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研究生：	孫子傑 Sun, Zih-Jie
論文名稱：	台灣中老年人糖尿病前期與高腎絲球過濾率之相關性研究 The Relationship between Prediabetes and Glomerular Hyperfiltration among Middle-Aged and Elderly Adults in Taiwan
指導教授：	盧豐華 Lu, Feng-Hwa
共同指導教授:	張智仁 Chang, Chih-Jen
學位類別：	碩士 Master
系所名稱：	醫學院 - 老年學研究所 Institute of Gerontology
論文出版年：	2014
畢業學年度：	102
語文別：	英文
論文頁數：	76
中文關鍵詞：	糖尿病前期、空腹血糖異常、葡萄糖耐受不良、高腎絲球過濾率、新診斷糖尿病
外文關鍵詞：	prediabetes, impaired fasting glucose, impaired glucose tolerance, glomerular hyperfiltration, newly diagnosed diabetes
相關次數：	點閱：111 下載：3
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研究背景：台灣慢性腎臟病的盛行率高達11.93%，尤其是在中老年族群。由於高腎絲球過濾率常見於糖尿病初期，且與後續發生的腎病變有關，然而在糖尿病前期，過去研究較少且結果並不一致，因此本研究目的在於釐清糖尿病前期與高腎絲球過濾率間的相關性。
研究方法：本研究利用2000年1月至2009年8月至成大醫院接受健康檢查的受檢者之去連結資料庫，選取年齡40歲以上且資料完整者，經再排除已知有腎臟疾病、癌症、高血壓、有糖尿病病史但無用藥及有糖尿病且有用藥者，結果有9616人為本研究之研究對象。腎絲球過濾率是採估計腎絲球過濾率，計算法採慢性腎臟疾病流行病學共同研究公式(Chronic Kidney Disease Epidemiology Collaboration equation)。高腎絲球過濾率定義為大於健康族群特定年齡和性別之腎絲球過濾率的第95百分位。而糖尿病前期的判定，則採用美國糖尿病學會2010年的診斷標準，包括空腹血糖值介於100至125 mg/dL(空腹血糖異常)、75公克口服葡萄糖耐受性試驗兩小時後血糖值介於140至199 mg/dL(葡萄糖耐受不良)、或糖化血色素介於5.7至6.4%等三種。另收集人口學、生理、心理及社會等變項，最後採複線性及多元邏輯式迴歸分析向後選取法進行統計分析。
研究結果：高腎絲球過濾率的比例隨著升高的血糖狀況而增加。複迴歸分析的結果顯示空腹血糖與估計腎絲球過濾率有顯著正相關((β =0.027, p =0.002)，其他有顯著正相關的變項包括教育程度(1-6年)和喝酒。至於年齡、男性、總膽固醇、高密度脂蛋白膽固醇、尿酸、規律運動和憂鬱則有顯著負相關。多元邏輯迴歸分析結果顯示糖尿病前期(除葡萄糖耐受不良外)與新診斷糖尿病兩者在控制其他變項後仍與高腎絲球過濾率的風險有關，其中合併有空腹血糖異常和葡萄糖耐受不良者的高腎絲球過濾率風險最高(調整勝算比=1.74, 95%信賴區間：1.17-2.58)且與新診斷糖尿病者相當。
結論：空腹血糖值與估計腎絲球過濾率呈正相關，而糖尿病前期與高腎絲球過濾率的風險有關，尤其是合併有空腹血糖異常和葡萄糖耐受不良者，與新診斷糖尿病者的風險相當。因此，對具有糖尿病前期者，尤其合併有空腹血糖異常和葡萄糖耐受不良時，需積極追蹤腎功能，並在有產生高腎絲球過濾率時及早治療高血糖狀況，以避免後續腎病變的發生。

Background: The prevalence of chronic kidney disease (CKD) in Taiwan is up to 11.93%, especially among middle-aged and elderly adults. Glomerular hyperfiltration (GHF) often appears in early diabetes, and is associated with the occurrence of subsequent nephropathy. However, only a few studies reported inconsistent results regarding the relationship between prediabetes and GHF. Therefore, the aim of this study is to clarify the relationship between prediabetes and GHF.
Methods: This study used a secondary data without personal ID, including the examinees who undertook health examinations in National Cheng Kung University Hospital between January 2000 and August 2009. We included those aged 40 or over with complete data, and excluded those with renal diseases, cancer, anti-hypertensive medications, cardiovascular medications, anti-diabetic medications, and diabetic history. Finally, 9616 subjects entered into the analyses. The estimated glomerular filtration rate (eGFR) was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Hyperfiltration was defined as eGFR above the age- and sex-specific 95th percentile for healthy subjects. According to the 2010 criteria of American Diabetes Association, prediabetes was diagnosed when fasting plasma glucose was 100 mg/dL to 125 mg/dL (impaired fasting glucose, IFG), two-hour plasma glucose in the 75-g oral glucose tolerance test was 140 mg/dL to 199 mg/dL (impaired glucose tolerance, IGT), or Hemoglobin A1c (HbA1c) was between 5.7 and 6.4%. Multiple linear and multinomial logistic regression analyses with backward selection were performed with considering demographic, biological, psychological and behavior variables.
Results: The proportions of hyperfiltration increased with increased glycemic status. Multiple linear regression analyses showed that there was a positive and significant association between fasting glucose and eGFR (β =0.027, p =0.002). Other positively associated variables included education (1-6 years) and current alcohol drinking. Age, male gender, total cholesterol, HDL cholesterol, uric acid, regular exercise, and depression were inversely associated with eGFR. Multiple logistic regressions showed that prediabetes, except IGT, and newly diagnosed diabetes were both associated with the risk of hyperfiltration after adjustment for other variables. Combined IFG&IGT had the similar risk of hyperfiltration (adjusted OR: 1.74, 95%CI: 1.17–2.58) with newly diagnosed diabetes.
Conclusions: Fasting glucose was positively associated with eGFR, and prediabetes was associated with the risk of hyperfiltation. In particular, combined IFG&IGT had the similar risk of hyperfiltration with newly diagnosed diabetes. Therefore, renal function may need to be monitored actively in subjects with prediabetes, especially with combined IGT&IFG, and earlier treatment of hyperglycemia is necessary to prevent the development of nephropathy once hyperfiltration appears.

