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Abstract：
BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications.
METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates.
RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years).
CONCLUSIONS: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.
METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates.
RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years).
CONCLUSIONS: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.
摘要：
背景：2型糖尿病与胰腺癌的过度风险相关，但是风险的大小和时间风险关系尚不清楚，关于抗糖尿病药物的作用的信息有限。
方法：我们分析了胰腺癌病例对照联盟15项病例对照研究的个体水平数据，包括8305例病例和13987例对照。汇总赔率比(OR)由多元逻辑回归模型估计，针对相关协变量进行调整。
结果：总体而言，1155（15％）例和1087（8％）对照组在癌症诊断（或访谈，对于控件)，对应于1.90的OR(95%置信区间，CI，1.72-2.09）。在选定的协变量的各层中观察到一致的风险估计，包括体重指数和吸烟。胰腺癌的风险随着糖尿病的持续时间而降低，但糖尿病诊断后20年或更长时间仍存在明显的超额风险(OR1.30,95%CI1.03-1.63).在糖尿病患者中，长期口服抗糖尿病药物与胰腺癌风险降低相关(OR0.31,95%CI0.14~0.69,≥15年).相反，短期使用胰岛素与胰腺癌风险相关(OR5.60,95%CI3.75-8.35,<5年),但不是更长的使用时间（OR0.95，95%CI0.53-1.70，≥15年）。
结论：这项研究提供了迄今为止糖尿病患者胰腺癌风险过高的最明确的量化。它还表明，30％的超额风险在糖尿病诊断后持续超过二十年，因此支持糖尿病在胰腺癌中的因果作用。口服抗糖尿病药物可以降低胰腺癌的风险，而胰岛素显示出不一致的持续时间-风险关系。
方法：我们分析了胰腺癌病例对照联盟15项病例对照研究的个体水平数据，包括8305例病例和13987例对照。汇总赔率比(OR)由多元逻辑回归模型估计，针对相关协变量进行调整。
结果：总体而言，1155（15％）例和1087（8％）对照组在癌症诊断（或访谈，对于控件)，对应于1.90的OR(95%置信区间，CI，1.72-2.09）。在选定的协变量的各层中观察到一致的风险估计，包括体重指数和吸烟。胰腺癌的风险随着糖尿病的持续时间而降低，但糖尿病诊断后20年或更长时间仍存在明显的超额风险(OR1.30,95%CI1.03-1.63).在糖尿病患者中，长期口服抗糖尿病药物与胰腺癌风险降低相关(OR0.31,95%CI0.14~0.69,≥15年).相反，短期使用胰岛素与胰腺癌风险相关(OR5.60,95%CI3.75-8.35,<5年),但不是更长的使用时间（OR0.95，95%CI0.53-1.70，≥15年）。
结论：这项研究提供了迄今为止糖尿病患者胰腺癌风险过高的最明确的量化。它还表明，30％的超额风险在糖尿病诊断后持续超过二十年，因此支持糖尿病在胰腺癌中的因果作用。口服抗糖尿病药物可以降低胰腺癌的风险，而胰岛素显示出不一致的持续时间-风险关系。
