## Protocol Section
### Identification Module
**NCT ID:** NCT06428968

**Brief Title:** Investigating the Insulin Resistance in Individuals With Type 2 Diabetes

**Official Title:** Investigating the Central and Peripheral Insulin Resistance in Individuals With Type 2 Diabetes

#### Organization Study ID Info
**ID:** T2DM2024
#### Organization
**Class:** OTHER
**Full Name:** Central South University
### Status Module
#### Completion Date
**Date:** 2025-06-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-15

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-07
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Central South University

#### Responsible Party

**Investigator Affiliation:** Central South University

**Investigator Full Name:** Renrong Wu

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

**Detailed Description:** Participants screened through inclusion and exclusion criteria will accept cross-sectional evaluation. The information of demographic data, medical history, previous and current medication regimen, details of complications, and family history regarding metabolic diseases will be collected. The assessments includes physical examination, anthropometry, blood test(blood routine, liver function, renal function, blood lipids, fasting blood glucose, serum insulin，thyroid function and glycosylated hemoglobin A 1c), MRI scan( High-resolution T1-weighted Anatomical Images, Diffusion Tensor Imaging, Resting-state functional MRI and Arterial Spin Labeling) and psychiatry scales(Hamilton Depression Scale, Young Mania Rating Scale and Self-reporting Inventory-90); cognitive function will be assessed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia(MATRICS) Consensus Cognitive Battery; biological samples also will be collected and stored to explore related mechanisms.

### Conditions Module

**Conditions:**

- Type 2 Diabetes

**Keywords:**

- Insulin resistance

- Cognitive impairments

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** SCREENING

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Individual with type 2 diabetes

**Intervention Names:**

- Drug: 160 units nasal insulin spray

**Label:** Individual with type 2 diabetes

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: 160 units nasal insulin spray

**Label:** Healthy volunteers

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Healthy volunteers

- Individual with type 2 diabetes

**Description:** 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.

**Name:** 160 units nasal insulin spray

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

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

**Time Frame:** Baseline

**Description:** 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.

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

**Time Frame:** Baseline

**Description:** 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).

**Measure:** 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.

**Time Frame:** Baseline

**Description:** 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.

**Measure:** The difference of c-fMRI between type 2 diabetes and healthy volunteers.

**Time Frame:** Baseline

#### Secondary Outcomes

**Description:** Diffusion Tensor Imaging (DTI) will be performed using diffusion-weighted echo planar imaging sequences. The analysis of DTI will be conducted to investigate the difference of brain structure and morphology between type 2 diabetes and healthy volunteers.

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

**Time Frame:** Baseline

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** jinghuangserena001@csu.edu.cn

**Name:** Jing Huang, MD

**Phone:** 15874290980

**Role:** CONTACT

**Contact 2:**

**Email:** xiaojingmei@csu.edu.cn

**Name:** Jingmei Xiao, MD

**Phone:** 17673129702

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Changsha

**Country:** China

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

**State:** Hunan

**Zip:** 410011

#### Overall Officials

**Official 1:**

**Affiliation:** Department of Psychiatry, The Second Xiangya Hospital of Central South University

**Name:** Renrong Wu, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000044882

- Term: Glucose Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000004700

- Term: Endocrine System Diseases

- ID: D000006946

- Term: Hyperinsulinism

### Condition Browse Module - Browse Branches

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

### Condition Browse Module - Browse Leaves

- ID: M29705

- Name: Cognitive Dysfunction

- Relevance: LOW

- As Found: Unknown

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: HIGH

- As Found: Diabetes

- ID: M7119

- Name: Diabetes Mellitus, Type 2

- Relevance: HIGH

- As Found: Type 2 Diabetes

- ID: M10370

- Name: Insulin Resistance

- Relevance: HIGH

- As Found: Insulin Resistance

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M25403

- Name: Glucose Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9997

- Name: Hyperinsulinism

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003920

- Term: Diabetes Mellitus

- ID: D000003924

- Term: Diabetes Mellitus, Type 2

- ID: D000007333

- Term: Insulin Resistance

### Intervention Browse Module - Ancestors

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M10365

- Name: Insulin

- Relevance: HIGH

- As Found: Day 1

- ID: M173166

- Name: Insulin, Globin Zinc

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000007328

- Term: Insulin

### Misc Info Module

- Version Holder: 2024-05-31
