Associations of prediabetes with all-cause and cardiovascular mortality: A meta-analysis

Figures & data

Figure 1. Flow of papers through review. RRs = relative risks; CIs = confidence intervals.

Table I. Study characteristics.

Study (ref.)	Country/region	Prediabetes definition and prevalence (%)	Sample size (% women)	Age (y), average (range or SD)	Follow- up (y)	Baseline CVD excluded	Events for analysis
Yeboah 2011 (The MESA) (6)	America	IFG 100 (13.9%)	6,753 (52.9%)	62.2 (45–84)	7.5	Yes	All-cause mortality
Laukkanen 2013 (7)	Finland	IFG 100 (20.1%)	2,641 (0%)	52.9 (40–62)	18.8	No	All-cause and CVD mortality
Pankow 2007 (ARIC study) (8)	America	IFG 100 (42%); IGT (31%); IFG 100 and IGT (17%)	6,888 (47%)	62.3 (52–75)	6.3	Yes	All-cause mortality
Wang 2007 (9)	Finland	IFG 100 (NA); IFG 110 (NA); IGT (NA)	1,025 (63.2%)	NA (65–74)	13.5	No	CVD mortality
Ma 2012 (KMCC study) (10)	Korea	IFG 100 (15.9%)	16,048 (60%)	55.7 (≥ 20)	9.4	No	CVD mortality
Deedwania 2013 (CHS) (11)	America	IFG 100 (47%)	4,602 (57%)	73 (≥ 65)	13	No	All-cause and CVD mortality
DECODE 2001 (13)	Europe	IFG 110 (10.1%); IGT (11.4%)	22,514 (31.7%)	53 (30–89)	8.8	No	All-cause and CVD mortality
Saydah 2001 (NHANES II) (14)	America	IFG 110 (NA); IGT (17.0%); IFG 110 and/or IGT (NA)	3,092 (54.3%)	49.6 (30–74)	13.5	No	All-cause and CVD mortality
Rodriguez 2002 (Honolulu Heart program) (15)	Japan	IFG 110 (22.4%); IGT (26.7%); IFG 110 and/or IGT (41.3%)	2,034 (0%)	NA (71–93)	7	Yes	All-cause and CVD mortality
Barr 2007 (AusDiab Study) (16)	Australia	IFG 110 (5.8%); IGT (12.4%)	10,428 (54.8%)	51.4 (≥ 25)	5.2	No	All-cause and CVD mortality
Stengard 1992 (22)	Finland	IGT (36.7%)	637 (0%)	72.4 (65–84)	5	No	All-cause and CVD mortality
Mazza 2001 (CASTEL) (23)	Italy	IFG 110 (NA)	3,282 (61.0%)	73.8 (≥ 65)	14	No	Stroke mortality
Henry 2002 (24)	France	IFG 110 (17.0%)	63,443 (0%)	NA (21–60)	8	Yes	All-cause and CVD mortality
Hu 2003 (DECODE) (25)	Europe	IFG 110 and/or IGT (21.9%)	17,579 (53.5%)	55.5 (30–89)	8.3	No	All-cause and CVD mortality
Lu 2003 (Strong Heart Study) (26)	America	IFG 110 (10.8%)	4,304 (56.1%)	56.1 (45–74)	9	No	All-cause and CVD mortality
Ma 2003 (Singapore National Health Survey) (27)	Singapore	IFG 110 and/or IGT (16.8%)	3,492 (48.3%)	NA (18–69)	9	No	All-cause mortality
Hunt 2004 (San Antonio Heart Study) (28)	America	IFG 110 (2.2%)	2,815 (56.9%)	43.4 (25–46)	12.7	Yes	All-cause and CVD mortality
Nakagami 2004 (DECODA) (29)	Asia	IFG 110 (6.8%); IGT (16.2%); IFG 110 and/or IGT (18.4%)	6,817 (54.2%)	50 (30–89)	5	No	All-cause and CVD mortality
Hiltunen 2005 (30)	Finland	IGT (34.0%)	379 (62.8%)	76 (NA)	9.8	No	All-cause mortality
Wild 2005 (Edinburgh Artery Study) (31)	Scotland	IFG 110 (11.9%); IGT (8.3%)	1,496 (49.3%)	64.8 (55–74)	12.6	No	CVD mortality
Tsai 2008 (32)	China	IFG 110 (6.9%)	35,259 (34.2%)	50.9 (≥ 40)	15	Yes	All-cause and CVD mortality
Valdés 2009 (33)	Spain	IFG 110 and/or IGT (17.2%)	1,034 (54.2%)	50.2 (30–75)	6	No	All-cause mortality
Kokubo 2010 (The Suita study) (34)^a	Japan	IGT (NA); IFG 110 and/or IGT (NA)	4,647 (NA)	55.8 (NA)	13	Yes	All-cause and CVD mortality
Magliano 2010 (35)	Mauritius	IFG 110 (5.7%); IGT (20.6%)	9,559 (NA)	54.4 (20–82)	15.1	No	All-cause and CVD mortality
Kowall 2011 (KORA survey S4) (36)	Germany	IFG 110 and/or IGT (23.7%)	1,466 (48.3%)	64.1 (55–74)	8.8	No	All-cause and CVD mortality
Madssen 2012 (The HUNT 1 study) (37)	Norway	IFG 110 and/or IGT	47,951 (51.6%)	60 (≥ 40)	18	No	CVD mortality

