UVA研究表明NRTIs可以降低2型糖尿病患病風險

StephenW

UVA Study Suggests NRTIs Could Reduce Risk of Developing Type 2 Diabetes
September 29, 2020
Patrick Campbell

An analysis of data from 5 major databases suggests NRTIs could reduce incidence of type 2 diabetes.

Jayakrishna Ambati, MD
Jayakrishna Ambati, MD

A new study suggests use of therapies in a class known for treating hepatitis B and human immunodeficiency virus (HIV) could be useful in the management of a different disease.

Results of the study, which pooled data from 5 major databases, suggest use of nucleoside reverse-transcriptase inhibitors (NRTIs) was associated with a 33% decrease in risk of developing type 2 diabetes.

“The large scale of these clinical data and the size of the protective effect provide evidence that inflammasome inhibition in humans is beneficial,” said study investigator Jayakrishna Ambati, MD, professor at the University of Virginia School of Medicine, in a statement. “We are hopeful that prospective clinical trials will establish that inflammasome inhibitors known as Kamuvudines, which are less-toxic derivatives of NRTIs, will be effective not only in diabetes but also in macular degeneration and Alzheimer’s disease.”

While previously published data have suggested potential mechanistic benefits of NRTIs on the development of type 2 diabetes, Ambati and a team of UVA clinicians sought to determine whether this would translate into a clinical benefit in a real-world setting. With this in mind, they designed the current study as an analysis of real-world data related to use of NRTIs from multiple databases.

Specific databases included in the investigators’ analyses included Veterans Health Administration database, the Truven database, the PearlDiver database, the Medicare database, and the Clinformatics database. Of note, the study was originally designed to examine associations between exposure to NRTIs and development of type 2 diabetes in the Veterans Health Administration database and then assess the validity of these findings through analysis of the other 4 databases. In total, a cohort of 128,861 patients was obtained from the 5 databases.

In the main analysis, investigators identified a total of 79,744 patients with confirmed diagnoses of HIV or hepatitis B without a prior diagnosis of type 2 diabetes. During the follow-up period, 12,311 patients developed type 2 diabetes and results of the analysis suggested users of NRTIs were at a 34% lower risk of developing type 2 diabetes than their counterparts not receiving NRTIs (HR, 0.665; 95% CI, 0.625-0.708; P <.0001).

From the Truven database, investigators identified a cohort of 23,634 patients. Of these, 1630 went on to develop type 2 diabetes. In adjusted models, users of NRTIs were at a 39% lower risk of developing type 2 diabetes (HR, 0.614; 95% CI, 0.524-0.718; P <.0001). From the PearlDiver database, investigators identified a cohort of 16,045 patients. Of these, 1068 went to on to develop type 2 diabetes during the follow-up period. In adjusted models, users of NRTIs were at a 26% lower risk of developing type 2 diabetes.

In the Medicare database, investigators identified a cohort of 3097 patients. Of these, 707 went on to develop type 2 diabetes during the follow-up period. In adjusted models, users of NRTIs were at a 17% lower risk of develop type 2 diabetes (HR, 0.828; 95% CI, 0.646-1.062; P=.137). In the Clinformatics datable, investigators identified a cohort of 6341 patients. Of these, 1067 went on to develop type 2 diabetes during the follow-up period. In adjusted models, users of NRTIs were at a 27% lower risk of developing type 2 diabetes (HR, 0.727; 95% CI, 0.572-0.924; P=.009).

In a pooled analysis including all 128,861 patients from the 5 databases, investigators found the adjusted risk of diabetes was 33% lower among patients with NRTI exposure (HR, 0.673; 95% CI, 0.638-0.710; P <.0001; 95% Prediction Interval, 0.618-0.734).

This study, “Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development,” was published in Nature Communications.

StephenW

UVA研究表明NRTIs可以降低2型糖尿病患病風險
2020年9月29日
帕特里克·坎貝爾

對來自5個主要數據庫的數據進行的分析表明，NRTIs可以降低2型糖尿病的發病率。

Jayakrishna Ambati，醫學博士
Jayakrishna Ambati，醫學博士

一項新研究表明，在治療乙型肝炎和人類免疫缺陷病毒（HIV）的一類已知療法中，可用於治療其他疾病。

研究結果匯總了來自5個主要數據庫的數據，表明使用核苷逆轉錄酶抑製劑（NRTIs）與2型糖尿病風險降低33％有關。

弗吉尼亞大學醫學院教授Jayakrishna Ambati醫學博士在一份聲明中說：“大量的臨床數據和保護作用的大小提供了證據，證明抑制人體中的炎症小體是有益的。” “我們希望，前瞻性的臨床試驗能夠確定被稱為Kamuvudines的炎性體抑製劑，它們是NRTI的低毒衍生物，不僅對糖尿病有效，而且對黃斑變性和阿爾茨海默氏病也有效。”

儘管先前發表的數據表明NRTIs在2型糖尿病發展中具有潛在的機械益處，但Ambati和一組UVA臨床醫生試圖確定這是否將轉化為現實環境中的臨床益處。考慮到這一點，他們將當前研究設計為與來自多個數據庫的NRTI使用相關的真實數據分析。

研究者分析中包括的特定數據庫包括退伍軍人健康管理局數據庫，Truven數據庫，PearlDiver數據庫，Medicare數據庫和Clinformatics數據庫。值得注意的是，該研究最初旨在檢查退伍軍人健康管理局數據庫中NRTIs暴露與2型糖尿病發展之間的關聯，然後通過分析其他4個數據庫來評估這些發現的有效性。從這5個數據庫中總共獲得128861名患者。

在主要分析中，研究人員鑑定了總共79,744例確診為HIV或乙型肝炎但未事先診斷為2型糖尿病的患者。在隨訪期間，有12,311名患者患上2型糖尿病，分析結果表明，與未接受NRTIs的患者相比，使用NRTIs的患者患2型糖尿病的風險低34％（HR，0.665； 95％CI，0.625） -0.708； P <.0001）。

研究人員從Truven數據庫中識別出23634名患者。其中，1630年繼續發展為2型糖尿病。在調整後的模型中，使用NRTI的用戶患2型糖尿病的風險降低39％（HR，0.614； 95％CI，0.524-0.718； P <.0001）。從PearlDiver數據庫中，研究人員確定了16045名患者。在隨訪期間，其中1068人繼續發展為2型糖尿病。在調整後的模型中，使用NRTI的用戶患2型糖尿病的風險降低了26％。

在Medicare數據庫中，研究人員確定了3097名患者。其中有707位在隨訪期間繼續發展為2型糖尿病。在調整後的模型中，使用NRTI的用戶患2型糖尿病的風險降低了17％（HR，0.828； 95％CI，0.646-1.062； P = .137）。在Clinformatics數據庫中，研究人員確定了6341名患者。在隨訪期間，其中1067人繼續發展為2型糖尿病。在調整後的模型中，使用NRTI的用戶患2型糖尿病的風險降低了27％（HR，0.727； 95％CI，0.572-0.924； P = .009）。

在包括來自5個數據庫的所有128,861位患者的匯總分析中，研究人員發現，在接受NRTI暴露的患者中，調整後的糖尿病風險降低了33％（HR，0.673； 95％CI，0.638-0.710； P <.0001； 95％預測時間間隔，0.618-0.734）。

這項研究，“重新利用抗炎性NRTIs來改善胰島素敏感性和減少2型糖尿病的發生”，發表在《自然通訊》上。