Abstract
Background.
For older adults with type 2 diabetes (T2D) treated with insulin or sulfonylureas, Endocrine Society guideline recommends HbA1c between 7 to <7.5% for those in good health, 7.5 to <8% for those in intermediate health, and 8 to <8.5% for those in poor health. Our aim was to examine associations between attained HbA1c below, within (reference), or above recommended target range and risk of complication or mortality.
Methods.
Retrospective cohort study of adults ≥65 years old with T2D treated with insulin or sulfonylureas from an integrated healthcare delivery system. Cox proportional hazards models of complications during 2019 were adjusted for sociodemographic and clinical variables. Primary outcome was a combined outcome of any microvascular or macrovascular event, severe hypoglycemia, or mortality during 12-month follow-up.
Results.
Among 63,429 patients (mean age: 74.2 years, 46.8% women), 8,773 (13.8%) experienced a complication. Complication risk was significantly elevated for patients in good health (n=16,895) whose HbA1c was above (HR 1.97, 95% CI 1.62–2.41) or below (HR 1.29, 95% CI 1.02–1.63) compared to within recommended range. Among those in intermediate health (n=30,129), complication risk was increased for those whose HbA1c was above (HR 1.45, 95% CI 1.30–1.60) but not those below the recommended range (HR 0.99, 95% CI 0.89–1.09). Among those in poor health (n=16,405), complication risk was not significantly different for those whose HbA1c was below (HR 0.98, 95% CI 0.89–1.09) or above (HR 0.96, 95% CI 0.88–1.06) recommended range.
Conclusions.
For older adults with T2D in good health, HbA1c below or above the recommended range was associated with significantly elevated complication risk. However, for those in poor health, achieving specific HbA1c levels may not be helpful in reducing the risk of complications.
Keywords: type 2 diabetes, diabetes complications, diabetes management
Decisions about optimal glycemic goals in patients with type 2 diabetes mellitus (T2D) are often complicated, especially in older adults (age 65 or older) with multiple chronic conditions who are treated with insulin or sulfonylurea. Professional societies recognize that glycemic goals for older adults depend on overall patient health, including medical complexity and functional status. Overall health in older adults has been defined by frameworks that guide the clinician to consider multiple factors. One such framework developed by Blaum et al.1 was incorporated into the Endocrine Society clinical practice guideline2 and the American Diabetes Association Standards of Care for older adults.3 This framework uses a combination of functional impairments and comorbidities to categorize patients into good, intermediate, or poor health. These categories, in turn, are used for setting optimal glycemic target ranges for older patients with T2D who use medications that increase the risk of hypoglycemia: hemoglobin A1c (HbA1c) between 7.0% to <7.5%, for those in good health, 7.5% to <8.0% for those in intermediate health, and 8.0 to <8.5% for those in poor health (Table 1).
Table 1:
Endocrine Society guideline recommendations for glycemic control in older adults on hypoglycemia-prone medications according to health status.
| GOOD HEALTH | INTERMEDIATE | POOR HEALTH | |
|---|---|---|---|
| HbA1c Target Range | HbA1c 7% to <7.5% | HbA1c 7.5% to <8% | HbA1c 8% to <8.5% |
| Potentially Overtreated | HbA1c <7% | HbA1c <7.5% | HbA1c <8% |
| Potentially Undertreated | HbA1c ≥7.5% | HbA1c ≥8% | HbA1c ≥8.5% |
Clinical guidelines lack empirical evidence for setting specific glycemic target ranges in older adults based on these health status categories. The target ranges are based on expert opinion that considers the benefits (reduced microvascular and macrovascular complications) vs. the harms (principally hypoglycemia) of medications (i.e., insulin or sulfonylurea). However, there are no clinical trials that specifically evaluate these target ranges in older adults, and the observational evidence linking HbA1c, health status, and outcomes is likewise limited. To address this gap in the evidence, we evaluated the associations between achieved HbA1c levels and subsequent short-term (12-month) risk of microvascular and macrovascular complications, severe hypoglycemia, and all-cause mortality across the three health status categories for older adults prescribed insulin and/or sulfonyulurea treatment. Specifically, we categorized achieved HbA1c as being below recommended target range (i.e., potentially overtreated), within target range (reference), or above target range (i.e., potentially undertreated). The purpose of these observational analyses is to help clinicians and patients understand the association of achieved glycemia with clinical risk by health category. These real-world data can aid discussions related to prognosis, treatment planning, and potential risk reduction.
