Mortality From Chronic Liver Diseases in Diabetes
Mortality From Chronic Liver Diseases in Diabetes
Objectives: Mortality from chronic liver diseases (CLDs) is increased in diabetes, but little is known about the etiology. The aim of this study was to assess mortality rates from CLD by etiology in known diabetic subjects living in the Veneto Region, Northern Italy.
Methods: A total of 167,621 diabetic subjects, aged 30–89 years (54.6% men), were identified in the year 2007 and their vital status was assessed between 2008 and 2010. Standardized mortality ratios (SMR) with 95% confidence intervals (CIs) were computed with regional mortality rates as reference. The underlying cause of death and all comordidities reported on the certificate were scrutinized in order to identify CLD deaths and their main etiologies. The latter were grouped into the following three categories: (i) virus-related, (ii) alcohol-related, and (iii) non-virus, non-alcohol-related (mainly represented by nonalcoholic fatty liver disease, NAFLD).
Results: Analyses were based upon 473,374 person-years of follow-up and 17,134 deaths. We observed an increased risk of dying from CLD in diabetic subjects with an SMR of 2.47 (95% CI=2.19–2.78) in men and 2.70 (2.24–3.23) in women. SMRs were 2.17 (1.90–2.47), 2.25 (1.98–2.54), and 2.86 (2.65–3.08) for virus-related, alcohol-related, and non-virus, non-alcohol-related CLD, respectively.
Conclusions: Diabetic patients have a twofold to threefold higher risk of dying of CLD, mainly associated with a non-virus and non-alcohol-related etiology, which is largely attributable to NAFLD. An early diagnosis and treatment of NAFLD, if any, may have a beneficial clinical impact on the survival of diabetic patients.
Diabetes reduces lifetime by about 6 years, compared with that of subjects without diabetes, because it increases the risks of death from all causes, including chronic liver diseases (CLDs). A ~2.5-fold higher risk of death from CLD was observed in a cohort study on 7,148 type 2 diabetes patients as well as in a recent large study on more than one million subjects. It is known that CLD occurs due to different etiologies, such as alcohol and drug use, and viral, autoimmune, and metabolic causes. Nonalcoholic fatty liver disease (NAFLD), the most common cause of CLD among adults with or without type 2 diabetes in Western countries, has emerged as a public health problem of epidemic proportions worldwide. Notably, patients with type 2 diabetes and NAFLD are also more likely to develop the more advanced forms of NAFLD, such as nonalcoholic steatohepatitis, advanced fibrosis, cirrhosis, and, in some cases, hepatocellular carcinoma. In recent years, NAFLD has been recognized as a major risk factor of morbidity and mortality in type 2 diabetes. It is noteworthy that the prevalence of NAFLD is increasing and keeping pace with the steady worldwide growth of obesity, type 2 diabetes, and the metabolic syndrome. However, although it is known that mortality from CLD is increased in subjects with diabetes, to our knowledge, no information is currently available about the etiology of CLD-related deaths in this patient population.
In fact, mortality statistics are generally limited to the underlying cause of death. However, comorbidities are mentioned in death certificates and they might be used to provide a more comprehensive assessment of diseases that may contribute, more or less directly, to death. The analysis of all diseases reported on death certificates (multiple cause of death analysis) permits more extensive capture of CLD-related deaths, and allows the retrieval of the etiology of CLD. Although suffering from the underreporting of causes and types of liver diseases, the analysis of multiple causes of death data has been applied in US studies to assess the burden of hepatitis C virus (HCV) infection- and alcohol-related CLD in the overall population and in high-risk subgroups. The main aim of our study was to analyze all information available in death certificates in an entire region in Italy to investigate the etiology of CLD-associated mortality in diabetes.
Abstract and Introduction
Abstract
Objectives: Mortality from chronic liver diseases (CLDs) is increased in diabetes, but little is known about the etiology. The aim of this study was to assess mortality rates from CLD by etiology in known diabetic subjects living in the Veneto Region, Northern Italy.
Methods: A total of 167,621 diabetic subjects, aged 30–89 years (54.6% men), were identified in the year 2007 and their vital status was assessed between 2008 and 2010. Standardized mortality ratios (SMR) with 95% confidence intervals (CIs) were computed with regional mortality rates as reference. The underlying cause of death and all comordidities reported on the certificate were scrutinized in order to identify CLD deaths and their main etiologies. The latter were grouped into the following three categories: (i) virus-related, (ii) alcohol-related, and (iii) non-virus, non-alcohol-related (mainly represented by nonalcoholic fatty liver disease, NAFLD).
Results: Analyses were based upon 473,374 person-years of follow-up and 17,134 deaths. We observed an increased risk of dying from CLD in diabetic subjects with an SMR of 2.47 (95% CI=2.19–2.78) in men and 2.70 (2.24–3.23) in women. SMRs were 2.17 (1.90–2.47), 2.25 (1.98–2.54), and 2.86 (2.65–3.08) for virus-related, alcohol-related, and non-virus, non-alcohol-related CLD, respectively.
Conclusions: Diabetic patients have a twofold to threefold higher risk of dying of CLD, mainly associated with a non-virus and non-alcohol-related etiology, which is largely attributable to NAFLD. An early diagnosis and treatment of NAFLD, if any, may have a beneficial clinical impact on the survival of diabetic patients.
Introduction
Diabetes reduces lifetime by about 6 years, compared with that of subjects without diabetes, because it increases the risks of death from all causes, including chronic liver diseases (CLDs). A ~2.5-fold higher risk of death from CLD was observed in a cohort study on 7,148 type 2 diabetes patients as well as in a recent large study on more than one million subjects. It is known that CLD occurs due to different etiologies, such as alcohol and drug use, and viral, autoimmune, and metabolic causes. Nonalcoholic fatty liver disease (NAFLD), the most common cause of CLD among adults with or without type 2 diabetes in Western countries, has emerged as a public health problem of epidemic proportions worldwide. Notably, patients with type 2 diabetes and NAFLD are also more likely to develop the more advanced forms of NAFLD, such as nonalcoholic steatohepatitis, advanced fibrosis, cirrhosis, and, in some cases, hepatocellular carcinoma. In recent years, NAFLD has been recognized as a major risk factor of morbidity and mortality in type 2 diabetes. It is noteworthy that the prevalence of NAFLD is increasing and keeping pace with the steady worldwide growth of obesity, type 2 diabetes, and the metabolic syndrome. However, although it is known that mortality from CLD is increased in subjects with diabetes, to our knowledge, no information is currently available about the etiology of CLD-related deaths in this patient population.
In fact, mortality statistics are generally limited to the underlying cause of death. However, comorbidities are mentioned in death certificates and they might be used to provide a more comprehensive assessment of diseases that may contribute, more or less directly, to death. The analysis of all diseases reported on death certificates (multiple cause of death analysis) permits more extensive capture of CLD-related deaths, and allows the retrieval of the etiology of CLD. Although suffering from the underreporting of causes and types of liver diseases, the analysis of multiple causes of death data has been applied in US studies to assess the burden of hepatitis C virus (HCV) infection- and alcohol-related CLD in the overall population and in high-risk subgroups. The main aim of our study was to analyze all information available in death certificates in an entire region in Italy to investigate the etiology of CLD-associated mortality in diabetes.