Nonalcoholic fatty liver disease in patients with type 2 diabetes

doi:10.1016/S1542-3565(04)00014-X

Clinical Gastroenterology and Hepatology

Volume 2, Issue 3, March 2004, Pages 262-265

https://doi.org/10.1016/S1542-3565(04)00014-X Get rights and content

Abstract

$Background & Aims:$ Nonalcoholic fatty liver disease (NAFLD) is reported commonly in patients with type 2 diabetes mellitus (DM), which has been suggested as a risk factor for the progressive form of NAFLD, or nonalcoholic steatohepatitis. The aim of this study was to assess the outcome of patients with NAFLD and DM. $Methods:$ A cohort of patients with NAFLD was identified, and patients with other causes of liver disease (alcohol, medication, etc.) were excluded. Clinical, pathological, and mortality data were available for this cohort. Patients were categorized and compared according to the presence or absence of DM. $Results:$ Of 132 patients with NAFLD, 44 patients (33%) had an established diagnosis of DM. Patients with DM were older and had greater serum glucose and triglyceride levels and a greater aspartate aminotransferase-alanine aminotransferase ratio. Liver biopsy specimens from patients with DM showed more vacuolated nuclei and acidophilic bodies. Cirrhosis (histological or clinical) occurred in 25% of patients with DM (11 of 44 patients) and NAFLD compared with only 10.2% (9 of 88 patients) of patients without DM with NAFLD (P = 0.04). After adjusting for potential confounders (age, body mass index, and the presence of cirrhosis), both overall mortality (risk ratio [RR], 3.30; 95% confidence interval [CI], 1.76–6.18; P = 0.002) and mortality related to liver disease (RR, 22.83; 95% CI, 2.97–175.03; P = 0.003) were greater in diabetic patients with NAFLD. Markers of hepatic dysfunction (low albumin level, high total bilirubin level, and prolonged prothrombin time) were the only independent predictors of increased mortality. $Conclusions:$ Patients with NAFLD and DM are at risk for the development of an aggressive outcome, such as cirrhosis and mortality. This study supports the potential role of insulin resistance in the development of poor clinical outcomes in patients with NAFLD.

Section snippets

Development of the NAFLD database

The NAFLD database was created by looking at liver biopsies processed at the Cleveland Clinic Department of Pathology (Cleveland, OH) from January 1, 1979, to December 31, 1987. Pathological features identified excess fat with or without other pathological findings. Specimens with other causes of liver disease (e.g., alcohol, medication, hepatitis C, iron overload) were systematically excluded.3, 4, 26 Data included a large number of clinical and pathological features, as well as long-term

Identification of the NAFLD cohort

A total of 4238 liver biopsy specimens were processed at the Cleveland Clinic Department of Pathology during the period of this study. Of these, 772 specimens (18%) showed excessive fatty accumulation (± other features) as their primary diagnosis. Specimens with other causes of liver disease were excluded. Specimens from the remaining 157 patients (3.7%) fulfilled criteria for the final diagnosis of NAFLD. Of these, 132 patients (84%) had complete clinical and pathological data and constituted

Discussion

This analysis indicates that patients with DM and NAFLD have more aggressive disease with respect to cirrhosis and mortality than NAFLD patients without DM. The increased risk remained significant even after adjusting for potentially important confounders that can affect survival. The 18.2% liver-related mortality rate reported here is much greater than that of patients without DM with NAFLD and those reported for the general population.3, 4 Although a number of factors were associated with

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Cited by (340)

