Cohort Study of Non-alcoholic Fatty Liver Disease, NAFLD fibrosis score, and the Risk of Incident Diabetes in a Korean population

Chang, Yoosoo; Jung, Hyun Suk; Yun, Kyung Eun; Cho, Juhee; Cho, Yong Kyun; Ryu, Seungho

doi:10.1038/ajg.2013.349

Cited by 149 publications

(111 citation statements)

References 46 publications

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“…Despite this close association of hepatic steatosis with insulin resistance, a causal relationship between NAFLD and glucose metabolism has not been clearly established. Only a few studies evaluating NAFLD as a risk factor for the development of diabetes have been reported (4,5,7). In the context of a suspected causal relationship, the results obtained at week 6 appear to provide further information.…”

Section: Discussionmentioning

confidence: 98%

“…Recent study results have shown that NAFLD independently increases one's risk of diabetes and cardiovascular diseases (4)(5)(6)(7)(8), which suggests that treatment of fatty liver might ameliorate the risk of type 2 diabetes and cardiovascular diseases. Unfortunately, the only established treatment is weight loss by lifestyle intervention, including qualitative dietary changes and exercise, although recent randomized controlled trials have shown promising beneficial effects of pharmacological treatment with antioxidants, insulin sensitizers, pentoxifylline, ursodeoxycholic acid, and lipidlowering drugs (9).…”

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confidence: 99%

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Improvement of Nonalcoholic Fatty Liver Disease With Carnitine-Orotate Complex in Type 2 Diabetes (CORONA): A Randomized Controlled Trial

et al. 2015

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OBJECTIVEWe aimed to evaluate the effects of carnitine-orotate complex in patients with nonalcoholic fatty liver disease (NAFLD) and diabetes. RESEARCH DESIGN AND METHODSEight hospitals in Korea participated in this randomized, controlled, double-blind trial of patients with diabetes and NAFLD. Seventy-eight patients were randomly assigned in a 1:1 ratio to receive carnitine-orotate complex (824 mg, three times daily) or matching placebo. The primary study outcome was decline in alanine aminotransferase (ALT) to the normal range. Secondary study outcomes were change in ALT, radiological hepatic steatosis, parameters for anthropometry, liver function, lipid profiles, and glycemic control. Hepatic steatosis was assessed using Hounsfield units on noncontrast computed tomography (CT) imaging with hepatic attenuation. RESULTSAfter 12 weeks of treatment, compared with placebo group, carnitine-orotate complex-treated participants had a significantly higher rate of normalization of serum ALT level (17.9% vs. 89.7%, P < 0.001). On hepatic CT analysis, participants treated with carnitine-orotate complex showed an increased liver attenuation index (0.74 6 8.05 vs. 6.21 6 8.96, P < 0.008). A significant decrease in HbA 1c was observed in the carnitine-orotate complex group (20.33 6 0.82% [23.6 6 9.0 mmol/mol], P = 0.007), but no significant change was seen in the placebo group. CONCLUSIONSTreatment with carnitine-orotate complex improves serum ALT and may improve hepatic steatosis as assessed by CT in patients with diabetes and NAFLD. Further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.Ectopic fat accumulation in a visceral organ is associated with insulin resistance (1). As an example of such ectopic fat accumulation, nonalcoholic fatty liver disease (NAFLD) is now recognized as the hepatic component of metabolic syndrome and is even reportedly associated with insulin resistance independent of obesity and other metabolic components. Therefore, NAFLD can be a major determinant of insulin

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Improvement of Nonalcoholic Fatty Liver Disease With Carnitine-Orotate Complex in Type 2 Diabetes (CORONA): A Randomized Controlled Trial

et al. 2015

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“…Lonardo et al (2) showed in a systematic review that NAFLD is strongly associated with future metabolic syndrome and T2DM. In addition, several longitudinal studies evaluated the association between NAFLD detected on ultrasound (US) and T2DM (6)(7)(8)(9)(10)(11)(12)(13)(14). Most of these studies observed a significant positive association between NAFLD at baseline and T2DM incidence (6)(7)(8)(9)(10)(11)(12)(13), but longterm cohort studies with a follow-up period of .10 years are limited (14).…”

mentioning

confidence: 99%

Independent Association Between Improvement of Nonalcoholic Fatty Liver Disease and Reduced Incidence of Type 2 Diabetes

