Research Article Details

Article ID: A02363
PMID: 34402473
Source: Eur J Gastroenterol Hepatol
Title: Glucagon is associated with NAFLD inflammatory progression in type 2 diabetes, not with NAFLD fibrotic progression.
Abstract: OBJECTIVES: Higher prevalence of progressive stages of nonalcoholic fatty liver disease (NAFLD) and hyperglucagonemia were observed in type 2 diabetes. We aim to investigate whether islet alpha cell dysfunction (evaluated by glucagon) associates with NAFLD progression in type 2 diabetic adults. METHODS: A total of 4937 diabetic participants were enrolled from seven communities in Shanghai, China. Probable nonalcoholic steatohepatitis (NASH) was defined by the presence of NAFLD and metabolic syndrome. Probable NAFLD fibrosis score was used to identify patients with different risk stratification of bridging fibrosis (stage 3) or cirrhosis (stage 4). RESULTS: After adjustment for age, sex, duration of diabetes, current smoking, waist circumference, C-peptide, HbA1c, dyslipidemia, hypertension and use of incretins and SGLT2 inhibitor, glucagon quartiles were negatively associated with probable NASH (Q4 vs. Q1 OR 0.71, 95% confidence interval, 0.53-0.96, P for trend=0.010), though they were not associated with simple NAFLD (P for trend=0.176). Furthermore, glucagon was not significantly associated with fibrotic progression of liver steatosis in diabetic patients with NAFLD (P for trend=0.889). CONCLUSIONS: Significant associations were observed among glucagon and inflammatory progression of NAFLD, but not with fibrotic progression. Further understanding the association between islet alpha cell and liver may lead to development of treatment strategies for NAFLD patients with type 2 diabetes.
DOI: 10.1097/MEG.0000000000002269

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S03 Anti-fibrosis fibrosis Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 Details
S05 Anti-inflammatory inflammatory Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T02 Sodium/glucose cotransporter 2 SLC5A2 inhibitor Transporter P31639 SC5A2_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I13 3146 Lipid metabolism disorder An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism disease of metabolism/ inherited metabolic disorder Details
I12 10763 Hypertension An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease Details
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D155 Glucagon Biological drug DB00040 GCGR agonist Antidiabetic drug Under clinical trials Details
D549 SGLT2 inhibitor Chemical drug -- SGLT2 inhibitor -- Under clinical trials Details