Studies: ARIC = The Atherosclerosis Risk in Communities Study; AusDiab Study = Australian Diabetes, Obesity, and Lifestyle Study; CASTEL = Cardiovascular STudy in the Elderly; CHS = Cardiovascular Health Study; DECODE = Diabetes Epidemiology: Collaborative analysis of Diagnostic criteria in Europe; DECODA = Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia Study; HUNT 1 study = Nord-Trøndelag Health Study; KORA = Cooperative Health Research in the Region of Augsburg; MESA = Multi-Ethnic Study of Atherosclerosis; KMCC = Korea Multi-center Cancer Cohort; NHANES II = The Second National Health and Nutrition Examination Survey

CVD = cardiovascular disease; IFG 100 = impaired fasting glucose (fasting glucose 100–125 mg/dL); IFG 110 = impaired fasting glucose (fasting glucose 110–125 mg/dL); IGT = impaired glucose tolerance; NA = not available.

^aPaper in abstract, data of all-cause mortality were only available for females.

Figure 2. Forest plot of the comparison: prediabetes versus normoglycaemia, outcome: all-cause mortality. IFG 100 = impaired fasting glucose (fasting glucose 100–125 mg/dL); IFG 110 = impaired fasting glucose (fasting glucose 110–125 mg/dL); IGT = impaired glucose tolerance.

Figure 3. Forest plot of the comparison: prediabetes versus normoglycaemia, outcome: CVD mortality. IFG 100 = impaired fasting glucose (fasting glucose 100–125 mg/dL); IFG 110 = impaired fasting glucose (fasting glucose 110–125 mg/dL); IGT = impaired glucose tolerance.

Table II. Subgroup analyses of the association between prediabetes and all-cause mortality.

	IFG 100			IFG 110			IGT			IFG 110 and/or IGT
Subgroups	No. of studies	RR (95% CI)	P/I^2 value^a	No. of studies	RR (95% CI)	P/I^2 value^a	No. of studies	RR (95% CI)	P/I^2 value^a	No. of studies	RR (95% CI)	P/I^2 value ^a
Ethnicity			–			0.81/0%			0.76/0%			0.92/0%
Asians	0	–		3	1.14 (1.02, 1.27)		3	1.30 (1.10, 1.53)		3	1.20 (1.01, 1.43)
Non-Asians	4	1.07 (0.92, 1.26)		7	1.12 (1.03, 1.21)		7	1.33 (1.24, 1.43)		4	1.22 (1.10, 1.35)
Sex			0.008/85.8%			0.89/0%			0.79/0%			0.60/0%
Male	1	1.31 (1.11, 1.55)		4	1.14 (1.04, 1.24)		5	1.36 (1.25, 1.48)		2	1.17 (1.03, 1.33)
Female	0	–		2	1.07 (0.79, 1.44)		4	1.28 (1.11, 1.48)		1	1.31 (1.09, 1.57)
Both	3	1.01 (0.92, 1.11)		7	1.11 (1.03, 1.19)		7	1.34 (1.25, 1.43)		6	1.23 (1.12, 1.35)
Participant’s average age			0.008/85.8%			0.17/46.8%			0.14/54.7%			0.79/0%
< 55 years	1	1.31 (1.11, 1.55)		7	1.12 (1.05, 1.21)		5	1.36 (1.26, 1.47)		3	1.24 (1.01, 1.51)
≥ 55 years	3	1.01 (0.92, 1.11)		2	0.95 (0.76, 1.19)		5	1.20 (1.03, 1.39)		3	1.20 (1.09, 1.33)
Follow-up duration			0.21/35.5%			0.67/0%			0.73/0%			0.72/0%
< 10 years	2	0.94 (0.75, 1.17)		6	1.16 (1.00, 1.34)		7	1.34 (1.24, 1.44)		6	1.22 (1.11, 1.33)
≥ 10 years	2	1.15 (0.91, 1.46)		4	1.11 (1.00, 1.24)		3	1.30 (1.14, 1.48)		1	1.14 (0.80, 1.62)
Possibility of enrolling patients with diabetes			0.43/0%			0.37/0%			0.62/0%			–
None	2	1.02 (0.92, 1.12)		7	1.10 (1.01, 1.19)		9	1.33 (1.24, 1.42)		7	1.21 (1.11, 1.32)
Might be enrolled	2	1.16 (0.85, 1.57)		3	1.17 (1.05, 1.31)		1	1.17 (0.71, 1.93)		0
Adjustment of confounders			–			0.83/0%			0.81/0%			0.60/0%
Adequate^b	4	1.07 (0.92, 1.26)		7	1.13 (1.04, 1.23)		9	1.33 (1.24, 1.43)		6	1.21 (1.11, 1.32)
Not adequate	0			3	1.11 (1.00, 1.24)		1	1.30 (1.11, 1.53)		1	1.39 (0.83, 2.33)

