Background
Behavioral and lifestyle factors are key contributors to cardiovascular complications among adults with diabetes [
1]. Despite the fact that changes in diet, physical activity, smoking and alcohol use are recognized as a cornerstone of type 2 diabetes treatment [
2], there is limited evidence as to whether changes in these behaviors affect risk of cardiovascular disease (CVD) events. Behavioral intervention trials have demonstrated short-term improvements in cardiovascular risk factors among adults with diabetes randomized to specialist-led physical activity and diet interventions [
3‐
7]. For example, in the
Action for Health in Diabetes (
Look AHEAD) trial, > 2 metabolic equivalent (MET) increases in physical fitness were associated with improvements in HbA
1c, high-density lipoprotein (HDL) and triglycerides [
8], although there were no apparent associations with CVD incidence [
9]. However, the majority of type 2 diabetes patients do not receive behavioral treatment. Results from selective trial cohorts may not be generalizable to broader patient populations, and behavior changes achieved in such trials may not be realistic in the absence of a costly specialist-led intervention.
There is limited evidence from population-based cohorts as to the CVD benefits of behavior change. In an observational study of adults with self-reported diabetes enrolled in the
Nurses’ Health Study and
Health Professionals Follow-
up Study, participants who made at least 2 healthy behavior changes after diabetes diagnosis had lower 10-year hazard of CVD compared to participants who made no changes. However, this study did not assess the impact of individual behavior changes on CVD and did not determine behavior change targets that may be effective to reduce CVD risk [
10]. In the
ADDITION-
Cambridge study, we showed that participants who increased physical activity or decreased alcohol consumption in the year following diabetes diagnosis had lower 5-year hazard of CVD, and the total number of healthy behavior changes also had a protective association with CVD [
11]. Despite the suggestion that improvements in behaviors decrease risk of CVD, this study had a low number of CVD events due to the relatively short follow up, which precluded our ability to consider magnitude of behavior change, instead focusing on whether participants increased or decreased their behaviors. Participants in these two studies did not receive an intensive behavioral intervention and results suggest that modest and achievable behavior changes could reduce risk of CVD events in people with type 2 diabetes. However, further research is needed to establish meaningful and clinically relevant behavior change targets.
We have expanded on the prior analyses in the
ADDITION-
Cambridge study [
12] by considering magnitudes of behavior changes and by including a further 5 years of follow-up for CVD and mortality outcomes. We have also examined the association between behavior changes and CVD risk factors [HbA
1c; systolic and diastolic blood pressure; triglycerides; total- and LDL-cholesterol]. Our objective was to assess the associations of behavior changes in the year following diabetes diagnosis with CVD risk factors and 10-year incidence of CVD events and all-cause mortality, in a cohort of adults with screen-detected type 2 diabetes who had not received intensive behavioral treatment.
Results
Among 852 study participants, mean age at diagnosis (SD) was 61.0 (7.2) years, 61% of participants were male, 97% were white, 33% were in a managerial or professional occupation, and 51% left full-time education after age 16. Participants were followed for an average of 9.7 years from the date of diabetes diagnosis. Characteristics and measured CVD risk factors were generally similar among men and women (Table
1), so analyses were conducted among the full cohort. Use of lipid- and glucose-lowering medication increased across the study period. However, prevalence of glucose-lowering medication use was generally low at 1 year (29% in women and 32% in men), likely due to the fact that participants were in the early stages of diabetes progression and mean HbA
1c at baseline was quite low (Table
1). Of the 116 incident CVD events during the study period, 39 were revascularizations, 29 were CVD deaths, 29 were strokes, 18 were MI, and 1 was a non-traumatic amputation.
