Impact of diabetes mellitus on risk of cardiovascular disease and all-cause mortality: Evidence on health outcomes and antidiabetic treatment in United States adults

Table 1 Baseline characteristics of participants, United States National Health Interview Surveys 2000-2009

	Male							Female
	Non-DM (n = 109507)			DM (n = 9892)				Non-DM (n = 140337)			DM (n = 12413)
	No.a	Rateb (SEP)		No.a	Rateb (SEP)		P value	No.a	Rateb	(SEP)	No.a	Rateb	(SEP)	P valuec
Age, mean, yr	44.9		(0.10)	60.3		(0.14)	< 0.0001	46.6		(0.1)	60.7		(0.16)	< 0.0001
Race/ethnicity
NH-White	71683	74.5	(0.25)	6062	70.9	(0.55)	< 0.0001	89088	73.8	(0.25)	6782	66.6	(0.55)	< 0.0001
NH-Black	13345	10.4	(0.18)	1712	14.2	(0.40)		21517	12.5	(0.20)	2923	19.2	(0.46)
Hispanics	19251	10.7	(0.17)	1646	10.4	(0.36)		23779	9.8	(0.15)	2260	10.7	(0.36)
Others	5228	4.4	(0.10)	472	4.5	(0.25)		5953	3.9	(0.08)	448	3.4	(0.21)
Education
Less than HS	19941	15.3	(0.18)	2682	24.0	(0.52)	< 0.0001	25377	15.0	(0.16)	4066	28.8	(0.50)	< 0.0001
HS Graduated	30474	28.0	(0.21)	2887	30.6	(0.58)		39612	28.4	(0.19)	3873	33.1	(0.54)
≥ College	58314	56.6	(0.30)	4231	45.3	(0.58)		74451	56.5	(0.27)	4370	38.1	(0.53)
Smoking status
No smoker	54430	49.6	(0.24)	3667	36.7	(0.58)	< 0.0001	87384	60.8	(0.21)	7344	58.2	(0.51)	< 0.0001
Former smoker	26644	24.9	(0.19)	4293	44.6	(0.60)		24800	19.1	(0.14)	3075	26.4	(0.47)
Current smoker	27507	25.5	(0.19)	1834	18.7	(0.46)		27211	20.1	(0.16)	1893	15.4	(0.35)
Alcohol consumption
Never	16415	14.3	(0.19)	1660	16.5	(0.43)	< 0.0001	41116	27.0	(0.23)	5159	39.7	(0.55)	< 0.0001
Former	15028	13.8	(0.15)	3348	34.0	(0.61)		19335	14.1	(0.13)	3389	28.2	(0.51)
Current	75204	71.8	(0.22)	4668	49.5	(0.62)		77255	58.9	(0.25)	3670	32.1	(0.54)
Exercise
Inactive	38394	34.5	(0.32)	4485	47.0	(0.62)	< 0.0001	55965	38.9	(0.29)	6416	55.2	(0.62)	< 0.0001
Insufficiently active	27605	27.2	(0.18)	2178	24.6	(0.50)		40073	31.0	(0.18)	2724	25.1	(0.49)
Sufficiently active	38609	38.3	(0.26)	2473	28.3	(0.59)		38637	30.0	(0.22)	2158	19.8	(0.45)
BMI, kg/m2
Overweight	46884	43.5	(0.18)	3595	36.2	(0.55)	< 0.0001	38254	28.1	(0.15)	3250	28.0	(0.45)	< 0.0001
Obesity	24128	22.4	(0.17)	4372	46.1	(0.59)		31193	22.4	(0.15)	6168	52.8	(0.53)
Medical condition
Hypertension	25582	23.7	(0.19)	6501	66.3	(0.56)	< 0.0001	35594	25.6	(0.17)	8662	69.8	(0.48)	< 0.0001
Coronary heart Dis	7020	6.6	(0.09)	2598	27.2	(0.48)	< 0.0001	6435	4.7	(0.07)	2450	20.3	(0.41)	< 0.0001
Stroke	2243	2.1	(0.05)	956	9.6	(0.30)	< 0.0001	3244	2.4	(0.05)	1233	10.0	(0.32)	< 0.0001
CVD	8434	7.8	(0.10)	3019	31.4	(0.51)	< 0.0001	8699	6.4	(0.09)	3109	25.6	(0.43)	< 0.0001

