糖尿病是代謝性症候群之主要角色，在現代國家佔高盛行率。而糖尿病高血糖狀態下之癲癇發作，臨床上並不少見。此項併發症，常有癲癇重積狀態，若無適當處理，會造成神經學上重要的障礙。
大部份關於糖尿病高血糖狀態下之癲癇發作的了解來自於病例描述報告，並無完整追蹤期，且糖尿病高血糖與癲癇發作之復發率與嚴重度、血糖值及醣化血色素之間的關連，尚未完全清楚。我們針對糖尿病高血糖狀態相關之癲癇發作，作了完整的臨床對照分析，發現高血糖會惡化癲癇發作嚴重度，且此類型之癲癇發作與控制不良之糖尿病狀態有關，較高的醣化血色素值與癲癇之復發有相關。
動物研究指出，癲癇發作可能惡化腦損傷，造成認知功能缺損。而糖尿病高血糖本身亦可能造成認知功能缺損。我們的動物實驗，了解到糖尿病高血糖狀態下所誘發之癲癇發作比在非糖尿病狀態下所誘發者較嚴重及有較高之癲癇發作易感性。同時，糖尿病高血糖狀態下所誘發之癲癇發作會對腦部造成更大損傷，造成更大認知功能缺損。
至今糖尿病高血糖相關之癲癇發作其致病機轉未完全明瞭。我們希望能藉由探測糖尿病高血糖狀態下相關之癲癇發作之機轉，使用有效的藥物來預防，或是進行及早之治療。ATP敏感性鉀離子通道 (KATP)，扮演著調節神經細胞代謝與電氣活性之重要角色，是我們的研究標的。我們的 in vitro神經元及腦海馬迴切片之研究，藉由電生理之方法，發現在正常細胞外之葡萄糖之濃度上升時，會透過KATP之關閉來使神經細胞興奮，增高興奮傳遞現象；且此興奮會為KATP之打開劑diazoxide所抑制。
我們進一步探討與證實，使用diazoxide，能對in vivo糖尿病高血糖相關之癲癇發作，有抑制之作用，且對癲癇發作之後的學習記憶的行為表現及腦損傷有保護之作用。此機轉也進一步為in vitro電生理研究與神經元模擬研究證實。
因此，對於成年之癲癇病患，應該仔細檢查是否有糖尿病。積極的血糖控制，可能會對糖尿病癲癇病患之癲癇發作之治療，有所助益。我們的實驗也再次顯現，積極的血糖控制對癲癇發作下，防治腦部損傷之重要性。而KATP之減弱可能是糖尿病高血糖相關之癲癇發作之致病機轉。因此，我們了解臨床上之高血糖相關之癲癇發作及其影響，包括其機轉，將能對糖尿病高血糖相關之癲癇發作之防治有重要貢獻。

As a major role in metabolic syndrome, diabetes is an important disease in modern society. Epileptic seizure, including status epilepticus, related to diabetic hyperglycemia (DH) is not uncommon in clinical practice. This seizure disorder deserves attention as it significantly affects neurological outcome if untreated.
Most of the clinical knowledge in the seizures in DH derived from limited case studies. The role of DH in the severity and recurrence of epileptic seizures remains unclear. In our clinical comparative study of newly diagnosed unprovoked seizures in adult patients with or without DH, we have found that DH would potentiate seizure severity and seizures in hyperglycemia tend to develop in poorly controlled diabetes. Severe seizures might be associated with recurrent seizures in patients with DH. The glycated hemoglobin might be an important factor in this setting.
Seizures might lead to cognitive impairment and DH itself is associated with cognitive deficits. It is still not known whether seizures, including status epilepticus, in state of DH would cause more extensive damage than seizures without DH. In our experimental study, we found that DH would increase seizure susceptibility, and worsen seizure severity. The brain damage in DH group was more severe than that in non-DH group, in terms of behavioral, pathological and electrophysiological aspects.
The direct mechanisms in DH-related seizures are not completely understood. ATP-sensitive potassium channels (KATP), important metabolic couplers to electrical activity, are potential mechanistic candidates. We found that increment of extracellular glucose would directly attenuate KATP in single neurons and neural network, leading to increased neuron excitability and propagation.
For the therapeutic point-of-view, we further studied if KATP opener-diazoxide could have a protective role in DH-related seizures. We found diazoxide could reduce the seizure-related damage both behaviorally and pathologically, verified by electrophysiological and simulation studies.
In conclusion, DH should be investigated in adult patients with newly diagnosed epileptic seizures and aggressive blood sugar control might benefit seizure management in patients with DH. This finding that rats with DH had more brain damage after status epilepticus than rats without DH emphasizes the importance of intensively treating DH and seizures in diabetic patients with epilepsy. This phenomenon of KATP-attenuation could be one of the underlying mechanisms of glucose-related neuron hyper-excitability and propagation. Our study identified the clinical risk factors, delineated the potential mechanism and provided a potential therapeutic gateway in treating this diabetic hyperglycemia-related seizure disorder.

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