Table 1
Characteristics of type 2 diabetes patients at time of diagnosis (baseline) and 1 year later
Cohort characteristics |
BMI (kg/m2), mean (SD) | 34.7 (6.0) | 33.1 (6.1) | 32.7 (5.4) | 31.7 (5.2) |
Missing, n (%) | 2 (0.6%) | 50 (15.2%) | 3 (0.6%) | 74 (14.2%) |
Weight (kg), mean (SD) | 88.2 (16.1) | 84.3 (16.5) | 98.5 (17.8) | 95.6 (17.1) |
N missing | 1 (0.3%) | 50 (15.2%) | 3 (0.6%) | 74 (14.2%) |
Smoking, n (%) |
Current | 47 (14.3%) | 33 (11.5%) | 104 (19.9%) | 77 (17.0%) |
Former | 123 (37.4%) | 113 (39.4%) | 268 (51.3%) | 243 (53.8%) |
Never | 159 (48.3%) | 141 (49.1%) | 150 (28.7%) | 132 (29.2%) |
Missing, n (%) | 1 (0.3%) | 43 (13.0%) | 0 (0.0%) | 70 (13.4%) |
CVD risk factors |
HbA1c (%), mean (SD) | 7.2 (1.6) | 6.5 (0.8) | 7.4 (1.7) | 6.5 (0.9) |
mmol/mol, mean | 55.2 | 47.5 | 57.4 | 47.5 |
Missing, n (%) | 12 (3.6%) | 55 (17.0%) | 9 (1.7%) | 76 (14.6%) |
Blood pressure (mmHg), mean (SD) |
Systolic | 140 (20) | 133 (18) | 143 (20) | 138 (18) |
Diastolic | 80 (9) | 77 (9) | 83 (11) | 80 (10) |
Missing, n (%) | 2 (0.6%) | 52 (15.8%) | 0 (0.0%) | 73 (14.0%) |
Lipids (mmol/l), mean (SD) |
Total cholesterol | 5.6 (1.1) | 4.7 (0.9) | 5.2 (1.1) | 4.4 (1.0) |
Missing, n (%) | 10 (3.0%) | 51 (15.5%) | 9 (1.7%) | 73 (14.0%) |
LDL | 3.4 (1.0) | 2.6 (0.8) | 3.2 (1.0) | 2.5 (0.9) |
Missing, n (%) | 15 (4.5%) | 58 (17.6%) | 35 (6.7%) | 90 (17.2%) |
Triglyceride | 1.9 (1.1) | 1.8 (1.0) | 2.2 (1.8) | 2.0 (1.5) |
Missing, n (%) | 10 (3.0%) | 51 (15.5%) | 10 (1.9%) | 73 (14.0%) |
Medication use, n (%) |
Glucose-lowering |
Yes | 1 (0.3%) | 81 (28.7%) | 3 (0.6%) | 143 (32.1%) |
No | 327 (99.7%) | 201 (71.3%) | 519 (99.4%) | 303 (67.9%) |
Missing, n (%) | 2 (0.6%) | 48 (14.5%) | 0 (0.0%) | 76 (14.6%) |
Antihypertensive |
Yes | 212 (64.6%) | 207 (73.4%) | 278 (53.3%) | 297 (66.6%) |
No | 116 (35.4%) | 75 (26.6%) | 244 (46.7%) | 149 (33.4%) |
Missing, n (%) | 2 (0.6%) | 48 (14.5%) | 0 (0.0%) | 76 (14.6%) |
Lipid-lowering |
Yes | 70 (21.3%) | 186 (66.0%) | 136 (26.1%) | 292 (65.5%) |
No | 258 (78.7%) | 96 (34.0%) | 386 (73.9%) | 154 (34.5%) |
Missing, n (%) | 2 (0.6%) | 48 (14.5%) | 0 (0.0%) | 76 (14.6%) |
Health behaviors |
Total physical activity (MET hours/day), median (Q1, Q3) | 8.9 (5.6, 12.0) | 8.7 (6.1, 12.4) | 10.6 (6.9, 16.3) | 11.4 (7.3, 17.4) |
Missing, n (%) | 2 (0.6%) | 42 (12.7%) | 1 (0.2%) | 69 (13.2%) |
Energy intake (kcal/day), mean (SD) | 1832 (650) | 1660 (645) | 2057 (734) | 1762 (570) |
Missing, n (%) | 5 (1.5%) | 43 (13.0%) | 7 (1.3%) | 72 (13.8%) |
Fiber intake (g/day), mean (SD) | 17.6 (6.9) | 19.8 (11.1) | 16.4 (6.6) | 18.3 (11.1) |
Missing, n (%) | 5 (1.5%) | 43 (13.0%) | 7 (1.3%) | 72 (13.8%) |
