幽門桿菌感染和血漿中ghrelin與leptin值對經腹腔鏡減肥手術的術後體重結果影響

行政院國家科學委員會專題研究計畫 成果報告

幽門桿菌感染和血漿中 ghrelin 與 leptin 值對經腹腔鏡減

肥手術的術後體重結果影響

研究成果報告(精簡版)

計 畫 類 別 ： 個別型 計 畫 編 號 ： NSC 95-2314-B-002-093- 執 行 期 間 ： 95 年 08 月 01 日至 96 年 07 月 31 日 執 行 單 位 ： 國立臺灣大學醫學院一般醫學科 計 畫 主 持 人 ： 吳明賢 共 同 主 持 人 ： 李威傑 計畫參與人員： 學士級-專任助理：陳瀅淑 共同主持人：李威傑 處 理 方 式 ： 本計畫可公開查詢 中 華 民 國 96 年 10 月 31 日

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行政院國家科學委員會專題研究計畫成果報告

幽門桿菌感染和血漿中ghrelin 與leptin 值對經腹腔鏡減肥手術的術後體 重結果影響

The Influence of Helicobacter pylori infection and plasma levels of ghrelin and leptin on the postoperative body weight outcomes of laparoscopic bariatric surgery

計畫類別：■個別型計畫 □整合型計畫 計畫編號： NSC 95-2314-B-002-093 執行期間： 95年 8月 1日至 96年 7月 31日 個別型計畫：計畫主持人：吳明賢醫師 處理方式： □可立即對外提供參考 ■一年後可對外提供參考 □兩年後可對外提供參考 (必要時，本會得展延發表時限) 執行單位：台大醫學院一般醫學科 中華民國 96 年 10 月 29 日

II 中 文 摘 要 背景：肥胖已成為全球重要的公衛和健康議題，隨著外科治療肥胖的使 用增加，臨床醫師必須對此類患者術前、術中和術後的相關問題有一定程度 的了解，以便提供適當的處理。雖然減肥手術的成功與發炎介質的滅少有關， 但是胃內最重要的發炎病因－幽門桿菌感染對於最終手術結果顯響的資料卻 極為有限。最近的研究已發現 ghrelin 和 leptin 濃度的改變可能與不同減肥 手術的預後有關，然而這些結果並不一致，而且並無同時針對幽門桿菌感染 和不同型式 ghrelin 的動態變化在此類病人影響的研究報告。 病人和方法：68 位接受腹腔鏡胃部繞道手術(LMGBP)的患者，測量手術 前(M0)、術後一個月(M1)、三個月(M3)、六個月(M6)、十二個月(M12)的系 列血中 leptin 和 ghrelin 濃度變化，並分析與體重減輕間的相關性。 結果：leptin 值在 M1, M3, M6 及 M12 明顯較 M0 為低(p<0.001)，但是 ghrelin 值則在術後與術前未見明顯改變。經多因子分析後發現術後 12 個月 的 excess BMI loss(%EBL) 與 術 前 高 ghrelin 濃 度 (p=0.004) 和 前 高 術 BMI(p=0.002)呈負相關。

結論：接受腹腔鏡胃繞道手術減重之患者，術前較高的 ghrelin 濃度和 較大的 BMI 值，可做為術後 12 個月%EBL 的預測參考。

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Abstract

Background: Obesity has become a major public health problem of global significance. With the increased use of surgical treatment for obesity, it is imperative for clinicians to familiarize relevant issues for providing optimal management of patients before, during and after these operations. The success of weight loss surgery is related to the reduction of inflammatory mediators but data regarding the influence of H. pylori, the most important etiologic factor of gastric inflammation, on eventual weight outcomes following bariatric surgery are scarce. Recent researches have documented that changes in ghrelin and leptin levels following bariatric surgery have offered an explanation for weight-reducing effects in different kinds of operation. However, the results are inconclusive and no studies have looked at the impact of H. pylori and dynamic alterations of various forms of ghrelin in this special subset of patients.

Patients Methods: Serial fasting serum leptin and ghrelin concentrations were measured in 68 morbidly obese patients before (M0) and 1(M1), 3(M3), 6(M6), and 12(M12) months after LMGBP surgery. The correlations between ghrelin, insulin and leptin concentrations and weight reduction were analyzed.