Methods:
Source Population
Patients were members of a large, integrated healthcare delivery system, Kaiser Permanente Northern California (“KPNC”), who were identified in the KPNC Diabetes Registry (“Registry”), a well-characterized population, maintained continuously since 1993.4–6 Registry inclusion is based on a validated algorithm incorporating multiple data sources including pharmacy records, laboratory data, and outpatient, emergency room and inpatient diagnoses of diabetes.7
Patients were included if they were 65 years or older at baseline (1/1/2019), had a diagnosis of T2D prior to 1/1/2018, and were dispensed insulin or insulin secretagogue (sulfonylureas, meglitinides) within 6 months prior to baseline. We excluded patients who had a gap ≥3 months in health plan membership in the 24 months prior to baseline or a gap ≥3 months in prescription benefits in the 12 months prior to baseline to maximize capture of important covariates. Patients were excluded if they were identified as having type 1 or unknown type of diabetes or did not have an HbA1c test result during the 12 months prior to baseline.
Health Status
Patients were categorized into three mutually exclusive groups: good, intermediate, or poor health. Health status categories (Supplemental Table 1) were adapted from the American Diabetes Association Standards of Care 20223 definitions excluding functional impairments which are not readily available in electronic health records (see Supplement Table 1). Patients in good health had few coexisting chronic conditions, those in intermediate health had multiple chronic conditions, and those in poor health had end-stage renal disease, heart failure, metastatic cancer, or used home oxygen.
Exposure of Interest
The exposure of interest was the last HbA1c result prior to baseline (1/1/2019). To align with the Endocrine Society guideline, patients were categorized as having an HbA1c below recommended target range (i.e., potentially overtreated), within target range (reference), or above target range (i.e., potentially undertreated) (Table 1).
Other Covariates
Age, sex, race/ethnicity, diabetes duration, neighborhood deprivation index8 (by quartile), Charlson Comorbidity Index, chronic kidney disease (CKD) stage, use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), use of statins, frailty (any use of oxygen, walking aids, or wheelchairs), smoking, anemia, hypoglycemia requiring emergency department (ED) visit or hospitalization, prevalent cardiovascular disease, hypertension, peripheral vascular disease, diabetic foot disease, liver disease, chronic obstructive pulmonary disease (COPD), depression, dementia, and metastatic cancer were ascertained within 24 months of baseline.
Outcomes
The primary outcome was a combined outcome of any of the following diabetes complications or mortality during 1 year of follow-up:
Microvascular complications: dialysis or renal transplant, or doubling of serum creatinine, hospital admission for lower extremity amputation, proliferative diabetic retinopathy.
Macrovascular complications: hospital admission for myocardial infarction, stroke, or congestive heart failure.
Severe hypoglycemia leading to an ED visit or hospitalization.
Mortality.
Each outcome group and mortality was also assessed separately in secondary analyses.
Statistical Analysis
Across the three health status categories, we compared the rates of the combined outcome (diabetes complications or mortality) for patients whose HbA1c was below (potentially overtreated), within (reference), and above (potentially undertreated) their target range. We then specified Cox proportional hazards models of time to the first event included in the combined outcome and calculated the hazard rate ratios for these groups. The crude models were further adjusted for demographic variables and covariates listed above.