Fat as percentage of energy intake, mean (SD) | 32.7 (6.0) | 30.4 (6.0) | 33.2 (6.3) | 31.3 (6.3) |
Missing, n (%) | 5 (1.5%) | 43 (13.0%) | 7 (1.3%) | 72 (13.8%) |
Plasma vitamin C (µmol/l), mean (SD) | 56.7 (23.4) | 60.9 (24.9) | 49.7 (21.7) | 50.4 (22.5) |
Missing, n (%) | 41 (12.4%) | 62 (18.8%) | 45 (8.6%) | 86 (16.5%) |
Alcohol (mean units/week), mean (SD) | 3.3 (5.9) | 3.0 (5.1) | 10.3 (13.2) | 9.0 (11.4) |
Missing, n (%) | 8 (2.4%) | 48 (14.5%) | 6 (1.1%) | 74 (14.2%) |
Among participants with non-missing covariate information, 218 (31%) increased their physical activity by ≥ 2 MET hours/day, 361 (53%) decreased their alcohol intake by ≥ 2 units/week, 303 (44%) decreased their total energy intake by ≥ 300 kcal/day, 256 (37%) decreased their daily fat intake by ≥ 4%, 250 (37%) increased their fiber intake by ≥ 3 g/day, and 199 (34%) increased their plasma vitamin C levels ≥ 10 µmol/l between baseline and 1 year (Table
2). After summing the number of healthy changes in the behavior change score, 36 (6%) made no healthy changes between baseline and 1 year, 145 (26%) made 1 healthy change, 217 (38%) made 2 healthy changes, and 167 (30%) made 3 or 4 healthy changes (Table
2). Those who increased total physical activity, fiber intake, and plasma vitamin C during the first year in study had lower baseline values of these behaviors compared to participants who decreased these behaviors. Similarly, participants who decreased daily total energy, fat intake, and alcohol use during the first year in study had higher baseline values for these measures (Table
2).
Table 2
Hazard ratios for the association of behavior changes from baseline to 1 year and CVD and all-cause mortality at 10 years follow-up
Total physical activity (MET hours/day) |
Increased ≥ 2 MET hours | 10.1 (6.6) | 16.4 (8.8) | 6.3 (4.5) | 30/218 | 1.10 [0.61, 1.98] | 27/218 | 0.87 [0.47, 1.60] |
Maintained within 2 MET hours | 9.1 (5.3) | 9.1 (5.4) | 0.0 (1.1) | 36/277 | 1 | 41/277 | 1 |
Decreased ≥ 2 MET hours | 16.6 (8.8) | 10.1 (6.3) | − 6.5 (5.5) | 26/198 | 0.92 [0.55, 1.55] | 25/198 | 0.90 [0.50, 1.63] |
Alcohol (mean units/week) |
Decreased ≥ 2 units or abstained | 8.5 (13.6) | 5.1 (9.3) | − 3.4 (6.1) | 38/361 | 0.56 [0.36, 0.87] | 52/362 | 1.06 [0.67, 1.67] |
Maintained within 2 units | 5.5 (6.4) | 5.5 (6.3) | 0.0 (0.8) | 38/213 | 1 | 25/214 | 1 |
Increased ≥ 2 units | 9.2 (8.2) | 15.6 (13.4) | 6.4 (7.7) | 15/101 | 0.72 [0.34, 1.53] | 15/101 | 1.13 [0.67, 1.93] |
Energy intake (kcal/day) |
Decreased ≥ 300 kcal | 2376 (721) | 1590 (490) | − 786 (472) | 38/303 | 0.78 [0.46, 1.33] | 34/303 | 0.56 [0.34, 0.92] |
Maintained within 300 kcal | 1682 (469) | 1653 (482) | − 29 (164) | 37/279 | 1 | 44/279 | 1 |
