In Type 2 Diabetes, Lowering Risk Factors Means Longer Life

Miriam E. Tucker

April 18, 2022

For people with type 2 diabetes, reductions in four risk factors — A1c, body mass index (BMI), systolic blood pressure, and low-density lipoprotein (LDL) cholesterol — can add months to years of life expectancy, a new modeling study shows.  

The findings were published online April 18 in JAMA Network Open by Hamed Kianmehr, PhD, of the Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, and colleagues.

Using trial data to project long-term health outcomes, Kianmehr and colleagues quantified the amount of longevity gained depending on age, baseline levels of the four risk factors, and the degree of reduction in those factors.

"Better control of biomarkers can potentially increase the life expectancy by 3 years in an average person with type 2 diabetes in the US. For individuals with very high levels of A1c, systolic blood pressure, LDL cholesterol, and BMI, controlling biomarkers can potentially increase life expectancy by more than 10 years," Kianmehr and colleagues write.

The study report includes a heatmap of estimated remaining life-years by age and risk factor level that can be used as a clinical reference to support shared decision-making with patients. "Our findings can be used by clinicians and patients in selecting optimal treatment goals, to motivate patients in achieving them, and to measure potential health benefits for interventions and programs to improve diabetes care in the US," they say.

The Building, Relating, Assessing, and Validating Outcomes (BRAVO) risk engine is a validated simulation model recently developed using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and calibrated to the general US population using data from the National Health and Nutrition Examination Survey.

The study included 421 adults aged 51-80 years with type 2 diabetes without cardiovascular disease, of whom 46% were women.

Blood Glucose Lowering Advantage Greater With Higher Baseline Level

Overall, a A1c reduction from the highest (mean 9.9%) to the lowest (5.9%) quartile was associated with an additional 3.8 life-years. And reducing A1c from the highest quartile to the second-highest (mean 7.7%) was associated with an average of 3.4 life-years gained.  

However, reducing A1c further from 7.7% to the second-lowest quartile level (mean 6.8%) only added about 6 months of life, while dropping even further from 6.8% to the lowest quartile didn't add further life-years.

This finding was consistent with the ACCORD trial, in which the intensive glycemic group (A1c target < 6.0%) had increased mortality rates compared with the control group (A1c target 7%-8%), prompting that part of the study to be halted, as reported by Medscape Medical News.  

However, only a small proportion of ACCORD participants were taking glucagon-like peptide 1 (GLP-1) receptor agonists and none were taking sodium-glucose cotransporter-2 (SGLT2) inhibitors, Kianmehr and colleagues note. "Whether achieving intensive goals through these newer drugs can produce different results from the ACCORD trial is of great interest to the diabetes community...As we await such evidence, our study highlights the importance of controlling A1c levels between 7.0% and 8.0%," they write.

Body Weight Reduction a "Clinical and Public Health Priority"

Reductions from the highest BMI quartile (mean 41.4 kg/m2) to the third (33.0 kg/m2), second (28.6 kg/m2), and first (24.3 kg/m2) quartiles were associated with an additional 2.0, 2.9, and 3.9 life-years, respectively.

"Thus, body weight reduction among persons with diabetes and obesity continues to be a clinical and public health priority," the authors write.  

Systolic Blood Pressure Lowering Less Impactful, but Still Important

Compared with individuals in the fourth quartile for systolic blood pressure (160.4 mmHg), reductions to the third (139.1 mmHg), second (128.2 mmHg), and first (114.1 mmHg) quartiles were associated with life-years gained of 1.1, 1.5, and 1.9 years, respectively.

The fact that the impact of fourth-to-first quartile lowering for systolic blood pressure was less than that for A1c or BMI doesn't mean blood pressure control isn't important, the authors point out, because "our population-level estimates are not designed for clinicians to prioritize one treatment over the other because treatment outcomes varied substantially based on patients' individual characteristics."

Moreover, "Systolic blood pressure control is cost-saving from a public health perspective. The relatively lower cost of antihypertensive medications and the established strong causal relationship between systolic blood pressure and macrovascular complications make systolic blood pressure control high clinical and economic value."

As for LDL cholesterol, lowering from the fourth quartile (146.2 mg/dL) to the third (107 mg/dL), second (84.0 mg/dL), and first (59 mg/dL) quartiles were associated with 0.5, 0.7, and 0.9 additional life-years, respectively.  

The Earlier the Risk Factors Are Addressed, the Better

The heatmap used red (shorter life expectancy), orange (intermediate life expectancy), and yellow (longer life expectancy) shading to show the effects of age and gender on overall biomarker results. For example, a woman aged 50-60 years old with a BMI 30 kg/m2, systolic blood pressure 160 mmHg, and A1c 10% can add 3 years to her life by reducing her systolic blood pressure to 120 mmHg and another 1.2 years by dropping her BMI to 25 kg/m2.  

And for a man aged 50-60 years with a BMI 35 kg/m2, systolic blood pressure 160 mmHg, A1c 8%, and LDL cholesterol 130 mg/dL, reducing his BMI from 35 kg/m2 to 30 kg/m2 could add an extra 1.4 years of life. However, a man aged 71-80 years with those same biomarker levels could only add 0.6 years by dropping his BMI to 30 kg/m2.

These findings emphasize the importance of biomarker control at an earlier age and "the potential need for a trade-off between life quality and treatment for elderly patients when the benefit of biomarker control is limited," Kianmehr and colleagues note.

The study was funded in part by the US National Institutes of Health. Kianmehr has reported no relevant financial relationships.

JAMA Netw Open. Published online April 18, 2022. Full text  

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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