脂肪肝與糖尿病及動脈粥狀硬化有密切關聯


  【24drs.com】根據兩篇新研究,非酒精性脂肪肝是心臟代謝風險的獨立預測因子。
  
  德國Saarlande大學醫學中心內科教授Frank Lammert博士表示,整體而言,這些結果可說是非酒精性脂肪肝造成的心血管疾病風險超出傳統風險因素的重要證據;對臨床實務的關鍵資訊是,這些疾病彼此密切相關,臨床醫師必須有所警覺。
  
  Lammert博士未參與此次研究,是在歐洲肝臟研究協會2014國際肝臟研討會中,這兩篇研究發表時提出前述論述。
  
  日本的研究中,非酒精性脂肪肝和第二型糖尿病風險增加有關,在10年追蹤期間內改善此病可以降低風險。
  
  法國的研究中,非酒精性脂肪肝是頸動脈粥狀硬化的預測因子,與典型的心血管風險因素無關;非酒精性脂肪肝患者中,頸動脈內膜中層厚度(C-IMT)、頸動脈斑塊和Framingham分數都比較高。
  
  日本的研究中,3,074名無糖尿病或A型、B型肝炎,且未過量飲酒的患者,在間隔至少10年之間進行了兩次超音波健康檢查。
  
  日本札幌Teine Keijinkai醫院胃腸科中心Hajime Yamazaki醫師發表研究結果時表示,開始時,24%的研究對象被發現有非酒精性脂肪肝。
  
  平均追蹤期間11.3年,開始時有非酒精性脂肪肝的728名病患有16.1%發生第二型糖尿病,沒有非酒精性脂肪肝的2,346人則是只有3.1%發生,這個關聯的粗風險比是6.05 (P< .001)。
  
  校正年紀、性別、身體質量指數、家族糖尿病、血脂異常病史等因素之後,多變項分析發現風險比依舊顯著,達2.82 (P< .001)。
  
  追蹤超音波顯示,開始時有非酒精性脂肪肝疾病者有110人改善,其餘618人無改善。
  
  Yamazaki醫師解釋,無法從這些資料得知改善原因,但是,多數案例中,可能是生活型態改變的結果。
  
  狀況改善者的第二型糖尿病發生率低於沒有改善者(6.4% vs 17.8%),非酒精性脂肪肝改善和第二型糖尿病的粗風險比為0.31 (P= .004);進行多變項分析後則是0.30 (P= .003)。
  
  Yamazaki醫師表示,臨床訊息重點是,降低脂肪肝以預防糖尿病;這次是最大型且追蹤最久的研究,顯示非酒精性脂肪肝和第二型糖尿病的關聯,也是首度顯示改善脂肪肝可降低第二型糖尿病風險。
  
  他解釋,因為超音波健康檢查是東亞國家之臨床實務的一部份,這篇研究是可行的,其他地區可能無法進行這類研究,但是其他人口的研究結果可能類似。
  
  Lammert博士指出,雖然此篇研究無法評估因果關係,或許對多數患者而言,肝臟疾病和糖尿病之間有關聯,因為肝臟與葡萄糖體內平衡相當有關。
  
  巴黎Pierre et Marie Curie大學、de La Pitie-Salpetriere醫院的Raluca Pais博士發表了法國的橫斷面與縱向研究結果。
  
  橫斷面研究部份包括了5,671名20-75歲、有兩種以上心血管風險因素者,全都進行至少一次頸動脈超音波,以測量C-IMT和頸動脈斑塊。
  
  Pais博士報告指出,1,871名患有非酒精性脂肪肝者的C-IMT(0.64 vs 0.61 mm;P< .001),頸動脈斑塊盛行率(44% vs 37%;P< 0.001)以及Framingham風險分數(15 vs 8;P< 0.001)都是顯著大於沒有此病的3,800人,全都與年紀、性別、身體質量指數、高血壓、抽菸無關。
  
  對至少進行兩次C-IMT測量的1,872名病患進行的8年追蹤中,開始時有非酒精性脂肪肝者的頸動脈斑塊風險增加 34% (P< .02)。
  
  她表示,無論血清值丙胺酸轉胺酶(ALT)多少,這些關聯仍然成立;有CVD風險的病患或許應篩檢脂肪肝,不論其轉胺酶值多少,因為非酒精性脂肪肝是心血管風險的獨立預測因子,超出代謝症候群等傳統風險因素。我們不知道非酒精性脂肪肝是否是心血管疾病標記或者和疾病病理或惡化有關,至少可以認為是個標記,其他則有待解答。
  
  Lammert博士在簡報中建議肝臟科病患應篩檢心血管風險,心臟科患者應照會肝臟專家評估。他表示,我們應將風險分類,且確認哪些病患可以從同時由心臟科和肝臟科醫師治療中獲益,不能只是碰巧發現。
  
  另外,也建議肝臟科醫師聚焦在沒有傳統心血管風險因素的非酒精性脂肪肝患者,至少有一種這類基因分組已經確定,未來必須更進一步地釐清。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_logon=W&x_idno=7069&x_classno=0
  

Fatty Liver Disease Tied to Diabetes, Atherosclerosis

By Miriam E. Tucker
Medscape Medical News

LONDON, United Kingdom — Nonalcoholic fatty liver disease is an independent predictor of cardiometabolic risk, according to 2 new studies.

