scholarly journals Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control

Diabetologia ◽  
2021 ◽  
Author(s):  
Johanne Tremblay ◽  
Mounsif Haloui ◽  
Redha Attaoua ◽  
Ramzan Tahir ◽  
Camil Hishmih ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
High Risk ◽  
Glucose Control ◽  
Risk Group ◽  
Cardiovascular Death ◽  
Polygenic Risk ◽  
Renal Complications ◽  
Intensive Blood Pressure

Abstract Aims/hypothesis Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk. Methods We developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study. Results The model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10−21 and p = 9.6 × 10−31, respectively) and a 4.4-fold (p = 6.8 × 10−33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. Conclusions/interpretation This novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy. Graphical abstract

scholarly journals Intensive risk factor management and cardiovascular autonomic neuropathy in type 2 diabetes: the ACCORD Trial

2020 ◽  
Author(s):  
Yaling Tang ◽  
Hetal Shah ◽  
Carlos Roberto Bueno Junior ◽  
Xiuqin Sun ◽  
Joanna Mitri ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Autonomic Neuropathy ◽  
Pressure Control ◽  
Cardiovascular Autonomic Neuropathy ◽  
Risk Factor Management ◽  
Traditional Risk Factors ◽  
Intensive Blood Pressure

<b>Objectives: </b>The effects of preventive interventions on cardiovascular autonomic neuropathy (CAN) remain unclear. We examined the effect of intensively treating traditional risk factors for CAN, including hyperglycemia, hypertension, and dyslipidemia, in persons with type 2 diabetes (T2D) and high cardiovascular risk participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. <p><b>Research Design and Methods: </b>CAN was defined as heart rate variability indices below the 5<sup>th</sup> percentile of the normal distribution. Of 10,250 ACCORD participants, 71% (n=7,275) had a CAN evaluation at study entry and at least once after randomization. The effects of intensive interventions on CAN were analyzed among these subjects through generalized linear mixed models. </p> <p><b>Results: </b>As compared to standard intervention, intensive glucose treatment reduced CAN risk by 16% (OR=0.84, 95%CI 0.75–0.94, p=0.003) – an effect driven by individuals without cardiovascular disease (CVD) at baseline (OR= 0.73, 95%CI 0.63–0.85, p<0.0001) rather than those with CVD (OR=1.10, 95%CI 0.91–1.34, p=0.34) (p for interaction=0.001). Intensive blood pressure intervention decreased CAN risk by 25% (OR=0.75, 95% CI 0.63–0.89, p=0.001), especially in patients ≥65 years old (OR=0.66, 95% CI 0.49–0.88, p=0.005) (p for interaction =0.05). Fenofibrate did not have a significant effect on CAN (OR=0.91, 95%CI 0.78–1.07, p=0.26). </p> <p><b>Conclusions: </b> These data confirm a beneficial effect of intensive glycemic therapy and demonstrate, for the first time, a similar benefit of intensive blood pressure control on CAN in T2D. A negative CVD history identifies T2D patients who especially benefit from intensive glycemic control for CAN prevention. </p>

Abstract 190: Use of Intensive Glycemic Management in Older Adults With Diabetes. An Analysis From the Diabetes Collaborative Registry

2018 ◽  
Vol 11 (suppl_1) ◽  
Author(s):  
Suzanne V Arnold ◽  
Kasia J Lipska ◽  
Jingyan Wang ◽  
Leo Seman ◽  
Sanjeev N Mehta ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
High Risk ◽  
Glucose Control ◽  
Low Risk ◽  
Minimal Risk ◽  
Tight Control ◽  
Poor Control ◽  
Intensively Managed

Background: Older adults with diabetes are less likely to benefit and more likely to be harmed by intensive glucose control. Prior research has shown that many older adults continue to be intensively managed despite guidelines that recommend that treatment targets should be relaxed in these patients. As many new agents have been introduced with minimal risk of hypoglycemia, we examined contemporary data to understand to what extent older patients with diabetes are still intensively managed with agents that can cause hypoglycemia. Methods: We examined A1c and treatment data in adults ≥75 years with type 2 diabetes from 151 US outpatient sites in DCR. Patients were categorized as poor control (A1c >9%), moderate control (A1c >8-9%), conservative control (A1c 7-8%), tight control/low-risk agents (A1c <7% on meds with low risk for hypoglycemia), and tight control/high-risk agents (A1c <7% on insulin, sulfonylureas, or meglitinides). Adults with A1c <7% on no glucose-lowering medications were excluded. We used hierarchical logistic regression to examine patient and site factors associated with tight control/high-risk agents vs. conservative control or tight control/low-risk agents. Results: Among 30,696 older adults with diabetes, 5,596 (18%) had moderate or poor control, 9,227 (30%) conservative control, 7,893 (26%) tight control/low-risk agents, and 7,980 (26%) tight control/high-risk agents (Fig. A). Older age, male sex, heart failure, chronic kidney disease, and coronary artery disease were each independently associated with a greater odds of tight control/high-risk agents (Fig. B). After adjusting for patient factors, there were no differences among practice specialties (endocrinology, primary care, cardiology) in how aggressively patients were managed. Conclusion: Despite greater availability of agents that do not cause hypoglycemia, a quarter of older adults with type 2 diabetes are tightly controlled with high-risk medications. These results suggest potential overtreatment of a substantial proportion of patients. Efforts are needed to provide more specific guidance on how to safely treat older adults with diabetes (both through targeting treatment with low-risk agents and through de-escalation of glucose control) and then to efficiently translate that guidance into busy clinical practice.

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