Abstract:Key Points
Question
Among persons with diabetes, are diabetic retinopathy (DR) and diabetic kidney disease (DKD) associated with higher risk of mortality?
Findings
In this cohort study that included 2964 Asian (Chinese, Malay, and Indian) persons with diabetes followed up for a median of 8.8 years, the presence of DR was associated with higher all-cause mortality independent of presence of DKD. Persons with both DKD and DR had the highest rate of mortality,… Show more
“…In a meta-analysis of studies on type 2 diabetes, Kramer et al 34 showed that DR was associated with 2.41fold increased risk of mortality. In Asians with type 2 diabetes, Sabanayagam et al 35 reported that DR was associated with 1.54-fold increased risk of mortality, and this result is consistent with our own previous study in which we found that DR was associated with 1.58-fold increased risk of mortality in patients without albuminuria. 36 The role of adiposity is ambiguous in patients with DR. 37 DR has been shown to be associated with obesity.…”
Purpose: An "obesity paradox" has been observed in patients with type 2 diabetes. However, the optimal body mass index (BMI) for survival may be influenced by the stage of diabetes. We examined the relationship between BMI and mortality in patients with type 2 diabetes and the influence of diabetic retinopathy (DR). Patients and Methods: This is a retrospective cohort composing patients with type 2 diabetes who were admitted due to poor glucose control. Presence of DR was confirmed by ophthalmologists. The primary outcome was all-cause mortality. The association between BMI and mortality was assessed using a Cox proportional hazards model with adjustment for age, sex, and traditional risk factors. Results: A total of 2053 patients were enrolled. Over median follow-up of 6.7 years, there were 1060 deaths. Patients were classified into five categories based on admission BMI (kg/m 2): <18.5, 18.5-23, 23-25, 25-27 (reference), 25-30 and >30. Mortality risk was significantly higher in the <18.5 kg/m 2 , 18.5-23 kg/m 2 , and 23-25 kg/m 2 categories than in the reference category (P <0.001). The similar obesity paradox was observed in the subgroup of patients without DR. However, in patients with DR, only patients with BMI <18.5 kg/m 2 had significantly increased mortality than those in the reference category. The presence of DR significantly modified the shape of the association between BMI and mortality (P = 0.019). Conclusion: The obesity paradox exists in patients with poorly controlled type 2 diabetes. The presence of DR appears to significantly influence the shape of the association between BMI and mortality.
“…In a meta-analysis of studies on type 2 diabetes, Kramer et al 34 showed that DR was associated with 2.41fold increased risk of mortality. In Asians with type 2 diabetes, Sabanayagam et al 35 reported that DR was associated with 1.54-fold increased risk of mortality, and this result is consistent with our own previous study in which we found that DR was associated with 1.58-fold increased risk of mortality in patients without albuminuria. 36 The role of adiposity is ambiguous in patients with DR. 37 DR has been shown to be associated with obesity.…”
Purpose: An "obesity paradox" has been observed in patients with type 2 diabetes. However, the optimal body mass index (BMI) for survival may be influenced by the stage of diabetes. We examined the relationship between BMI and mortality in patients with type 2 diabetes and the influence of diabetic retinopathy (DR). Patients and Methods: This is a retrospective cohort composing patients with type 2 diabetes who were admitted due to poor glucose control. Presence of DR was confirmed by ophthalmologists. The primary outcome was all-cause mortality. The association between BMI and mortality was assessed using a Cox proportional hazards model with adjustment for age, sex, and traditional risk factors. Results: A total of 2053 patients were enrolled. Over median follow-up of 6.7 years, there were 1060 deaths. Patients were classified into five categories based on admission BMI (kg/m 2): <18.5, 18.5-23, 23-25, 25-27 (reference), 25-30 and >30. Mortality risk was significantly higher in the <18.5 kg/m 2 , 18.5-23 kg/m 2 , and 23-25 kg/m 2 categories than in the reference category (P <0.001). The similar obesity paradox was observed in the subgroup of patients without DR. However, in patients with DR, only patients with BMI <18.5 kg/m 2 had significantly increased mortality than those in the reference category. The presence of DR significantly modified the shape of the association between BMI and mortality (P = 0.019). Conclusion: The obesity paradox exists in patients with poorly controlled type 2 diabetes. The presence of DR appears to significantly influence the shape of the association between BMI and mortality.
