探討血清膽固醇與第二型糖尿病周邊神經病變的相關性

因社會變遷使飲食及生活模式改變，第二型糖尿病在全球皆有年輕化趨勢，18歲以上國人糖尿病盛行率為11.1%，且在台灣目前糖尿病高居十大死因第六名。糖尿病是一個全身性的慢性疾病，必須長期控制以維持生活品質，常見併發症如：神經病變、腎臟病變、視網膜病變及大血管併發症等，而隨著發病年齡越年輕將來面臨併發症的機率也越高。 近期研究發現脂質像(lipid profile)失調是誘發糖尿病神經病變的病理因素之一，其中過多的膽固醇被認為是神經病變的重要誘發因素，但是過低的膽固醇同樣也在疾病進展中發揮影響力，其中近年國外一項研究發現在100名患第二型糖尿病成人的橫斷面隊列研究中，神經病變的數量與血清總膽固醇水平呈現負相關，潛在解釋可能是過低的血清膽固醇水平會對周邊神經有不良的影響，特別是神經元結構中負責傳遞神經訊號的軸突外圍是由髓鞘包覆，而髓鞘由許旺氏細胞(Schwann cell)構成，其主要成分包括神經鞘磷脂和膽固醇，因此過低的膽固醇可能會影響周邊神經的結構，但其中的關聯性目前仍不十分清楚。 本研究為一項橫斷面研究，研究對象為糖尿病共同照護網收案的第二型糖尿病成人，由醫療電子系統蒐集研究對象的基本資料、自主神經檢查報告(Sudomotor testing)、血液生化值、飲食紀錄及身體檢查值等，排除對象為慢性神經系統疾病、化學治療及懷孕個案，使用SPSS軟體進行統計分析，進一步確認糖尿病神經病變與膽固醇水平是否存在關聯性。 主要研究目的為探討總膽固醇、低密度脂蛋白膽固醇及高密度脂蛋白膽固醇與第二型糖尿病神經病變關係；次要目的為分析飲食攝取三大營養素比例與血清膽固醇關係，預期由我們的研究結果釐清血清膽固醇與第二型糖尿病神經病變的相關性，並藉此建立新的治療論點。 本研究最終納入1085位個案，依據Sudomotor testing神經病變嚴重程度分數將個案分為兩組，分別為自主神經功能重度降低組及自主神經功能中度降低組再進行統計分析，在cholesterol (CHO)、High Density Lipoprotein-Cholesterol (HDL-C) 、Low Density LipoproteinCholesterol (LDL-C)與自主神經病變的相關性分析結果發現皆與神經病變嚴重程度呈現顯著相關(P<0.05)，病齡與自主神經病變的相關性分析結果發現與神經病變嚴重程度呈現顯著正相關(P<0.05)，同時發現糖化血色素值(Glycated Hemoglobin, HbA1c)與自主神經病變嚴重程度相關性不顯著；次要結果分析飲食攝取三大營養素比例發現高脂肪攝取與血清膽固醇呈現顯著正相關(P<0.05)。 我們的研究結果也與先前發現類似，過低的膽固醇可能在糖尿病神經病變疾病進展中發揮影響力，然而本研究僅蒐集了橫斷面數據，未來若採前瞻性世代研究及使用神經傳導檢查(Nerve Conduction Velocity,NCV)進行分析，亦或是申請健保資料庫運用大數據分析，將能提供更有力的證據，可望有助於糖尿病患者併發症的臨床照護。 我們使用SUDOSCAN測試提高研究結果準確性，其次操作簡易和時間短。過去研究大多是驗證SUDOSCAN之臨床診斷準確性，未將其報告結果與血脂或其他因子進行相關性風險分析，未來研究若使用SUDOSCAN結果作為DPN風險因子評估分析可能極具淺力及臨床意義。

There is a global trend toward younger populations developing type 2 diabetes as a result of social changes that lead to altered dietary and lifestyle patterns. In Taiwan, 11.1% of people over the age of 18 have diabetes, making it the sixth most common cause of death in the country at this time. Diabetes is a systemic chronic illness that needs to be managed over time in order to preserve quality of life. Nephropathy, neuropathy, retinopathy, and macrovascular complications are frequent side effects. The future risk of complications increases with a younger onset age. Excess cholesterol is thought to be a major trigger for dyslipidemia, one of the pathological factors causing diabetic neuropathy, according to recent research. Nonetheless, the advancement of the disease is also influenced by low cholesterol levels. The number of cases of neuropathy and serum total cholesterol levels were found to be inversely correlated in a recent international cross-sectional cohort study involving 100 adults with type 2 diabetes. One possible explanation is that peripheral nerves may be negatively impacted by abnormally low serum cholesterol levels. This is because the myelin sheath, which surrounds axons and is essential for nerve signal transmission, is made up of Schwann cells, which are primarily made of cholesterol and sphingomyelin. Therefore, peripheral nerve structure may be affected by low cholesterol levels, though this relationship is still unknown. A cross-sectional analysis of adult patients with type 2 diabetes from the Diabetes Shared Care Network was conducted for this study. Medical electronic systems were used to gather data, which included nutritional records, blood biochemistry, physical examination values, reports on Sudomotor testing, and basic patient information. Pregnancy, chemotherapy, and long-term neurological conditions were among the exclusion criteria. Using SPSS software, statistical analysis was carried out to look into any possible connections between cholesterol levels and diabetic neuropathy. This study aims to investigate the correlation between type 2 diabetic neuropathy and total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). A secondary goal is to examine the connection between serum cholesterol and the percentage of the three main nutrients that are consumed through diet. We anticipate that our findings will clarify the correlation between serum cholesterol and type 2 diabetic neuropathy, thus establishing new therapeutic perspectives. The study comprised 1,085 patients in total. Patients were classified into two groups: those with severely reduced autonomic function and those with moderately reduced autonomic function, based on the results of the Sudomotor testing for neuropathy severity. Significant relationships (P<0.05) were found by statistical analysis between the severity of autonomic neuropathy and cholesterol (CHO), HDL-C, LDL-C, and LDLC. Additionally, a significant positive correlation (P<0.05) was found in the analysis between the length of the disease and the severity of autonomic neuropathy; however, there was no significant correlation found between the severity of autonomic neuropathy and glycated hemoglobin (HbA1c). A substantial positive correlation (P<0.05) was found in secondary results between high fat intake and serum cholesterol levels. Our results are consistent with earlier studies that hypothesize a possible relationship between low cholesterol and the development of diabetic neuropathy. This investigation, however, was restricted to crosssectional data. Prospective cohort studies in the future that make use of nerve conduction velocity (NCV) tests or analyze sizable datasets from health insurance databases may yield stronger findings and improve the clinical management of diabetes complications. We used the SUDOSCAN test, which has a short testing duration and is user-friendly, to improve the accuracy of our results. Previous research did not examine the relationship between SUDOSCAN's findings and lipid profiles or other variables, instead focusing on validating the technology's clinical diagnostic accuracy. Prospective and clinically significant research utilizing SUDOSCAN results for risk factor analysis of diabetic peripheral neuropathy (DPN) may be conducted in the future.