Type2diabetesNCT06289387
Combining Gene Variants to Improve Risk Prediction for Metabolic (Dysfunction)- Associated Fatty Liver Disease and Its Progression to Cirrhosis in Indian Individuals With Type 2 Diabetes
An observational study of Type2diabetes, run by Medanta, The Medicity, India at 1 site in India.
Trial summary
Type 2 diabetes and metabolic (dysfunction)-associated fatty liver disease (MAFLD) often exist together. The prevalence of MAFLD is about 15-30% in healthy people and around 60-70% in people with type 2 diabetes. Moreover, type 2 diabetes accelerates the progression of liver disease in MAFLD. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Type2diabetes
- How many people
- 1,000 participants
- Where
- 1 siteIndia
- Study dates
- 20 Jan 2024to 29 Jul 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Individuals with or without diabetes will be enrolled
Who may be able to join
- Individuals with or without T2DM between ages 30 to 70 years
Who cannot join
- Age below 30 years Patients with hepatitis B, hepatitis C or HIV disease Patients with significant alcohol intake (>14 drinks/week in men and >10 drinks/week in women).
- Patients on corticosteroids and chemotherapeutic agents.
Trial locations and contacts
1 site in 1 country.
India1 site
Medanta Division of Endocrinology & Diabetes
Gurgaon, Haryana, 122001
About this study
Official title: Combining Gene Variants to Improve Risk Prediction for Metabolic (Dysfunction)- Associated Fatty Liver Disease and Its Progression to Cirrhosis in Indian Individuals With Type 2 Diabetes: a Cross-sectional Study
Type 2 diabetes and metabolic (dysfunction)-associated fatty liver disease (MAFLD) often exist together. The prevalence of MAFLD is about 15-30% in healthy people and around 60-70% in people with type 2 diabetes. Moreover, type 2 diabetes accelerates the progression of liver disease in MAFLD.
MAFLD is a spectrum of liver conditions, ranging from simple fatty liver (low risk for progression), progressing to steatohepatitis (MASH) with no or mild fibrosis, advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although diabetes is the strongest predictor of advanced fibrosis in MAFLD, however, only a small proportion of people with type 2 diabetes and MAFLD (about 5-7%) develop a clinically significant liver disease, but the burden of MAFLD is such that even a small proportion of patients developing cirrhosis will lead to a huge strain on the health care system in India. MAFLD is predicted to be the leading indication for liver transplantation in coming years. At present, MAFLD/MASH is the second most common indication for liver transplantation in the USA as well as in India.
The question is why around 5-7% patients amongst MAFLD population develop fibrosis and cirrhosis. A growing body of evidence suggest that the disease develops because of a complex process in which several factors, including genetic susceptibility and environmental insults, are involved. There are several gene variants that have been incriminated in the development and progression of MAFLD. The most common genes associated with MAFLD are PNPLA3, TM6SF2, GCKR, and MBOAT7. The loss-of-function gene variant HSD17B13 seems to protect from NAFLD. There are a few studies from India about the role of PNPLA3 and TM6SF2 in MAFLD. However, these studies used USG for the diagnosis of MAFLD, which does not provide any information regarding fibrosis of the liver. The data regarding other three genetic variants are scarce from Indian individuals.
Read the detailed description
Type 2 diabetes and metabolic (dysfunction)-associated fatty liver disease (MAFLD) often exist together. The prevalence of MAFLD is about 15-30% in healthy people and around 60-70% in people with type 2 diabetes. Moreover, type 2 diabetes accelerates the progression of liver disease in MAFLD.
MAFLD is a spectrum of liver conditions, ranging from simple fatty liver (low risk for progression), progressing to steatohepatitis (MASH) with no or mild fibrosis, advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although diabetes is the strongest predictor of advanced fibrosis in MAFLD, however, only a small proportion of people with type 2 diabetes and MAFLD (about 5-7%) develop a clinically significant liver disease, but the burden of MAFLD is such that even a small proportion of patients developing cirrhosis will lead to a huge strain on the health care system in India. MAFLD is predicted to be the leading indication for liver transplantation in coming years. At present, MAFLD/MASH is the second most common indication for liver transplantation in the USA as well as in India.
