Glucose and insulin metabolism in cirrhosis

doi:10.1016/0168-8278(89)90169-4

Journal of Hepatology

Volume 8, Issue 1, January 1989, Pages 107-114

https://doi.org/10.1016/0168-8278(89)90169-4 Get rights and content

Abstract

Glucose intolerance, overt diabetes mellitus. and insulin resistance are characteristic features of patients with cirrhosis. Insulin secretion, although increased in absolute terms, is insufficient to offset the presence of insulin resistance. The defect in insulin-mediated glucose disposal involves peripheral tissues, primarily muscle, and most likely reflects a disturbance in glycogen synthesis Hepatic glucose production is normally sensitive to insulin; at present, it is unknown whether hepatic glucose uptake is impaired in cirrhosis. One of the more likely candidates responsible for the insulin-resistant state is insulin itself. The hyperinsulinemia results from three abnormalities: dimimshed hepatic extraction, portosystemic/intrahepatic shunting, and enhanced insulin secretion.

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Cited by (132)

Glucose turnover at whole-body and skeletal muscle level in response to parenteral nutrition in male patients with alcoholic liver cirrhosis
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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.
Characterization of glucose metabolism in youth with vs. without cystic fibrosis liver disease: A pilot study
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Citation Excerpt :
The pathogenesis linking cirrhosis and diabetes in CF has not been explored. In non-CF populations, diabetes is prevalent in 40–70% of patients with cirrhosis [12]; fasting and prandial hyperinsulinemia, which are attributed to reduced insulin clearance and sensitivity, are proposed as culprits for diabetes development [13]. In CF, limited studies suggest that worsening glycemia correlates with increased insulin clearance.
Diabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease.
In this two-center cross-sectional study, 20 youth with CF with and without liver disease underwent a 3-hour oral glucose tolerance test. Subjects were categorized by liver disease (LD) status [no LD, mild LD, severe LD] and diabetes status. Measures of glucose excursion, islet cell secretory responses, insulin sensitivity and clearance were obtained.
Participants with severe LD had the highest fasting, peak, and glucose area under the curve over 3 h (AUC_3h) among individuals with CFRD (interaction p < 0.05). In parallel with glycemic changes, prandial β-cell secretory response (AUC _{C-peptide 3h}) was lower in those with severe LD compared to mild or no LD (p < 0.01). There was a trend of higher HOMA-IR in those with severe LD (p = 0.1) as well as lower fasting insulin clearance in those with mild and severe LD compared to no LD (p = 0.06) and lower prandial insulin clearance in severe LD among those with CFRD (interaction p = 0.1).
In this small cohort, subjects with severe LD tended to have more impaired glycemia, insulin secretion, insulin sensitivity and clearance. Larger studies are imperative to define the pathogenesis to inform clinical care guidelines in terms of CFRD screening, diagnosis, and treatment options.
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This effect is accentuated when cirrhotic patients are advised to limit dietary protein intake to reduce ammonia production and theoretically reduce the risk of HE. Liver fibrosis prevents adequate glycogen storage, reduces glycogenolysis, triggers catabolism of muscle and fat for gluconeogenesis and ketogenesis, and ultimately leads to sarcopenia and adipopenia.54,56–62 To further complicate the problem, decompensated cirrhotic patients tend to have low oral intake in the setting of symptomatic ascites and may also have a degree of malabsorption and/or maldigestion from portal enteropathy or in the setting of cholestasis.56,59,63–66
Challenges in diagnosing and monitoring diabetes in patients with chronic liver diseases
2018, Diabetes and Metabolic Syndrome: Clinical Research and Reviews
Citation Excerpt :
Hyperinsulinemia is associated with a reduction in insulin receptor affinity, a reduction in the number of receptors exposed on the cell surface and functional changes to these receptors. Thus, hyperinsulinemia may induce insulin resistance [21–23]. Other phenomena secondary to chronic liver disease that appear to contribute to insulin resistance in cirrhotic individuals include the accumulation of advanced glycation end products and hypoxia-inducible factor [25].
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.
Clinical significance of serum adiponectin and resistin levels in liver cirrhosis
2018, Annals of Hepatology
Introduction. Despite reports of increased incidence of intrahepatic cholangiocarcinoma (iCCA) in the United States, the impact of age or influences of race and ethnicity are not clear. Disparities in iCCA outcomes across various population subgroups also are not readily recognized due to the rarity of this cancer. We examined ethnic, race, age, and gender variations in iCCA incidence and survival using data from the Surveillance, Epidemiology, and End Results Program (1995-2014).
Materials and methods. We assessed age-adjusted incidence rates, average annual percentage change in incidence, and hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality.
Results. Overall, 11,127 cases of iCCA were identified, with an age-adjusted incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from 0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate of increase of 5.49%. The iCCA incidence rate was higher among persons age 45 years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000), among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non-Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had poorer 5-year all-cause mortality (HR = 1.11, 95%CI: 1.05-1.19) and poorer iCCA-specific mortality (HR = 1.15, 95%CI: 1.07-1.24). Survival rates were poor also for individuals age 45 years or older, men, Blacks, and American Indians/Alaska Natives.
Conclusion. The results demonstrate ethnic, race, age and gender disparities in iCCA incidence and survival, and confirm continued increase in iCCA incidence in the United States.

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ReviewGlucose and insulin metabolism in cirrhosis

Abstract

Lancet

Metabolism

Metabolism

Gastroenterology

J Hepatol

Gastroenterology

Metabolism

Lancet

Metabolism

Liver diseases and dianetes mellitus

Insulin resistance in cirrhosis: evidenec for a postreceptor defect

Clin Endocrinol

Hyperinsulincmia and insulin resistance of cirrhosis: the importance of insulin hypersecretion

Clin Endocrinol

Mechanism of insulin resistance in human liver cirrhosis

J Clin Invest

Degradation and secretion of insulin in hepatic cirrhosis

J Clin Endocrinol Metab

C-peptide as a measure of the secretion and hepatic extraction of insulin

Diabetes

Insulinresistenz bei Lebererkrankungen

Z Gastroenterol

The euglyeemic clamp technique in patients with liver cirrhosis

Horm Metabol Res

Insulin action in cirrhosis

Hepatology

Glucose clamp technique: a method for quantifying insulin secretion and resistance

Am J Physiol

The glucose-fatty acid cycle does not explain the insulin resistance of cirrhosis (Abstract)

Gastroenterology

Review
Glucose and insulin metabolism in cirrhosis