GLUCOSE TOLERANCE AND DIABETES IN CHRONIC LIVER DISEASE

doi:10.1016/S0140-6736(67)90334-0

The Lancet

Volume 290, Issue 7525, 18 November 1967, Pages 1051-1056

https://doi.org/10.1016/S0140-6736(67)90334-0 Get rights and content

Abstract

In twenty-eight unselected patients with well-investigated chronic liver disease, confirmed by liver biopsy, 32% had unequivocal "diabetes mellitus ", 25% had "impaired " glucose tolerance, and 43% had "normal" glucose tolerance. Evidence is provided to show that "hepatogenous diabetes " is a nosological entity which is insufficiently recognised in the English literature. We postulate that chronic hepatic disease produces endogenous insulin resistance and hyperinsulinæmia before glucose tolerance is impaired, and that diabetes ensues when β-cell decompensation occurs. The cause of insulin resistance and the eventual β-cell decompensation remains an enigma.

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Cited by (311)

Glucose turnover at whole-body and skeletal muscle level in response to parenteral nutrition in male patients with alcoholic liver cirrhosis
2024, Clinical Nutrition ESPEN
Cirrhosis is associated with insulin resistance and impaired glucose tolerance, which may be caused by impairments at different tissue levels (liver, skeletal muscle, and/or beta cell).
Here, glucose kinetics at whole-body and skeletal muscle level in patients with cirrhosis (Child-Pugh A and B) were studied during parenteral nutrition using the isotope dilution technique and arteriovenous balance approach across the leg. As opposed to the euglycemic hyperinsulinemic clamp or glucose tolerance tests applied in previous studies, this approach provides a nutrient composition more similar to a normal meal while circumventing any possible portal-systemic shunting, impaired hepatic uptake and incretin effect.
We confirmed the presence of hepatic and peripheral insulin resistance in our patient population. Endogenous glucose production was less suppressed in response to parenteral nutrition. However, glucose uptake in skeletal muscle was increased.
Our results suggests that in our study participants with cirrhosis, the hepatic and peripheral insulin resistance is compensated for by increased insulin secretion and thus, increased glucose uptake in muscle. Hereby, glucose homeostasis is maintained.
Four sidenotes about glucagon peptides
2023, Peptides
Century old glucagon is a classic pancreatic hormone. But today we also know that the glucagon gene is expressed at high levels at extrapancreatic sites – particularly so in the gut. Major hormonal glucagon gene products in the digestive tract are the two glucagon-like peptides (GLP-1 and ‐2). Of these, truncated GLP-1 has in recent decades attracted massive interest due to its incretin effect, and the subsequent GLP-1 derived design of potent diabetes and obesity drugs. Truncated GLP-1 has consequently become an important contributor to gastrointestinal endocrinology. The gastrointestinal branch of endocrinology today includes more than 100 bioactive peptides encoded by some 30 different hormone genes. Therefore, the gut is the largest endocrine organ in the body. In addition to a general discussion of glucagon peptides in the hierarchy of gut hormones, this review also includes three short notes about glucagon studies from the 1970s. These studies dealt with reactive hypoglycemia, chronic liver disease, and the secretory response of pancreatic glucagon to gastrin/cholecystokinin stimulation. Considering today’s possibilities in molecular endocrinology, revisits to the questions raised by these studies might be worthwhile.
Hepatogenous Diabetes - A Report from Central India
2022, Journal of Clinical and Experimental Hepatology
Cirrhosis of liver is associated with loss of liver function, portal hypertension, and pancreatic β-cell dysfunction leading to hepatogenous diabetes (HD). Often HD is an underestimated and understudied problem, particularly in the Indian subcontinent, where the prevalence of both Chronic liver disease (CLD) and diabetes is high. Hence this study was planned to highlight the prevalence of HD and its association with the severity of cirrhosis.
A total of 121 cirrhotic patients without a history of diabetes were included in this prospective cross-sectional study. Seventy five g oral glucose tolerance test (OGTT) was done in all patients. Fasting serum insulin levels were done to calculate insulin resistance (IR) using homeostatic model assessment-insulin resistance (HOMA-IR). Upper gastrointestinal endoscopy was done to detect varices. Patients were divided into HD group and non-HD group for comparison of results.