The question is why around 5-7% patients amongst MAFLD population develop fibrosis and cirrhosis. A growing body of evidence suggest that the disease develops because of a complex process in which several factors, including genetic susceptibility and environmental insults, are involved. There are several gene variants that have been incriminated in the development and progression of MAFLD. The most common genes associated with MAFLD are PNPLA3, TM6SF2, GCKR, and MBOAT7. The loss-of-function gene variant HSD17B13 seems to protect from NAFLD. There are a few studies from India about the role of PNPLA3 and TM6SF2 in MAFLD. However, these studies used USG for the diagnosis of MAFLD, which does not provide any information regarding fibrosis of the liver. The data regarding other three genetic variants are scarce from Indian individuals.
- PNPLA3 rs738409 C/G polymorphism: The nonsynonymous rs738409 C/G variant in PNPLA3 (patatin-like phospholipase domain containing 3), which encodes the amino acid substitution I148M, is regarded as the major genetic component of MAFLD and MASH. The risk effect of rs738409 on developing fatty liver in the context of MAFLD is the strongest ever reported for a common variant modifying the genetic susceptibility of MAFLD (5.3% of the total variance). The rs738409 is not only significantly associated with the accumulation of fat in the liver (the lipid fat content in carriers of the GG homozygous genotype is 73% higher compared with that measured in the carriers of the CC genotype) but also with the histological disease severity and progression of MAFLD (odds ratio-OR 1.88 per G allele; 95% confidence interval-CI 1.03-3.43; GG vs. CC homozygous carriers OR 3.488, 95% CI 1.859-6.545). PNPLA3 is a lipase involved in hepatocellular lipid remodelling and retinol metabolism.
- TM6SF2: In 2014, two exome and genome wide association studies identified the rs58542926 C > T genetic variant of the transmembrane 6 superfamily member 2 gene (TM6SF2), which encodes the loss-of-function lysine (E) to glutamic acid (K) at position 167 substitution (E167K), as a determinant of hepatic fat content, serum aminotransferases, and lower serum lipoproteins. The same studies demonstrated that silencing of TM6SF2 reduces secretion of VLDL resulting in intrahepatic retention of triglycerides and steatosis in mice and in hepatocytes in vitro. TM6SF2 is involved in hepatic VLDL secretion.
- GCKR: A variant in GCKR locus (glucokinase regulatory gene) has recently gained attention of researchers due to its biological plausibility in the disease pathogenesis. Specifically, the missense variant rs780094 was associated with a modest risk of having a fatty liver. Interestingly, GCKR mutations have been involved in the maturity-onset diabetes in young individuals, given that diabetes/glucose intolerance/insulin resistance is a well-known risk factor for MAFLD. No Indian data.
- MBOAT7 rs641738 C/T polymorphism: The MBOAT7 polymorphism rs641738 was identified as a risk factor for MAFLD, especially in people of European decent. This association is mediated by lower hepatic protein expression of MBOAT7 resulting in changes in the hepatic phosphatidylinositol acyl-chain remodeling. The mechanism linking altered PI remodeling to MAFLD development and progression is not clear. The data form India is scarce.