Results:
The sampling frame included 160,923 patients with diabetes who were active KPNC members ≥65 years of age as of 1/1/2019; 8,551 patients were excluded due to gaps in health plan membership or prescription benefits, 3,914 due to identification as type 1 or unknown diabetes type, 5,350 due to diagnosis of diabetes on or after 1/1/2018, 11,683 due to lacking HbA1c result in 2018, and 67,996 due to having no insulin or sulfonylurea medications dispensed during the 6 months prior to baseline.
The final study cohort included the remaining 63,429 patients, with a mean age of 74.2 (SD 6.7 years; 46.8% were women (Table 2). Of these individuals, 26.6% were categorized as good health, 47.5% intermediate health, and 25.9% poor health. Overall, crude 12-month rate of diabetes complications or mortality was 13.8% (6.5% for microvascular events, 4.0% for macrovascular events, 1.9% for severe hypoglycemia, 3.9% for mortality).
Table 2:
Baseline characteristics of the study cohort stratified by health status.
| Overall | Good health | Intermediate health | Poor health | p-value | |
|---|---|---|---|---|---|
| Number | 63,429 | 16,895 | 30,129 | 16,405 | N/A |
| Age Category | <0.001 | ||||
| 65–69 | 19960 (31.5%) | 7740 (45.8%) | 8900 (29.5%) | 3320 (20.2%) | |
| 70–74 | 18730 (29.5%) | 5394 (31.9%) | 9166 (30.4%) | 4170 (25.4%) | |
| 75–79 | 12065 (19.0%) | 2426 (14.4%) | 6048 (20.1%) | 3591 (21.9%) | |
| 80+ | 12674 (20.0%) | 1335 (7.9%) | 6015 (20.0%) | 5324 (32.5%) | |
| Sex, female | 29705 (46.8%) | 6204 (36.7%) | 15832 (52.5%) | 7669 (46.7%) | <0.001 |
| Race/Ethnicity | <0.001 | ||||
| White | 29774 (46.9%) | 6623 (39.2%) | 14717 (48.8%) | 8434 (51.4%) | |
| Black | 5584 (8.8%) | 1250 (7.4%) | 2640 (8.8%) | 1694 (10.3%) | |
| Hispanic | 10700 (16.9%) | 3047 (18.0%) | 5234 (17.4%) | 2419 (14.7%) | |
| Asian | 13548 (21.4%) | 5048 (29.9%) | 5672 (18.8%) | 2828 (17.2%) | |
| Other | 3823 (6.0%) | 927 (5.5%) | 1866 (6.2%) | 1030 (6.3%) | |
| Diabetes duration >=10 years | 47103 (74.3%) | 10882 (64.4%) | 23160 (76.9%) | 13061 (79.6%) | <0.001 |
| Quartiles of neighborhood deprivation | <0.001 | ||||
| 1st Quartile (least deprived) | 16809 (26.5%) | 4750 (28.1%) | 7755 (25.7%) | 4304 (26.2%) | |
| 2nd Quartile | 23329 (36.8%) | 6201 (36.7%) | 11178 (37.1%) | 5950 (36.3%) | |
| 3rd Quartile | 12360 (19.5%) | 3282 (19.4%) | 5874 (19.5%) | 3204 (19.5%) | |
| 4th Quartile (most deprived) | 10931 (17.2%) | 2662 (15.8%) | 5322 (17.7%) | 2947 (18.0%) | |
| Charlson Comorbidity Index category | <0.001 | ||||
| 1 | 7949 (12.5%) | 4823 (28.5%) | 2816 (9.3%) | 310 (1.9%) | |