IFG 100 = impaired fasting glucose (fasting glucose 100–125 mg/dL); IFG 110 = impaired fasting glucose (fasting glucose 110–125 mg/dL); IGT = impaired glucose tolerance.

^aFor heterogeneity among subgroups.

^bAdequate adjustment denoted adjustment of at least six of seven factors: age, sex, hypertension or systolic blood pressure or antihypertensive drug, body mass index or other measure of overweight/obesity, physical activity, cholesterol concentration or statin use, and smoking.

Table III. Subgroup analyses of the association between prediabetes and cardiovascular mortality.

	IFG 100			IFG 110			IGT			IFG 110 and/or IGT
Subgroups	No. of studies	RR (95% CI)	P/I^2 value^a	No. of studies	RR (95% CI)	P/I^2 value^a	No. of studies	RR (95% CI)	P/I^2 value^a	No. of studies	RR (95% CI)	P/I^2 value^a
Ethnicity			0.56/0%			0.32/0%			0.55/0%			0.85/0%
Asians	1	1.05 (0.74, 1.49)		3	1.17 (1.06, 1.28)		3	1.33 (1.01, 1.75)		2	1.24 (0.92, 1.67)
Non-Asians	3	1.20 (0.91, 1.57)		10	1.30 (1.07, 1.60)		7	1.21 (1.09, 1.35)		4	1.20 (1.05, 1.37)
Sex			0.09/57.9%			0.91/0%			0.43/0%			0.94/0%
Male	2	1.40 (1.09, 1.80)		5	1.15 (1.04, 1.27)		4	1.35 (1.18, 1.55)		3	1.24 (1.06, 1.46)
Female	1	1.29 (0.90, 1.84)		3	1.16 (0.75, 1.80)		4	1.33 (1.10, 1.61)		2	1.23 (0.95, 1.59)
Both	3	1.04 (0.92, 1.18)		11	1.21 (1.02, 1.42)		8	1.22 (1.10, 1.35)		5	1.20 (1.06, 1.36)
Participant’s average age			0.05/74.2%			0.68/0%			0.18/45.5%			0.45/0%
< 55 years	1	1.51 (1.07, 2.13)		7	1.21 (0.99, 1.49		5	1.18 (1.05, 1.32)		2	1.09 (0.81, 1.46)
≥ 55 years	3	1.04 (0.92, 1.18)		5	1.12 (0.84, 1.50)		5	1.37 (1.14, 1.66)		4	1.23 (1.08, 1.41)
Follow-up duration			0.82/0%			0.41/0%			0.15/52.9%			0.55/0%
< 10 years	1	1.05 (0.74, 1.49)		6	1.16 (1.05, 1.29)		5	1.15 (1.00, 1.31)		4	1.24 (1.07, 1.44)
≥ 10 years	3	1.10 (0.97, 1.24)		7	1.26 (1.07, 1.47)		5	1.33 (1.15, 1.55)		2	1.14 (0.93, 1.41)
Possibility of enrolling patients with diabetes			0.54/0%			0.08/66.8%			0.78/0%
None	2	1.10 (0.83, 1.44)		9	1.09 (0.96, 1.24)		9	1.23 (1.11, 1.36)		6	1.21 (1.07, 1.36)	–
Might be enrolled	2	1.26 (0.88, 1.80)		4	1.27 (1.13, 1.43)		1	1.13 (0.62, 2.06)		0
Adjustment of confounders			0.95/0%			0.21/36.2%			0.20/38.9%			–
Adequate	2	1.18 (0.77, 1.81)		7	1.15 (1.04, 1.27)		7	1.17 (1.03, 1.33)		6	1.21 (1.07, 1.36)
Not adequate	2	1.20 (0.97, 1.48)		6	1.30 (1.10, 1.53)		3	1.33 (1.14, 1.56)		0

IFG 100 = impaired fasting glucose (fasting glucose 100–125 mg/dL); IFG 110 = impaired fasting glucose (fasting glucose 110–125 mg/dL); IGT = impaired glucose tolerance.

^aFor heterogeneity among subgroups.

^bAdequate adjustment denoted adjustment of at least six of seven factors: age, sex, hypertension or systolic blood pressure or antihypertensive drug, body mass index or other measure of overweight/obesity, physical activity, cholesterol concentration or statin use, and smoking.

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