Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: A cohort study

Abstract

Background The influence of overall lifestyle behaviors on diabetic microvascular complications remains unknown. In addition, the potential mediating biomarkers underlying the association is unclear. This study aimed to examine the associations of the combined lifestyle factors with risks of total and individual microvascular complications among patients with type 2 diabetes (T2D) and to explore the potential mediation effects of metabolic biomarkers. Methods and findings This retrospective cohort study included 15,104 patients with T2D free of macro- and microvascular complications at baseline (2006 to 2010) from the UK Biobank. Healthy lifestyle behaviors included noncurrent smoking, recommended waist circumference, regular physical activity, healthy diet, and moderate alcohol drinking. Outcomes were ascertained using electronic health records. Over a median of 8.1 years of follow-up, 1,296 cases of the composite microvascular complications occurred, including 558 diabetic retinopathy, 625 diabetic kidney disease, and 315 diabetic neuropathy, with some patients having 2 or 3 microvascular complications simultaneously. After multivariable adjustment for sociodemographic characteristics, history of hypertension, glycemic control, and medication histories, the hazard ratios (95% confidence intervals (CIs)) for the participants adhering 4 to 5 low-risk lifestyle behaviors versus 0 to 1 were 0.65 (0.46, 0.91) for diabetic retinopathy, 0.43 (0.30, 0.61) for diabetic kidney disease, 0.46 (0.29, 0.74) for diabetic neuropathy, and 0.54 (0.43, 0.68) for the composite outcome (all Ps-trend ≤0.01). Further, the population-attributable fraction (95% CIs) of diabetic microvascular complications for poor adherence to the overall healthy lifestyle (<4 low-risk factors) ranged from 25.3% (10.0%, 39.4%) to 39.0% (17.7%, 56.8%). In addition, albumin, HDL-C, triglycerides, apolipoprotein A, C-reactive protein, and HbA1c collectively explained 23.20% (12.70%, 38.50%) of the associations between overall lifestyle behaviors and total diabetic microvascular complications. The key limitation of the current analysis was the potential underreporting of microvascular complications because the cases were identified via electronic health records. Conclusions Adherence to overall healthy lifestyle behaviors was associated with a significantly lower risk of microvascular complications in patients with T2D, and the favorable associations were partially mediated through improving biomarkers of glycemic control, systemic inflammation, liver function, and lipid profile.

Association of healthy lifestyle with incident cardiovascular diseases among hypertensive and normotensive Chinese adults

“…Meanwhile, because adherence to a healthy lifestyle can also reduce the risk of hypertension (32, 33), people without hypertension are recommended to follow a healthy lifestyle as well. Furthermore, due to the potential mediating effect of lipid profile on lifestyle and CVD (34), lipid was not included as a confounder in models, which was consistent with other studies (13,(28)(29)(30).…”

Healthy lifestyle choices and microvascular complications: New insights into diabetes management

“…In this issue of PLOS Medicine , an accompanying study by Tingting Geng and colleagues provides a new perspective on the association of overall lifestyle factors with the risk of microvascular complications [ 7 ]. This retrospective study included 15,104 people with type 2 diabetes free of macro or microvascular complications at baseline from the UK Biobank.…”

“…Thus, the 2 observational studies taken from different study populations give us confidence in the positive findings of lifestyle interventions in the prevention of microvascular complications. However, both highlight that there is an extremely low number of people with diabetes who adhere to a healthy lifestyle: in the new study, Tingting Geng and colleagues found only 10.3% were adherent to 4 to 5 low-risk lifestyle behaviours in UK Biobank [ 7 ]. Similarly, Zhijia Sun and colleagues found only 14.4% were adherent in the Chinese Kadoorie Biobank [ 8 ].…”

“…Since there has recently been greater attention paid to ethnic and social health inequalities [ 12 , 13 ], further research on lifestyle behaviours and diabetes complications may benefit from stratified analyses to identify whether the findings differ between patient demographics. This may necessitate studies in more diverse cohorts, however, as the UK Biobank data used in the present study is limited in terms of ethnic diversity, with the majority of the population from white ethnicity [ 7 ]. Additionally, lifestyle factors in the study by Geng and colleagues were assessed at a single time point [ 7 ]; future longitudinal studies need to include measurement of lifestyle behaviours at multiple time points to allow for a flexible modelling approach that accounts for time-varying covariance.…”

“…This may necessitate studies in more diverse cohorts, however, as the UK Biobank data used in the present study is limited in terms of ethnic diversity, with the majority of the population from white ethnicity [ 7 ]. Additionally, lifestyle factors in the study by Geng and colleagues were assessed at a single time point [ 7 ]; future longitudinal studies need to include measurement of lifestyle behaviours at multiple time points to allow for a flexible modelling approach that accounts for time-varying covariance. This will provide insight into both the extent to which patients’ lifestyle habits change over time and how this affects the incidence and progress of diabetic complications.…”