Increased ≥ 300 kcal | 1617 (546) | 2284 (829) | 668 (301) | 16/102 | 1.36 [0.69, 2.69] | 14/102 | 1.19 [0.56, 2.52] |
Fat as percentage of energy intake (%) |
Decreased ≥ 4% | 35.6 (5.4) | 27.4 (5.7) | − 8.3 (3.9) | 37/256 | 1.03 [0.64, 1.65] | 38/256 | 0.95 [0.59, 1.53] |
Maintained within 4% | 32.4 (5.4) | 32.0 (5.2) | − 0.3 (2.3) | 40/314 | 1 | 37/314 | 1 |
Increased ≥ 4% | 28.0 (6.2) | 35.7 (5.7) | 7.8 (3.5) | 14/114 | 0.87 [0.41, 1.85] | 17/114 | 1.22 [0.58, 2.57] |
Fibre intake (g/day) |
Increased > 3 g/day | 15.0 (5.5) | 24.1 (15.7) | 9.0 (14.1) | 32/250 | 0.94 [0.57, 1.55] | 32/250 | 0.99 [0.57, 1.71] |
Maintained within 3 g/day | 16.0 (5.5) | 16.1 (5.5) | 0.1 (1.7) | 41/296 | 1 | 44/296 | 1 |
Decreased ≥ 3 g/day | 22.8 (7.9) | 15.5 (5.7) | − 7.4 (5.0) | 18/138 | 1.36 [0.63, 2.94] | 16/138 | 0.93 [0.42, 2.06] |
Plasma vitamin C (µmol/l) |
Increased > 10 µmol/l | 41.6 (18.2) | 67.4 (23.8) | 25.8 (16.3) | 22/199 | 0.68 [0.41, 1.13] | 29/199 | 1.18 [0.69, 2.01] |
Maintained within 10 µmol/l | 53.1 (21.6) | 53.0 (22.0) | 0.0 (5.5) | 34/236 | 1 | 31/236 | 1 |
Decreased ≥ 10 µmol/l | 65.5 (21.4) | 40.6 (19.0) | − 24.9 (12.5) | 21/156 | 0.97 [0.58, 1.65] | 17/156 | 0.85 [0.41, 1.77] |
Behavior change score |
0 changes | n/a | n/a | n/a | 9/36 | 1 | 5/37 | 1 |
1 change | n/a | n/a | n/a | 25/145 | 0.60 [0.26, 1.37] | 16/146 | 0.68 [0.23, 2.00] |
2 changes | n/a | n/a | n/a | 23/217 | 0.39 [0.18, 0.82] | 40/220 | 1.15 [0.45, 2.89] |
3–4 changes | n/a | n/a | n/a | 19/167 | 0.42 [0.19, 0.95] | 14/170 | 0.46 [0.13, 1.54] |
Decreasing or abstaining from alcohol consumption in the year following diabetes diagnosis was associated with lower hazard of CVD at 10 years [HR (95% CI) decrease ≥ 2 units vs maintaining alcohol intake: 0.56 (0.36, 0.87)]. Decreasing total energy intake by ≥ 300 kcal per day was associated with lower hazard of all-cause mortality vs maintaining intake [HR (95% CI) 0.56 (0.34, 0.92)] (Table
2). Total number of healthy behavior changes was associated with a lower CVD hazard at 10 years [HR (95% CI) 2 changes vs 0 changes: 0.39 (0.18, 0.82); 3–4 changes vs. 0 changes: 0.42 (0.19, 0.95)].
Participants who made at least 3 healthy behavior changes had lower cholesterol and LDL at 1 year of follow-up compared to participants who made no healthy changes. Those who decreased daily energy intake by ≥ 300 kcal had lower LDL compared to those who maintained energy intake, and those who decreased fat intake had lower diastolic blood pressure compared to those who maintained their intake. Participants who increased plasma vitamin C had lower triglycerides compared to those who maintained plasma vitamin C levels (Table
3).