| 2–3 | 18341 (28.9%) | 7182 (42.5%) | 9224 (30.6%) | 1935 (11.8%) | |
| 4+ | 37139 (58.6%) | 4890 (28.9%) | 18089 (60.0%) | 14160 (86.3%) | |
| Chronic Kidney Disease stage | <0.001 | ||||
| Stage 0 | 5352 (8.5%) | 2521 (15.0%) | 2287 (7.6%) | 544 (3.3%) | |
| Stage 1 | 2589 (4.1%) | 1000 (6.0%) | 1184 (3.9%) | 405 (2.5%) | |
| Stage 2 | 30348 (48.0%) | 11164 (66.4%) | 13323 (44.3%) | 5861 (35.9%) | |
| Stage 3A | 13162 (20.8%) | 1416 (8.4%) | 7935 (26.4%) | 3811 (23.3%) | |
| Stage 3B | 8193 (13.0%) | 567 (3.4%) | 4311 (14.3%) | 3315 (20.3%) | |
| Stage 4 | 2650 (4.2%) | 131 (0.8%) | 1011 (3.4%) | 1508 (9.2%) | |
| Stage 5/Dialysis | 921 (1.5%) | 2 (0.0%) | 25 (0.1%) | 894 (5.5%) | |
| Cardiovascular disease | 16412 (25.9%) | 743 (4.4%) | 7464 (24.8%) | 8205 (50.0%) | <0.001 |
| Hypertension | 58159 (91.7%) | 13424 (79.5%) | 29053 (96.4%) | 15682 (95.6%) | <0.001 |
| Peripheral vascular disease | 11838 (18.7%) | 1095 (6.5%) | 5189 (17.2%) | 5554 (33.9%) | <0.001 |
| COPD | 16335 (25.8%) | 902 (5.3%) | 8985 (29.8%) | 6448 (39.3%) | <0.001 |
| Depression | 15346 (24.2%) | 811 (4.8%) | 9138 (30.3%) | 5397 (32.9%) | <0.001 |
| Dementia | 4119 (6.5%) | 0 (0.0%)* | 0 (0.0%)* | 4119 (25.1%) | <0.001 |
| Frailty (use of oxygen, wheelchair, or hospital bed) | 5000 (7.9%) | 83 (0.5%) | 1220 (4.0%) | 3697 (22.5%) | <0.001 |
| HbA1c Level | <0.001 | ||||
| HbA1c <6% | 2912 (4.6%) | 523 (3.1%) | 1212 (4.0%) | 1177 (7.2%) | |
| HbA1c 6-<7% | 16355 (25.8%) | 4067 (24.1%) | 7715 (25.6%) | 4573 (27.9%) | |
| HbA1c 7-<8% | 24280 (38.3%) | 7037 (41.7%) | 11768 (39.1%) | 5475 (33.4%) | |
| HbA1c 8-<9% | 11184 (17.6%) | 3055 (18.1%) | 5369 (17.8%) | 2760 (16.8%) | |
| HbA1c 9-<10% | 4652 (7.3%) | 1206 (7.1%) | 2180 (7.2%) | 1266 (7.7%) | |
| HbA1c 10%+ | 4046 (6.4%) | 1007 (6.0%) | 1885 (6.3%) | 1154 (7.0%) | |
| Diabetes medications (within 6 months prior to baseline) | |||||
| Metformin | 39387 (62.1%) | 13450 (79.6%) | 19279 (64.0%) | 6658 (40.6%) | <0.001 |
| Insulin | 30166 (47.6%) | 6050 (35.8%) | 14483 (48.1%) | 9633 (58.7%) | <0.001 |
| Sulfonylureas | 45323 (71.5%) | 13857 (82.0%) | 21703 (72.0%) | 9763 (59.5%) | <0.001 |
| Thiazolidinediones | 2716 (4.3%) | 1000 (5.9%) | 1377 (4.6%) | 339 (2.1%) | <0.001 |
| DPP-4 inhibitors | 876 (1.4%) | 274 (1.6%) | 427 (1.4%) | 175 (1.1%) | <0.001 |
| SGLT-2 inhibitors | 105 (0.2%) | 35 (0.2%) | 50 (0.2%) | 20 (0.1%) | 0.160 |
| GLP-1 receptor agonists | 167 (0.3%) | 44 (0.3%) | 83 (0.3%) | 40 (0.2%) | 0.814 |
All patients with a diagnosis of dementia are categorized as having poor health.
