A Proposal for an Out-of-Range Glycemic Population Health Safety Measure for Older Adults With Diabetes

Conclusions

The findings support two conclusions with differing implications regarding glycemic control for patients 65–75 years of age, all of whom had at least one significant comorbid condition and almost all of whom received agents that are hypoglycemia prone (i.e., insulin, sulfonylureas). On the basis of the NQF-endorsed HbA_1c <8% (64 mmol/mol) measure (10), nearly two-thirds (65.7%) of all patients were receiving quality care. Alternatively, on the basis of the OOR measure, about one-half (47.4%) were significantly UT or OT according to current guideline recommendations. The magnitude is comparable for patients >75 years of age, who are not included in NQF-endorsed glycemic measures. Only 28.4% of patients aged 65–75 years and 27.1% of those >75 years had HbA_1c results between 7.5 and 8.5% (58–69 mmol/mol), which we defined as IR. In a sensitivity analysis, we noted higher rates of an even-lower HbA_1c threshold <6.5% (47.5 mmol/mol) than poor A1C (>9% [75 mmol/mol]) control.

These results highlight that the determination of quality rankings depends on the perspective taken and technical specifications of measures. Our perspective is that a major clinical focus of glycemic management for an older population, especially those with significant disease burden, should address the risk for and/or presence of symptoms and adverse events related to either glycemic control or medications. Therefore, we propose designating the OOR measure as an accountability patient safety measure to address a population health need not currently addressed by endorsed measures. Our proposal also is consistent with the need to increase clinician and patient awareness that an A1C test result is within a range (16,17).

The emphasis on prevention of short-term medication harms is consistent with the NQF-endorsed patient safety measure, which has no upper age limit and is used by the Centers for Medicare & Medicaid Services to monitor the anticoagulant effect of Coumadin using the international normalized ratio (20). Maintaining the international normalized ratio within a range is the goal for maximizing benefit (i.e., protect patients from blood clots) while minimizing risk (i.e., risk of hemorrhage attributable to excessive anticoagulation).

However, it is important from both an individual patient and a population health perspective to balance avoidance of harms with decreasing long-term risk of microvascular complications. Therefore, the availability of an IR quality improvement measure would enable most high-risk patients to be managed safely over time within a range appropriate for and agreed to by the individual patient in the context of shared decision making (2–6).

This approach is consistent with the major randomized controlled trials of intensive treatment of patients with a longer duration of diabetes (21–23). These trials demonstrated that the absolute risk reduction (benefits) of HbA_1c lowering on microvascular complications are modest over 5–10-year periods and were most significant for the onset and progression of renal disease. Although major guidelines differ about how comorbid severity is defined, all recommend that glycemic targets reflect illness burden, life expectancy, and individual risk for hypoglycemic events.

The prevalence of significant comorbid illness in older adults with diabetes in the VA is similar in magnitude, given methodological differences in illness severity ascertainment, to the comorbid illness burden in the U.S. A recent study that used the National Health and Nutrition Examination Survey (NHANES), which is representative of the nation’s noninstitutionalized civilians, reported that of older adults (>65 years; mean 74 years) with diabetes, 50.7% were relatively healthy, 28.1% had complex/intermediate health, and 21.2% had very complex/poor health (24). Very complex health status was defined as having two or more impairments in activities of daily living or receiving dialysis. A study limitation was that the prevalence of poor health was underestimated because conditions such as end-stage (stage III–IV) congestive heart failure, oxygen-dependent lung disease, and metastatic cancer could not be ascertained. Complex health status was defined as three or more chronic conditions, including congestive heart failure, lung disease, significant-stage chronic kidney disease, coronary heart disease, stroke, urinary incontinence, major depression, active cancer, and substance abuse.

Additionally, substudies from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial demonstrated that hypoglycemic risk is not limited to severe illnesses or even to patients with very low A1C levels. Even modest elevations of serum creatinine levels (>1.3 mg/dL) and mildly impaired cognitive impairment were associated with an increased risk of severe hypoglycemia in both the control and the treatment arms (25,26). Such factors may contribute to episodes of severe hypoglycemia in patients with higher HbA_1c values in clinical practice (27).