Table 3
Beta coefficients and 95% confidence intervals from multivariable linear regression models of the association of behavior changes in the year following diabetes diagnosis and cardiovascular risk factors measured 1 year after diagnosis
Physical activity |
Increased ≥ 2 MET hours/day | 211 | − 0.05 [− 0.16, 0.05] | 212 | -0.02 [− 0.18, 0.14] | 206 | − 0.03 [− 0.16, 0.10] | 212 | − 0.02 [− 0.14, 0.10] | 213 | − 1.41 [− 4.40, 1.57] | 213 | 0.08 [− 1.76, 1.93] |
Maintained within 2 MET hours/day | 266 | 1 | 271 | 1 | 263 | 1 | 271 | 1 | 271 | 1 | 271 | 1 |
Decreased ≥ 2 MET hours/day | 189 | 0.05 [− 0.08, 0.19] | 190 | -0.00 [− 0.18, 0.17] | 183 | − 0.03 [− 0.21, 0.14] | 190 | 0.04 [− 0.07, 0.15] | 191 | 2.34 [− 1.36, 6.05] | 191 | 1.06 [− 0.28, 2.40] |
Alcohol |
Decreased ≥ 2 units/week or abstained | 350 | 0.10 [− 0.02, 0.21] | 352 | − 0.05 [− 0.18, 0.08] | 343 | − 0.02 [− 0.14, 0.10] | 352 | − 0.01 [− 0.11, 0.09] | 354 | − 1.38 [− 4.50, 1.73] | 354 | − 1.32 [− 3.25, 0.61] |
Maintained within 2 units/week | 206 | 1 | 210 | 1 | 203 | 1 | 210 | 1 | 210 | 1 | 210 | 1 |
Increased ≥ 2 units/week | 97 | − 0.11 [− 0.33, 0.11] | 97 | 0.16 [− 0.04, 0.36] | 94 | 0.05 [− 0.11, 0.21] | 97 | 0.02 [− 0.10, 0.14] | 97 | 2.61 [− 1.75, 6.97] | 97 | 0.96 [− 1.40, 3.32] |
Energy intake |
Decreased ≥ 300 kcal | 295 | − 0.14 [− 0.32, 0.03] | 297 | − 0.08 [− 0.22, 0.06] | 290 | − 0.13 [− 0.23, − 0.03] | 297 | − 0.03 [− 0.14, 0.07] | 296 | 1.95 [− 2.13, 6.03] | 296 | 0.16 [− 1.63, 1.95] |
Maintained within 300 kcal | 267 | 1 | 271 | 1 | 262 | 1 | 271 | 1 | 273 | 1 | 273 | |
Increased > 300 kcal | 95 | 0.03 [− 0.15, 0.22] | 96 | 0.06 [− 0.14, 0.25] | 91 | − 0.06 [− 0.21, 0.08] | 96 | 0.05 [− 0.10, 0.20] | 97 | 3.72 [− 0.32, 7.76] | 97 | 0.94 [− 1.46, 3.33] |
Fat as % of energy intake |
Decreased ≥ 4% | 249 | − 0.10 [− 0.25, 0.05] | 250 | − 0.08 [− 0.23, 0.06] | 245 | − 0.05 [− 0.18, 0.07] | 250 | − 0.05 [− 0.14, 0.05] | 252 | 0.43 [− 2.94, 3.79] | 252 | − 1.78 [− 3.52, − 0.03] |
Maintained within 4% | 298 | 1 | 304 | 1 | 290 | 1 | 304 | 1 | 304 | 1 | 304 | 1 |
Increased ≥ 4% | 110 | 0.04 [− 0.14, 0.22] | 110 | 0.13 [− 0.08, 0.35] | 108 | 0.17 [− 0.01, 0.35] | 110 | − 0.02 [− 0.16, 0.11] | 110 | 2.61 [− 1.25, 6.47] | 110 | 0.65 [− 2.04, 3.34] |
Fibre intake |
Increased > 3 g/day | 239 | 0.07 [− 0.08, 0.22] | 239 | − 0.05 [− 0.19, 0.09] | 231 | − 0.04 [− 0.18, 0.09] | 239 | 0.02 [− 0.09, 0.12] | 241 | 0.17 [− 2.66, 2.99] | 241 | 0.09 [− 1.62, 1.80] |
Maintained within 3 g/day | 285 | 1 | 290 | 1 | 281 | 1 | 290 | 1 | 291 | 1 | 291 | 1 |
Decreased ≥ 3 g/day | 133 | 0.12 [− 0.09, 0.34] | 135 | 0.06 [− 0.09, 0.22] | 131 | − 0.08 [− 0.22, 0.06] | 135 | 0.10 [− 0.01, 0.20] | 134 | 3.09 [− 0.43, 6.62] | 134 | 1.79 [− 0.37, 3.94] |
Plasma vitamin C |
Increased > 10 µmol/l | 199 | − 0.08 [− 0.25, 0.10] | 199 | − 0.06 [− 0.31, 0.19] | 194 | − 0.00 [− 0.21, 0.21] | 199 | − 0.16 [− 0.28, − 0.05] | 199 | − 2.65 [− 6.32, 1.02] | 199 | − 1.34 [− 3.23, 0.55] |
Maintained within 10 µmol/l | 231 | 1 | 236 | 1 | 227 | 1 | 236 | 1 | 236 | 1 | 236 | 1 |
Decreased ≥ 10 µmol/l | 154 | 0.08 [− 0.12, 0.29] | 156 | − 0.03 [− 0.23, 0.18] | 152 | − 0.03 [− 0.23, 0.16] | 156 | − 0.02 [− 0.11, 0.08] | 155 | − 0.67 [− 4.15, 2.81] | 155 | − 0.87 [− 3.05, 1.31] |
Behavior change score |
0 changes | 35 | 1 | 36 | 1 | 34 | 1 | 36 | 1 | 36 | 1 | 36 | 1 |
