Hepatogenous Diabetes: A Primer

Abstract

As liver is one of the primary organs involved in glucose homeostasis, it is not surprising that patients with liver dysfunction in chronic liver disease usually develop impaired glucose tolerance and subsequently overt diabetes later in their natural course. Diabetes that develops after the onset of cirrhosis of liver is usually referred to as hepatogenous diabetes (HD). It is an underrecognized and a hallmark endocrinological event in chronic liver disease. HD is associated with a higher risk of developing hepatic decompensations, such as ascites, variceal bleeding, hepatic encephalopathy, renal dysfunction, refractory ascites, and hepatocellular carcinoma along with reduced survival rates than normoglycemic patients with cirrhosis of liver. It is quite different from type 2 diabetes mellitus with the absence of classical risk factors, dissimilar laboratory profiles, and decreased incidence of microvascular complications. Furthermore, the management of patients with HD is challenging because of altered pharmacokinetics of most antidiabetic drugs and increased risk of hypoglycemia and other adverse effects. Hence, a clear understanding of the epidemiology, pathophysiology, clinical implications, laboratory diagnosis, and management of HD is essential for both hepatologists as well as endocrinologists, which is narrated briefly in this review.

Keywords: FBG, fasting blood glucose; FFDs, free fatty acids; HCC, hepatocellular carcinoma; NAFLD, non alcoholic fatty liver disease; OGTTs, oral glucose tolerance tests; chronic liver disease; cirrhosis; diabetes mellitus; glucose metabolism; nonalcoholic fatty liver disease.

Figure 1

Prevalence of diabetes across all etiologies of cirrhosis of liver. NAFLD and cryptogenic are most commonly associated with diabetes. NAFLD, nonalcoholic fatty liver disease; ALD, alcohol-related liver disease; HCV, hepatitis C virus; HBV, hepatitis B virus.

Figure 2

Prevalence of impaired glucose tolerance and overt diabetes according to severity of liver cirrhosis. Higher prevalence is noted with more severe liver disease. Figure at ‘A’ shows rising prevalence of IGT and DM as patients worsen from Child’s A to Child’s C and Figure-‘B’ shows rising prevalence of IGT/DM as the MELD score rises.¹¹ CTP, Child-Turcotte-Pugh class; MELD, model for end-stage liver disease; NGT, normal glucose tolerance; IGT, impaired glucose tolerance; DM, diabetes mellitus.

Figure 3

Simplified scheme of pathogenesis of hepatogenous diabetes. Both insulin resistance and pancreatic beta-cell dysfunction play a part. See text for details. AGEs, advanced glycation end products; ALD, alcohol-related liver disease; HCV, hepatitis C virus; NAFLD, nonalcoholic fatty liver disease.

Figure 4

Algorithm for management of hepatogenous diabetes. FBS, fasting blood sugar; PPBS, postprandial blood sugar; DPP 4 inhibitor, dipeptidyl peptidase 4 inhibitor; SGLT 2 inhibitor, sodium-glucose co-transporter-2 inhibitor.