- HSD17B13 rs72613567:TA: A gene variant that describes a link between hepatic phospholipids and the risk of advanced MAFLD is the splicing variant rs72613567 (T > TA) with an adenine insertion in HSD17B13 that encodes for the hepatic lipid droplet protein hydroxysteroid 17-beta dehydrogenase 13. The HSD17B13 rs72613567 variant leads to the synthesis of a truncated loss-of-function enzyme that protects against advanced MAFLD, MASH and fibrosis. Surprisingly, the gene variant does not influence the development of steatosis, as several studies showed no difference in the degree of steatosis between rs72613567 carriers and noncarriers; however, it decreases the risk of chronic liver damage in MAFLD patients we aimed to assess the role of these five gene variants (PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13) in the development of steatosis and fibrosis (as assessed by transient elastography), and correlation of these gene variants with body composition (body fat percentage, lean mass and bone mineral content- as assessed by dual-energy X-ray absorptiometry), in Indian individuals with type 2 diabetes
- Conditions
- Type2diabetes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Individuals with or without diabetes | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Role of the PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 genetic variants in the development and progression of MASLD.
To evaluate the role of the PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 genetic variants in the development and progression of MASLD (steatosis, fibrosis, cirrhosis as measured by transient elastography, MRI-PDFF, dynamic MRI of the liver) in Indian individuals with type 2 diabetes
Measured: One Year
Secondary outcomes (6)
Correlation between body fat percentage (DEXA-measured) and the genetic variants
To examine correlation between body fat percentage (DEXA-measured) and the genetic variants (PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13).
Measured: One Year
Correlation between lean body mass (as measured by DEXA) and the genetic variants
To examine correlation between lean body mass (as measured by DEXA) and the genetic variants (PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13).
Measured: One Year
Correlation between bone mineral content (DEXA-measured) and the genetic variants
To examine correlation between bone mineral content (DEXA-measured) and the genetic variants (PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13).
Measured: One Year
Correlation between fibrosis-4 score (FIB-4) and the genetic variants
To examine correlation between fibrosis-4 score (FIB-4) and the genetic variants (PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13).
Measured: One Year
Correlation between MASLD fibrosis score (NFS) and the genetic variants
To examine correlation between MASLD fibrosis score (NFS) and the genetic variants (PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13).
Measured: One Year
Correlation between serum creatinine levels (eGFR) and the genetic variants
To examine correlation between serum creatinine levels (eGFR) and the genetic variants (PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13).
Measured: One Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2024
- Study start20 Jan 2024
- Primary completion29 Jul 2025
- Study completion29 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Type2diabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Ecologic or community
- Time perspective
- Cross-sectional
- Enrolment
- 1,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medanta, The Medicity, India
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Mohammad Shafi Kuchay, Medanta, The Medicity, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06289387
- Sponsor's protocol ID
- MMDEF001
- Status last verified
- Jul 2025
- First submitted
- 26 Feb 2024
- Last updated
- 3 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B, Choi PC, Kowo M, Chan AW, Merrouche W, Sung JJ, de Ledinghen V. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010 Feb;51(2):454-62. doi: 10.1002/hep.23312.
PubMed 20101745Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology. 2011 Jun;53(6):1883-94. doi: 10.1002/hep.24283. Epub 2011 May 14.
PubMed 21381068Kozlitina J, Smagris E, Stender S, Nordestgaard BG, Zhou HH, Tybjaerg-Hansen A, Vogt TF, Hobbs HH, Cohen JC. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014 Apr;46(4):352-6. doi: 10.1038/ng.2901. Epub 2014 Feb 16.
PubMed 24531328Dongiovanni P, Petta S, Maglio C, Fracanzani AL, Pipitone R, Mozzi E, Motta BM, Kaminska D, Rametta R, Grimaudo S, Pelusi S, Montalcini T, Alisi A, Maggioni M, Karja V, Boren J, Kakela P, Di Marco V, Xing C, Nobili V, Dallapiccola B, Craxi A, Pihlajamaki J, Fargion S, Sjostrom L, Carlsson LM, Romeo S, Valenti L. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology. 2015 Feb;61(2):506-14. doi: 10.1002/hep.27490.