^aNo. = Observed number;

^bRate for weighted rate using SAS for complex survey;

^cT test for continuous variable, and χ² test for categorical variables. Education ≥ College including those with associate degrees. Overweight: Body mass index (BMI) 25 to 29.9 kg/m². Obesity: BMI ≥ 30 kg/m². CVD: Cardiovascular disease; DM: Diabetes mellitus; SEP: Standard error of proportion.

Table 2 Mortality (per 1000 person year) from all-cause, heart disease, cerebrovascular disease and cardiovascular disease by December 31, 2011 for baseline participants with or without diabetes, United States National Health Interview Surveys 2000-2009

		Male					Female
		Non-DM		DM			Non-DM		DM
		Event	Rate	Event	Rate	P value	Event	Rate	Event	Rate	P value
All-cause
No. of death		8363		2278			9485		2450
Age	18-54.9	1765	2.9	317	14.1	< 0.0001	1384	1.9	249	8.6	< 0.0001
	55-64.9	1271	12.5	473	27.8	< 0.0001	989	7.6	403	21.6	< 0.0001
	65-74.9	1874	30.7	677	46.0	< 0.0001	1681	18.3	693	37.6	< 0.0001
	≥ 75	3453	86.5	811	103.1	< 0.0001	5431	63.2	1105	79.3	< 0.0001
Heart disease
No. of death		1707		543			1603		506
Age	18-54.9	288	0.5	62	2.8	< 0.0001	115	0.2	41	1.4	< 0.0001
	55-64.9	244	2.4	116	6.8	< 0.0001	108	0.8	72	3.9	< 0.0001
	65-74.9	350	5.7	164	11.1	< 0.0001	241	2.6	132	7.2	< 0.0001
	≥ 75	825	20.7	201	25.6	0.032	1139	13.2	261	18.7	< 0.0001
CBVD
No. of death		376		112			621		134
Age	18-54.9	50	0.1	4	0.2	0.063	58	0.1	8	0.3	0.002
	55-64.9	38	0.4	19	1.1	< 0.001	33	0.3	19	1.0	< 0.0001
	65-74.9	67	1.1	35	2.4	< 0.001	96	1.0	34	1.8	0.003
	≥ 75	221	5.5	54	6.9	0.694	434	5.0	73	5.2	0.371
CVD
No. of death		2083		655			2224		640
Age	18-54.9	338	0.6	66	2.9	< 0.0001	173	0.2	49	1.7	< 0.0001
	55-64.9	282	2.8	135	7.9	< 0.0001	141	1.1	91	4.9	< 0.0001
	65-74.9	417	6.8	199	13.5	< 0.0001	337	3.7	166	9.0	< 0.0001
	≥ 75	1046	26.2	255	32.4	0.038	1573	18.3	334	24.0	< 0.0001

P values were given by χ² test. Mortality rates (per 1000) were estimated using Poisson regression. CBVD: Cerebrovascular disease; CVD: Cardiovascular disease; DM: Diabetes mellitus.

Table 3 Multivariate adjusted hazard ratios (HR, 95%CI) of diabetes mellitus for mortality from all-cause, heart disease, cerebrovascular disease and cardiovascular disease by gender