Taken together, these findings "contribute to a large body of evidence showing nonalcoholic fatty liver disease may pose a cardiovascular risk above and beyond that conferred by traditional risk factors," said Frank Lammert, MD, PhD, professor of internal medicine at the Saarlande University Medical Center in Homburg, Germany.

"I think the key message for clinical practice is that these diseases are closely correlated, and clinical practitioners should be aware of this," he told Medscape Medical News.

Dr. Lammert, who was not involved in either study, spoke during a press briefing here at European Association for the Study of the Liver International Liver Congress 2014, where results from the 2 studies were presented.

In the Japanese study, the presence of nonalcoholic fatty liver disease was associated with an increased risk for type 2 diabetes, and improvement in the disease over a 10-year follow-up period appeared to reduce the risk.

In the French study, nonalcoholic fatty liver disease was found to be a predictor of carotid atherosclerosis, independent of the classic cardiovascular risk factors. In patients with nonalcoholic fatty liver disease, carotid intima-media thickness (C-IMT), carotid plaques, and Framingham scores were greater.

Type 2 Diabetes

In the Japanese study, 3074 patients who did not have diabetes or hepatitis A or B and who did not consume excessive amounts of alcohol underwent 2 ultrasound health checks at least 10 years apart.

At baseline, 24% of the cohort was found to have nonalcoholic fatty liver disease, said Hajime Yamazaki, MD, from the Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan, who presented the results.

At a mean follow-up of 11.3 years, 16.1% of the 728 patients with nonalcoholic fatty liver disease at baseline had developed type 2 diabetes, compared with just 3.1% of the 2346 who did not. The crude odds ratio for the association was 6.05 (P < .001).

After multivariate analysis adjusted for a variety of confounders, including age, sex, body mass index, family history of diabetes, and dyslipidemia, the odds ratio remained significant, at 2.82 (P < .001).

Follow-up ultrasound showed improvement in 110 of the patients with nonalcoholic fatty liver disease at baseline; in the other 618, there was no improvement.

The reason for the improvement could not be determined from these data, but in most cases, it was likely the result of lifestyle changes, Dr. Yamazaki explained.

The incidence of type 2 diabetes lower in those whose condition improved than in those whose condition did not (6.4% vs 17.8%). The crude odds ratio for improvement in nonalcoholic fatty liver disease and type 2 diabetes was 0.31 (P = .004); on multivariate analysis, it was 0.30 (P = .003).

"The clinical message is that it is important to reduce fatty liver to prevent diabetes," he told Medscape Medical News.

This study is the largest and longest to show an association between nonalcoholic fatty liver disease and type 2 diabetes, and the first-ever to show a reduction in type 2 diabetes with improvement in fatty liver disease, he said.

This study was possible because ultrasound health checks are part of clinical practice in East Asian countries. It is unlikely that this type of study could be conducted elsewhere, but results would probably be similar in other populations, he explained.

Although cause and effect couldn't be assessed in this study, "for many of the patients — maybe for the majority — there is a causal link between liver disease and diabetes because the liver plays a central role in glucose homeostasis," Dr. Lammert pointed out.

Cardiovascular Disease

Results from the 2-part cross-sectional and longitudinal French study were presented by Raluca Pais, MD, PhD, from Universite Pierre et Marie Curie and Hopital de La Pitie-Salpetriere in Paris.

The cross-sectional part involved 5671 patients 20 to 75 years of age who had 2 or more cardiovascular risk factors. All had undergone at least 1 carotid ultrasound to measure C-IMT and carotid plaques.

C-IMT was significantly higher in the 1871 subjects with nonalcoholic fatty liver disease than in the 3800 without the disease (0.64 vs 0.61 mm; P < .001), as were the prevalence of carotid plaques (44% vs 37%; P < 0.001) and Framingham risk scores (15 vs 8; P < 0.001). All were independent of age, sex, body mass index, hypertension, and tobacco use, Dr. Pais reported.

At 8-year follow-up in a subset of 1872 patients who had at least 2 C-IMT measurements, those with nonalcoholic fatty liver disease at baseline had a 34% increased risk for carotid plaques (P < .02).

These associations held true regardless of serum alanine aminotransferase levels, she said.

"Patients at risk for CVD should probably be screened for fatty liver, regardless of the transaminase levels, because nonalcoholic fatty liver disease is an independent predictor of cardiovascular risk, beyond traditional risk factors like metabolic syndrome," she told Medscape Medical News. "We don't know if nonalcoholic fatty liver disease is a marker or actively involved in the pathogenesis and progression of cardiovascular disease. It's at least a marker; for the rest, we don't yet have the answer."

Clinical Implications

During the briefing, Dr. Lammert advised that patients who enter a liver unit be assessed for cardiovascular risk and that those seen in cardiology settings be evaluated by a liver specialist.

"We should stratify the risk and define the subgroup of patients who would benefit from being treated by both a cardiologist and a hepatologist. It shouldn't happen by chance," he said.

He also advised that liver specialists focus on patients who present with nonalcoholic fatty liver disease without traditional cardiovascular risk factors, noting that at least 1 such genetic subgroup has been identified. "We need to define this better," said Dr. Lammert.

Dr. Yamazaki, Dr. Pais, and Dr. Lammert have disclosed no relevant financial relationships.

European Association for the Study of the Liver (EASL) International Liver Congress 2014: Abstracts 23 and 26. Presented April 10, 2014.

    
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