1 change | 144 | − 0.23 [− 0.69, 0.23] | 145 | − 0.16 [− 0.44, 0.12] | 139 | − 0.11 [− 0.36, 0.15] | 145 | − 0.01 [− 0.20, 0.18] | 144 | − 0.78 [− 6.42, 4.86] | 144 | − 1.08 [− 4.33, 2.17] |
2 changes | 215 | − 0.20 [− 0.58, 0.18] | 217 | − 0.40 [− 0.64, − 0.15] | 211 | − 0.18 [− 0.38, 0.02] | 217 | − 0.13 [− 0.32, 0.06] | 217 | 1.07 [− 4.23, 6.38] | 217 | − 2.47 [− 5.61, 0.67] |
3–4 changes | 165 | − 0.11 [− 0.49, 0.27] | 167 | − 0.40 [− 0.64, − 0.15] | 165 | − 0.21 [− 0.42, − 0.01] | 167 | − 0.14 [− 0.33, 0.05] | 167 | − 2.05 [− 7.59, 3.49] | 167 | − 2.63 [− 5.86, 0.61] |
Missing behavior change information was associated with sex, SES and higher baseline BMI; unskilled workers were more likely to have missing information compared to professional workers, and women were more likely to have missing information compared to men. Accounting for missing information using multiple imputation did not meaningfully change the observed associations between behavior changes and CVD or mortality (Additional file
1). Results were also robust to adjusting for weight change from baseline to 1 year (Additional file
2) and adjusting for individual behavior changes (Additional file
3). The associations between behavior change score and CVD were similar when considering an alternate behavior change scoring method where each dietary change counted for 0.5 points (Additional file
4).
Discussion
In this population-based study of adults with screen-detected diabetes, modest changes in health behaviors in the year following diabetes diagnosis were associated with a 44–58% lower hazard of CVD 10 years after diabetes diagnosis. Specifically, reducing alcohol intake by ≥ 2 units/week was associated with an estimated 44% lower hazard compared to maintaining alcohol intake. Those who reduced total energy intake by ≥ 300 kcal/day also had 44% lower hazard of all-cause mortality compared to those who maintained their intake, but this was not associated with CVD events. Those who made at least 2 overall healthy changes had lower hazard of CVD compared to those who made no healthy changes. The observed associations between behaviors, CVD and mortality were independent of weight change and baseline behaviors, and were robust to sensitivity analyses.
Our study is the first to have assessed the impacts of moderate changes in health behaviors relative to maintenance of behaviors after diabetes diagnosis to show that moderate changes that were achievable with no behavioral intervention may reduce incidence of CVD events. The study highlights the important role of lifestyle management in diabetes treatment, which is particularly relevant in light of results from the Diabetes Remission Clinical Trial (DiRECT) which demonstrated the benefits of lifestyle change on diabetes status [
28] and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial which showed that intensification of glucose-lowering treatment may increase mortality [
29]. The results of this study are supported by results from the
Nurses’ Health Study and the
Health Professionals Follow-
up Study, in which improvements in a behavior score (reflecting changes in diet, physical activity and alcohol consumption) from before to after diabetes diagnosis was associated with a 21% lower hazard of CVD events at 10 years [
10]. A previous analysis in
ADDITION-
Cambridge which considered changes in behaviors after diabetes diagnosis and 5-year incidence of CVD showed similar associations between alcohol reduction and ≥ 2 behavior changes and incidence of CVD [
11].
