When Sugar Reaches the Liver: Phenotypes of Patients with Diabetes and NAFLD

Abstract

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) have been traditionally linked to one another. Recent studies suggest that NAFLD may be increasingly common in other types of diabetes such as type 1 diabetes (T1DM) and less frequently ketone-prone and Maturity-onset Diabetes of the Young (MODY) diabetes. In this review, we address the relationship between hyperglycemia and insulin resistance and the onset and progression of NAFLD. In addition, despite the high rate of patients with T2DM and other diabetes phenotypes that can alter liver metabolism and consequently develop steatosis, fibrosis, and cirrhosis, NALFD screening is not still implemented in the daily care routine. Incorporating a clinical algorithm created around a simple, non-invasive, cost-effective model would identify high-risk patients. The principle behind managing these patients is to improve insulin resistance and hyperglycemia states with lifestyle changes, weight loss, and new drug therapies.

Non-alcoholic fatty liver disease in type 1 diabetes: Prevalence and pathophysiology

“…In T1D, subcutaneous insulin injections are required to maintain normal blood glucose levels and it is unlikely that all injected insulin reaches the liver through the portal vein as in endogenous insulin production, then implying a relative state of insulin resistance and increased insulin requirement ( 25 , 39 ) ( 23 , 40 ).…”

“…To correct their low blood sugar level, they use sugar-rich beverages which are often fructose-rich nutrients such as sodas/soft drinks, fruit juices or processed food. This behavior can occur every day for a lot of T1D and contribute not only to weight gain or obesity, but also to the activation of lipogenesis leading therefore to NAFLD susceptibility ( 40 , 46 ).…”

“…GLP-1 agonists have also shown to upregulate CEACAM1 transcription, thus increasing insulin clearance, which helps protecting the liver from insulin resistance and from fat deposition ( 36 ). In some studies, GLP-1 blood concentrations have been shown to be lower in patients with T1D and as such could also be one of the factors contributing to NAFLD development ( 40 , 52 – 54 ). This hypothesis should be further studied since other work seems to support the fact that there is no significant difference in GLP-1 blood concentrations between T1D patients and the general population ( 55 , 56 ).…”

Oligonucleotide therapies for nonalcoholic steatohepatitis

“… 1 NAFLD and nonalcoholic steatohepatitis (NASH) have long been considered to be metabolic diseases, as in the majority of NASH patients the disease is also accompanied by metabolic abnormalities, including obesity, insulin resistance (IR) or type 2 diabetes (T2D), hypertriglyceridemia, and dyslipidemia. 2 , 3 , 4 , 5 , 6 Despite obscure symptoms at a very early stage, NASH may gradually progress to cirrhosis and other end-stage liver diseases such as hepatocellular carcinoma (HCC), requiring eventual liver transplantation. 7 As NASH has brought huge life-threatening concerns and economic burdens around the world, effective therapeutic approaches are urgently desired.…”

Alleviation of Hepatic Steatosis by Alpha-Defensin Is Associated with Enhanced Lipolysis

“…Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease worldwide. NAFLD is a complex disease associated with hepatic steatosis, which is affected by a variety of environmental and genetic factors [ 1 , 2 , 3 , 4 , 5 ]. It is largely considered a hepatic manifestation of the metabolic syndrome.…”