PubMed 25251399Holmen OL, Zhang H, Fan Y, Hovelson DH, Schmidt EM, Zhou W, Guo Y, Zhang J, Langhammer A, Lochen ML, Ganesh SK, Vatten L, Skorpen F, Dalen H, Zhang J, Pennathur S, Chen J, Platou C, Mathiesen EB, Wilsgaard T, Njolstad I, Boehnke M, Chen YE, Abecasis GR, Hveem K, Willer CJ. Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk. Nat Genet. 2014 Apr;46(4):345-51. doi: 10.1038/ng.2926. Epub 2014 Mar 16.
PubMed 24633158Mancina RM, Dongiovanni P, Petta S, Pingitore P, Meroni M, Rametta R, Boren J, Montalcini T, Pujia A, Wiklund O, Hindy G, Spagnuolo R, Motta BM, Pipitone RM, Craxi A, Fargion S, Nobili V, Kakela P, Karja V, Mannisto V, Pihlajamaki J, Reilly DF, Castro-Perez J, Kozlitina J, Valenti L, Romeo S. The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent. Gastroenterology. 2016 May;150(5):1219-1230.e6. doi: 10.1053/j.gastro.2016.01.032. Epub 2016 Feb 2.
PubMed 26850495Abul-Husn NS, Cheng X, Li AH, Xin Y, Schurmann C, Stevis P, Liu Y, Kozlitina J, Stender S, Wood GC, Stepanchick AN, Still MD, McCarthy S, O'Dushlaine C, Packer JS, Balasubramanian S, Gosalia N, Esopi D, Kim SY, Mukherjee S, Lopez AE, Fuller ED, Penn J, Chu X, Luo JZ, Mirshahi UL, Carey DJ, Still CD, Feldman MD, Small A, Damrauer SM, Rader DJ, Zambrowicz B, Olson W, Murphy AJ, Borecki IB, Shuldiner AR, Reid JG, Overton JD, Yancopoulos GD, Hobbs HH, Cohen JC, Gottesman O, Teslovich TM, Baras A, Mirshahi T, Gromada J, Dewey FE. A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease. N Engl J Med. 2018 Mar 22;378(12):1096-1106. doi: 10.1056/NEJMoa1712191.
PubMed 29562163
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining Gene Variants to Improve Risk Prediction for Metabolic (Dysfunction)- Associated Fatty Liver Disease and Its Progression to Cirrhosis in Indian Individuals With Type 2 Diabetes: a Cross-sectional Study
- ClinicalTrials.gov ID
- NCT06289387
- Acronym / sponsor ID
- MMDEF001
- Conditions
- Type2diabetes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,000 participants (actual)
- Lead sponsor
- Medanta, The Medicity, IndiaUniversity, hospital or other
- Study start
- 20 Jan 2024 (actual)
- Primary completion
- 29 Jul 2025 (actual)
- Study completion
- 29 Jul 2025 (actual)
- First posted
- 1 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Type 2 diabetes and metabolic (dysfunction)-associated fatty liver disease (MAFLD) often exist together. The prevalence of MAFLD is about 15-30% in healthy people and around 60-70% in people with type 2 diabetes. Moreover, type 2 diabetes accelerates the progression of liver disease in MAFLD.
MAFLD is a spectrum of liver conditions, ranging from simple fatty liver (low risk for progression), progressing to steatohepatitis (MASH) with no or mild fibrosis, advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although diabetes is the strongest predictor of advanced fibrosis in MAFLD, however, only a small proportion of people with type 2 diabetes and MAFLD (about 5-7%) develop a clinically significant liver disease, but the burden of MAFLD is such that even a small proportion of patients developing cirrhosis will lead to a huge strain on the health care system in India. MAFLD is predicted to be the leading indication for liver transplantation in coming years. At present, MAFLD/MASH is the second most common indication for liver transplantation in the USA as well as in India.
