Hepatogenous diabetes: Knowledge, evidence, and skepticism

Abstract

The diabetogenic potential of liver cirrhosis (LC) has been known for a long time, and the name "hepatogenous diabetes" (HD) was coined in 1906 to define the condition. Diabetes mellitus (DM) that develops as a consequence of LC is referred to as HD. In patients with LC, the prevalence rates of HD have been reported to vary from 21% to 57%. The pathophysiological basis of HD seems to involve insulin resistance (IR) and pancreatic β-cell dysfunction. The neurohormonal changes, endotoxemia, and chronic inflammation of LC initially create IR; however, the toxic effects eventually lead to β-cell dysfunction, which marks the transition from impaired glucose tolerance to HD. In addition, a number of factors, including sarcopenia, sarcopenic obesity, gut dysbiosis, and hyperammonemia, have recently been linked to impaired glucose metabolism in LC. DM is associated with complications and poor outcomes in patients with LC, although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research. In fact, there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC. Currently, T2DM and HD are being treated in a similar manner although no standardized guidelines are available. The different pathophysiological basis of HD may have an impact on treatment options. This review article discusses the existence of HD as a distinct entity with high prevalence rates, a strong pathophysiological basis, clinical and therapeutic implications, as well as widespread skepticism and knowledge gaps.

Impacts of development of acute-on-chronic liver failure and bacteria infections on pancreatic β-cell function and glucose homeostasis in patients with liver cirrhosis

“…Increased IR have been observed in both patients with liver cirrhosis and sepsis. In patients with liver cirrhosis, the pathophysiological mechanisms of IR remain partly understood, hyperinsulinemia resulted from decreased hepatic extraction and portosystemic shunting of insulin have been associated with high IR (2). In patients with sepsis, increased cytokines, cortisol, growth hormone, and catecholamine levels likely have a role in the development of IR (24).…”

“…In a previous study we have also found that diabetes was associated with poor short-term prognosis in patients with acute-on-chronic liver failure (ACLF)(6). It has been suggested that liver dysfunction had "toxic effect" on pancreatic β-cell and diabetes resulted from impaired pancreatic β-cell function and increased insulin resistance (IR) in patients with liver cirrhosis (2,7), however, the evidences to support this hypothesis are still scare. Hyperglycemia has also been found in patients with acute hepatitis, acute liver failure and sepsis(8-10).…”

“…More and more studies have shown that GMDs is one of the most common complications in patients with liver cirrhosis, up to 80% of patients with liver cirrhosis had GMDs (1). Diabetes second to the impairment of liver function is recognized as hepatogenous diabetes (HD) (2).…”

Investigation of the pathogenesis of liver cirrhosis associated with type 2 diabetes mellitus via bioinformatic analysis

“…Liver cirrhosis and T2DM are common chronic diseases that are interrelated. The development of liver cirrhosis causes dysfunction in the receptors of the liver and pancreas, which leads to decreased insulin binding, resulting in insulin resistance and therefore the development of T2DM [7]. Cytokines may act as an important factor affecting the co-occurrence of the two diseases.…”

Advances in the treatment of hepatogenous diabetes: A review

“…[18,19] Intestinal dysbiosis, hyperammonemia, sarcopenia, and other factors may also contribute to the pathogenesis of HD. [11]…”