Evaluation of Neuregulin-4 (NRG4) Levels in Obese and Non-Obese Patients With Type 2 Diabetes Mellitus

NCT07734558 | Not Yet Recruiting

• 1 other identifier: KAEK/2026.04.1 l8
• Study Type: observational
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective observational study aims to evaluate serum Neuregulin-4 (NRG4) concentrations in obese and non-obese adults with Type 2 Diabetes Mellitus (T2DM) and to investigate their association with obesity status, insulin resistance, and different antidiabetic treatment regimens. Participants will be categorized into five predefined groups according to obesity status and treatment regimen, including SGLT2 inhibitor users, non-SGLT2 oral antidiabetic therapy users, SGLT2 combination therapy users, newly diagnosed treatment-naïve patients, and healthy controls. Clinical, anthropometric, and laboratory parameters including fasting plasma glucose, HbA1c, estimated glomerular filtration rate (eGFR), body mass index, waist circumference, waist-to-hip ratio, and serum NRG4 concentrations will be evaluated. The study aims to determine whether NRG4 may serve as a novel biomarker reflecting metabolic status and treatment response in patients with T2DM.

Conditions

Type 2 Diabetes Mellitus (T2DM); Obesity Type 2 Diabetes Mellitus; Insulin Resistance

Keywords

Neuregulin-4; NRG4; Type 2 Diabetes Mellitus; Obesity; Adipokine

Outcome Measures

Primary Outcomes (1)

• Serum Neuregulin-4 (NRG4) Levels in Obese and Non-Obese Type 2 Diabetic Patients

  The primary outcome of this study is the evaluation and comparison of serum Neuregulin-4 (NRG4) levels among obese and non-obese patients with Type 2 Diabetes Mellitus receiving different antidiabetic treatment modalities, as well as healthy control subjects.

  Baseline (Day 0)

Secondary Outcomes (4)

• Glycated Hemoglobin (HbA1c)

  Baseline (Day 0)

• Fasting Plasma Glucose

  Baseline (Day 0)

• Estimated Glomerular Filtration Rate (eGFR)

  Baseline (Day 0)

• Body Mass Index (BMI)

  Baseline (Day 0)

Study Arms (5)

SGLT2 Group

Type 2 Diabetes Mellitus patients receiving only SGLT2 inhibitor treatment will be included in this group. Serum NRG4 levels and metabolic parameters will be evaluated.

Non-SGLT2 OAD Group

Type 2 Diabetes Mellitus patients receiving metformin with or without insulin therapy, but not receiving SGLT2 inhibitors, will be included in this group.

SGLT2 Combination Group

Type 2 Diabetes Mellitus patients receiving metformin with or without insulin together with SGLT2 inhibitor therapy will be included in this group.

Newly Diagnosed DM Group

Newly diagnosed treatment-naive Type 2 Diabetes Mellitus patients who have not received any antidiabetic therapy will be included in this group.

Healthy Control Group

Age-matched participants without Diabetes Mellitus diagnosis will be included as healthy controls for comparison of serum NRG4 levels and metabolic parameters.

Eligibility Criteria

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

Study Population

The study population will consist of obese and non-obese adult participants aged 18-65 years who are admitted to the outpatient clinic. The study will include newly diagnosed treatment-naive Type 2 Diabetes Mellitus patients, patients with at least 6 months of Type 2 DM diagnosis receiving different antidiabetic treatment combinations, and healthy control participants without diabetes mellitus.

You may qualify if:

• Age 18-65 years
• Newly diagnosed treatment-naïve T2DM
• T2DM treated for at least 6 months
• BMI \>30 kg/m²
• BMI \<25 kg/m²
• No pregnancy
• No breastfeeding
• No active infection
• No inflammatory disease
• Written informed consent

You may not qualify if:

• Age \<18 years
• Pregnancy
• Breastfeeding
• Active infection
• Rheumatologic disease
• Refusal to participate

Sponsors & Collaborators

• GÜLDEN ANATACA: lead

Study Sites (1)

Kanuni Sultan Süleyman Training and Research Hospital

Istanbul, Turkey (Türkiye)

Location

Related Publications (7)

• Tutunchi H, Mobasseri M, Aghamohammadzadeh N, Hooshyar J, Naeini F, Najafipour F. Serum neuregulin 4 (NRG-4) level and non-alcoholic fatty liver disease (NAFLD): A case-control study. Int J Clin Pract. 2021 Oct;75(10):e14555. doi: 10.1111/ijcp.14555. Epub 2021 Jun 29.

  PMID: 34159710 BACKGROUND

• Cai C, Lin M, Xu Y, Li X, Yang S, Zhang H. Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study. BMC Med. 2016 Oct 24;14(1):165. doi: 10.1186/s12916-016-0703-6.

  PMID: 27772531 BACKGROUND

• Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z, Cozacov Z, Zhou D, Okunade AL, Su X, Li S, Bluher M, Lin JD. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med. 2014 Dec;20(12):1436-1443. doi: 10.1038/nm.3713. Epub 2014 Nov 17.

  PMID: 25401691 BACKGROUND

• Yan P, Xu Y, Wan Q, Feng J, Li H, Yang J, Zhong H, Zhang Z. Plasma Neuregulin 4 Levels Are Associated with Metabolic Syndrome in Patients Newly Diagnosed with Type 2 Diabetes Mellitus. Dis Markers. 2018 Mar 12;2018:6974191. doi: 10.1155/2018/6974191. eCollection 2018.

  PMID: 29721105 BACKGROUND

• Kurek Eken M, Sahin Ersoy G, Yayla Abide C, Sanverdi I, Devranoglu B, Kutlu T, Cevik O. Association between circulating neuregulin 4 levels and metabolic, aterogenic, and AMH profile of polycystic ovary syndrome. J Obstet Gynaecol. 2019 Oct;39(7):975-980. doi: 10.1080/01443615.2019.1581754. Epub 2019 May 7.

  PMID: 31064233 BACKGROUND

• Villarroya F, Cereijo R, Villarroya J, Giralt M. Brown adipose tissue as a secretory organ. Nat Rev Endocrinol. 2017 Jan;13(1):26-35. doi: 10.1038/nrendo.2016.136. Epub 2016 Sep 12.

  PMID: 27616452 BACKGROUND

• Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. Front Endocrinol (Lausanne). 2016 Apr 13;7:30. doi: 10.3389/fendo.2016.00030. eCollection 2016.

  PMID: 27148161 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral venous blood samples will be collected from all participants for the measurement of serum Neuregulin-4 (NRG4) levels. Blood samples will be centrifuged, and serum aliquots will be stored at -80°C until laboratory analysis. NRG4 is a brown adipose tissue-derived adipokine associated with glucose metabolism, insulin resistance, obesity, lipid metabolism, and inflammatory pathways. Serum NRG4 levels will be analyzed to evaluate their relationship with obesity, Type 2 Diabetes Mellitus, and different antidiabetic treatment modalities. No genetic or DNA analysis will be performed on the retained samples.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance; Obesity

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

GÜLDEN ANATACA

CONTACT

+905059284244; ganataca@yahoo.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: specialist

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: July 29, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)