Among individuals in good health (n=16,895), 27.2% were potentially overtreated and 51.5% were potentially undertreated (Figure 1). An HbA1c value either below or above the recommended target range was associated with significantly higher rates of the combined outcome (Table 3). After full adjustment, the hazard ratios for the combined outcome remained higher among patients who had been potentially overtreated (HR 1.29, 95% CI 1.02–1.63) or potentially undertreated (HR 1.97, 95% CI 1.62–2.41) compared with those whose HbA1c had been within the recommended range (reference).
Figure 1:
Crude rates of microvascular events, macrovascular events, severe hypoglycemia, and mortality across health status groups (good, intermediate, and poor health). Rates are per 1,000 person-years.
Table 3:
Complication rates (microvascular, macrovascular, severe hypoglycemia, mortality) and risk associated with potential overtreatment and undertreatment across health status categories.
| ADA Health Status | HbA1c Category | Number of Patients | Complication Rate (per 1,000 person-years) | Crude HR (95% CI) for Complications | Adjusted HR (95% CI) for Complications |
|---|---|---|---|---|---|
| Good | Total | 16895 | |||
| Below Reference | 4590 | 42.9 | 1.29 (1.02–1.63) |
1.30 (1.02–1.65) |
|
| Reference (HbA1c 7% to <7.5%) |
3606 | 33.3 | Reference | Reference | |
| Above Reference | 8699 | 65.6 | 1.97 (1.62–2.41) |
1.89 (1.53–2.33) |
|
| Intermediate | Total | 30129 | |||
| Below Reference | 15027 | 93.3 | 0.99 (0.89–1.09) |
0.93 (0.83–1.03) |
|
| Reference (HbA1c 7.5% to <8%) |
5668 | 94.5 | Reference | Reference | |
| Above Reference | 9434 | 136.7 | 1.45 (1.30–1.61) |
1.31 (1.18–1.45) |
|
| Poor | Total | 16405 | |||
| Below Reference | 11225 | 376.0 | 0.96 (0.88–1.06) |
0.94 (0.85–1.03) |
|
| Reference (HbA1c 8% to <8.5%) |
1688 | 390.4 | Reference | Reference | |
| Above Reference | 3492 | 383.8 | 0.98 (0.89–1.09) |
1.03 (0.93–1.15) |
Among individuals in intermediate health (n=30,129), 49.9% were potentially overtreated and 31.3% were potentially undertreated. After full adjustment, compared to those whose HbA1c had been within the recommended range, individuals who had been potentially undertreated had a higher risk for the combined outcome (HR 1.45, 95% CI 1.30–1.60). However, individuals whose HbA1c had been below recommended range did not have a higher risk of the combined outcome (HR 0.99, 95% CI 0.89–1.09) (Table 3).
Among individuals in poor health (n=16,405), 68.4% were potentially overtreated and 21.3% were potentially undetreated. After full adjustment, neither individuals who had been potentially overtreated (HR 0.96, 95% CI 0.88–1.06) or potentially undertreated (HR 0.98, 95% CI 0.89–1.09) had a higher risk of the combined outcome compared with those whose HbA1c had been within the recommended range (Table 3).
These patterns were generally consistent when considering each outcome separately for adults with poor and intermediate health (Supplementary Figure). Among adults in poor health, there was no relationship between HbA1c target attainment and any individual health outcome. Among adults in intermediate health, HbA1c above the target range was associated with higher rates of microvascular events and mortality, but not macrovascular events or severe hypoglycemia. Among adults in good health, an HbA1c level either below or above the recommend range was associated with higher rates of macrovascular events and severe hypoglycemia, but only HbA1c above the recommended range was associated with a significantly higher risk of microvascular events and mortality.