	Male (n = 119399)			Female (n = 152750)			Excess HR1
Mortality	HR	(95%CI)	P value	HR	(95%CI)	P value	Rate, %	P value
DM vs non-DM
Model 1
All-cause	1.56	(1.49-1.64)	< 0.0001	1.69	(1.61-1.78)	< 0.0001	8.3	0.02
Heart Dis	1.72	(1.53-1.93)	< 0.0001	2.02	(1.81-2.25)	< 0.0001	17.4	0.05
CBVD	1.48	(1.18-1.85)	0.001	1.43	(1.15-1.77)	0.001	-3.5	0.35
CVD	1.67	(1.51-1.86)	< 0.0001	1.85	(1.69-2.03)	< 0.0001	10.5	0.16
Model 2
All-cause	1.54	(1.47-1.62)	< 0.0001	1.62	(1.55-1.71)	< 0.0001	5.5	0.13
Heart Dis	1.70	(1.51-1.91)	< 0.0001	1.95	(1.74-2.17)	< 0.0001	14.5	0.09
CBVD	1.48	(1.18-1.86)	0.001	1.39	(1.12-1.72)	0.003	-6.2	0.70
CVD	1.66	(1.49-1.84)	< 0.0001	1.79	(1.63-1.96)	< 0.0001	7.8	0.29
Model 3
All-cause	1.47	(1.39-1.55)	< 0.0001	1.55	(1.47-1.63)	< 0.0001	5.5	0.15
Heart Dis	1.62	(1.44-1.82)	< 0.0001	1.80	(1.60-2.03)	< 0.0001	11.2	0.21
CBVD	1.35	(1.04-1.75)	0.023	1.40	(1.12-1.75)	0.003	3.4	0.85
CVD	1.57	(1.40-1.75)	< 0.0001	1.68	(1.52-1.86)	< 0.0001	7.4	0.35
Model 4
All-cause	1.42	(1.35-1.49)	< 0.0001	1.50	(1.42-1.58)	< 0.0001	5.6	0.15
Heart Dis	1.58	(1.33-1.69)	< 0.0001	1.65	(1.48-1.89)	< 0.0001	4.4	0.19
CBVD	1.28	(0.99-1.66)	0.06	1.33	(1.06-1.66)	0.013	3.9	0.83
CVD	1.46	(1.31-1.63)	< 0.0001	1.58	(1.42-1.75)	< 0.0001	8.2	0.32
Model 5 - in those without baseline CVD
All-cause	1.32	(1.23-1.41)	< 0.0001	1.40	(1.32-1.50)	< 0.0001	6.1	0.19
Heart Dis	1.22	(1.03-1.45)	0.019	1.43	(1.21-1.69)	< 0.0001	17.2	0.19
CBVD	1.24	(0.93-1.67)	0.137	1.41	(1.10-1.82)	0.008	13.7	0.53
CVD	1.22	(1.04-1.43)	0.017	1.45	(1.26-1.67)	< 0.0001	18.9	0.08

¹Excess HR = [(HR in female/HR in male) - 1] × 100. Significant test was estimated based on sex × DM interaction. P-values were given by Cox regression models. Model 1: Adjusted for age and race/ethnicity (NH-White, NH-Black, Hispanics, and all other race group); Model 2: Adjusted for Model 1 plus education; Model 3: Adjusted for Model 2 plus smoking, alcohol, and physical activity status; Model 4: Adjusted for Model 2 plus smoking, alcohol, physical activity status, hypertension. DM: Diabetes mellitus; CBVD: Cerebrovascular disease; CVD: Cardiovascular disease.

Table 4 Proportion of antidiabetic medication use in patients with diabetes by gender

	Male		Female
	%	(SEP)	%	(SEP)	P value
By groups
Monotherapy	38.11	(1.19)	40.36	(1.06)	0.291
Combination	51.89	(1.27)	49.38	(1.10)
No drug	10.00	(0.83)	10.26	(0.66)
Monotherapy
Biguanides (Metformin)	27.32	(1.89)	33.24	(1.57)	0.008
SU	25.86	(1.72)	21.88	(1.34)
Insulin	37.20	(1.85)	33.01	(1.42)
Others	9.63	(1.16)	11.87	(0.95)
Combination
Metformin + SU	20.05	(1.34)	21.94	(1.10)	0.422
TZD + Any (insulin excluded)	13.56	(1.25)	13.11	(0.87)
Insulin + Any (TZD excluded)	15.25	(1.38)	16.91	(1.07)
Metformin + SU + TZD	7.72	(0.86)	6.75	(0.69)
Metformin + SU + Insulin	6.89	(0.87)	4.97	(0.61)
Any other combinations	36.52	(1.85)	36.32	(1.44)

P values were given by χ² test. Others include alpha glucosidase inhibitors, meglinitides, dipeptidyl peptidase 4 inhibitors, amylin analogs, and incretin mimetics. TZD: Thiazolidinedione; SU: Sulfonylureas; SEP: Standard error of proportion.

