Abstract
OBJECTIVE
Adults with type 1 diabetes (T1D) are aging successfully. The impact of diabetes duration on clinical and functional status as people age with T1D is not well known.
RESEARCH DESIGN AND METHODS
We performed a cross-sectional study of older adults (age ≥65 years) with T1D.
RESULTS
We evaluated 165 older adults, mean age 70 ± 10 years. After adjustment for age, sex, and A1C, longer duration of T1D, ≥50 years, was associated with a higher likelihood of depression (odds ratio [OR] 2.8; P = 0.008), hypoglycemia unawareness (OR 2.6; P = 0.01), lower scores on 6-Minute Walk Test (OR 0.99; P = 0.01) and the Physical Component Summary (PCS) of Short Form-36 (SF-36) (OR 0.96; P = 0.02), and greater daily medication use (OR 1.1; P = 0.004) compared with those with duration <50 years.
CONCLUSIONS
In older adults with T1D, duration of diabetes impacts clinical and functional status, independent of age and glycemic control, and should be considered in development of management strategies for safety and success.
Introduction
People with type 1 diabetes (T1D) are living longer and remaining functional in their older age. In this clinically heterogeneous population, diabetes duration can vary widely, as people may have been diagnosed many decades ago or as recently as late adulthood.
In this cross-sectional study, we analyzed the impact of duration of T1D on clinical and functional status in older adults.
Research Design and Methods
We performed a cross-sectional analysis of baseline data from two ongoing studies that included older adults (age ≥65 years) with T1D, Technological Advances in Glucose Management in Older Adults (ClinicalTrials.gov, NCT03078491) and Assessing the Impact of Aging on Adults with T1D and T2D, between April 2017 and March 2021. Eligibility criteria included a diagnosis of T1D, age ≥65 years, and stable use of diabetes technology for glucose monitoring (blood glucose monitoring or continuous glucose monitoring [CGM]) and insulin administration (pump or multiple daily insulin injections) for at least 6 months prior to assessment. People using automated insulin delivery systems were excluded. The institutional review board approved the study protocols at the Joslin Diabetes Center.
A clinical assessment included measures for cognitive function (Montreal Cognitive Assessment [MoCA]) (1), depression (Geriatric Depression Scale [GDS] [2,3], on antidepressant medications, or diagnosis of depression), impaired awareness of hypoglycemia (IAH) (Clarke survey) (4), hypoglycemia fear (Hypoglycemia Fear Survey-II [HFS-II]) (5), diabetes distress (Diabetes Distress Scale [DDS]) (6), and quality of life (the Short Form-36 [SF-36]: Physical Component Summary [PCS] and Mental Component Summary [MCS] scores) (7). The 6-Minute Walk Test (6MWT) measured how far a person can walk in 6 min (8).
CGM Parameters
CGM data were downloaded from a 2-week period from all participants. A minimum of 192 h of CGM data were required for inclusion in the study analyses. The coefficient of variation (CV%) was calculated (9).
Statistical Analysis
Descriptive demographic and clinical data statistics are reported as number and percentage of the cohort for categorical variables. For continuous variables, data are reported as mean ± SD for data with normal distribution and median (1st, 3rd interquartile) for data with nonnormal distribution. Logistic regression results are reported as odds ratio (OR) (95% CI). SAS 9.4 software was used for all analyses, including Pearson and Spearman correlations, Student t tests, Fisher exact tests, general linear models, and multinomial logistic regression models. A P value of 0.05 was considered statistically significant.
Results
We evaluated 165 patients with T1D. Stratified by T1D duration, our cohort had 53 participants with T1D duration ≥50 years and 112 participants with T1D duration <50 years. Table 1 shows the characteristics of the overall cohort, divided based on diabetes duration. Overall, the two groups with duration ≥50 years and <50 years did not differ in age, sex, BMI, cognitive function, comorbidities, living status, use of insulin pump and CGM, hypoglycemia fear, or hypoglycemia parameters on CGM.
Table 1.
