Clinical implications of diabetes in chronic liver disease: Diagnosis, outcomes and management, current and future perspectives

Table 2 Studies depicting implications of diabetes on complications of patients with liver cirrhosis

Ref.	Design	Population, n	Outcomes	Limitations
Sigal et al[59], United States, 2006	Cross-sectional	65 HCV-LC; 31% diabetics	HE and severe HE was higher in diabetics. DM was independent risk factor for HE	Small sample size. HE was not standardized
Tietge et al[81], Germany, 2004	Case-control, prospective	100 LC, 35% diabetics, 62 post-LT	Pre-LT IGT or DM was the major risk factor for post-LT DM	Only 31 patients were prospectively evaluated
Takahashi et al[77], Japan, 2011	Prospective	203 CHC	Two hours post-challenge hyperglycaemia associated with HCC	Patients received IFN
Jeon et al[64], Republic of Korea, 2013	Prospective	195 LC, 55.4% with HD	HD correlated with HVPG, VH and large varices. Most patients with VH within 6 mo, had post-prandial hyperglycaemia	Risk stratification of varices and prophylaxis for VH were not taken into account
Zheng et al[75], China, 2013	Retrospective case-control	1568 CLD, 852 with HCC	DM associated with increased risk of HCC regardless of cirrhosis. Synergistic interaction between DM and HBV for HCC	Hospital based study. Temporal relationship between DM and HCC could not be established
Yang et al[63], Taiwan, 2014	Prospective	146 LC, 25% diabetics	DM was predictor of VH. Patients with VH had worse glycaemic control (HBA1c ≥ 7%)	DM associated with decompensated cirrhosis, renal disease and VH
Jepsen et al[60], Denmark, 2015	Database from randomized trials	863 LC, 22% diabetics	Diabetics had more episodes of first-time overt HE in one year. First-time HE progression beyond grade 2 higher in diabetics	Diagnosis of DM was not standardized. Vaptan could be a confounder
Yang et al[73], United States, 2016	Retrospective	739 LC, 34% diabetics	DM increased the risk of HCC in patients with non-HCV cirrhosis	Single-centre probably with referral bias
Tergast et al[69], Germany, 2018	Prospective case-control	475 decompensated LC, 118 diabetics	DM increased risk for SBP and was higher with HbA1c values ≥ 6.4%	Criteria for diagnosis of DM not clearly defined
Wang et al[65], China, 2020	Retrospective	207 LC, 137 diabetics; 68 had HD	Rebleeding rate following EST or EVL higher in diabetics, including HD at 1, 3, and 6 mo	Relatively small number of patients with shorter follow-up
Labenz et al[61], Germany, 2020	Prospective	240 LC, 27% diabetics	DM associated with covert HE at inclusion and follow-up. The risk of covert HE and overt HE was more pronounced when HbA1c ≥ 6.5%	Spontaneous porto-systemic shunts, GIB, drugs were not taken into account

DM: Diabetes mellitus; EST: Endoscopic sclerotherapy; EVL: Endoscopic variceal ligation; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; HD: Hepatogenous diabetes; HE: Hepatic encephalopathy; IGT: Impaired glucose tolerance; OGTT: Oral glucose tolerance test; VH: Variceal hemorrhage; LT: Liver transplantation; HVPG: Hepatic venous pressure gradient; HBV: Hepatitis B virus; IFN: Interferon; GIB: Gastrointestinal bleeding; SBP: Spontaneous bacterial peritonitis; LC: Liver cirrhosis; HbA1c: Glycated hemoglobin.