Results: The leptin levels wre significantly reduced at 1,3,6 and 12 months after surgery, respectively (vs. M0, p<0.001), whereas the ghrelin concentrations were not significantly changed after surgery. The percent of excess BMI lost (%EBL) 12 months after surgery was negatively correlated with higher preoperative ghrelin concentrations (p=0.004) and larger preoperative BMI (p=0.002)in the multivariate anlaysis.

Conculsion: Higher preoperative ghrelin concentrations and larger BMI are predictive of less %EBL at 12 months after LMGBP surgery.

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Table 1. Anthropometric, biochemical parameters, and hormonal levels before and after LMGBP

Before LMGBP

3 months 6 months 12 months

Age (yr) 31.68.9 - - -Body height (cm) 164.37.6 - - -Hip circumference (cm) 126.715.8 - - -Waist circumference (cm) 113.218.1 100.716.8a _96.314.3a _87.912.5a Body weight (kg) 108.0 22.8 89.320.3a 81.918.5a 74.415.5a BMI (kg/m2) 39.77.2 32.96.3a _30.25.7a _27.454.8a Systolic pressure (mm Hg) 131.318.2 133.622.6 126.424.1 121.115.5b Diastolic pressure (mm Hg) 83.311.4 77.913.9b _76.021.5c _70.711.9a Fasting glucose (mg/dL) 101.229.1 84.08. 6a _81.75.9a _81.26.2a Triglycerides (mg/dL) 143.394.1 110.142.5a _88.727.5a _71.621.1a HDL cholesterol (mg/dL) 46.711.8 39.29.8a _43.711.4b _52.110.4a Total cholesterol (mg/dL) 194.536.8 166.935.6a _154.027.2a _149.229.4a C-reactive protein 0.53 0.50 0.230.25 0.250.41 0.351.73 Ghrelin (pmol/liter) 18.7 7.9 17.24.9 18.15.9 17.25.5 Leptin (ng/ml) 25.6 10.4 11.27.7a 8.35.3a 6.44.2a Insulin (U/ml) 18.213.1 5.85.5a _4.72.6a _4.02.4a HOMA index 81.155.5 22.525.8a 17.110.0a 14.28.8a LMGBP: laparoscopic mini-gastric bypass; BMI: body mass index; HDL:

high-density lipoprotein; HOMA: homeostasis model of assessment. a p

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Table 2. Multivariate regression analysis of the correlations between change in fasting hormonal concentrations and changes in body weight after surgery

% body weight M0-M3 M0-M6 M0-M12 Ghrelin correlation coefficient -0.264 -0.222 -.0171 p-value 0.043 0.109 0.150 Leptin correlation coefficient 0.074 0.399 0.433 p-value 0.564 0.004 0.001 Insulin correlation coefficient 0.289 0.105 0.091 p-value 0.027 0.431 0.439

The data had been adjusted for age, gender, and preoperative body mass

index. : changes in body weight and hormonal levels; M0: before surgery; M3: 3 months after surgery; M6: 6 months after surgery; M12: 12 months

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Table 3. Multivariate regression analysis of correlations between preoperative characters and %EBL and %EWL 12 months after surgery

%EBL %EWL correlation coefficient p-value correlation coefficient p-value Age 0.030 0.783 -0.019 0.857 Gender 0.064 0.699 0.102 0.524 BMI -0.633 0.002 -0.703 <0.001 Waist-Hip Ratio -0.105 0.404 -0.083 0.495 Diabetes Mellitus -0.177 0.217 -0.078 0.570 Hypertension -0.124 0.290 -0.106 0.344 C-reactive protein 0.143 0.334 0.121 0.393 Ghrelin -0.364 0.004 -0.414 0.001 Leptin -0.035 0.813 0.049 0.734 Insulin -0.044 0.705 -0.013 0.910

%EBL: percent of excess body mass index lost; %EWL: percent of excess

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已發表或接受之論文

1. Liou JM, Lin JT, Lee WJ, Wang HP, Lee YC, Chiu HM, Wu MS (corresponding author). The serial change of ghrelin and leptin levels and their relations to weight loss after laparoscopic mini-gastric bypass surgery. Obes Surg (accepted)