Lower socioeconomic status (28) and decreased health literacy (29) were associated with an increased risk of hypoglycemia, even in members of a large regional health maintenance organization. The risk for hypoglycemia-related hospital admissions was 27% higher in the last week of the month relative to the first week in low-income patients compared with high-income patients in California (29). One proposed explanation for this finding was food insufficiency (30). The NQF is studying the use of socioeconomic factor risk adjustment for plan comparisons (31). However, clinicians must make treatment decisions that take into account factors not easily ascertained, including the capacity for diabetes self-management, social support, and finances.

Given the complexity of glycemic management in a high-risk adult population, it is perhaps not surprising that practicing physicians’ incorporation of guidelines into practice varies considerably. In a recent scenario-based survey evaluating endocrinologists’ perspectives on individualized glycemic target goals based on clinical factors, wide variation existed, with many choosing HbA_1c targets both lower and greater than 8% (64 mmol/mol), even in patients with significant comorbid conditions (32). In addition, individual patient preferences differ. For example, patients have ranked gastrointestinal effects as more important than hypoglycemia (33). Some older adults express a preference to forego insulin therapy even if this decision would shorten their life expectancy (34).

We recognize that management of diabetes continues to evolve and that we can expect the development of new and more effective medications. These medications include those with lower risks of hypoglycemia (e.g., dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium–glucose cotransporter 2 inhibitors) and/or those that may have additional benefits above and beyond their antihyperglycemic effects. A recent Food and Drug Administration safety review relaxed the restrictions on metformin usage in chronic kidney disease (35). Therefore, consistent with evolving recommendations for antihyperglycemic medications (14,15,36), future measures of glycemic control should exclude patients who are not receiving hypoglycemia-prone drugs. Reflecting prescribing practices in 2012–2013, >98% of our study population received sulfonylurea agents and/or insulin.

However, there will always be existing and new safety concerns. Balancing the benefits and risks of polypharmacy in older adults with diabetes, therefore, is important (37). In addition to hypoglycemia, other adverse outcomes could include nausea, dehydration, urinary tract infection, and worsening renal function that could result in potentially preventable emergency department visits or hospitalizations in vulnerable populations.

This study has significant strengths, including linked demographic, laboratory, pharmacy, and administrative data, which have enabled us to identify patients taking any combination of antihyperglycemic medications as well as to identify whether the prescription was current. We also could identify serum creatinine values in the population. We note as limitations an inability to assess the severity of comorbid conditions. Although the use of ICD-10-CM taxonomies is expected to permit better discrimination of more severe stages of common conditions, including cardiac, pulmonary, and liver disease, than is possible with ICD-9-CM coding, significant differences exist in comparability (38). Consequently, our taxonomy, technical specifications, and findings will need further validation. We also note a lack of prospective outcome data to know whether OOR measures identify patients who subsequently experience significant adverse events.

In conclusion, our proposed OOR measure attempts to align the concepts of quality (individualizing targets on the basis of the principle of absolute risk reduction), safety (potential reduction in medication harms), and value to health care systems and payers (potential decreased costs of both OT and UT) and to patients (improved quality of life, satisfaction). Our approach is consistent with the recent Centers for Medicare & Medicaid Services proposed rule for addressing medication safety for beneficiaries taking hypoglycemic agents in support of the Merit-based Incentive Payment System and Alternative Payment Models (39). The proposed measure would focus on patients prescribed antidiabetic agents (e.g., insulin, sulfonylureas) and require physicians to document an individualized glycemic treatment goal that takes into account patient-specific factors, including age, comorbidities, and risk for hypoglycemia at least annually. This approach also emphasizes, in an increasingly data driven, technological medical age, that the needs, preferences, and safety of the patient must always be individualized and should always be paramount (40).