Stakeholders in the type 1 diabetes community are recommending the use of standardized definitions for several diabetes outcome measurements beyond HbA1c, with the goal of including such outcomes in research for future therapies, according to a consensus report published in Diabetes Care.
The report, produced by the Type 1 Diabetes Outcomes Program, includes recommended standard definitions for hypoglycemia, hyperglycemia, so-called time-in-range when using continuous glucose monitoring, diabetic ketoacidosis and patient-reported outcomes. A steering committee including representatives from the American Diabetes Association, the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the Endocrine Society, JDRF International, the Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society and T1D Exchange formed the Type 1 Diabetes Outcomes Program, which also included input from diabetes researchers, industry and people with diabetes through advisory committees.
“This consensus report is a significant step towards providing standardized methods for improving how we evaluate therapies and technologies designed to treat and assist in the management of [type 1 diabetes] and the prevention of its complications,” William T. Cefalu, MD, chief scientific, medical and mission officer for the ADA, said in a press release. “Together, expanded data provided by CGM, along with uniform definitions, will ultimately help us provide more carefully crafted and individualized diabetes care plans, and thus improve health outcomes as well as patient quality of life.”
Cefalu added that partnerships such as the Type 1 Diabetes Outcomes Program, convened by JDRF, are essential to bringing about these changes.
The steering committee reviewed published evidence and expert opinion to develop, identify and define clinically meaningful ways to measure outcomes beyond HbA1C in people with type 1 diabetes.
The committee defined three levels of hypoglycemia:
- level 1, defined as a measurable glucose concentration of less than 70 mg/dL but greater than 54 mg/dL;
- level 2, defined as a glucose measurement of less than 54 mg/dL; and
- level 3, defined as a “severe event characterized by altered mental and/or physical status requiring assistance.”
The researchers noted these new definitions are “slight modifications” to the recently published ADA and EASD joint position statement on hypoglycemia. These new recommendations are considered an update to that joint statement, they wrote.
The committee also defined two distinct levels of hyperglycemia:
- level 1, defined as a glucose level of at least 180 mg/dL but less than 250 mg/dL; and
- level 2, defined as a glucose level of at least 250 mg/dL.
“Further research is needed to better understand the effects of individual episodes of hyperglycemia as opposed to sustained hyperglycemia over time,” the researchers wrote.
Time in range; DKA
The committee noted that it was important to keep the time-in-range definition wide, to accommodate variations across the population with type 1 diabetes, but also limited enough to preclude the possibility of negative outcomes. For this reason, time-in-range was defined as the percentage of blood glucose readings in the range of 70 mg/dL to 180 mg/dL per unit of time, they wrote.
“For individuals without type 1 diabetes, 70 mg/dL to 140 mg/dL represents a normal glycemic range,” the researchers wrote. “However, spending most of the day in this range is not generally achievable for people with type 1 diabetes because they do not have physiological insulin secretion.”
The committee also defined DKA in individuals with type 1 diabetes as an elevated serum or urine ketones and a serum bicarbonate of at least 15 mmol/L or a blood pH of at least 7.3.
Much of what people with type 1 diabetes experience is not captured through standard clinical measurements, the committee wrote, noting that measurements of patient-reported outcomes, first defined by the FDA in guidance released in 2009, can capture and fill in “important information gaps.”
Work to further develop and validate tools for diabetes health-related quality of life is ongoing, they wrote.
In the report, researchers stressed that HbA1C remains an important measure of diabetes outcomes, adding that the newly standardized definitions of additional outcomes provide “supplemental methods” to capture a more comprehensive understanding of how interventions might affect the health people with diabetes.
“Knowledge gaps, including around [patient-reported outcomes], were identified and should be addressed by future research,” the researchers wrote. “The steering committee recommends use of the defined clinically meaningful outcomes beyond HbA1c in the research, development and evaluation of type 1 diabetes therapies.” – by Regina Schaffer
Disclosures: Please see the study for the authors’ relevant financial disclosures.