FormalPara Key Summary Points

Why carry out this study?

Glycated Hemoglobin A1c (HbA1c) is an important measure to assess glycemic control and predict diabetes complications.

Limited information exists on trends in HbA1c among people with diabetes (PwDs) using insulin.

What was learned from the study?

The study findings suggest that approximately 25% of PwDs or less achieve guideline-recommended and individualized glycemic targets.

Generally, the percentage of PwDs achieving HbA1c targets had not changed over the past 10 years, highlighting the need for improved therapeutic tools for people with type 1 and type 2 diabetes who use insulin.

Introduction

Glycemic control is a key element of diabetes management to avoid microvascular and macrovascular complications [1, 2]. Glycated hemoglobin A1c (HbA1c) is an important measure to assess glycemic control and predict diabetes complications [1, 3]. The American Diabetes Association (ADA) recommends an HbA1c goal of < 7% for non-pregnant adults (18–64 years) [1]. The ADA also emphasizes the need for individualized treatment targets based on various factors [1]. People with type 1 diabetes mellitus (T1DM) are insulin deficient and, as such, require exogenous insulin which can be delivered via multiple daily injections (MDI) or pumps, while people with type 2 diabetes mellitus (T2DM) often initiate insulin use when glycemic targets are not achieved with other agents [4].

Prior studies evaluating glycemic targets have shown that 21–64% of people with diabetes (PwDs) achieve the ADA-recommended glycemic target of < 7%, with the range in results possibly depending on differences in study characteristics, including the population studied (e.g. diabetes type), treatment regimen, and data source (e.g. clinical trial data) [5,6,7,8,9]. However, limited information exists on trends in HbA1c among PwDs who use insulin [9]. Therefore, to address this gap, this study aimed to describe the trends in HbA1c among PwDs using mealtime insulin (MTI) or basal-only insulin, using the most recent National Health and Nutrition Examination Survey (NHANES) data.

Methods

This retrospective analysis used NHANES survey data collected between 2009 and 2020; due to COVID-19, NHANES was suspended in March 2020 [10]. A complex, multistage, probability sampling design to select NHANES participants, in which generally two counties (each a primary sampling unit/cluster) are selected from strata defined by geography and proportions of minority populations; the specific methodology of the survey is described elsewhere [11, 12]. People aged 18–64 years diagnosed with T1DM or T2DM who indicated current use of insulin were included. T1DM was defined as a diagnosis of diabetes before 30 years of age with the use of insulin within 1 year of diabetes diagnosis; all others were considered T2DM [13]. Pregnant women were excluded, and the diagnosis definition included “other than during pregnancy.” If individuals used a medication classified as MTI (MULTUM system), they were categorized in the “T2DM-MTI group”. If individuals used basal insulins and not MTI, they were classified into the “T2DM basal-only” group.

The percentages of individuals achieving the ADA-recommended goal of < 7% were evaluated in addition to percentages of people achieving their healthcare provider (HCP)-recommended targets (i.e., individualized goals). Means and standard errors (SE) were used to describe each of the demographic and clinical variables. Analyses among groups were conducted using analysis of variance (and pairwise Student’s t-tests) for continuous variables and Chi-square tests for categorical variables. Trends over time for continuous and binary variables were analyzed using linear and logistic regression, respectively, adjusting for age, gender, and race/ethnicity. The analysis included the strata, clusters, and weighting of the complex survey design. Missing data in this study were handled according to the NHANES guidelines which recommend that if missing data for a variable are ≤ 10%, it is usually acceptable to continue the analysis without adjustment [14]. The key variable in this analysis (i.e., HbA1c) was missing among insulin users 4.8% of the time. Therefore, analyses proceeded without any adjustment for missing data. A threshold level of a two-tailed p-value < 0.05 was considered to be statistically significant.

This study was secondary research using NHANES data, which is a publicly available de-identified data source. As such, Institutional Review Board review or formal consent from participants to release or publish the information is not applicable. Ethical approval for the NHANES study was obtained from the National Center for Health Statistics (NCHS) Research Ethics Review Board (NHANES–NCHS Research Ethics Review Board Approval; https://www.cdc.gov/). This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.

Results

Baseline Characteristics and Demographics

A total of 510 people from NHANES 2009–2020 (T1DM: n = 85; T2DM-MTI: n = 257; T2DM basal-only: n = 168) were included in the analysis (Table 1). The majority of the groups were represented by males (50–68%), with a mean age of 41, 53, and 54 years in the T1DM, T2DM-MTI, and T2DM basal-only groups, respectively. The most common complications reported were hypertension and retinopathy, with complications generally being more common among the T2DM groups with the exception of retinopathy (Table 1).