Epidemiology of NAFLD – Focus on diabetes
2024, Diabetes Research and Clinical Practice
There is increasing appreciation of the complex interaction between nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D) and insulin resistance. Not only is the prevalence of NAFLD disease high among patients with T2D, the liver disease is also more progressive. Currently, the global prevalence of NAFLD in the general population (2016–2019) is 38 %. The prevalence of T2D among those with NAFLD is approximately 23 % while the prevalence of NAFLD among those with T2D can be as high as 70 %. The prevalence of nonalcoholic steatohepatitis (NASH) is approximately 7 % in the general population and 37 % among patients with T2D. Globally, the MENA and Latin America regions of the world appear to have the highest burden of both NAFLD and T2D. Compared to those with NAFLD but without T2D, those with NAFLD and T2D are at a much higher risk for disease progression to cirrhosis and for decompensated cirrhosis, hepatocellular carcinoma, and all-cause mortality. Given that highly effective new treatments are available for T2D, high risk NAFLD with T2D should be considered for these regimens. This requires implementation of risk stratification algorithms in the primary care and endocrinology practices to identify those patients at highest risk for adverse outcomes.
Type 2 diabetes, hepatic decompensation, and hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: an individual participant-level data meta-analysis
2023, The Lancet Gastroenterology and Hepatology
Data are scarce regarding the development of hepatic decompensation in patients with non-alcoholic fatty liver disease (NAFLD) with and without type 2 diabetes. We aimed to assess the risk of hepatic decompensation in people with NAFLD with and without type 2 diabetes.
We did a meta-analysis of individual participant-level data from six cohorts in the USA, Japan, and Turkey. Included participants had magnetic resonance elastography between Feb 27, 2007, and June 4, 2021. Eligible studies included those with liver fibrosis characterisation by magnetic resonance elastography, longitudinal assessment for hepatic decompensation and death, and included adult patients (aged ≥18 years) with NAFLD, for whom data were available regarding the presence of type 2 diabetes at baseline. The primary outcome was hepatic decompensation, defined as ascites, hepatic encephalopathy, or variceal bleeding. The secondary outcome was the development of hepatocellular carcinoma. We used competing risk regression using the Fine and Gray subdistribution hazard ratio (sHR) to compare the likelihood of hepatic decompensation in participants with and without type 2 diabetes. Death without hepatic decompensation was a competing event.
Data for 2016 participants (736 with type 2 diabetes; 1280 without type 2 diabetes) from six cohorts were included in this analysis. 1074 (53%) of 2016 participants were female with a mean age of 57·8 years (SD 14·2) years and BMI of 31·3 kg/m² (SD 7·4). Among 1737 participants (602 with type 2 diabetes and 1135 without type 2 diabetes) with available longitudinal data, 105 participants developed hepatic decompensation over a median follow-up time of 2·8 years (IQR 1·4–5·5). Participants with type 2 diabetes had a significantly higher risk of hepatic decompensation at 1 year (3·37% [95% CI 2·10–5·11] vs 1·07% [0·57–1·86]), 3 years (7·49% [5·36–10·08] vs 2·92% [1·92–4·25]), and 5 years (13·85% [10·43–17·75] vs 3·95% [2·67–5·60]) than participants without type 2 diabetes (p<0·0001). After adjustment for multiple confounders (age, BMI, and race), type 2 diabetes (sHR 2·15 [95% CI 1·39–3·34]; p=0·0006) and glycated haemoglobin (1·31 [95% CI 1·10–1·55]; p=0·0019) were independent predictors of hepatic decompensation. The association between type 2 diabetes and hepatic decompensation remained consistent after adjustment for baseline liver stiffness determined by magnetic resonance elastography. Over a median follow-up of 2·9 years (IQR 1·4–5·7), 22 of 1802 participants analysed (18 of 639 with type 2 diabetes and four of 1163 without type 2 diabetes) developed incident hepatocellular carcinoma. The risk of incident hepatocellular carcinoma was higher in those with type 2 diabetes at 1 year (1·34% [95% CI 0·64–2·54] vs 0·09% [0·01–0·50], 3 years (2·44% [1·36–4·05] vs 0·21% [0·04–0·73]), and 5 years (3·68% [2·18–5·77] vs 0·44% [0·11–1·33]) than in those without type 2 diabetes (p<0·0001). Type 2 diabetes was an independent predictor of hepatocellular carcinoma development (sHR 5·34 [1·67–17·09]; p=0·0048).
Among people with NAFLD, the presence of type 2 diabetes is associated with a significantly higher risk of hepatic decompensation and hepatocellular carcinoma.
National Institute of Diabetes and Digestive and Kidney Diseases.