Discussion:
In this observational study of older adults with T2D, relatively few (14%) of the older adults treated with medications that cause hypoglycemia had an HbA1c within the glycemic target range recommended by the Endocrine Society. Among older adults in poor health, only 10% achieved an HbA1c within the target range. For older adults in good or intermediate health, achievement of HbA1c within the recommended range was generally associated with better outcomes compared with achievement of HbA1c either above or below the recommended range. However, in older adults in poor health, this was not the case. There was no statistically significant association between attainment of HbA1c within the recommended range and diabetes complications or mortality compared with an HbA1c below or above that range. In these adults with poor health, a focus on achieving specific levels of glycemic control, at least as measured by HbA1c, may not be helpful in reducing the risk of complications over the short term. Other measures, such as the use of medications to lower glucose levels that do not cause hypoglycemia (e.g., SGLT-2 inhibitors), or non-glycemic approaches (e.g., focus on blood pressure or lifestyle modifications), may be more important.
Clinical guidelines, including those developed by the Endocrine Society, acknowledge that the evidence for setting specific glycemic target ranges in older adults based on health status categories is lacking. In a prior observational study,9 older adults with diabetes who attained an HbA1c <7% were not at elevated risk of mortality or hospitalizations, regardless of health status category. In addition, those in poor health with an HbA1c ≥ 8% (n=66) were at increased risk of hospitalization and mortality compared with those who achieved an HbA1c of 7 to <8% (n=90).9 Notably, this study was limited by very small sample sizes among patients in the poor health status group and adjusted for hypoglycemia-prone medication use, but not other comorbidities.
Our study reveals interesting patterns that, in large part, support the current Endocrine Society guidelines. First, among older patients in good health, the risk of complications is relatively low compared to the risk in patients in intermediate and poor health (~2-fold higher and ~7-8-fold greater risk than those in good health, respectively). However, having an HbA1c above or below the recommended range is associated with worse outcomes. These results support the Endocrine Society recommendations for optimal range of glycemic control among these healthier older adults.
Second, although severe hypoglycemia is a harm associated with intensive glycemic control, our results demonstrate that patients with HbA1c levels above the recommended target are not protected from severe hypoglycemia. In fact, the risk of severe hypoglycemia among patients on insulin and/or sulfonylureas is U-shaped with respect to HbA1c among those in good health and relatively flat among those in intermediate or poor health. These results are consistent with prior work.10–12 It is possible that high baseline HbA1c may lead to efforts to intensify the treatment regimen, leading to hypoglycemia. It is also possible that simply relaxing glycemic control may not lower the risk of hypoglycemia. Other strategies, such as simplifying glycemic regimen, structured education, technology use, and greater clinician support may play a greater role in risk reduction.13,14
Third, while older patients in poor health have, by far, the highest risk of diabetes-related complications and mortality, their risk is not significantly associated with recently achieved HbA1c. In individuals with end stage comorbidities, recent glycemic control may be a weak predictor and/or driver of adverse events.15 For example, in a patient with progressive kidney disease, strict glycemic control may do little to avert renal failure; instead, application of renally protective pharmacotherapy (e.g., SGLT-2 inhibitors16–18 and/or nonsteroidal selective mineralocorticoid receptor antagonists19) may be more effective. Furthermore, HbA1c may be an inaccurate reflection of ambient glucose levels in individuals with end stage renal disease or heart failure, or those with other commonly co-occurring comorbidities, such as anemia.20 Our results support professional society guidelines which discourage clinicians from a focus on HbA1c levels in their sickest T2D patients.21
Our study has some limitations to consider. This is an observational study and cannot prove causal relationships. While we carefully adjusted for a wide range of socio-demographic and clinical factors, residual confounding may still play a role. We relied on primary and principal diagnosis codes from ED visits and hospitalizations to define the outcomes; for some outcomes, such as severe hypoglycemia, this likely led to under ascertainment.22 In addition, we did not have data on functional impairments, assessment of frailty, or NYHA class of heart failure and the definition of health status was limited by data available from electronic health records. Similarly, our classifications of health status were based on Endocrine Society guidelines and rely on electronic medical records and/or claims for a specified set of conditions. Thus, it is possible that some patients categorized as having “good health” may have other, serious conditions not included on our list. HbA1c can be influenced by a number of factors, including end stage renal disease or anemia, and may not reflect true glycemic status. Unfortunately, additional measures of glycemic control (e.g., time in range captured by continuous glucose monitoring) were unavailable in this study. Finally, consistent with accepted practice for exploratory epidemiologic analyses, we did not adjust for multiple comparisons.23,24 However, our findings reveal consistent patterns across categories of health status.
