Diabetic Kidney Damage
Diabetic nephropathy is one of the most serious long-term complications of type 2 diabetes mellitus (TTDM). It is characterized by persistent albumin in the urine, a declining filtration capacity of the kidneys, and an increased risk of end-stage kidney disease that may require dialysis.
Globally, diabetic nephropathy is among the leading causes of chronic kidney disease and accounts for nearly half of all new end-stage kidney disease cases. Up to 40% of people with T2DM are projected to develop some form of kidney involvement during their illness. This complication lowers quality of life, raises healthcare costs, and substantially increases both cardiovascular events and overall mortality.
Despite advances in blood sugar and blood pressure control, preventing the onset and progression of diabetic nephropathy remains difficult. This has intensified the search for early, reliable, and easy-to-measure risk markers that can support timely intervention and better risk stratification.
Atherogenic Index of Plasma: A Simple Lipid Marker With Renal Signals
The atherogenic index of plasma (AIP) is calculated as the base-10 logarithm of the ratio of triglycerides to high-density lipoprotein cholesterol. It reflects the balance between “harmful” and “protective” lipid fractions.
Higher AIP values are considered a surrogate for small dense LDL particles and have been linked to endothelial dysfunction, oxidative stress, and insulin resistance—all mechanisms that may contribute to kidney damage in diabetes. Clinically, AIP is already used as a simple, low-cost biomarker to estimate cardiovascular and metabolic risk in people with type 2 diabetes.
Several recent studies have suggested that AIP might also be connected to diabetic nephropathy, but findings across individual studies have been inconsistent. Some showed a strong association, while others reported no clear link.
What This Meta-analysis Set Out to Clarify
Min and colleagues conducted a systematic review and meta-analysis to answer a focused question:
Is a higher AIP associated with a higher risk of diabetic nephropathy in people with type 2 diabetes?
They searched major medical databases for observational studies in adults with T2DM that compared the incidence or prevalence of diabetic nephropathy between higher and lower AIP categories. Only full-length, peer-reviewed English articles were included, and study quality was evaluated using standardized criteria.
Diabetic nephropathy was defined according to each original study, usually by albuminuria, reduced kidney filtration rate, or both, in the absence of other primary kidney diseases.
Who Was Studied?
The analysis included 10 studies (11 datasets) from several countries, published between 2022 and 2025. Together, they enrolled 25,773 patients with type 2 diabetes, of whom about 27% had diabetic nephropathy.
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Study designs: 7 cross-sectional studies and 3 prospective cohort studies
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Mean age: 53.8–63.4 years
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Male proportion: 43.7–67.7%
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AIP categorization: based on previous thresholds, medians, tertiles, or quartiles, with high AIP defined between 0.15–0.51
All studies adjusted for important clinical factors, typically including age, sex, body mass index, blood pressure, glycemic markers, lipids, and comorbidities. Most studies were assessed as high quality.
Key Finding: High AIP Is Linked to More Diabetic Nephropathy
Across all 11 datasets, individuals with higher AIP had a 51% higher risk of diabetic nephropathy compared with those with lower AIP. Sensitivity analyses—removing one study at a time—did not materially change the result.
When the analysis was limited to the three cohort studies, the association remained similar, supporting the robustness of the finding.
Publication bias appeared minimal: the funnel plot was symmetric, statistical testing did not show bias, and no missing studies were suggested through additional analyses.
The certainty of the evidence was rated as moderate, primarily because all studies were observational.
Older Adults Show a Stronger Association
Age emerged as an influential factor:
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In studies with an average age below 58 years, high AIP was associated with a moderately increased risk.
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In those with an average age 58 years or older, the association was stronger.
Further analysis showed that increasing age strengthened the AIP–nephropathy link and explained a meaningful portion of the variability between studies.
Subgroup analyses found similar associations regardless of study design, sex distribution, AIP cutoff values, nephropathy definitions, or study quality.
How Might AIP Be Involved in Kidney Injury?
High AIP reflects an imbalance between triglycerides and HDL cholesterol and signals the presence of small dense LDL particles. Triglyceride-rich lipoproteins may promote kidney injury through lipotoxicity, inflammation, and oxidative stress. Low HDL cholesterol may reduce antioxidant and anti-inflammatory functions, further affecting vascular and kidney health.
These pathways are consistent with the established role of dyslipidemia in diabetic microvascular complications.
Practical Takeaways for the Field
For researchers and clinicians, this work suggests that:
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AIP is an inexpensive, readily available biomarker that could help identify people with type 2 diabetes at higher risk of kidney complications, particularly older adults.
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In resource-limited settings, AIP may serve as a practical complement to traditional kidney markers, supporting earlier intervention through glycemic control, lipid management, and kidney-protective therapies.
However, because the current evidence is observational, AIP cannot yet be considered a causal factor or a stand-alone predictor. Additional research with prospective designs, standardized AIP thresholds, consistent definitions of diabetic nephropathy, and better adjustment for factors such as diabetes duration and statin use is needed. Interventional studies examining whether lowering AIP improves kidney outcomes would be especially valuable.
Conclusion
This meta-analysis supports elevated atherogenic index of plasma as a meaningful marker associated with diabetic nephropathy in type 2 diabetes, with a stronger link observed in older individuals. The findings highlight the potential of lipid-based indices in refining kidney risk assessment, while underscoring the need for further longitudinal and interventional studies before AIP can be fully incorporated into routine prediction tools.
