Table S1 of Epidemiologic Studies of Ingested Arsenic in Water or Urine and Diabetes Mellitus

Table S2 of Odds Ratios of Type II Diabetes Mellitus and Urine Arsenic Concentrations

Table S1. Table of Epidemiologic Studies of Ingested Arsenic in Water or Urine and Diabetes Mellitus:

Table S1. Epidemiologic Studies of Ingested Arsenic in Water or Urine and Diabetes Mellitus
Study, Location, Design		Arsenic exposure levels^a		Results^b		Notes
HIGH EXPOSURE STUDIES:
Rahman et al., 1998^1 Bangladesh Cross-sectional		Unexposed (water) 0-500 µg/L 500-1000 µg/L > 1000 µg/L		PR=1.0 (ref) PR=2.6 (1.2-5.7) PR=3.9 (1.8-8.2) PR=8.8 (2.7-28.4)		Exposed subjects were those with hyperkeratosis due to arsenic.
Nabi et al., 2005^2 Bangladesh Cross-sectional		Mean = 235 µg/L (urine)		PR=2.8 (ng)		PR for diabetes mellitus in 115 arsenicosis patients compared to 120 unexposed controls.
Rahman et al., 1999^3 Bangladesh Cross-sectional		Unexposed (water) < 500 µg/L 500-1000 µg/L > 1000 µg/L		PR=1.0 (ref) PR=1.1 (0.5-2.0) PR=2.2 (1.3-3.8) PR=2.6 (1.5-4.6)		PRs are for glycosuria in subjects with arsenic-caused skin lesions.
Tseng et al., 2000^4 Taiwan Prospective		< 17,000 µg/L-years ≥ 17,000 µg/L-years (water)		RR=1.0 (ref) RR=2.1 (1.1-4.2)		446 initially non-diabetics followed for approximately 3 years. 41 developed diabetes.
Tsai et al., 1999^5 Taiwan Ecologic		Median = 780 µg/L (water)		SMR=1.35 (1.16-1.55) in males and 1.55 (1.39-1.72) in females		SMRs for blackfoot disease endemic area. Ecologic study without individual data on exposure and confounding factors.
Wang et al., 2003^6 Taiwan Ecologic		Non-endemic areas Endemic areas		3.5% (3.5-3.6%) 7.5% (7.4-7.7%)		Prevalence rates of non-insulin dependent diabetes mellitus in arseniasis endemic & non-endemic areas.
Lai et al., 1994^7 Taiwan Retrospective cohort		0 µg/L-years (water) 100-15,000 µg/L-years ≥ 15,100 µg/L-years		OR=1.0 (ref) OR=6.61 (0.86-51.0) OR=10.05 (1.30-77.9)		ORs for cumulative arsenic exposure.
MEDIUM EXPOSURE STUDIES:
Coronado-Gonźalez et al., 2007^8 Mexico Case-control	< 63.5 µg/g (urine) 63.5-104 µg/g > 104 µg/g		OR=1.0 (ref) OR=2.16 (1.23-3.79) OR=2.84 (1.64-4.92)		Dividing arsenic by creatinine could elevate ORs.
Lewis et al., 1999^9 Utah Cohort mortality	Median = 14-166 µg/L (water)		Males: 0.79 (0.48-1.22) Females: 1.23 (0.86-1.71)		No data on potential confounding variables.