In conclusion, older patients treated with hypoglycemia-prone medications rarely attain HbA1c within the range recommended by the Endocrine Society. Individuals with poor health are at the highest risk of microvascular and macrovascular events, severe hypoglycemia, and mortality, and achievement of HbA1c within recommended ranges was not significantly associated with better outcomes, suggesting that other factors are likely to be more important predictors and/or drivers of these outcomes in these sickest T2D patients.
Supplementary Material
Figure 2:
Percentage of older patients with type 2 diabetes by health status who attained HbA1c level below (potentially overteated), within (on target), and above (potentially undertreated) the range recommended by the Endocrice Society guidelines.
Key Points:
For older adults with type 2 diabetes in good health, glycemic control below or above the recommended HbA1c range was associated with significantly elevated risk of complications.
Older adults with type 2 diabetes in poor health had a high risk of complications, but glycemic control either below or above the recommended HbA1c range was not associated with complication risk.
Why Does this Paper Matter?
For older adults with type 2 diabetes in poor health, achieving specific HbA1c levels may not be helpful in reducing the risk of complications.
Funding Sources:
This study was funded via the following grants: NIA: R01 AG063391; R56 AG074986 and NIDDK: P30 DK092924; P30 DK092949. Dr. Lipska receives grants from NIH, other support from Centers for Medicare & Medicaid Services (CMS) to develop and evaluate publicly reported quality measures, and royalties from UpToDate to write and edit content.
Footnotes
Sponsor’s role: Sponsor had no role in the design, methods, data collections, analysis, and preparation of the paper.
Disclosures:
Abstract was accepted for presentation at the 2023 ADA Scientific Sessions Meeting.
Supplemental materials include definitions for the health status categories based on the American Diabetes Association Standards of Care 2022 adapted for this study and the hazard ratios for the individual outcomes (microvascular events, macrovascular events, severe hypoglycemia and mortality) associated with attainment of HbA1c above and below the recommended target ranges for patients treated with insulin and/or sulfonylureas.
Contributor Information
Kasia J Lipska, Yale School of Medicine, New Haven, CT.
Elbert S Huang, University of Chicago, Chicago, IL.
Jennifer Y Liu, Kaiser Permanente Northern California, Oakland, CA.
Melissa M Parker, Kaiser Permanente Northern California, Oakland, CA.
Neda Laiteerapong, University of Chicago, Chicago, IL.
Richard W Grant, Kaiser Permanente of Northern California, Oakland, CA.
Howard H Moffet, Kaiser Permanente Northern California, Oakland, CA.
Andrew J Karter, Kaiser Permanente Northern California, Oakland, CA.