The question is why around 5-7% patients amongst MAFLD population develop fibrosis and cirrhosis. A growing body of evidence suggest that the disease develops because of a complex process in which several factors, including genetic susceptibility and environmental insults, are involved. There are several gene variants that have been incriminated in the development and progression of MAFLD. The most common genes associated with MAFLD are PNPLA3, TM6SF2, GCKR, and MBOAT7. The loss-of-function gene variant HSD17B13 seems to protect from NAFLD. There are a few studies from India about the role of PNPLA3 and TM6SF2 in MAFLD. However, these studies used USG for the diagnosis of MAFLD, which does not provide any information regarding fibrosis of the liver. The data regarding other three genetic variants are scarce from Indian individuals.
Detailed description
Type 2 diabetes and metabolic (dysfunction)-associated fatty liver disease (MAFLD) often exist together. The prevalence of MAFLD is about 15-30% in healthy people and around 60-70% in people with type 2 diabetes. Moreover, type 2 diabetes accelerates the progression of liver disease in MAFLD.
MAFLD is a spectrum of liver conditions, ranging from simple fatty liver (low risk for progression), progressing to steatohepatitis (MASH) with no or mild fibrosis, advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although diabetes is the strongest predictor of advanced fibrosis in MAFLD, however, only a small proportion of people with type 2 diabetes and MAFLD (about 5-7%) develop a clinically significant liver disease, but the burden of MAFLD is such that even a small proportion of patients developing cirrhosis will lead to a huge strain on the health care system in India. MAFLD is predicted to be the leading indication for liver transplantation in coming years. At present, MAFLD/MASH is the second most common indication for liver transplantation in the USA as well as in India.
The question is why around 5-7% patients amongst MAFLD population develop fibrosis and cirrhosis. A growing body of evidence suggest that the disease develops because of a complex process in which several factors, including genetic susceptibility and environmental insults, are involved. There are several gene variants that have been incriminated in the development and progression of MAFLD. The most common genes associated with MAFLD are PNPLA3, TM6SF2, GCKR, and MBOAT7. The loss-of-function gene variant HSD17B13 seems to protect from NAFLD. There are a few studies from India about the role of PNPLA3 and TM6SF2 in MAFLD. However, these studies used USG for the diagnosis of MAFLD, which does not provide any information regarding fibrosis of the liver. The data regarding other three genetic variants are scarce from Indian individuals.
- PNPLA3 rs738409 C/G polymorphism: The nonsynonymous rs738409 C/G variant in PNPLA3 (patatin-like phospholipase domain containing 3), which encodes the amino acid substitution I148M, is regarded as the major genetic component of MAFLD and MASH. The risk effect of rs738409 on developing fatty liver in the context of MAFLD is the strongest ever reported for a common variant modifying the genetic susceptibility of MAFLD (5.3% of the total variance). The rs738409 is not only significantly associated with the accumulation of fat in the liver (the lipid fat content in carriers of the GG homozygous genotype is 73% higher compared with that measured in the carriers of the CC genotype) but also with the histological disease severity and progression of MAFLD (odds ratio-OR 1.88 per G allele; 95% confidence interval-CI 1.03-3.43; GG vs. CC homozygous carriers OR 3.488, 95% CI 1.859-6.545). PNPLA3 is a lipase involved in hepatocellular lipid remodelling and retinol metabolism.
- TM6SF2: In 2014, two exome and genome wide association studies identified the rs58542926 C > T genetic variant of the transmembrane 6 superfamily member 2 gene (TM6SF2), which encodes the loss-of-function lysine (E) to glutamic acid (K) at position 167 substitution (E167K), as a determinant of hepatic fat content, serum aminotransferases, and lower serum lipoproteins. The same studies demonstrated that silencing of TM6SF2 reduces secretion of VLDL resulting in intrahepatic retention of triglycerides and steatosis in mice and in hepatocytes in vitro. TM6SF2 is involved in hepatic VLDL secretion.
