The Role of Gut Hormones and Hepcidin in Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This study aims to investigate the potential of the gut hormones GLP-1, PP, PYY and the iron regulatory hormone hepcidin as biomarkers for progression to complications in diabetes mellitus.

Detailed Description
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Iron overload and mechanisms inducing insulin resistance are reciprocally linked. Dietary iron absorption, and iron uptake in liver and adipose tissue, are regulated through the hormone hepcidin. Iron is implicated in microvascular and macrovascular disease pathways and therefore hepcidin may represent a biomarker for progression to complications in type 2 diabetes mellitus. Serum pancreatic polypeptide levels correlate with visceral adiposity and may therefore contribute to the diagnosis of, and risk stratification in, the metabolic syndrome. Hypothesis: Measuring iron status, incretin hormones and serum pancreatic polypeptide will facilitate discrimination of patients at risk of vascular complications of T2DM and clinically significant non-alcoholic fatty liver disease. Statistical analysis: Serum/plasma level of hormone under investigation corrected for age, sex, BMI, diabetes duration, blood pressure, lipid profile, smoking status, treatment for diabetes, hypertension and dyslipidaemia, and HbA1c using multinomial logistic regression and Cox regression models.

Official Title
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The Role of Gut Hormones and Hepcidin in Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: all Exclusion Criteria: lack of capacity for informed consent; vulnerable individuals

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NGT, no insulin resistance<br>Individuals with normal glucose tolerance without a diagnosis of IGF, IGT or Diabetes Mellitus. No intervention. | |
| IFG/IGT/T2DM<br>Individuals with a diagnosis of impaired glucose tolerance, impaired fasting glucose or type 2 diabetes mellitus. No intervention. | |
| Insulin resistance without IGT<br>e.g. polycystic ovarian syndrome. No intervention. | |
| IGT, no insulin resistance<br>e.g. T1DM. No intervention. | |
| Previous metabolic surgery<br>Previous metabolic surgery for weight loss or treatment of T2DM. No intervention. | Other: No intervention<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microvascular complication of diabetes mellitus - prevalence and incidence | Prevalence at enrolment and subsequent incidence of background diabetic retinopathy, preproliferative or proliferative retinopathy, or diabetic maculopathy; microalbuminuria defined as two episodes > 3 months apart of ACR > 2.5 (male) or > 3.5 (female) mg/umol. Assessed through patient recall and examination of electronic medical record. | 5 years | 
| Macrovascular complication of diabetes mellitus - prevalence and incidence | Prevalence at enrolment and subsequent incidence of composite endpoint of coronary artery disease (MI, ACS, percutaneous intervention), cerebrovascular disease (CVA, TIA), and peripheral arterial disease (ischaemic peripheral ulcer, revascularisation procedure, amputation). Assessed through patient recall and examination of electronic medical record. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression to NAFLD or NASH | As defined by ultrasound criteria of NAFLD or evidence of fibrosis as measured using transient elastography, respectively | 5 years |