In our study, reduction in alcohol consumption was associated with lower hazard of CVD events. Few studies have assessed changes in alcohol consumption and CVD incidence, although one study showed that short-term abstention from alcohol was associated with improvement in insulin resistance and CVD risk factors [
30]. The mechanisms by which alcohol consumption impacts CVD risk remains unclear. Metabolism of ethanol from alcoholic beverages may lead to generation of reactive oxygen species in the blood, which can contribute to atherogenesis [
31] and may thereby increase risk of a future CVD event. However, several studies have reported protective associations between light to moderate alcohol consumption, CVD and mortality [
32‐
36], although these studies did not assess changes in alcohol consumption. In contrast, a Mendelian randomization meta-analysis showed a lower risk of CVD associated with lower alcohol consumption [
37]. Our result is in agreement with a previous study in
ADDITION-
Cambridge which showed that participants who reduced or abstained from alcohol intake had an estimated 62% lower 5-year hazard of CVD compared to participants who increased their alcohol intake [
11]. Our sensitivity analyses suggested that the protective association between alcohol reduction and CVD was independent of weight loss. We also did not observe any clear associations between change in alcohol intake and CVD risk factors. Therefore, weight loss and improvement in traditional CVD risk factors may not be the primary mechanism by which alcohol reduction may lead to lower incidence of CVD.
In the current study, increases in total physical activity of ≥ 2 MET hours per day were not associated with risk of CVD. This is in contrast to studies that have found protective associations of increases in physical activity and CVD [
9,
11]. Differences in results may be related to the degree of physical activity achieved, maintenance of physical activity levels over time, and differences in error in the tools used to measure physical activity. The
Look AHEAD trial showed a non-statistically significant 32% lower 10-year hazard of CVD among adults with diabetes who had > 2 MET increases in physical fitness in 1 year [
9]. However, in the
Look AHEAD trial, changes in fitness levels were achieved via intensive lifestyle intervention, and study participants may have been more able to engage in physical activity compared to the general diabetes patient population [
38]. We speculate that the amount and duration of change in physical activity achieved among the
ADDITION cohort may not have been sufficient to yield reduction in CVD events. There is substantial research supporting a biological role of physical activity to improve cardiovascular health. Past studies have shown that exercise improves endothelial function [
39], improves cardiovascular risk factors including glycaemia and lipid levels [
40] and reduces incidence of CVD [
41]. We did not objectively measure physical activity or physical fitness but relied on self-reported activity. Misreport of physical activity likely contributed to misclassification of changes in physical activity, which would bias our results toward the null and reduce our ability to detect any association between physical activity and CVD.
There are several limitations to consider when interpreting results from this study. There were baseline differences in health behaviors by category of behavior change, which may have affected our ability to detect associations between changes in behaviors and the outcomes of interest; however, we adjusted for baseline values of the behaviors to address this confounding. We considered relative increases or decreases vs maintenance of behaviors, but could not assess finer categorizations of behavior changes due to limitations of sample size. This study used validated questionnaires to assess diet, physical activity and alcohol intake [
21,
22], and objective measurement of plasma vitamin C, however self-reported exposure information may have been misclassified due to recall error or other misreport. The EPIC Physical Activity Questionnaire has shown moderate within-individual repeatability (correlation coefficients > 0.60) [
21], and the amount of error in the tool may impede our ability to discern small changes in physical activity over time. Alcohol intake is often underreported [
42,
43], and total energy intake may be underreported by individuals with higher BMI [
44]. However, because we have assessed within-individual changes in the behaviors rather than between-individual changes, our results may be less sensitive to imprecision in the absolute measure of the behavior. Misclassification of behavior changes would likely bias results towards the null, as we do not anticipate that misclassification would be related to the outcomes.