et al. 2015

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OBJECTIVEOnly a few studies have evaluated the long-term effects of nonalcoholic fatty liver disease (NAFLD) on type 2 diabetes mellitus (T2DM), and none have examined whether NAFLD improvement reduces T2DM incidence. We investigated the association between NAFLD improvement and T2DM incidence. RESEARCH DESIGN AND METHODSBetween 2000 and 2012, 4,604 participants who underwent a health check twice with >10 years between were enrolled. Exclusion criteria were positive hepatitis B surface antigen, positive hepatitis C antibody, ethanol intake >20 g/day, and diabetes. The 3,074 eligible participants were divided into an NAFLD group (n = 728) and a non-NAFLD group (n = 2,346) according to ultrasonography-detected fatty liver. The NAFLD group was categorized into an improved group (n = 110) and a sustained NAFLD group (n = 618) based on fatty liver disappearance at the second visit. Incident T2DM odds ratios (ORs) were estimated by logistic regression models adjusted for age, sex, BMI, impaired fasting glucose, family history of diabetes, dyslipidemia, hypertension, and physical exercise. RESULTST2DM occurred in 117 participants (16.1%) in the NAFLD group and 72 (3.1%) in the non-NAFLD group. NAFLD at baseline was associated with T2DM incidence (multivariate OR 2.37 [95% CI 1.60-3.52]). T2DM occurred in 7 participants (6.4%) in the improved group and in 110 (17.8%) in the sustained NAFLD group. NAFLD improvement was associated with reduced T2DM incidence (multivariate OR 0.27 [95% CI 0.12-0.61]). CONCLUSIONS

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“…There are now about 20 observational studies that have assessed the association between NAFLD and the risk of new-onset type 2 diabetes [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Section: Epidemiological Evidence Linking Nafld To the Risk Of New-onmentioning

confidence: 99%

“…Collectively, although there is now convincing evidence that NAFLD is associated with an increased risk of new-onset type 2 diabetes [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25], and there is emerging evidence that this risk varies according to the severity of NAFLD (as detected either by ultrasonography or by use of non-invasive fibrosis scoring systems) [9,[12][13][14], further evidence is unquestionably needed in non-Asian populations, as nearly all of the studies summarised in Table 1 have been conducted in various Asian populations, and most of the evidence obtained to date has been obtained in South Korean individuals. However, a recent analysis from the Multi-Ethnic Study of Atherosclerosis study involving more than 3,000 United States nondiabetic individuals has confirmed that NAFLD as detected by computed tomography was independently associated with a two-fold increased risk of developing type 2 diabetes [25].…”

Section: Epidemiological Evidence Linking Nafld To the Risk Of New-onmentioning

confidence: 99%

Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon?

Targher

Marchesini

Byrne

2016

Diabetes & Metabolism

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Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liverrelated mortality and morbidity. Over the last 10 years, it has also become increasingly evident that NAFLD is a multisystem disease, affecting many extra-hepatic organ systems and interacting with the regulation of multiple metabolic pathways. NAFLD is potentially involved in the aetiology and pathogenesis of type 2 diabetes via its direct contribution to hepatic/peripheral insulin resistance and the systemic release of multiple hepatokines that may adversely affect glucose metabolism and insulin action and secretion. In this updated review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong link between NAFLD and the risk of developing type 2 diabetes. We also briefly examine the conventional and the more innovative pharmacological approaches for the treatment of NAFLD that may influence the risk of developing type 2 diabetes. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractNonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liver-related mortality and morbidity. Over the last 10 years, it has also become increasingly evident that NAFLD is a multisystem disease, affecting many extra-hepatic organ systems and interacting with the regulation of multiple metabolic pathways. NAFLD is potentially involved in the aetiology and pathogenesis of type 2 diabetes via its direct contribution to hepatic/peripheral insulin resistance and the systemic release of multiple hepatokines that may adversely affect glucose metabolism and insulin action and secretion. In this updated review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong link between NAFLD and the risk of developing type 2 diabetes. We also briefly examine the conventional and the more innovative pharmacological approaches for the treatment of NAFLD that may influence the risk of developing type 2 diabetes.

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Cohort Study of Non-alcoholic Fatty Liver Disease, NAFLD fibrosis score, and the Risk of Incident Diabetes in a Korean population

Abstract: In this cohort study of a healthy Korean population, NAFLD and its severity using NFS were independently and strongly associated with increased incidence of diabetes in men and women-even with a euglycemic range of glucose and HbA1c.

Cited by 149 publications

References 46 publications

Improvement of Nonalcoholic Fatty Liver Disease With Carnitine-Orotate Complex in Type 2 Diabetes (CORONA): A Randomized Controlled Trial

Improvement of Nonalcoholic Fatty Liver Disease With Carnitine-Orotate Complex in Type 2 Diabetes (CORONA): A Randomized Controlled Trial

Independent Association Between Improvement of Nonalcoholic Fatty Liver Disease and Reduced Incidence of Type 2 Diabetes

Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon?

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