| |
Diabetes & Liver Disease: does diabetes cause liver disease
- pdf of article attached
|
| |
| |
Download the PDF here
the authors suggest that diabetes may result in liver damage just as it can result in more recognizable harm to the kidney, the nervous system & neuropathy, cardiovascular and eye. But liver damage may be more irreparable than to these other organ systems.
"we posit that the presence of overt diabetes reflects more severe insulin resistance, a greater fatty load in the liver19,20 and potentially worse hepatic inflammation and injury.21,22 At the same time, we do not know whether the hepatocyte is directly susceptible to glucotoxicity."
Newly diagnosed diabetes mellitus as a risk factor for serious liver disease
CMAJ Canadian Medical Association journal
Liane Porepa 1, Joel G Ray 2, Paula Sanchez-Romeu 3, Gillian L Booth 2
1 The Department of Medicine, University of Toronto, Toronto, Ont.
2 The Department of Medicine, University of Toronto, Toronto, Ont.; the Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ont.; and the Institute for Clinical Evaluative Sciences, Toronto, Ont.
3 The Institute for Clinical Evaluative Sciences, Toronto, Ont.
Abstract
Background: The negative impact of diabetes mellitus is well recognized, yet little is known about the effect of this disease on the liver, an organ susceptible to nonalcoholic fatty liver disease related to insulin resistance. We evaluated whether adults with newly diagnosed diabetes were at increased risk of serious liver disease.
Methods: We used administrative health databases for the province of Ontario (1994-2006) to perform a population-based matched retrospective cohort study. The exposed group comprised 438 069 adults with newly diagnosed diabetes. The unexposed comparison group - those without known diabetes - consisted of 2 059 708 individuals, matched 5:1 to exposed persons, by birth year, sex and local health region. We excluded individuals with preexisting liver or alcohol-related disease. The primary study outcome was the subsequent development of serious liver disease, namely, liver cirrhosis, liver failure and its sequelae, or receipt of a liver transplant.
Results: The incidence rate of serious liver disease was 8.19 per 10 000 person-years among those with newly diagnosed diabetes and 4.17 per 10 000 person-years among those without diabetes. The unadjusted hazard ratio was 1.92 (95% confidence interval [CI] 1.83-2.01). After adjustment for age, income, urban residence, health care utilization and pre-existing hypertension, dyslipidemia, obesity and cardiovascular disease, the hazard ratio was 1.77 (95% CI 1.68-1.86).
Interpretation: Adults with newly diagnosed diabetes appeared to be at higher risk of advanced liver disease, also known as diabetic hepatopathy. Whether this reflects nonalcoholic fatty liver disease or direct glycemic injury of the liver remains to be determined.
Author Conclusions
Our observed incidence rate for serious liver disease of 8.19 per 10 000 person-years among adults with newly diagnosed diabetes was lower than published rates for diabetes-related end-stage renal disease (20 to 30 per 10 000 person-years)27 and sight-threatening diabetic retinopathy (45 per 10 000 per- son-years).28 Each of these conditions seriously affects quality of life. However, when the liver fails, there is no equivalent form of management, such as hemodialysis or retinal photo- coagulation. Thus, although diabetic hepatopathy is poten- tially less common, it may be appropriate for addition to the list of target-organ conditions related to diabetes, such as glomerulopathy, retinopathy and neuropathy. Annual screening for liver disease might be accomplished by means of a simple biochemical analyte such as alanine aminotransferase. However, before screening can be considered, the efficacy of primary and secondary preventive measures, such as weight loss and glycemic and lipid control, must be validated by good evidence akin to that completed for adults and children with isolated fatty liver and no diabetes.29
Interpretation
In this study, adults with newly diagnosed diabetes had a significantly
greater risk of serious liver disease than those without diabetes. This result held across demographic strata and with adjustment for other known risk factors for nonalcoholic fatty liver disease. Diabetes, with or without pre-existing hypertension, dyslipidemia or obesity, conferred a higher risk of serious liver disease than any of the three other conditions in isolation.
Our research complements a large cohort study conducted
by the US Department of Veterans Affairs, which found a similarly higher risk of chronic nonalcoholic liver disease among veterans with diabetes who had been admitted to hospital. 9 Although our findings and those of the US study edge forward the idea that diabetes may be harmful to the liver, the question remains of whether this effect extends beyond the metabolic syndrome. In the United Kingdom Prospective Diabetes Study, the metabolic syndrome was present in 61% of adults with diabetes,13 which indicates that it is not easy to entirely separate the effects of these related conditions. We found that obesity and arterial hypertension were each individually associated with a modestly increased risk of serious liver disease; however, the risk was highest in the presence of diabetes. In other studies, the combination of diabetes and the metabolic syndrome posed a higher risk for stroke14 and myocardial infarction15 than either condition alone. For a variety of reasons, the same phenomenon may be true for liver disease. Hepatic fat content (fatty liver, NASH) increases in these individuals in parallel to insulin resistance and glucose dysregulation.16 The final evolution to type 2 diabetes is marked by β-cell failure,17 at which point hyperglycemia develops in parallel with increases in plasma triglycerides and the hepatic insulin resistance index, potentially further augmenting the fatty liver burden.18 Thus, we posit that the presence of overt diabetes reflects more severe insulin resistance, a greater fatty load in the liver19,20 and potentially worse hepatic inflammation and injury.21,22 At the same time, we do not know whether the hepatocyte is directly susceptible to glucotoxicity.
| |
| |
| |
|
|
|