- GCKR: A variant in GCKR locus (glucokinase regulatory gene) has recently gained attention of researchers due to its biological plausibility in the disease pathogenesis. Specifically, the missense variant rs780094 was associated with a modest risk of having a fatty liver. Interestingly, GCKR mutations have been involved in the maturity-onset diabetes in young individuals, given that diabetes/glucose intolerance/insulin resistance is a well-known risk factor for MAFLD. No Indian data.
- MBOAT7 rs641738 C/T polymorphism: The MBOAT7 polymorphism rs641738 was identified as a risk factor for MAFLD, especially in people of European decent. This association is mediated by lower hepatic protein expression of MBOAT7 resulting in changes in the hepatic phosphatidylinositol acyl-chain remodeling. The mechanism linking altered PI remodeling to MAFLD development and progression is not clear. The data form India is scarce.
- HSD17B13 rs72613567:TA: A gene variant that describes a link between hepatic phospholipids and the risk of advanced MAFLD is the splicing variant rs72613567 (T > TA) with an adenine insertion in HSD17B13 that encodes for the hepatic lipid droplet protein hydroxysteroid 17-beta dehydrogenase 13. The HSD17B13 rs72613567 variant leads to the synthesis of a truncated loss-of-function enzyme that protects against advanced MAFLD, MASH and fibrosis. Surprisingly, the gene variant does not influence the development of steatosis, as several studies showed no difference in the degree of steatosis between rs72613567 carriers and noncarriers; however, it decreases the risk of chronic liver damage in MAFLD patients we aimed to assess the role of these five gene variants (PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13) in the development of steatosis and fibrosis (as assessed by transient elastography), and correlation of these gene variants with body composition (body fat percentage, lean mass and bone mineral content- as assessed by dual-energy X-ray absorptiometry), in Indian individuals with type 2 diabetes
Study design
- Observational model
- Ecologic or community
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Individuals with or without diabetes | – | – |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals with or without diabetes will be enrolled
Key inclusion criteria (1 listed)
- Individuals with or without T2DM between ages 30 to 70 years
Key exclusion criteria (2 listed)
- Age below 30 years Patients with hepatitis B, hepatitis C or HIV disease Patients with significant alcohol intake (>14 drinks/week in men and >10 drinks/week in women).
- Patients on corticosteroids and chemotherapeutic agents.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Role of the PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 genetic variants in the development and progression of MASLD.
Time frame: One Year
To evaluate the role of the PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 genetic variants in the development and progression of MASLD (steatosis, fibrosis, cirrhosis as measured by transient elastography, MRI-PDFF, dynamic MRI of the liver) in Indian individuals with type 2 diabetes
6 secondary outcomes
Correlation between body fat percentage (DEXA-measured) and the genetic variants
Time frame: One Year
Correlation between lean body mass (as measured by DEXA) and the genetic variants
Time frame: One Year
Correlation between bone mineral content (DEXA-measured) and the genetic variants
Time frame: One Year
Correlation between fibrosis-4 score (FIB-4) and the genetic variants
Time frame: One Year
Correlation between MASLD fibrosis score (NFS) and the genetic variants
Time frame: One Year
Correlation between serum creatinine levels (eGFR) and the genetic variants
Time frame: One Year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2025.
- Results publication: PubMed 20101745Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B, Choi PC, Kowo M, Chan AW, Merrouche W, Sung JJ, de Ledinghen V. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010 Feb;51(2):454-62. doi: 10.1002/hep.23312.
- Results publication: PubMed 21381068Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology. 2011 Jun;53(6):1883-94. doi: 10.1002/hep.24283. Epub 2011 May 14.
- Results publication: PubMed 24531328Kozlitina J, Smagris E, Stender S, Nordestgaard BG, Zhou HH, Tybjaerg-Hansen A, Vogt TF, Hobbs HH, Cohen JC. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014 Apr;46(4):352-6. doi: 10.1038/ng.2901. Epub 2014 Feb 16.