Table 5 Multivariate adjusted hazard ratios (HR, 95%CI) of antidiabetic medication use for mortality from all-cause and cardiovascular disease in patients with diabetes

	All-cause mortality						Mortality from CVD
	Model 1			Model 2			Model 1			Model 2
	HR	(95%CI)	P value	HR	(95%CI)	P value	HR	(95%CI)	P value	HR	(95%CI)		P value
Medication use vs no-use	0.87	(0.68-1.11)	0.251	0.93	(0.73-1.18)	0.556	0.88	(0.54-1.44)	0.613	0.96	(0.60-1.54)		0.873
Monotherapy (ref: Non-drug use)
Biguanides (Metformin)	0.53	(0.36-0.77)	0.001	0.55	(0.38-0.80)	0.002	0.82	(0.42-1.61)	0.564	0.87	(0.45-1.68)		0.681
SU	0.89	(0.66-1.21)	0.456	0.91	(0.67-1.23)	0.529	1.10	(0.66-1.83)	0.716	1.11	(0.67-1.84)		0.696
Insulin	1.65	(1.26-2.16)	< 0.001	1.71	(1.31-2.24)	< 0.0001	1.51	(0.86-2.66)	0.153	1.58	(0.92-2.70)		0.094
Combination
Metformin + SU	0.75	(0.55-1.01)	0.059	0.81	(0.60-1.10)	0.168	0.77	(0.41-1.43)	0.403	0.87	(0.48-1.57)		0.632
TZD + Any (insulin excluded)	0.87	(0.60-1.26)	0.468	0.98	(0.67-1.42)	0.905	0.43	(0.23-0.82)	0.011	0.52	(0.28-0.98)		0.042
Insulin + Any (TZD excluded)	1.27	(0.90-1.78)	0.171	1.33	(0.94-1.86)	0.103	1.37	(0.69-2.72)	0.365	1.45	(0.75-2.81)		0.264
Metformin + SU + TZD	0.40	(0.25-0.65)	< 0.001	0.43	(0.27-0.70)	0.001	0.54	(0.24-1.18)	0.120	0.58	(0.27-1.25)		0.164
Metformin + SU + Insulin	0.64	(0.41-1.01)	0.053	0.67	(0.43-1.05)	0.080	0.75	(0.44-1.29)	0.293	0.80	(0.47-1.37)		0.418
Other combination	0.63	(0.46-0.86)	0.004	0.68	(0.50-0.93)	0.016	0.59	(0.31-1.09)	0.091	0.64	(0.35-1.19)		0.157

Others: Include alpha glucosidase inhibitors, meglinitides, dipeptidyl peptidase 4 inhibitors, amylin analogs, and incretin mimetics. P values were given by Cox regression models. Model 1: Adjusted for age, sex, race/ethnicity, and survey year; Model 2: Adjusted for Model 1 plus anti-hypertension and anti-hyperlipidemia drugs. TZD: Thiazolidinedione; SU: Sulfonylureas.