Characteristics of study population (n = 165), stratified by duration of T1D
| Total | <50 years’ duration | ≥50 years’ duration | P | |
|---|---|---|---|---|
| N | 165 | 112 | 53 | |
| Age (years) | 70 ± 10 | 70 ± 9 | 70 ± 11 | 0.79 |
| BMI (kg/m2) | 26 ± 4 | 26 ± 4 | 26 ± 4 | 0.92 |
| Female sex | 85 (52) | 60 (54) | 25 (47) | 0.41 |
| Race (non-Hispanic White) | 159 (97) | 107 (96) | 52 (98) | 1.00 |
| Education (college diploma or higher) | 146 (89) | 97 (87) | 49 (93) | 0.33 |
| Living alone | 31 (21) | 18 (18) | 13 (28) | 0.18 |
| Total number of medications/day | 10 ± 4 | 9 ± 4 | 11 ± 5 | 0.02 |
| Comorbidities/medical conditions | 10 ± 4 | 10 ± 3 | 11 ± 4 | 0.24 |
| Cognitive dysfunction (MoCA <26) | 91 (55) | 62 (56) | 28 (53) | 0.72 |
| Depression | 50 (30) | 29 (26) | 21 (40) | 0.08 |
| Fallen in past 6 months | 33 (20) | 18 (16) | 15 (28) | 0.07 |
| 6MWT score (m) | 427 ± 81 | 440 ± 76 | 401 ± 86 | 0.01 |
| DDS total score | 2 ± 0.5 | 2 ± 0.5 | 2 ± 0.6 | 0.92 |
| SF-36 PCS | 50 ± 10 | 51 ± 10 | 48 ± 12 | 0.08 |
| SF-36 MCS | 49 ± 10 | 50 ± 10 | 49 ± 11 | 0.50 |
| Diabetes characteristics | ||||
| Age at diagnosis (years) | 31 (16, 34) | 40 (31, 51) | 13 (9, 17) | <0.0001 |
| Duration of diabetes (years) | 40 ± 17 | 31 ± 12 | 59 ± 6 | <0.0001 |
| A1C (%) | 7.4 ± 0.9 (range 5.0, 9.9) | 7.5 ± 1.0 | 7.1 ± 0.7 | 0.002 |
| A1C (mmol/mol) | 57 ± 10 | 58 ± 10 | 54 ± 8 | 0.002 |
| Pump user | 102 (62) | 65 (59) | 37 (70) | 0.44 |
| CGM user | 95 (58) | 60 (54) | 35 (66) | 0.15 |
| One or more severe hypoglycemia events in last year | 27 (20) | 15 (16) | 12 (29) | 0.10 |
| HFS-II total score | 29 ± 18 | 29 ± 17 | 31 ± 20 | 0.57 |
| IAH | 60 (46) | 34 (38) | 26 (63) | 0.007 |
| CGM metrics | ||||
| % time ≤54 mg/dL | 0.8 (0.2, 2.2) | 1 (0.3, 2.4) | 0.6 (0, 2.2) | 0.62 |
| % time <70 mg/dL | 3.3 (1.6, 6.9) | 3.8 (1.7, 7.1) | 2.4 (1.3, 7.2) | 0.08 |
| % time >180 mg/dL | 34 ± 16 | 35 ± 17 | 31 ± 15 | 0.47 |
| % time >250 mg/dL | 11 ± 9.1 | 12 ± 9.2 | 9.2 ± 8.8 | 0.39 |
| % time in range 70–180 mg/dL | 61 ± 15 | 59 ± 15 | 64 ± 15 | 0.08 |
| GMI% | 7.1 ± 0.6 | 7.2 ± 0.6 | 7.1 ± 0.6 | 0.34 |
| CV% | 38 ± 7 | 38 ± 7 | 37 ± 7 | 0.74 |
Data are n (%), mean ± SD, or median (1st, 3rd interquartile) unless otherwise indicated. Values in boldface type are statistically significant for α of 0.05. GMI, glucose management indicator.
Next, we performed multivariant regression analysis to assess the relationship between diabetes duration and clinical characteristics of interest. After adjustment for age, sex, and A1C, duration of diabetes ≥50 years was associated with a higher likelihood of depression (OR 2.8 [95% CI 1.3, 6.1]; P = 0.008) and IAH (OR 2.6 [95% CI 1.2, 5.7]; P = 0.01). The group with diabetes duration ≥50 years also showed a trend toward association with decreased physical function, as seen by lower scores on the 6MWT (OR 0.99 [95% CI 0.98, 0.99]) and the PCS component of the SF-36 (OR 0.96 [95% CI 0.92, 1.0]; P = 0.02). Additionally, the group with diabetes duration ≥50 years showed a trend toward association with high daily medication use (OR 1.1 [95% CI 1.0, 1.2]; P = 0.004).
