Diabetes as a pan-cancer risk factor: Triangulated evidence from global burden, longitudinal cohorts, and Mendelian randomization

Table 1 Association between diabetic status and cancer prevalence

Case		Model 1			Model 2			Model 3
		OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value
1NHANES	Prediabetes	1.66	1.48-1.86	< 0.001	1.26	1.12-1.41	< 0.001	1.25	0.99-1.59	0.068
	Diabetes	2.46	2.16-2.81	< 0.001	1.59	1.36-1.85	< 0.001	1.64	1.18-2.28	0.004
2CHARLS	Prediabetes	0.95	0.77-1.17	0.632	0.85	0.67-1.08	0.179	1.69	0.98-2.89	0.057
	Diabetes	1.79	1.58-2.03	< 0.001	1.65	1.44-1.89	< 0.001	2.00	1.11-3.59	0.020

¹Normoglycemia as reference group in National Health and Nutrition Examination Survey (NHANES). Model 2 for NHANES adjusted for age, gender, and ethnicity. Model 3 for NHANES adjusted for age, gender, ethnicity, education level, family income, alcohol consumption, cigarette use, physical activity, hypertension, and body mass index.

²Normoglycemia as reference group in China Health and Retirement Longitudinal Study (CHARLS). Model 2 for CHARLS adjusted for age, gender, and race. Model 3 for CHARLS adjusted for age, gender, race, education level, family income, alcohol consumption, cigarette use, physical activity, dietary patterns, hypertension, and body mass index.

CHARLS: China Health and Retirement Longitudinal Study; NHANES: National Health and Nutrition Examination Survey; OR: Odds ratio.

Table 2 Association between diabetic status and survival in patients with cancer from the National Health and Nutrition Examination Survey

Case	Model 1			Model 2			Model 3
	HR	95%CI	P value	HR	95%CI	P value	HR	95%CI	P value
Prediabetes	0.93	0.78-1.10	0.387	0.89	0.75-1.06	0.187	0.91	0.76-1.09	0.312
Diabetes	1.37	1.15-1.63	< 0.001	1.28	1.07-1.53	0.007	1.25	1.03-1.51	0.023

Normoglycemia as reference group. Model 2 adjusted for age, gender and race. Model 3 adjusted for age, gender, race, education level, family income, alcohol consumption, cigarette use, physical activity, dietary patterns, hypertension, and body mass index. HR: Hazard ratio.

Table 3 Mendelian randomization analysis of the causal association between diabetes and cancer

Diabetes (exposure)	Cancer (outcome)	Method	Single nucleotide polymorphisms	P value	OR (95%CI)	P value for pleiotropy
finn-b-E4_DMNAS	ukb-e-2453_CSA	IVW	8	0.012	1.50 (1.09, 2.06)	0.685
		Weighted median	8	< 0.001	1.57 (1.21, 2.05)
		Simple mode	8	0.049	1.76 (1.10, 2.81)
		Weighted mode	8	0.009	1.59 (1.23, 2.04)
		MR Egger	8	0.121	1.65 (0.96, 2.82)

IVW: Inverse variance weighting; OR: Odds ratio; MR: Mendelian randomization.