are set up for the collection of observational indicators. Case group: Diabetic patients who "progressed to insulin deficiency" and those who "progressed to severe insulin deficiency". Control group: Patients who did not progress to insulin deficiency. The study period is 3 years.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus; Diabetes Mellitus, Type 1

• Study Type: Observational
• Enrollment (Estimated): 2950

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University
      • Contact: Yang Xiao, MD/PhD; Phone Number: 86-0731-85292154; Email: xiaoyang29@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This study will enroll newly-diagnosed diabetic patients whose clinical subtype is unclear. Participants must be aged between 14 and 50 years, with a diabetes diagnosis within the past year, confirmed by standard American Diabetes Association (ADA) criteria. A key pathophysiological criterion is a peak C-peptide level < 200 pmol/L, suggesting impaired insulin secretion.

Key Exclusion Criteria: Patients will be excluded for conditions that could confound the etiology of diabetes or pose additional risks, including:

Specific diabetes subtypes (e.g., gestational diabetes, monogenic diabetes, pancreatic diseases).

Comorbidities such as malignant tumors or severe organ dysfunction. Acute metabolic derangements (e.g., ketoacidosis). Conditions limiting life expectancy or ability to participate (e.g., expected survival < 3 years, psychiatric disorders).

Current pregnancy or lactation.

Description

Inclusion Criteria:

• Gender is not restricted.
• Age ranges from 14 to 50 years old.

• Diagnosis of diabetes within < 1 year:

  1. If there are diabetes symptoms and meet any of the following criteria:① Plasma glucose at any time ≥ 11.1 mmol/L (200 mg/dL), or② Fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL), or③ Plasma glucose 2 hours after OGTT/post - meal ≥ 11.1 mmol/L (200 mg/dL), or④ HbA1c ≥ 6.5%.
  2. If there are no diabetes symptoms, another test on a different day is required for diagnosis.
• Newly - diagnosed diabetes patients whose type diagnosis is considered unclear clinically.

Exclusion Criteria:

• Peak C-peptide < 200 pmol/L;
• Gestational diabetes, monogenic diabetes (neonatal diabetes, MODY), exocrine pancreatic diseases (cystic fibrosis), diabetes caused by drugs or chemicals;
• Those who have been under long-term treatment with hormones or immunosuppressants;
• Pregnant or lactating women;
• Those with concurrent malignant tumors or severe heart, liver, and kidney diseases;
• Those with an expected survival time of less than 3 years;
• Those with mental disorders or unable to cooperate with the investigation for other reasons;
• Acute phase of diabetic ketoacidosis;
• Stress conditions such as severe infection, fever, trauma, and major surgery;
• Patients lacking major clinical information;
• Those considered by the researcher as unfit to participate in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients with diabetes who 'progress to insulin deficiency and severe insulin deficiency'; Patients with diabetes who 'progress to insulin deficiency' and 'progress to severe insulin deficiency'
Patients who have not progressed to insulin deficiency; For each case, several controls (1:2) were randomly selected from patients in this cohort who had not progressed to insulin deficiency at the same follow - up time point.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-peptide	The primary endpoint is the occurrence of progression to insulin deficiency. Subjects who "progress to insulin deficiency" are defined as those whose C-peptide level drops to C-peptide < 250 pmol/L during the follow - up period;	"baseline"、"third year"

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting and 2 - hour blood glucose		"baseline"、"third year"
Glycosylated hemoglobin		"baseline"、"third year"
Whether insulin treatment is needed	Collect the medical history and current medication information of the subjects.	"baseline"、"third year"

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: May 31, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 31, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Genetic risk score
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Disease Attributes; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Disease Susceptibility; Genetic Predisposition to Disease; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Genetic Risk Score; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2025 T1DGRS LYF20250124

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No