Genetical Background of Non-alcoholic Fatty Liver Disease (NAFLD) in Diabetes Mellitus and in Chronic Kidney Disease

Diabetes Mellitus Clinical Trial

— NAFLDDMCKD  

Official title:

Genetical Background of Non-alcoholic Fatty Liver Disease (NAFLD) in Diabetes Mellitus and in Chronic Kidney Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02947568
• Other study ID #: Pecs_NAFLD_01
• Status: Active, not recruiting
• Start date: March 2016
• Est. completion date: December 31, 2020

Study information

• Verified date: February 2019
• Source: University of Pecs
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The present study investigates relationship between non-alcoholic fatty liver disease and its risk factors, such as genetic background and diseases, such as chronic kidney disease and diabetes mellitus.

Description:

Non-alcoholic fatty liver disease (NAFLD) is a multisystemic disease, also affecting extrahepatic organs (1,2,6). According to former data, not only the prevalence of chronic hepatic disease, chronic cardiovascular diseases, but also the prevalence of chronic kidney disease (CKD) is higher in NAFLD (4,7). A strong association has been shown between diabetes mellitus (DM) and NAFLD as well (3,5,10).

Many genetical factors have been studied in the background of NAFLD. Many studies have proved the effect of patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (8,9). Effect of numerous genetical polymorphisms has been suggested behind oxidative stress responsible for NAFLD (8).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 600
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• CKD (renal replacement therapy non excluded)

• DM

• CKD+DM

Exclusion Criteria:

• alcohol abuse

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Diabetes Mellitus
• Fatty Liver
• Kidney Diseases
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Renal Insufficiency, Chronic

Intervention

Other:
• non-interventional study

Locations

Country	Name	City	State
Hungary	2nd Department of Medicine and Nephrological Center	Pécs	Baranya

Sponsors (3)

Lead Sponsor	Collaborator
University of Pecs	Fresenius Medical Care North America, Teaching Hospital Markusovszky, Szombathely

Country where clinical trial is conducted

Hungary, 

References & Publications (1)

1. Alp H, Karaarsian S, Selver EB,Atabek ME, Altin H, Baysal T. Association between nonalcoholic fatty liver disease and cardiovascular risk in obese children and adolescents. Can J Cardiol 2013;29:1118-1125. 2. Byrne CD, Targher G: NAFLD: A multisystem disease. Review. Journal of Hepatology, 2015; 62:S47-S64. 3. Kasturiratne A, Weerasinghe S, Dassanayake AS, rajindrajith S, de Silva AP, Kato N, et al. Influence of non-alcoholic fatty liver disease on the development of diabetes mellitus. J Gastroenterol Hepatol 2013;60:384-391. 4. Li G, Shi W, Hug H, Chen Y, Liu L, Yin D. Nonalcoholic fatty liver disease associated with impairment of kidney function in nondiabetes population. Biochem Med 2012;22:92-99. 5. Okamoto M, Takeda Y, Yoda Y, Kobayashi K, Fujino MA, Yamagata Z. The association of fatty liver and diabetes risk. J Epidemiol 2003;13:15-21. 6. Pacifico L, Di MM, De MA, Bezzi M, Osborn JF, Catalano C, et al. Left ventricular dysfunction in obese children and adolescents with nonalcoholic fatty liver disease. Hepatology 2014;59:461-470. 7. Targher G, Choncol MB, Byrne CD. CKD a nonalcoholic fatty liver disease. Am J Kidney Dis 2014;64:638-652. 8. Wood KL, Miller MH, Dillon JF. systematic review of genetic association studies involving histologically confirmed non-alcoholic fatty liver disease BMJ Open Gastro 2015:2:e000019. doi10.1136/bmjgast-2014-000019 9. Zain SM, Mohamed R, Hyogo H, et al. A multi-ethnic study of a PNPLA3 variant and its association with disease severity in non-alcoholic fatty liver disease. Hum genet 2012;131:1145-1152. 10. Zuppini G, Fedeli U, Gennaro N, Saugo M, Targher G, Bonora E. Mortality from chronic liver diseases in diabetes. Am J Gastroenterol 2014;109:1020-1025.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association of NFS (NAFLD fibrosis score) and HSI (hepatic steatosis index) with underlying conditions	The association of hepatic steatosis with chronic kidney disease, diabetes mellitus and the the persence of these two will be assessed	2 years
Primary	Association of genetical factors with NFS and HSI	The association of hepatic steatosis with genetic factors will be assessed. In case of patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) : rs738409, rs2281135, rs2294918 single nuclear polimorfism (SNP) will be examined	2 years
Secondary	Association of hepatic steatosis with renal function	The association of serum creatinine, eGFR, blood urea nitrogen, serum sodium, serum potassium, serum calcium with NFS and HSI will be assessed	2 years
Secondary	Association of glucose metabolism parameters with hepaic steatosis indices	Association of HbA1C, fructosamine, blood glucose, serum insulin, HOMAIR, serum uric acid with NFS and HSI	2 years
Secondary	Association of liver function and hepatic setatosis indices	Association of serum bilirubine, serum GOT, serum GPT, serum GGT, serum ALP, serum LDH, INR, serum total protein, serum albumin with NFS and HSI	2 years
Secondary	Association of serum lipid profile and hepatic setatosis indices	Association of serum total cholesterol, serum HDL-cholesterol, serum LDL-cholesterol, serum triglyceride, serum carnitine with NFS and HSI	2 years
Secondary	Association of iron metabolism parameters with hepatic setatosis indices	association of serum iron, serum transferrine, serum transferrine saturation, serum ferritine with NFS and HSI	2 years
Secondary	The relationship between blood count, sedimentation and inflammation with hepatic setatosis indices	Association of blood count, erythrocyte sedimentation rate, CRP with NFS and HSI	2 years
Secondary	Assotion of serum proteins with hepatic setatosis indices	association of urinary total protein, urinary albumin, urinary total protein/creatinine ratio, urinary albumin/creatinine ratio with NFS and HSI	2 years
Secondary	Association of pathological tyrosine isoforms with hepatic setatosis indices	Association of serum meta-Tyr, serum ortho-Tyr, urinary meta-Tyr, urinary ortho-Tyr, urinary meta-Tyr/creatinine ratio, urinary ortho-Tyr/creatinine ratio with NFS and HSI	2 years