Table S1 - Continued

LOW EXPOSURE STUDIES:
Ruiz-Navarro et al., 1988^10 Spain Cross-sectional	3.44 ± 2.36 µg/L 3.68 ± 2.27 µg/L (urine)	Diabetics (n=38) Control subjects (n=49)	No difference in mean urine arsenic levels
Zierold et al., 2004^11 Wisconsin Retrospective cohort	< 2 µg/L (water) 2-10 µg/L >10 µg/L	OR=1.0 (ref) OR=1.35 (0.78-2.33) OR=1.02 (0.49-2.15)	1185 people with 20+ years well water use
Afridi et al., 2008^12 Pakistan Cross-sectional	5.59 ± 0.92 µg/L 4.7 ± 0.88 µg/L (urine)	Diabetics (n=110) Non-diabetics (n=115)	Data given for non-smokers. Similar results seen in smokers. Little difference in mean urine arsenic levels between diabetics and non-diabetics
Meliker et al., 2007^13 Michigan Ecologic	Mean = 11 µg/L (water)	Males: SMR =1.28 (1.18-1.37) Females: SMR = 1.27 (1.19-1.35)	No individual data on exposure or confounders.
Abbreviations: ng, not given; OR, odds ratios; PR, prevalence ratio; ref, reference category; RR, rate ratio; SMR, standardized mortality ratios; µg/g, microgram of arsenic per gram of creatinine. ^aExposure levels in the exposed subjects unless otherwise noted. ^bResults are prevalence ratios, rate ratios, SMRs, or odds ratios for diabetes mellitus unless otherwise noted. 95% confidence intervals are in parentheses.

References

1. Rahman M, Tondel M, Ahmad SA, Axelson O. Diabetes mellitus associated with arsenic exposure in Bangladesh. Am J Epidemiol 1998;148(2):198-203.

2. Nabi AH, Rahman MM, Islam LN. Evaluation of biochemical changes in chronic arsenic poisoning among Bangladeshi patients. Int J Environ Res Public Health 2005;2(3-4):385-93.

3. Rahman M, Tondel M, Chowdhury IA, Axelson O. Relations between exposure to arsenic, skin lesions, and glucosuria. Occup Environ Med 1999;56(4):277-81.

4. Tseng CH, Tai TY, Chong CK, Tseng CP, Lai MS, Lin BJ, Chiou HY, Hsueh YM, Hsu KH, Chen CJ. Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan. Environ Health Perspect 2000;108(9):847-51.

5. Tsai SM, Wang TN, Ko YC. Mortality for certain diseases in areas with high levels of arsenic in drinking water. Arch Environ Health 1999;54(3):186-93.

6. Wang SL, Chiou JM, Chen CJ, Tseng CH, Chou WL, Wang CC, Wu TN, Chang LW. Prevalence of non-insulin-dependent diabetes mellitus and related vascular diseases in southwestern arseniasis-endemic and nonendemic areas in Taiwan. Environ Health Perspect 2003;111(2):155-59.

7. Lai MS, Hsueh YM, Chen CJ, Shyu MP, Chen SY, Kuo TL, Wu MM, Tai TY. Ingested inorganic arsenic and prevalence of diabetes mellitus. Am J Epidemiol 1994;139(5):484-92.

8. Coronado-Gonzalez JA, Del Razo LM, Garcia-Vargas G, Sanmiguel-Salazar F, Escobedo-de la Pena J. Inorganic arsenic exposure and type 2 diabetes mellitus in Mexico. Environ Res 2007;104(3):383-9.

9. Lewis D, Southwick J, Ouellet-Hellstrom R, Rench J, Calderon R. Drinking water arsenic in Utah: a cohort mortality study. Environ Health Perspect 1999;107(5):359-65.

10. Ruiz-Navarro ML, Navarro-Alarcon M, Lopez Gonzalez-de la Serrana H, Perez-Valero V, Lopez-Martinez MC. Urine arsenic concentrations in healthy adults as indicators of environmental contamination: relation with some pathologies. Sci Total Environ 1998;216(1-2):55-61.

11. Zierold KM, Knobeloch L, Anderson H. Prevalence of chronic diseases in adults exposed to arsenic-contaminated drinking water. Am J Public Health 2004;94(11):1936-7.

12. Afridi HI, Kazi TG, Kazi N, Jamali MK, Arain MB, Jalbani N, Baig JA, Sarfraz RA. Evaluation of status of toxic metals in biological samples of diabetes mellitus patients. Diabetes Res Clin Pract 2008;80(2):280-8.