Conclusions
In our study we evaluated the impact of duration of T1D on clinical and functional factors in older adults, age ≥65 years. Our results show that a longer duration of T1D is associated with a higher likelihood of depression and hypoglycemia unawareness in older adults, independent of age, sex, and glycemic control. This observation is important for understanding how to manage older adults with T1D with different disease duration.
In our cohort, the two groups with T1D duration ≥50 years and <50 years did not differ in age, sex, BMI, cognitive dysfunction, or the number of overall comorbid conditions and diabetes-related complications. These findings are similar to those of other cross-sectional studies suggesting that patients with longer duration of T1D were relatively protected from diabetes-related complications (10,11). These study results should be interpreted cautiously considering an inherent survival bias, as only those who survive to older age are included. In addition, the management of T1D and its complications has changed considerably over the past half century. Overall, these studies may suggest that people with T1D who survive to reach age ≥65 years do not seem to carry a greater complication burden. Although in our study we did not find differences in overall comorbidities between groups, there was a trend toward more daily medications in the group with T1D ≥50 years, suggesting a higher therapeutic burden with a longer duration of T1D.
Interestingly, the groups with longer and shorter duration of diabetes also did not differ in duration of hypoglycemia or glycemic variability (CV%) measured by CGM. Although this finding is reassuring, a higher likelihood of hypoglycemic unawareness for participants with a duration ≥50 years is concerning for higher risk of hypoglycemia. Among our study participants, those with T1D duration ≥50 years were more than twice as likely to have hypoglycemia unawareness. Our findings are similar to those of another cross-sectional study, where a mail-in questionnaire was used, that for people with T1D, longer diabetes duration was associated with lower intensity of autonomic symptoms and a higher prevalence of IAH (12). Another network registry study showed that greater hypoglycemia unawareness and glucose variability in older adults with long-standing T1D are associated with an increased risk of severe hypoglycemia (13). Thus, all older adults with a long T1D duration should be carefully assessed for hypoglycemia unawareness.
We also found that older adults with T1D duration ≥50 years were twice as likely to have depression compared with those with duration <50 years. The association between diabetes duration and depression has been shown in previous cross-sectional studies (14,15). These results suggest the need for depression screening in individuals as they grow older with T1D. Our results also showed a trend toward an association of longer duration of T1D with a decline in physical function and use of more daily medications. The overall association of higher hypoglycemia unawareness and lower physical endurance can increase the risk of falls in older adults and is an important consideration in development of strategies for treating older adults with a long duration of T1D.
The limitations of our study include its cross-sectional, single-center nature and a heterogeneous (mostly White) population and small sample size. This analysis is also a subanalysis from an ongoing clinical trial, and the results of this study should be interpreted with caution and are considered hypothesis generating.
In summary, the results of our study show that in older adults with T1D, duration of diabetes impacts clinical and functional status, independent of age and glycemic control. These observations may help clinicians develop safe and successful diabetes treatment strategies.
Article Information
Acknowledgments. The authors acknowledge support by the Joslin Clinical Research Center and thank its philanthropic donors.
Funding. This study was supported by National Institutes of Health grants DP3 (1DP3DK112214-01) and P30 (P30DK036836). CGM materials were partially supplied by Dexcom.
The funding source had no role in the design or conduct of the study; collection, management, analyses, or interpretation of the data; or preparation or decision to submit the manuscript for publication.
Duality of Interest. M.N.M. has worked as a consultant for Sanofi and Lilly. E.T. has worked as a consultant for Medtronic. No other potential conflicts of interest relevant to this article were reported.
Author Contributions. M.M., C.S., and E.T. contributed to the development of the study concept and design. M.M., C.S., A.A., D.D., A.M., A.A.-C., K.W., and E.T. contributed to data acquisition, analysis, and interpretation. M.M., C.S., A.M., A.A.-C., K.W., and E.T. contributed to drafting of the manuscript. M.M., C.S., A.M., K.W., and E.T. contributed to critical revision of the manuscript of important intellectual content. M.M. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Footnotes
Clinical trial reg. no. NCT03078491, clinicaltrials.gov
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