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. 2022 Nov;14(11):727-738.
doi: 10.1111/1753-0407.13329. Epub 2022 Nov 9.

Long-term fasting glucose variability and risk of cancer in patients with type 2 diabetes mellitus: A retrospective population-based cohort study in Shanghai

Xiao-Rui Cui  1 , Jun Li  2 , Ya-Ting Yang  1 , Jing-Yi Wu  1 , Hui-Lin Xu  2 , Yong-Fu Yu  3 , Guo-You Qin  1   3
Affiliations

Long-term fasting glucose variability and risk of cancer in patients with type 2 diabetes mellitus: A retrospective population-based cohort study in Shanghai

Xiao-Rui Cui et al. J Diabetes. 2022 Nov.

Abstract
in English, Chinese

Backgrounds: Fasting blood glucose (FBG) variability may make an impact on adverse events in patients with diabetes mellitus. However, the association between long-term changes in FBG and cancer remains unclear. We aimed to investigate this association in a large-scale longitudinal study.

Methods: Data were collected from 46 761 patients with type 2 diabetes mellitus aged 20-80 years who participated in the Diabetes Standardized Management Program in Shanghai, China. We adopted four indicators, including standard deviation (SD), coefficient of variation (CV), variation independent of the mean (VIM), and average real variability (ARV) to describe FBG variability. Adjusted multivariable Cox regression analyses and restricted cubic splines were used to investigate the association between long-term FBG variability and cancer risk. We also determined the interactive effect of FBG variability with hypertension and FBG-mean with hypertension on cancer risk, respectively.

Results: In this study, we confirmed 2218 cancer cases (51.1% male) over a median follow-up of 2.86 years. In the multivariable-adjusted models, participants in the highest quartile of FBG variability had an increased risk of cancer compared with those in the lowest quartile. The nonlinear association was found when using FBG-VIM, FBG-ARV, and FBG-SD in restricted cubic spline plots. There was a significant interaction effect of FBG variability with hypertension on cancer, whereas the effect of FBG-mean with hypertension did not attain significance.

Conclusions: Our retrospective cohort study demonstrated a positive association between the long-term changes in FBG and cancer risk in patients with type 2 diabetes mellitus. FBG variability may independently predict cancer incidence.

背景: 空腹血糖(FBG)变异性可能对糖尿病患者的不良事件产生影响。然而，空腹血糖的长期变化与癌症之间的联系仍不清楚。本研究旨在一项大规模纵向研究中调查和量化这种关联。 方法: 对参加中国上海市糖尿病标准化管理项目的46,761例年龄在20到80岁的2型糖尿病患者进行调查。我们采用标准差(SD)、变异系数(CV)、独立于均值的变异(VIM)和平均实际变异(ARV)4个指标来描述FBG的变异性。调整后的多变量COX回归分析和限制三次样条法被用来调查长期空腹血糖(FBG)变异性与癌症风险之间的关系。我们还分别确定了空腹血糖变异性与高血压和空腹血糖均值与高血压之间的交互作用对癌症风险的影响。 结果: 在这项研究中，我们确认了2218例癌症病例(51.1%为男性)，平均随访时间为2.86年。在多变量校正模型中，FBG变异性最高四分位的参与者比那些最低四分位数的参与者患癌症的风险更高。在限制三次样条图中使用FBG-VIM、FBG-ARV和FBG-SD时，发现了非线性关联。FBG变异性与高血压之间存在显著的交互作用，而FBG均值与高血压之间的交互作用不显著。 结论: 我们的回顾性队列研究显示，FBG的长期变化与2型糖尿病患者的癌症风险呈正相关。FBG变异性可独立预测癌症发病率。.

Keywords: 2型糖尿病互作。; cancer; fasting glucose variability; hypertension; interaction; type 2 diabetes mellitus; 癌症; 空腹血糖变异性; 高血压.

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Figures

FIGURE 1
FIGURE 1
Flow chart for study participant filtration. FG, fasting glucose; T2DM, type 2 diabetes mellitus.
FIGURE 2
FIGURE 2
Shape of the association between variation independent of the mean (VIM) and the development of cancer with type 2 diabetes mellitus (T2DM). The solid lines: hazard ratio; dash areas: 95% confidence interval zone (CI). Data were adjusted for baseline variables, including gender, age, body mass index (BMI), family history of diabetes mellitus (DM), hypertension, hypoglycemic drugs, physical exercise, FBG‐mean, FBG at baseline, follow‐up frequency (Model 3). FBG, fasting blood glucose.
FIGURE 3
FIGURE 3
Shape of the association between average real variability (ARV) and the development of cancer with type 2 diabetes mellitus (T2DM). The solid lines: hazard ratio; dash areas: 95% confidence interval zone (CI). Data were adjusted for baseline variables, including gender, age, body mass index (BMI), family history of diabetes mellitus (DM), hypertension, hypoglycemic drugs, physical exercise, FBG‐mean, FBG at baseline, follow‐up frequency (Model 3). FBG, fasting blood glucose.
FIGURE 4
FIGURE 4
Shape of the association between coefficient of variation (CV) and the development of cancer with type 2 diabetes mellitus (T2DM). The solid lines: hazard ratio; dash areas: 95% confidence interval zone (CI). Data were adjusted for baseline variables, including gender, age, body mass index (BMI), family history of diabetes mellitus (DM), hypertension, hypoglycemic drugs, physical exercise, FBG‐mean, FBG at baseline, follow‐up frequency (Model 3). SD, standard deviation. FBG, fasting blood glucose.
FIGURE 5
FIGURE 5
Shape of the association between SD and the development of cancer with type 2 diabetes mellitus (T2DM). The solid lines: hazard ratio; dash areas: 95% confidence interval zone (CI). Data were adjusted for baseline variables, including gender, age, body mass index (BMI), family history of diabetes mellitus (DM), hypertension, hypoglycemic drugs, physical exercise, FBG‐mean, FBG at baseline, follow‐up frequency (Model 3). FBG, fasting blood glucose.
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