- Results publication: PubMed 25251399Dongiovanni P, Petta S, Maglio C, Fracanzani AL, Pipitone R, Mozzi E, Motta BM, Kaminska D, Rametta R, Grimaudo S, Pelusi S, Montalcini T, Alisi A, Maggioni M, Karja V, Boren J, Kakela P, Di Marco V, Xing C, Nobili V, Dallapiccola B, Craxi A, Pihlajamaki J, Fargion S, Sjostrom L, Carlsson LM, Romeo S, Valenti L. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology. 2015 Feb;61(2):506-14. doi: 10.1002/hep.27490.
- Results publication: PubMed 24633158Holmen OL, Zhang H, Fan Y, Hovelson DH, Schmidt EM, Zhou W, Guo Y, Zhang J, Langhammer A, Lochen ML, Ganesh SK, Vatten L, Skorpen F, Dalen H, Zhang J, Pennathur S, Chen J, Platou C, Mathiesen EB, Wilsgaard T, Njolstad I, Boehnke M, Chen YE, Abecasis GR, Hveem K, Willer CJ. Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk. Nat Genet. 2014 Apr;46(4):345-51. doi: 10.1038/ng.2926. Epub 2014 Mar 16.
- Results publication: PubMed 26850495Mancina RM, Dongiovanni P, Petta S, Pingitore P, Meroni M, Rametta R, Boren J, Montalcini T, Pujia A, Wiklund O, Hindy G, Spagnuolo R, Motta BM, Pipitone RM, Craxi A, Fargion S, Nobili V, Kakela P, Karja V, Mannisto V, Pihlajamaki J, Reilly DF, Castro-Perez J, Kozlitina J, Valenti L, Romeo S. The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent. Gastroenterology. 2016 May;150(5):1219-1230.e6. doi: 10.1053/j.gastro.2016.01.032. Epub 2016 Feb 2.
- Results publication: PubMed 29562163Abul-Husn NS, Cheng X, Li AH, Xin Y, Schurmann C, Stevis P, Liu Y, Kozlitina J, Stender S, Wood GC, Stepanchick AN, Still MD, McCarthy S, O'Dushlaine C, Packer JS, Balasubramanian S, Gosalia N, Esopi D, Kim SY, Mukherjee S, Lopez AE, Fuller ED, Penn J, Chu X, Luo JZ, Mirshahi UL, Carey DJ, Still CD, Feldman MD, Small A, Damrauer SM, Rader DJ, Zambrowicz B, Olson W, Murphy AJ, Borecki IB, Shuldiner AR, Reid JG, Overton JD, Yancopoulos GD, Hobbs HH, Cohen JC, Gottesman O, Teslovich TM, Baras A, Mirshahi T, Gromada J, Dewey FE. A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease. N Engl J Med. 2018 Mar 22;378(12):1096-1106. doi: 10.1056/NEJMoa1712191.
- Individual participant dataSharing planned: No
Related trials for Type2diabetes
Not yet recruitingPhase 2
The Effects of Glucagon on Hepatic Metabolism in People With Type 2 Diabetes After Caloric Restriction
Type2diabetes
Enrolling by invitation
Continued Access to the Endogenex System for Participants in the ReCET Pivotal Study
Type 2 Diabetes Mellitus, Type2diabetes
Recruiting
Understanding and Addressing Risks of Low Socioeconomic Status and Diabetes for Heart Failure
Type2diabetes, Heart Failure
Recruiting
A Randomized Controlled Trial of Diabetes Screening Immediately Postpartum (DIP) and Follow Up PP CARE
Pre-Gestational Diabetes, Type2diabetes
RecruitingPhase 4
SGLT2 Inhibition in Addition to Lifestyle Intervention and Risk for Complications in Subtypes of Patients With Prediabetes
Type2diabetes, PreDiabetes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type2diabetes, run by Medanta, The Medicity, India at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Role of the PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 genetic variants in the development and progression of MASLD. (time frame: One Year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06289387, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2025; AzTrials last refreshed its copy on 31 Oct 2026.