Among patients with type 2 diabetes (T2D) and hypertension, spending more time with both A1c and systolic blood pressure (SBP) in the target range over 1 year was associated with greater reductions in the risk for adverse kidney outcomes than achieving target levels for either measure alone, new research showed.

This “suggests a synergistic benefit,” the authors wrote in the study, published in the American Journal of Kidney Diseases.

Although A1c and blood pressure fluctuate over time, previous studies have linked time in the target range for these measures individually with adverse cardiovascular, kidney, and other outcomes. However, there has been a lack of research on the effects of achieving target ranges for both measures simultaneously.

Assessing the combined time in target ranges may therefore provide a more accurate picture of long-term glycemic and blood pressure control than single-point measurements.

Post Hoc Analysis of ACCORD Trial Data

To investigate, first author Guang Ning, MD, PhD, of the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine in Shanghai, China, and colleagues conducted a post hoc analysis of the ACCORD trial involving 6542 participants with T2D and established cardiovascular disease or multiple cardiovascular risk factors.

ACCORD participants were randomly assigned to intensive treatment targeting an A1c level below 6.0% or standard therapy targeting levels of 7.0%-7.9%. They were also randomly assigned to intensive SBP control targeting < 120 mm Hg or standard SBP control targeting < 140 mm Hg.

In the current post hoc analysis, participants who maintained A1c within the target range 100% of the time during the first 12 months had a 20% lower risk for the composite kidney outcome than those in the lowest tertile of (49.6% or less). The composite outcome included incident albuminuria, a decline in estimated glomerular filtration rate (eGFR) ≥ 40% from baseline, or kidney failure.

Similarly, participants who maintained SBP within target 100% of the time in the first 12 months had a 32% lower risk for the composite kidney outcome than those in the lowest tertile (50.7% or less).

Importantly, participants who maintained both A1c and SBP levels within the target range for more than 80% of the first 12 months had a 29% lower risk for the composite kidney outcome than those whose combined time in range was 80% or less.

A combined A1c and SBP time in the target range above 80%, compared with 80% or less time in range, was also associated with a lower risk for several secondary outcomes, including a 43% lower risk for all-cause mortality, a 33% lower risk for albuminuria, and an 18% lower risk for the composite outcome of a 40% or greater decline in eGFR from baseline or kidney failure.

No significant associations were observed between combined A1c and SBP time in target range and macroalbuminuria or kidney failure when analyzed as separate outcomes. However, the authors noted that the relatively low number of cases of macroalbuminuria limited statistical power.

The results were generally similar in a subgroup analysis of patients with chronic kidney disease at baseline.

Notably, these associations were not observed among patients assigned to the intensive SBP treatment arm.

“This attenuation may be partly explained by reduced variability in SBP within the intensive treatment group, leading to a narrower distribution of SBP time in target range and reduced contrast across categories of SBP time in target range,” the study authors wrote.

They added that the relatively small number of events in the intensive treatment subgroup was another limitation.

Overall, however, “our results confirm findings of the benefits associated with keeping A1c and SBP within target range as reported by previous studies focused on cardiovascular outcomes, adverse kidney outcomes, dementia, and mortality,” they concluded.

Differences From Continuous Glucose Monitoring (CGM) Time in Target Range

The authors emphasized that the “time in target range” used in their study differs from the glucose time in target range commonly used with CGM or 24-hour ambulatory blood pressure monitoring. Those measures reflect shorter monitoring periods, typically 2-12 weeks with CGM and over 24 hours with blood pressure.

“Neither metric reflects variability beyond the short monitoring period,” the authors noted. “In contrast, A1c and SBP time in target range provide a composite measure of glycemic and BP control and stability over a 12-month period in this study.”

Trends Over Time Matter

Commenting on the study, Patricia Underwood, PhD, assistant professor at the Connell School of Nursing and endocrine nurse practitioner at the VA Boston Healthcare System in Boston, underscored that “the most critical takeaway is that longitudinal trends in clinical measures matter.”

“The concept that reducing variability of A1c and blood pressure over time influences complication risks is important for clinicians and patients,” she told Medscape Medical News.

Underwood, who co-authored a previous study showing that A1c stability (ie, greater time spent in range) was associated with a reduced risk for Alzheimer’s disease and related dementias, said those findings and prior research on lower mortality and micro- and macrovascular complications suggest that longitudinal A1c is a “more reliable indicator of complication risk in diabetes” than single measurements.

“Most clinicians traditionally focus only on the most recent laboratory tests or clinical measurements, and they convey this same message to patients,” Underwood said. “Much less attention is paid to trends over time.”

“To support this shift, we need to create validated measures and comprehensive platforms that track and visualize long-term data for both clinicians and patients.”

She added that further research is needed to determine “how long clinical measures can be out of range before risks increase, whether that is weeks, months, or years.”

The authors and Underwood reported no relevant disclosures.