Possible health differences between participants who made behavior changes versus those who did not may have introduced unmeasured confounding. There were no apparent differences in demographic and lifestyle characteristics at baseline after stratifying by number of healthy behavior changes, though there were small differences in distributions of SES (Additional file
5). However, we adjusted for confounding by SES in all analyses. There were also no differences in CVD risk factors at baseline (Additional file
5), which supports the interpretation that the observed associations between behavior change score and CVD were not due to differences in underlying cardiovascular risk between these groups. While our results suggest that behavior changes in the first year after diabetes diagnosis are potentially important for CVD reduction independent of weight loss, the degree of maintenance of change may also be important; we were unable to consider modification by maintenance of behavior changes at 5 years in study as the number of CVD events between 5 and 10 years was small. Analyses of behavior changes and CVD events were subject to censoring due to the competing risk of non-CVD death, and we addressed this by censoring participants at the date of CVD event, death, or the end of the study period, whichever came first.
The
ADDITION cohort is a population-based sample, and all individuals determined to be eligible during screening enrolled in the study. This affords generalizability to the target population of adults in Eastern England with a new diagnosis of type 2 diabetes. Due to the screening-based nature of this study, we were able to capture behavior changes during the period immediately following diabetes diagnosis and assessed whether achievable changes during this period may be beneficial to reduce long-term disease burdens. However, because participants were screen-detected to have diabetes, many participants were in the early stages of diabetes progression and mean HbA
1c among the cohort was quite low (7%). This study had repeat measurement of behaviors and is one of few studies to have assessed long-term associations of behavior change after diabetes diagnosis with CVD and mortality [
10,
11]. We identified modest behavior changes that were associated with estimated lower hazards of CVD, which may be useful to inform interventions for behavior changes among newly diagnosed patients where resources cannot support behavioral treatment. We achieved 99.8% CVD and mortality ascertainment and all events were independently adjudicated. Furthermore, sensitivity analyses showed that our results were robust to missing information on health behaviors, and that the observed associations were independent of weight loss.
A substantial number of participants spontaneously made moderate changes to their behavior following diabetes diagnosis. However, receiving a diagnosis of diabetes may not be sufficient to trigger behavior changes in most patients and so behavioral interventions at the point of diagnosis could support more people to make changes [
45]. Intervening early in diabetes progression to control risk factors may help to avoid complications associated with intensification of diabetes treatment and may reduce long-term CVD events [
46]. The study results suggest that making small changes across a few behaviors may reduce CVD risk; these changes may be translated to a decrease of 2 units of alcohol per week (e.g. one glass of wine), a decrease in daily calorie intake by 300 kcal (e.g. one muffin), and an increase in 2 MET hours per day of physical activity (e.g. 30 min of casual walking or cycling).
Acknowledgements
We are grateful to the ADDITION-Cambridge independent trial steering committee (Nigel Stott (Chair), John Weinman, Richard Himsworth, and Paul Little). Aside from the authors, the ADDITION-Cambridge study team has included Amanda Adler, Judith Argles, Gisela Baker, Rebecca Bale, Roslyn Barling, Daniel Barnes, Mark Betts, Sue Boase, Ryan Butler, Parinya Chamnan, Kit Coutts, Sean Dinneen, Pesheya Doubleday, Mark Evans, Tom Fanshawe, Francis Finucane, Philippa Gash, Julie Grant, Wendy Hardeman, Robert Henderson, Greg Irving, Garry King, Ann-Louise Kinmonth, Joanna Mitchell, Richard Parker, Nicola Popplewell, A. Toby Prevost, Richard Salisbury, Lincoln Sargeant, Megan Smith, Stephen Sutton, Fiona Whittle and Kate Williams. We thank the Cambridge University Hospitals NHS Foundation Trust Department of Clinical Biochemistry and the NIHR Cambridge Biomedical Research Centre, Core Biochemical Assay Laboratory for carrying out the biochemical assays, and the following groups within the MRC Epidemiology Unit: data management (Adam Dickinson), information technology (Rich Hutchinson), technical (Matt Sims), study coordination (Gwen Brierley, Richard Salisbury) and data collection (Kit Coutts).
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