The translation of the preceding English text in Chinese:
糖尿病肾损伤
糖尿病肾病是 2 型糖尿病最严重的长期并发症之一，其特征包括尿液中持续出现白蛋白、肾脏过滤能力下降，以及可能需要透析的终末期肾病风险增加。
在全球范围内，糖尿病肾病是慢性肾病的主要原因之一，占所有新发终末期肾病病例的近一半。预计多达 40% 的 2 型糖尿病患者在疾病过程中会出现某种程度的肾脏受累。这种并发症会降低生活质量、增加医疗负担，并显著提高心血管事件和总体死亡率。
尽管血糖和血压管理取得进展，但预防糖尿病肾病的发生和进展依然具有挑战性。这促使研究者积极寻找早期、可靠且易于测量的风险标志物，以支持及时干预和更有效的风险分层。
血浆动脉粥样硬化指数：一种与肾脏相关的简单脂质标志物
血浆动脉粥样硬化指数（AIP）通过甘油三酯与高密度脂蛋白胆固醇比值的对数计算，可反映“有害”与“保护性”脂质成分之间的平衡。
AIP 升高被视为小而密 LDL 粒子的替代指标，并与内皮功能障碍、氧化应激和胰岛素抵抗相关，这些机制均可能促进糖尿病相关的肾损害。在临床上，AIP 已作为一种简单、低成本的指标，用于评估 2 型糖尿病患者的心血管和代谢风险。
多项研究提示 AIP 可能与糖尿病肾病相关，但不同研究的结果并不一致。有些研究显示关联明显，而有些则未观察到明确联系。
本次荟萃分析的目的
Min 及其团队开展系统综述和荟萃分析，以回答一个核心问题：AIP 升高是否与 2 型糖尿病患者的糖尿病肾病风险升高相关？
研究团队检索了主要医学数据库中有关成年 2 型糖尿病患者的观察性研究，这些研究比较了高 AIP 与低 AIP 人群糖尿病肾病的发生率或患病率。纳入研究均为全文、经同行评议的英文文献，且研究质量采用标准化方法评估。
糖尿病肾病的定义遵循原始研究，包括白蛋白尿、肾小球滤过率下降或两者兼有，并排除其他原发性肾病。
研究对象
分析共纳入 10 项研究（11 个数据集），来自多个国家，发表时间为 2022–2025 年，共计 25,773 名 2 型糖尿病患者，其中约 27% 为糖尿病肾病患者。
- 研究设计：7 项横断面研究，3 项前瞻性队列研究
- 平均年龄：53.8–63.4 岁
- 男性比例：43.7–67.7%
- AIP 分类：基于既往阈值、中位数、三分位或四分位数，高 AIP 阈值范围 0.15–0.51
所有研究均对重要临床因素进行了调整，包括年龄、性别、体质指数、血压、血糖指标、血脂和合并症等。大多数研究质量较高。
主要发现：AIP 升高与糖尿病肾病风险增加相关
在全部 11 个数据集中，高 AIP 人群发生糖尿病肾病的风险比低 AIP 人群高 51%。敏感性分析（逐一剔除每项研究）显示结果稳定。
在仅限三项队列研究的分析中，关联仍然一致，进一步支持结果的可靠性。
发表偏倚的迹象很小：漏斗图对称，统计检验未显示偏倚，补充分析也未提示缺失研究。
证据质量总体被评定为中等，主要原因在于所有纳入研究均为观察性设计。
老年患者的关联更明显
年龄是一个重要影响因素：
- 平均年龄低于 58 岁的研究中，高 AIP 的风险升高幅度较为温和。
- 平均年龄 58 岁及以上的研究中，高 AIP 与糖尿病肾病的关联更强。
进一步分析显示，随着年龄增加，AIP 与糖尿病肾病之间的关联增强，并解释了研究间差异的相当一部分。
分组分析还发现，无论研究设计、性别比例、AIP 阈值、肾病定义或研究质量如何，结果均保持一致。
AIP 如何可能参与肾损伤？
AIP 升高反映甘油三酯与 HDL 胆固醇之间的不平衡，提示存在小而密的 LDL 粒子。富含甘油三酯的脂蛋白可通过脂毒性、炎症和氧化应激促进肾损伤；HDL 较低可能削弱抗氧化和抗炎作用，从而进一步影响血管和肾脏健康。
这些机制符合脂质代谢紊乱在糖尿病微血管并发症中的既有作用。
研究与临床的关键启示
对研究人员和临床医师而言，本研究提示：
- AIP 是一种廉价且易获取的指标，可帮助识别肾病风险较高的 2 型糖尿病患者，尤其是老年人。
- 在资源有限的环境中，AIP 可作为传统肾脏指标的有效补充，支持早期干预，如更严格的血糖管理、血脂控制和肾脏保护治疗。
但由于目前证据来自观察性研究，AIP 尚不能视为因果因素或独立预测工具。仍需更多前瞻性研究，标准化 AIP 阈值，统一糖尿病肾病定义，并更好地控制糖尿病病程、他汀使用等关键混杂因素。此外，应开展干预研究，评估降低 AIP 是否能改善肾脏预后。
结论
本荟萃分析支持血浆动脉粥样硬化指数升高与糖尿病肾病相关，且在老年患者中关联更强。研究结果强调了基于脂质的指标在评估肾脏风险方面的潜在价值，同时指出，在将 AIP 纳入常规风险预测工具之前，仍需更多长期及干预性研究。
Reference:
Danyan Min, Junli Zhao, Miao Liu
Atherogenic index of plasma and risk of diabetic nephropathy in type 2 diabetes: A meta‑analysis.
Biomol Biomed [Internet]. 2025 Aug. 1 [cited 2025 Nov. 18];26(1):51–64.
Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/12731
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