REFERENCES
- 1.Blaum C, Cigolle CT, Boyd C, et al. Clinical complexity in middle-aged and older adults with diabetes: the Health and Retirement Study. Med Care 2010;48(4):327–334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab 2019;104(5):1520–1574. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Draznin B, Aroda VR, Bakris G, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022;45(Suppl 1):S125–s143. [DOI] [PubMed] [Google Scholar]
- 4.Karter AJ, Parker MM, Moffet HH, et al. Missed appointments and poor glycemic control: an opportunity to identify high-risk diabetic patients. Med Care 2004;42(2):110–115. [DOI] [PubMed] [Google Scholar]
- 5.Karter AJ, Ferrara A, Liu JY, Moffet HH, Ackerson LM, Selby JV. Ethnic disparities in diabetic complications in an insured population. JAMA 2002;287(19):2519–2527. [DOI] [PubMed] [Google Scholar]
- 6.Iribarren C, Karter AJ, Go AS, et al. Glycemic control and heart failure among adult patients with diabetes. Circulation 2001;103(22):2668–2673. [DOI] [PubMed] [Google Scholar]
- 7.Karter AJ, Schillinger D, Adams AS, et al. Elevated Rates of Diabetes in Pacific Islanders and Asian Subgroups: The Diabetes Study of Northern California (DISTANCE). Diabetes Care 2012. [DOI] [PMC free article] [PubMed]
- 8.Laraia BA, Karter AJ, Warton EM, Schillinger D, Moffet HH, Adler N. Place matters: neighborhood deprivation and cardiometabolic risk factors in the Diabetes Study of Northern California (DISTANCE). Social science & medicine (1982) 2012;74(7):1082–1090. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Rooney MR, Tang O, Echouffo Tcheugui JB, et al. American Diabetes Association Framework for Glycemic Control in Older Adults: Implications for Risk of Hospitalization and Mortality. Diabetes Care 2021;44(7):1524–1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Lipska KJ, Warton EM, Huang ES, et al. HbA1c and Risk of Severe Hypoglycemia in Type 2 Diabetes: The Diabetes and Aging Study. Diabetes Care 2013. [DOI] [PMC free article] [PubMed]
- 11.Zhong VW, Juhaeri J, Cole SR, et al. Proximal HbA1C Level and First Hypoglycemia Hospitalization in Adults With Incident Type 2 Diabetes. J Clin Endocrinol Metab 2019;104(6):1989–1998. [DOI] [PubMed] [Google Scholar]
- 12.Williams ME, Garg R, Wang W, Lacson R, Maddux F, Lacson E Jr. High Hemoglobin A1c levels and glycemic variability increase risk of severe hypoglycemia in diabetic hemodialysis patients. Hemodial Int 2014;18(2):423–432. [DOI] [PubMed] [Google Scholar]
- 13.Munshi MN, Slyne C, Segal AR, Saul N, Lyons C, Weinger K. Simplification of Insulin Regimen in Older Adults and Risk of Hypoglycemia. JAMA internal medicine 2016;176(7):1023–1025. [DOI] [PubMed] [Google Scholar]
- 14.McCall AL, Lieb DC, Gianchandani R, et al. Management of Individuals With Diabetes at High Risk for Hypoglycemia: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2022. [DOI] [PubMed]
- 15.Laiteerapong N, Ham SA, Gao Y, et al. The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (the Diabetes & Aging Study). Diabetes Care 2018. [DOI] [PMC free article] [PubMed]
- 16.Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med 2019;380(24):2295–2306. [DOI] [PubMed] [Google Scholar]
- 17.Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2020;383(15):1436–1446. [DOI] [PubMed] [Google Scholar]
- 18.Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2022. [DOI] [PubMed]
- 19.Bakris GL, Agarwal R, Anker SD, et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med 2020;383(23):2219–2229. [DOI] [PubMed] [Google Scholar]
- 20.Radin MS. Pitfalls in hemoglobin A1c measurement: when results may be misleading. J Gen Intern Med 2014;29(2):388–394. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.ElSayed NA, Aleppo G, Aroda VR, et al. 13. Older Adults: Standards of Care in Diabetes-2023. Diabetes Care 2023;46(Suppl 1):S216–s229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Karter AJ, Moffet HH, Liu JY, Lipska KJ. Surveillance of Hypoglycemia-Limitations of Emergency Department and Hospital Utilization Data. JAMA internal medicine 2018;178(7):987–988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Althouse AD. Adjust for Multiple Comparisons? It’s Not That Simple. Ann Thorac Surg 2016;101(5):1644–1645. [DOI] [PubMed] [Google Scholar]
- 24.Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology 1990;1(1):43–46. [PubMed] [Google Scholar]
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