Clinical trial NCT02413762: The Role of Gut Hormones and Hepcidin in Type 2 Diabetes Mellitus
Official title: The Role of Gut Hormones and Hepcidin in Type 2 Diabetes Mellitus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Imperial College London Diabetes Centre
Sponsor class: OTHER
First posted: 2015-04-10
Enrollment: 1512
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults resident in the UAE, attending ICLDC for normal healthcare.

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* all

Exclusion Criteria:

* lack of capacity for informed consent; vulnerable individuals

Primary outcomes:
measure: Microvascular complication of diabetes mellitus - prevalence and incidence
timeFrame: 5 years
measure: Macrovascular complication of diabetes mellitus - prevalence and incidence
timeFrame: 5 years
Secondary outcomes:
measure: Progression to NAFLD or NASH
timeFrame: 5 years
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: Imperial College London Diabetes Centre
Study officials:
affiliation: Imperial College London Diabetes Centre
name: Nader Lessan, MBBS FRCP MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sam AH, Sleeth ML, Thomas EL, Ismail NA, Mat Daud N, Chambers E, Shojaee-Moradie F, Umpleby M, Goldstone AP, Le Roux CW, Bech P, Busbridge M, Laurie R, Cuthbertson DJ, Buckley A, Ghatei MA, Bloom SR, Frost GS, Bell JD, Murphy KG. Circulating pancreatic polypeptide concentrations predict visceral and liver fat content. J Clin Endocrinol Metab. 2015 Mar;100(3):1048-52. doi: 10.1210/jc.2014-3450. Epub 2014 Dec 9.
citation: Sam AH, Busbridge M, Amin A, Webber L, White D, Franks S, Martin NM, Sleeth M, Ismail NA, Daud NM, Papamargaritis D, Le Roux CW, Chapman RS, Frost G, Bloom SR, Murphy KG. Hepcidin levels in diabetes mellitus and polycystic ovary syndrome. Diabet Med. 2013 Dec;30(12):1495-9. doi: 10.1111/dme.12262. Epub 2013 Aug 19.
citation: Fleming RE. Iron and inflammation: cross-talk between pathways regulating hepcidin. J Mol Med (Berl). 2008 May;86(5):491-4. doi: 10.1007/s00109-008-0349-8. No abstract available.
citation: Fargion S, Dongiovanni P, Guzzo A, Colombo S, Valenti L, Fracanzani AL. Iron and insulin resistance. Aliment Pharmacol Ther. 2005 Nov;22 Suppl 2:61-3. doi: 10.1111/j.1365-2036.2005.02599.x.
citation: Semple RK, Sleigh A, Murgatroyd PR, Adams CA, Bluck L, Jackson S, Vottero A, Kanabar D, Charlton-Menys V, Durrington P, Soos MA, Carpenter TA, Lomas DJ, Cochran EK, Gorden P, O'Rahilly S, Savage DB. Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. J Clin Invest. 2009 Feb;119(2):315-22. doi: 10.1172/JCI37432. Epub 2009 Jan 26.