中文摘要	I
Abstract	III
誌謝	V
Table of Contents	VI
List of Tables	VIII
List of Figures	X
Chapter 1 Introduction	1
1.1 Background	1
1.2 Objective	2
Chapter 2 Literature Review	3
2.1 Glomerular filtration rate (GFR)	3
2.2 Glomerular hyperfiltration (GHF)	5
2.3 Diabetes mellitus and glomerular hyperfiltration	10
2.3.1 Tubular hypothesis	10
2.3.2 Hemodynamic hypothesis	10
2.3.2.1 Renin angiotensin system (RAS)	11
2.3.2.2 Nitric oxide (NO) system	11
2.3.2.3 Cyclooxygenase 2 (COX2)-derived prostanoids	12
2.3.2.4 Protein kinase C (PKC)	12
2.3.2.5 Endothelin (ET)	13
2.3.3 Other possible mechanisms	13
2.4 Prediabetes	14
2.5 Prediabetes and glomerular hyperfiltration	16
2.6 Other associated factors	19
2.6.1 Biological factors	19
2.6.2 Psychological and demographic factors	19
2.6.3 Behavior factors	21
Chapter 3 Methods and Materials	23
3.1 Research framework	23
3.2 Study subjects	23
3.3 Data collection	24
3.4 Definition of prediabetes	25
3.5 Estimation of glomerular filtration rate (GFR)	25
3.6 Definition of hyprefiltration and hypofiltration	26
3.7 Statistical analysis	26
Chapter 4 Results	28
4.1 The reference values for hyperfiltration and hypofiltration	28
4.2 Comparisons of baseline characteristics between subjects with hyperfiltration and               normal filtration	28
4.3 eGFR and hyperfiltration status of different glycemic status	32
4.4 Simple and multiple regression analyses	32
Chapter 5 Discussion	45
5.1 Summary of the results	45
5.2 Prevalence of hyperfiltration	45
5.3 Factors associated with eGFR	46
5.4 Factors associated with GHF	49
5.5 Strengths	52
5.6 Limitations	52
Chapter 6 Conclusions	53
Chapter 7 References	54
Appendix	76
Human study approval	76

List of Tables
Table 1. Formulae for calculating GFR	4
Table 2. Stages of chronic kidney disease	5
Table 3. Various definitions of GHF in human studies over the last five years	9
Table 4. Diagnostic criteria for diabetes and hyperglycemia at a lower level than diabetes	16
Table 5. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation	26
Table 6. Comparisons of clinical characteristics between subjects with hyperfiltration and normal filtration (n=8994)	31
Table 7. Results of simple and multiple linear regression with backward selection estimating eGFR	39
Table 8. Simple and multiple logistic regression analyses of the effect of prediabetes-full criteria, newly diagnosed diabetes, and other variables on hyperfiltration in a population sample of 8994 subjects	40
Table 9. Simple and multiple logistic regression analyses of the effect of IGT, newly diagnosed diabetes, and other variables on hyperfiltration in a population sample of 8994 subjects	41
Table 10. Simple and multiple logistic regression analyses of the effect of IFG, newly diagnosed diabetes, and other variables on hyperfiltration in a population sample of 8994 subjects	42
Table 11. Simple and multiple logistic regression analyses of the effect of prediabetes-HbA1c, newly diagnosed diabetes, and other variables on hyperfiltration in a population sample of 8994 subjects	43
Table 12. Simple and multiple logistic regression analyses of the effect of isolated IGT, isolated IFG, combined IGT&IFG, newly diagnosed diabetes, and other variables on hyperfiltration in a population sample of 8994 subjects	44

List of Figures 
Figure 1. Clinical conditions associated with glomerular hyperfiltration.	6
Figure 2. Time course of GFR and albumin excretion rate(AER, mg/24h) according to the hyperfiltration theory proposed by Brenner and Coll.	7
Figure 3. Distribution of eGFR in subjects without prediabetes, prehypertension or proteinuria by age and gender. The 95th and 5th percentiles are shown in 10-year age groups.	29
Figure 4. The prevalence of hyperfiltration (n=497) and hypofiltration (n=622) in overall study subjects. (n=9616)	30
Figure 5. eGFR and hyperfiltration status of different glycemic status: Normoglycemia, Prediabetes-full criteria, and Newly diagnosed diabetes. *p for trend	34
Figure 6. eGFR and hyperfiltration status of different glycemic status: Normoglycemia, IGT, and Newly diagnosed diabetes. *p for trend	35
Figure 7. eGFR and hyperfiltration status of different glycemic status: Normoglycemia, IFG, and Newly diagnosed diabetes. *p for trend	36
Figure 8. eGFR and hyperfiltration status of different glycemic status: Normoglycemia, Prediabetes-HbA1c, and Newly diagnosed diabetes. *p for trend	37
Figure 9. eGFR and hyperfiltration status of different glycemic status: Normoglycemia, Isolated IFG, Isolated IGT, Combined IGT&IFG, and Newly diagnosed diabetes. *p for trend	38
                                    

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