Table 6 Multivariate adjusted hazard ratios (HR, 95%CI) of antidiabetic medication use for mortality from heart disease and cerebrovascular disease in patients with diabetes

	Heart disease mortality							Cerebrovascular disease (CBVD) mortality
	Model 1			Model 2				Model 1				Model 2
	HR	(95%CI)	P value	HR	(95%CI)		P value	HR	(95%CI)		P value	HR	(95%CI)	P value
Medication use vs no-use	1.01	(0.62-1.65)	0.982	1.08	(0.67-1.74)		0.741	0.58	(0.19-1.78)		0.339	0.67	(0.23-1.95)	0.457
Monotherapy
Biguanides (Metformin)	0.80	(0.38-1.67)	0.550	0.83	(0.40-1.70)		0.608	0.94	(0.22-4.01)		0.938	1.20	(0.30-4.82)	0.792
SU	1.26	(0.76-2.11)	0.373	1.27	(0.76-2.13)		0.364	0.71	(0.23-2.24)		0.560	0.76	(0.25-2.34)	0.629
Insulin	1.85	(1.06-3.24)	0.031	1.91	(1.12-3.26)		0.018	0.60	(0.16-2.23)		0.445	0.71	(0.23-2.21)	0.547
Combined
Metformin + SU	0.82	(0.41-1.67)	0.586	0.91	(0.47-1.80)		0.794	0.59	(0.14-2.47)		0.472	0.71	(0.17-2.94)	0.632
TZD + Any (insulin excluded)	0.55	(0.28-1.08)	0.082	0.68	(0.35-1.30)		0.242	0.14	(0.02-1.18)		0.070	0.15	(0.02-1.32)	0.088
Insulin + Any (TZD excluded)	1.79	(0.89-3.61)	0.103	1.85	(0.94-3.64)		0.074	0.44	(0.13-1.53)		0.196	0.50	(0.15-1.66)	0.257
Metformin + SU + TZD	0.61	(0.27-1.40)	0.245	0.65	(0.30-1.42)		0.280	0.34	(0.04-2.83)		0.316	0.41	(0.04-3.95)	0.438
Metformin + SU + Insulin	0.33	(0.19-0.59)	0.000	0.35	(0.20-0.62)		< 0.0001	1.66	(0.55-5.02)		0.368	1.91	(0.64-5.73)	0.245
Other combinations	0.71	(0.37-1.37)	0.307	0.78	(0.42-1.47)		0.444	0.28	(0.06-1.31)		0.106	0.31	(0.07-1.41)	0.129

Others: Include alpha glucosidase inhibitors, meglinitides, dipeptidyl peptidase 4 inhibitors, amylin analogs, and incretin mimetics. P values were given by Cox regression models. Model 1: Adjusted for age, sex, race/ethnicity, and survey year; Model 2: Adjusted for Model 1 plus anti-hypertension and anti-hyperlipidemia drugs. TZD: Thiazolidinedione; SU: Sulfonylureas.

Table 7 Age-race-adjusted rates of five selected predicators for cardiovascular disease in patients with diabetes at baseline, 2000-2009 National Health Interview Surveys

	Patients with DM at baseline
	Male (n = 9892)		Female (n = 12413)
	Rate	(SEP)	Rate	(SEP)	P value
Education
Less than HS	21.53	(0.50)	24.82	(0.47)	< 0.0001
HS Graduated	28.44	(0.59)	30.61	(0.55)	0.0100
≥ College	50.03	(0.60)	44.57	(0.56)	< 0.0001
Smoking status
No smoker	40.92	(0.58)	61.60	(0.53)	< 0.0001
Former smoker	36.03	(0.58)	17.81	(0.49)	< 0.0001
Current smoker	23.05	(0.46)	20.59	(0.35)	< 0.0001
Exercise
Inactive	42.80	(0.63)	49.34	(0.62)	< 0.0001
Insufficiently active	26.88	(0.52)	27.98	(0.49)	0.1000
Sufficiently active	30.32	(0.61)	22.68	(0.47)	< 0.0001
BMI, kg/m2
Overweight	34.21	(0.55)	25.82	(0.46)	< 0.0001
Obesity	47.13	(0.60)	53.88	(0.51)	< 0.0001
Medical condition
Hypertension	52.54	(0.58)	54.55	(0.46)	0.0100

Education ≥ College including those with associate degrees. Overweight: Body mass index (BMI) 25 to 29.9 kg/m². Obesity: BMI ≥ 30 kg/m². P values were given by χ² test. HS: High school.