“…After primary screening and removing duplicates, 210 potentially eligible articles were selected. After full-text review, 10 eligible cohort studies with 11,239 diabetic patients were finally included in the quantitative synthesis [ 11 – 20 ]. Fig.…”
Background
The prognostic significance of diabetic retinopathy (DR) for cardiovascular diseases (CVD) remained unclear. Therefore, we performed this meta-analysis to assess whether DR predicted CVD mortality in diabetic patients.
Methods
We searched PubMed, Embase, Web of Science and Cochrane Library for cohort studies reporting the association of DR and CVD mortality. Then we pooled the data for analysis.
Results
After screening the literature, 10 eligible studies with 11,239 diabetic subjects were finally included in quantitative synthesis. The pooled risk ratio (RR) of DR, mild DR, and severe DR for CVD mortality was 1.83 (95% confidence interval (CI): 1.42, 2.36; p < 0.001), 1.13 (95% CI 0.81, 1.59; p = 0.46), and 2.26 (1.31, 3.91; p = 0.003), respectively, compared to those without DR. In type 2 DM, the patients with DR had a significantly higher CVD mortality (RR: 1.69; 95% CI 1.27, 2.24; p < 0.001). Subgroup analysis also showed a significantly higher CVD mortality in DR according to various regions, study design, data source, and follow-up period (all RR > 1; all P values < 0.05). Data from 2 studies showed no significant correlation of DR and CVD mortality in diabetic patients receiving cardiovascular surgery (RR: 2.40; 95% CI 0.63, 9.18; P = 0.200).
Conclusions
DR is a risk marker of cardiovascular death, and severe DR predicts a doubled mortality of CVD in diabetes. These findings indicate the importance of early identification and management of diabetic patients with DR to reduce the risk of death.
“…In addition to macrovascular disease, diabetes increases the risk of microvascular complications, such as diabetic retinopathy and diabetic kidney disease (DKD). Several lines of evidence suggest that the presence of microvascular disease dramatically increases the risk of macrovascular complications (140)(141)(142). Whether this is due to a shared underlying mechanism or if one complication accelerates the other is unknown.…”
Section: Are Kidney Macrophages In Diabetic Kidney Disease Altered Inmentioning
With the increasing prevalence of diabetes worldwide, vascular complications of diabetes are also on the rise. Diabetes results in an increased risk of macrovascular complications, with atherosclerotic cardiovascular disease (CVD) being the leading cause of death in adults with diabetes. The exact mechanisms for how diabetes promotes CVD risk are still unclear, although it is evident that monocytes and macrophages are key players in all stages of atherosclerosis both in the absence and presence of diabetes, and that phenotypes of these cells are altered by the diabetic environment. Evidence suggests that at least five pro-atherogenic mechanisms involving monocytes and macrophages contribute to the accelerated atherosclerotic lesion progression and hampered lesion regression associated with diabetes. These changes include (1) increased monocyte recruitment to lesions; (2) increased inflammatory activation; (3) altered macrophage lipid accumulation and metabolism; (4) increased macrophage cell death; and (5) reduced efferocytosis. Monocyte and macrophage phenotypes and mechanisms have been revealed mostly by different animal models of diabetes. The roles of specific changes in monocytes and macrophages in humans with diabetes remain largely unknown. There is an ongoing debate on whether the changes in monocytes and macrophages are caused by altered glucose levels, insulin deficiency or insulin resistance, lipid abnormalities, or combinations of these factors. Current research in humans and mouse models suggests that reduced clearance of triglyceride-rich lipoproteins and their remnants is one important mechanism whereby diabetes adversely affects macrophages and promotes atherosclerosis and CVD risk. Although monocytes and macrophages readily respond to the diabetic environment and can be seen as protagonists in diabetes-accelerated atherosclerosis, they are likely not instigators of the increased CVD risk.
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