13. Meliker JR, Wahl RL, Cameron LL, Nriagu JO. Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis. Environ Health 2007;6:4.

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Table S2. Odds Ratios of Type 2 Diabetes Mellitus and Urine Arsenic Concentrations:

Table S2. Odds Ratios of Type 2 Diabetes Mellitus and Urine Arsenic Concentrations Including Results Adjusted for Urine Creatinine
		No.		Unadjusted		Adjusted^a			Adjusted^b
		Cases	Control	OR	95% CI	OR	95% CI		OR	95% CI
Total Arsenic
	£20^th percentile (£3.5 µg/L)	21	141	1.00	ref	1.00	ref		1.00	ref
	≥80^th percentile (≥18.3 µg/L)	17	142	0.80	0.41-1.59	0.88	0.39-1.97		0.90	0.35-2.34
	Lower tertile (£5.2 µg/L)	36	232	1.00	ref	1.00	ref		1.00	ref
	Middle tertile (5.3-11.8 µg/L)	32	230	0.90	0.54-1.49	0.87	0.48-1.55		0.87	0.47-1.61
	Upper tertile (>11.8 µg/L)	30	235	0.82	0.49-1.38	0.76	0.42-1.39		0.76	0.37-1.56
Arsenobetaine
	Below detection^c (£0.3 µg/L)	42	217	1.00	ref	1.00		ref	1.00	ref
	≥80^th percentile (≥6.2 µg/L)	15	142	0.55	0.29-1.02	0.59		0.29-1.19	0.59	0.29-1.22
	Lower tertile (£0.3 µg/L)	42	217	1.00	ref	1.00		ref	1.00	ref
	Middle (0.4-2.2 µg/L)	29	246	0.61	0.37-1.01	0.68		0.38-1.21	0.68	0.38-1.22
	Upper (>2.2 µg/L)	27	234	0.60	0.36-1.00	0.62		0.34-1.13	0.62	0.34-1.15
Estimated Inorganic Arsenic
	£20^th percentile (£2.7 µg/L)	20	142	1.00	ref	1.00		ref	1.00	ref
	≥80^th percentile (≥11.9 µg/L)	22	139	1.12	0.59-2.15	1.15		0.53-2.50	1.40	0.53-3.69
	Lower tertile (£4.1 µg/L)	36	227	1.00	ref	1.00		ref	1.00	ref
	Middle tertile (4.2-8.5 µg/L)	29	238	0.77	0.46-1.30	0.63		0.34-1.15	0.67	0.35-1.29
	Upper tertile (>8.5 µg/L)	33	232	0.90	0.54-1.49	0.98		0.53-1.80	1.13	0.52-2.48
Dimethylarsonic acid (DMA)
	£20^th percentile (£1.9 µg/L)^d	15	111	1.00	ref	1.00		ref	1.00	ref
	≥80^th percentile (≥7.0 µg/L)	21	146	1.06	0.53-2.16	1.05		0.45-2.44	1.13	0.42-3.07
	Lower tertile (£2.7 µg/L)	35	227	1.00	ref	1.00		ref	1.00	ref
	Middle tertile (2.8-5.0 µg/L)	37	252	0.95	0.58-1.56	1.02		0.57-1.82	1.05	0.56-1.95
	Upper tertile (>5.0 µg/L)	26	218	0.77	0.45-1.33	0.82		0.43-1.57	0.86	0.40-1.84
Abbreviations: CI, confidence interval; No., number; OR, odds ratios; ref, reference group ^aAdjusted for sex, age, ethnicity, education, body mass index, serum cotinine, and current use of hypertension medications. ^bAdjusted for sex, age, ethnicity, education, body mass index, serum cotinine, current use of hypertension medications and urine creatinine (in ug/L). cThe detection limit was used rather than the 20^th percentile since > 20% of people had arsenobetaine concentrations below detection. ^dThis group contains fewer than 159 subjects (the 20^th percentile) since a large number of subjects had DMA levels of 2 µg/L and were assigned to the 20-80^th percentile group.

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