Diabetic Kidney Disease, Cardiovascular Disease and Non-Alcoholic Fatty Liver Disease: A New Triumvirate?

Abstract

Non-alcoholic fatty liver disease is a highly prevalent disease worldwide with a renowned relation to cardiovascular disease and chronic kidney disease. These diseases share a common pathophysiology including insulin resistance, oxidative stress, chronic inflammation, dysbiosis and genetic susceptibilities. Non-alcoholic fatty liver disease is especially prevalent and more severe in type 2 diabetes. Patients with non-alcoholic fatty liver disease should have liver fibrosis assessment in order to identify those at the highest risk of adverse outcomes so that appropriate management strategies can be implemented. Early diagnosis and treatment of non-alcoholic fatty liver disease could ameliorate the burden of cardiovascular disease and chronic kidney disease.

Keywords: cardiovascular disease; diabetic kidney disease; non-alcoholic fatty liver disease.

Figure 1

NAFLD, CKD and CVD share common risk factors. Lipolysis of adipose tissue, dietary lipids, de novo lipogenesis, dysbiosis and genetic susceptibilities act in parallel, contributing to fat accumulation. It leads to insulin resistance (IR), enhancing liver trygliceride accumulation and results in compensatory hyperinsulinemia which increases the hepatic fatty acid uptake, alters triglycerides transportation and inhibits liver β-oxidation. There is an intensification of the pro-inflammatory cytokine activity that is associated with oxidative stress-mediated lipotoxicity, increased activity of RAS, platelet activation, inflammasome activation and mitochondrial dysfunction. These processes contribute to further exacerbation of IR, hepatocellular injury, inflammation and the progressive accumulation of excess extracellular matrix through hepatic stellate cells activation. NAFLD: Non-alcoholic Fatty Liver Disease, CKD: Chronic Kidney Disease; CVD: Cardiovascular Disease; IR: insulin resistance; RAS: renin-angiotensin-aldosterone system.

Figure 2

Assessment and Treatment of Non-alcoholic Fatty Liver Disease in Type 2 Diabetes. ACE: Angiotensin converting enzyme; ARB: Angiotensin-II receptor antagonists or blockers; BMI: body mass index; EGFR: estimated glomerular filtration rate; GLP-1: Glucagon-like Peptide-1; MS: Metabolic surgery; SGLT2: Sodium-glucose cotransporter 2; TG: Triglycerides; * Triumvirate Lifestyle Intervention.

Figure 3

Antidiabetic drugs in patients with type 2 diabetes, chronic kidney disease and non-alcoholic fatty liver disease: description of histological liver effects and cardiovascular recommendation. ↓: reduce; ⇆: neutral effect; N/A: no data available; * No histological evidence, GFR: glomerular filtration rate.