The bidirectional relationship between NAFLD and type 2 diabetes: A prospective population-based cohort study
2023, Nutrition, Metabolism and Cardiovascular Diseases
To explore the bidirectional relationship between NAFLD and type 2 diabetes and the possible directions of the main effect.
30 633 participants from the Jinchang cohort were enrolled. Firstly, cox proportional hazards regression model was used to assess the unidirectional causality between NAFLD and prediabetes and type 2 diabetes. Secondly, cross-lag path analysis model was conducted to estimate the bidirectional relationship between NAFLD and prediabetes and type 2 diabetes, and to determine the direction of the main effects. Finally, potential effect modifications were also considered by age, sex, hyperlipidemia, and overweight/obesity. We found that NAFLD increased the risk of prediabetes and type 2 diabetes with adjusted HR (95%CI) of 1.355(95%CI: 1.255–1.462) and 1.898(95%CI: 1.415–2.545), respectively. Prediabetes and type 2 diabetes also increased the risk of NAFLD, with adjusted HR (95%CI) of 1.245(95%CI: 1.115–1.392) and 1.592(95%CI: 1.373–1.846), respectively. Cross-lag path analysis showed that NAFLD significantly affected the incidence of prediabetes (β = 0.285, P < 0.001), while the effect on type 2 diabetes was not statistically significant. The effect of prediabetes and type 2 diabetes on the risk of NAFLD was weak, and the path coefficients were 0.076 and 0.037, respectively. Stratified analyses showed similar results.
This study provides evidence that there was a bidirectional causal association between NAFLD and type 2 diabetes, and the progression from NAFLD through prediabetes to type 2 diabetes may be the main pathway.
Special Population: Pediatric Nonalcoholic Fatty Liver Disease
2023, Clinics in Liver Disease
Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease
2023, Clinical Gastroenterology and Hepatology
Type 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.
Children with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike’s Information Criteria selection.
This study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0–2.8]), associated with BMI z-score (HR, 1.8 [1.0–3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0–1.7]), and fibrosis stage (HR, 1.3 [1.0–1.5]).
Children with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed.
Hypoglycemic mechanisms of Polygonatum sibiricum polysaccharide in db/db mice via regulation of glycolysis/gluconeogenesis pathway and alteration of gut microbiota
2023, Heliyon
Polygonatum rhizoma polysaccharide (PP) is a main ingredient of Polygonatum rhizoma, which is both food and traditional herbal medicine. In this study, we aimed to investigate the hypoglycemic effect of PP and the underlying mechanisms in db/db mice. Our finding showed that PP significantly ameliorates diabetic symptoms by reducing glucose levels in blood and urine and increasing insulin and leptin abundance in the serum. Histopathological examination revealed that PP improved the pathological state and increased hepatic glycogen storage in liver. Additionally, RT-qPCR results indicated that PP significantly down-regulated the expression of phosphoenolpyruvate carboxykinase 1. Furthermore, 16s rRNA sequencing results demonstrated that PP intervention resulted in an increase in beneficial bacteria genus and a reduction in harmful genus. Redundancy analysis revealed the correlation between intestinal flora and clinical factors. Taken together, these results suggest that PP has a significant hypoglycemic effect on type 2 diabetes (T2D) through up-regulating serum insulin and leptin, as well as hepatic glycogen storage, and down-regulating hepatic phosphoenolpyruvate carboxykinase 1 expression, as well as modulating gut microbiota composition. In conclusion, this study investigated the mechanisms of PP in the treatment of diabetes in db/db mice. To the best of our knowledge, this is the first study to explore the positive and negative correlations between gut microbiota and clinical factors, such as oxidative stress injury in liver and glucose related indicators in the blood.

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Original articleNonalcoholic fatty liver disease in patients with type 2 diabetes

Abstract

Section snippets

Development of the NAFLD database

Identification of the NAFLD cohort

Discussion

Hepatology

Gastroenterology

Hum Pathol

Liver Transpl

Gastroenterology

Hepatology

Gastroenterology

Hepatology

Gastroenterology

Nutrition

Hepatology

Non-alcoholic fatty liver diseasean overview

J Gastroenterol Hepatol

Clinical features and natural history of nonalcoholic steatosis syndromes

Semin Liver Dis

Original article
Nonalcoholic fatty liver disease in patients with type 2 diabetes