Investigating the Insulin Resistance in Individuals With Type 2 Diabetes

NCT06428968 | Recruiting

• 1 other identifier: T2DM2024
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Numerous studies have provided evidence of a correlation between Type 2 Diabetes Mellitus (T2DM) and cognitive dysfunction, specifically in the realms of complex attention, information processing, and executive function. These impairments have been observed in middle-aged and elderly individuals with T2DM, with longer diabetes duration, suboptimal glycemic control, and the presence of diabetic complications being contributing factors. Recent research in young adults and adolescents diagnosed with T2DM has revealed cognitive and brain structural alterations in this growing demographic, suggesting that early disease mechanisms, rather than solely vascular and age-related neurodegeneration, contribute to pathogenesis. However, there remains uncertainty regarding the interplay between central and peripheral insulin resistance and its impact on cognitive dysfunction in individuals with T2DM. This study aims to investigate central insulin resistance in T2DM, elucidating its association with peripheral insulin resistance and the effects on cognitive impairments.

Conditions

Type 2 Diabetes

Keywords

Insulin resistance; Cognitive impairments

Outcome Measures

Primary Outcomes (4)

• The difference of changes of brain cerebral blood flow by arterial spin labeling between type 2 diabetes and healthy volunteers.

  Whole brain cerebral blood flow (CBF) will be recorded by arterial spin labeling (ASL). the changes in CBF (c-CBF) before and after the application of 160 units nasal insulin spray of interventional participants will be calculated. The c-CBF is an index of central insulin response.

  Baseline

• The difference of the level of insulin signaling in Extracellular Vesicles of neuronal origin isolated from blood between type 2 diabetes and healthy volunteers.

  Phosphorylated insulin receptor substrate 1 and its downstream mediators represent the state of neuronal insulin resistance, whose improvement means better insulin signaling. For individuals with type 2 diabetes mellitus and healthy volunteers, blood samples will be collected and stored at -80℃ at baseline. The NEVs isolation and biomarker measurements will be processed uniformly, and the difference of the level of insulin signaling between two groups will be used for exploring underlying mechanism of disease.

  Baseline

• The difference of the score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery between type 2 diabetes and healthy volunteers.

  The cognitive function of interventional participants will be assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. Evaluator convert raw scores to scale scores, then to normalized T scores. T scores of seven domains and composite score are further calculated. The difference of T scores between two groups will be used for evaluating cognitive function. (higher score means better function).

  Baseline

• The difference of c-fMRI between type 2 diabetes and healthy volunteers.

  The resting-state functional MRI(fMRI) will be conducted at fasting state and after the application of 160 units nasal insulin spray. For every participants, the changes in fMRI (c-fMRI) under the application of nasal insulin spray will be analysed. The c-fMRI between type 2 diabetes and healthy volunteers may reflect the underlying mechanism of disease.

  Baseline

Secondary Outcomes (1)

• The difference of Diffusion Tensor Imaging scanned by MRI between type 2 diabetes and healthy volunteers

  Baseline

Study Arms (2)

Individual with type 2 diabetes

EXPERIMENTAL

Individual with type 2 diabetes

Drug: 160 units nasal insulin spray

Healthy volunteers

EXPERIMENTAL

Drug: 160 units nasal insulin spray

Interventions

160 units nasal insulin spray DRUG

Initially, a series of MRI scans, including high-resolution T1-weighted anatomical images, diffusion tensor imaging, resting-state functional MRI, and arterial spin labeling, will be conducted. Subsequently, 160 units of nasal insulin spray will be administered, followed by a second round of MRI scans after a 30-minute interval, encompassing high-resolution T1-weighted anatomical images, resting-state functional MRI, and arterial spin labeling.

Healthy volunteers; Individual with type 2 diabetes

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meeting the diagnostic criteria for Type 2 diabetes: typical symptoms of diabetes plus random blood glucose level of ≥11.1 mmol/l, or fasting blood glucose level of ≥7.0 mmol/l, or 2-hour post-OGTT (Oral Glucose Tolerance Test) blood glucose level of ≥11.1 mmol/l, or HbA1c level of ≥6.5%; for those without typical symptoms of diabetes, re-examination on a different day is required for confirmation.

You may not qualify if:

• Having history of substance dependence or abuse or whose symptoms are caused by diagnosable mental disorders;
• Having history of traumatic brain injury, seizures or other known neurological or organic diseases of the central nervous system;
• Having current suicidal or homicidal thoughts or any safety concern by research staff that cannot be manage in an inpatient setting;
• Taking drugs that could affect cognitive function.
• The routine blood tests showing significant abnormal renal, liver function or other somatic disease.
• Pregnant or lactating women.

Sponsors & Collaborators

• Central South University: lead

Study Sites (1)

Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Renrong Wu, PhD

  Department of Psychiatry, The Second Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jing Huang, MD

CONTACT

15874290980; jinghuangserena001@csu.edu.cn

Jingmei Xiao, MD

CONTACT

17673129702; xiaojingmei@csu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 24, 2024
• Study Start: September 6, 2024
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)