HD was seen in 52 (42.98%) patients; among them, 63.4% did not show evidence of HD by fasting plasma glucose (FPG) levels. Impaired glucose tolerance (IGT) was seen in 58 (47.93%) patients. Compared with the non-HD group, the HD group had significantly higher model for end-stage liver disease (MELD) score (P = 0.038), HOMA-IR (P < 0.001), incidence of large varices (P < 0.001) and variceal bleeding (P < 0.001). A statistically significant association was noted between HD and Hepatocellular carcinoma (HCC) (P < 0.001).
Patients with cirrhosis had a high prevalence of IGT, IR, and HD. The presence of HD is well associated with the severity of cirrhosis in the form of higher MELD score (>15), CTP score (>10), higher bilirubin levels, large varices, bleeding varices, and HCC. FPG levels and glycated hemoglobin (HbA1c) cannot be relied upon, and OGTT aids in the unmasking of HD in these patients.
Hepatogenous Diabetes: A Primer
2021, Journal of Clinical and Experimental Hepatology
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.
Combined liver and islet transplantation in hepatogenous diabetes, cluster exenteration, and cirrhosis with type 1 diabetes
2019, Transplantation, Bioengineering, and Regeneration of the Endocrine Pancreas: Volume 1
Liver cirrhosis is an increasing global public health burden, representing a relevant cause of morbidity and mortality worldwide. Hepatogenous diabetes (HD) is defined as an acquired condition of impaired glucose regulation due to the loss of liver function caused by cirrhosis, which exacerbates the poor long-term prognosis of cirrhotic patients. Nevertheless, HD has not yet been considered as a distinct clinical entity separated from classical type 2 diabetes mellitus. However, prompt diagnosis and treatment of HD may improve the clinical outcomes in cirrhotic patients. This chapter aims to describe the current understanding of epidemiologic and pathophysiological features of HD, along with the current diagnostic and therapeutic strategies for this disease, particularly focusing on the studies evaluating the effectiveness of liver transplantation alone or in combination with pancreatic islet transplantation. The safety and efficacy of combined liver and islet transplantation have been demonstrated in patients undergoing upper abdominal exenteration and liver replacement due to unresectable tumors.
In theory, liver transplantation should reverse impairment in glucose regulation and HD in patients with liver cirrhosis, although the results from different studies are not clear. On the other hand, only a few studies have evaluated the effectiveness of combined liver and islet transplantation in cirrhotic patients with type 1 diabetes mellitus and type 2 diabetes mellitus/HD, showing promising but tentative results. In conclusion, prospective randomized clinical trials will be needed in the future to better understand who are the best candidates for either liver transplantation alone or combined liver and islet transplantation.
Challenges in diagnosing and monitoring diabetes in patients with chronic liver diseases
2018, Diabetes and Metabolic Syndrome: Clinical Research and Reviews
Citation Excerpt :
The coexistence of changes in glucose metabolism and chronic liver disease is common, partially due to the high prevalence of both conditions. However, the liver plays a key role in glucose homeostasis, and its malfunction is related to the onset of hepatogenous diabetes [5,6]. Furthermore, even outside of the context of liver failure, various chronic liver diseases are associated with the appearance of DM through different mechanisms.
The prevalence and mortality of diabetes mellitus and liver disease have risen in recent years. The liver plays an important role in glucose homeostasis, and various chronic liver diseases have a negative effect on glucose metabolism with the consequent emergence of diabetes. Some aspects related to chronic liver disease can affect diagnostic tools and the monitoring of diabetes and other glucose metabolism disorders, and clinicians must be aware of these limitations in their daily practice. In cirrhotic patients, fasting glucose may be normal in up until 23% of diabetes cases, and glycated hemoglobin provides falsely low results, especially in advanced cirrhosis. Similarly, the performance of alternative glucose monitoring tests, such as fructosamine, glycated albumin and 1,5-anhydroglucitol, also appears to be suboptimal in chronic liver disease. This review will examine the association between changes in glucose metabolism and various liver diseases as well as the particularities associated with the diagnosis and monitoring of diabetes in liver disease patients. Alternatives to routinely recommended tests will be discussed.

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ORIGINAL ARTICLESGLUCOSE TOLERANCE AND DIABETES IN CHRONIC LIVER DISEASE

Abstract

Clin. Chimica Acta

Lancet

Gastroenterology

Diabetes

Archs intern. Med.

Étude sur quelques glycémies; la glycémie experimentale

Diabète

Proc. R. Soc. Med.

Dt. med. Wschr.

Yale J. Biol. Med.

Diabète

ORIGINAL ARTICLES
GLUCOSE TOLERANCE AND DIABETES IN CHRONIC LIVER DISEASE