Table 1 Baseline and demographic characteristics
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Aggregated over 2009–2020, the ADA-recommended HbA1c goal of < 7% was achieved by 25.2% of people in the T1DM, 25.2% in the T2DM-MTI, and 12.3% in the T2DM basal-only groups (Fig. 1a, overall). During this time, mean HbA1c was 8.0% in the T1DM group, 8.6% in the T2DM-MTI, and 8.6% in the T2DM basal-only groups (Table 1). Among those reporting HCP-recommended targets, 27%, 12.4%, and 16.1% of people in the T1DM, T2DM-MTI, and T2DM basal-only groups achieved these, respectively (Fig. 1b, overall). After adjusting for age, gender, and race/ethnicity, there was a significant effect of time period in the T2DM basal-only group for achieving ADA-recommended targets; an increasing percentage of individuals achieved their targets from 2017 through 2020 (Fig. 1a). However, there were no significant differences over time for PwDs achieving individualized treatment targets (Fig. 1b). Significant differences were not observed in the percentage of people with T1DM achieving ADA-recommended and individualized targets during the period evaluated. Future years of HbA1c trends using NHANES survey data may help to better understand these changes in HbA1c among PwDs. Throughout the study time period, the T1DM group had the smallest sample size and, therefore, the standard errors (not shown) of HbA1c were high for 2011–2012 (15.28%), 2015–2016 (21.08%), and 2017–2020 (14.36%).

Fig. 1
figure 1

Percentage of people with diabetes using insulin achieving the American Diabetes Association-recommended (< 7%) (a) and individualized HbA1c targets (b). HbA1c Glycated hemoglobin, MTI mealtime insulin, PwDs people with diabetes, T1DM type 1 diabetes mellitus, T2DM type 2 diabetes mellitus. Asterisk indicates that the p-value is significant at < 0.05 for increase over time in the basal-only group. Individualized target data were not available for 2009–2010

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Discussion

Using data from the most recent NHANES survey, this study provides a current evaluation of trends in HbA1c within a nationally representative sample of the US population with T1DM or T2DM using insulin. The results show that approximately 25% of PwDs using insulin achieved ADA-recommended or individualized glycemic targets. Although it appears that the percentage of people achieving targets has trended upwards from 2009 to 2020, this was significant only in the T2DM basal-only group for ADA-recommended targets. Overall, the percentages of PwDs achieving HbA1c < 7% in the current study were consistent with values reported in other real-world studies using T1D registry data (21%) and claims-based data (22–27%) [5,6,7]. Results from this study were also comparable with those from a previous cross-sectional study using NHANES data (1988–2012) that pooled diabetes and insulin types (PwDs using any insulin: 25.2–31.4%) [9]. The finding that more people in the T2DM basal-only group achieved guideline-recommended targets over time is consistent with prior research [6]. In that study, an increase in achieving HbA1c < 7% from 29.8% to 34.0% (1999–2012) was noted among PwDs who used any insulin [9].

Failure to achieve ADA-recommended glycemic targets leads to acute complications, such as diabetic ketoacidosis (hyperglycemic emergencies), and chronic complications, such as neuropathy, stroke, myocardial infarction, lower extremity ulcerations, and amputations [1, 15, 16]. In addition to clinical complications, the failure to intensify treatment to reduce HbA1c levels can contribute to higher healthcare costs and resource utilization [17, 18]. For example, a study conducted in a large population of 13.4 million people with T2D reported that a delay of 1 year in treatment intensification could result in a loss of 13,390 life-years and lead to higher healthcare costs [18]. The results of this study are consistent with known challenges in achieving glycemic targets arising from patient- and provider-related factors. These include delayed insulin treatment intensification, nonadherence, out-of-pocket costs, and lifestyle modifications of an individual [6]. In addition, disparities in factors related to social determinants of health, such as income, race/ethnicity, education, and access to specialized care for diabetes, could be barriers to achieving glycemic targets [19]. Identifying ways to reduce known barriers to achieving glycemic targets and tailoring individualized targets could help improve diabetes care for PwDs [6].

In recent years, several new diabetes technologies, including continuous glucose monitoring devices, insulin pumps with automated insulin delivery, and other connected devices (e.g., insulin pens) have been developed with the goal of improving diabetes management by increasing time in range and reducing hypoglycemia) [20, 21]. Emerging insulin delivery systems, such as connected insulin pens, may offer additional opportunities for improved adherence and glycemic control [21]. Faster acting MTI therapies have proven to be effective in improving post-prandial glucose among PwDs in clinical trials [20, 22,23,24,25]. Despite increasing availability of these diabetes technologies and therapies, there remains low utilization due to a variety of barriers for patients, caregivers, and the healthcare system [25]. Adoption of these newer technologies for diabetes management, through increased patient and provider education, and removal of barriers to therapy, may help facilitate improved diabetes outcomes in the future.

Limitations

Our study was limited by small absolute sample sizes for some years, resulting in uncertainty of estimates. However, estimates of aggregated years provided more certainty and demonstrated similar conclusions. Furthermore, we did not have access to information on diabetes type or duration of diabetes, although a standard algorithm was used to determine diabetes type. Further, ascertaining insulin use was limited to medicines reported in the 2 weeks prior to data collection.

Conclusions

This real-world study using data up through the most recent NHANES cycle provides an update to the existing literature about the trends in HbA1c in basal and mealtime insulin users. A notable percentage of PwDs using insulin are not achieving ADA-recommended or personalized HbA1c targets. This study highlights the need for improved therapeutic tools to better manage glycemic targets in PwDs.