Abstract
Aim:
The aim of this cross-sectional retrospective study was to estimate the prevalence of different physical and psychiatric disorders as well as multimorbidity in outpatients with type 1 diabetes (T1D) in Germany.
Methods:
A total of 6967 adult patients with T1D from 958 general or diabetologist practices in Germany between January 2015 and December 2019 from the Disease Analyzer database (IQVIA) were included. The main outcome of the study was the prevalence of different diabetes-related and nondiabetes-related disorders within 12 months prior to the last outpatient visit. Multivariate logistic regression models were fitted with multimorbidity differently defined as >2, >3, >4, and >5 different disorders as a dependent variable and age, sex, glycated hemoglobin (HbA1c) values, and insulin pump therapy as impact variables.
Results:
Mean age (standard deviation [SD]) was 45.3 (16.7) years; 42.9% were women, the mean HbA1c was 7.9% (SD: 1.4%). The most frequent disorder was arterial hypertension (31.2%), followed by dyslipidemia (26.4%), dorsalgia (20.4%), diabetic neuropathy (17.3%), and depression (14.6%). The proportion of thyroid gland disorders, retinopathy, urethritis, iron deficiency anemia, and psychiatric disorders was higher in women than in men. Hypertension and mental and behavioral disorders due to the use of tobacco were higher in men. On average, each patient was diagnosed with 3.1 different disorders. Age had the strongest association with multimorbidity, followed by HbA1c value and female sex.
Conclusion:
In summary, patients with T1D are often multimorbid, and the multimorbidity is associated with higher gender, female sex, and high HbA1c values. Understanding all of these factors can help practitioners create a risk profile for every patient.
Keywords: type 1 diabetes, multimorbidity, sex differences, HbA1c
Introduction
Type 1 diabetes (T1D) is a chronic autoimmune disorder that leads to the complete destruction of insulin-producing beta cells, which in turn usually leads to an absolute insulin deficiency in the body. Currently, insulin is the only therapeutic option for people with T1D, and it must be administered throughout the patient’s life. 1 Most adults with T1D receive multiple daily injection (MDI) therapy, but the number of insulin pump users is constantly increasing. 2
The goal of any diabetes management approach is to keep the patient’s glucose values within the target range and avoid hypoglycemia and hyperglycemia as often as possible. Keeping glucose values in target prevents long-term diabetes complications (eg, diabetic nephropathy and diabetic retinopathy) because it is known that constantly high glucose values can be toxic for blood vessels and nerves. Microvascular complications are the most common long-term diabetes-related comorbidities. The risk of developing diabetes-related complications increases with the duration of T1D and poor metabolic control (high glycated hemoglobin [HbA1c]).3-5
Diabetes management is a considerable everyday burden for people with T1D, and the effort to stay within the target range is not always successful. For some, the fear of developing diabetes complications feels like an ever-looming threat. Psychiatric disorders (eg, depression, anxiety, and eating disorders) are common comorbidities in patients with T1D.6-8 Women are known to be more often affected by these comorbidities than men.9,10
T1D is an autoimmune disorder, and patients with one autoimmune disease are prone to develop additional autoimmune diseases (eg, autoimmune thyroiditis or celiac disease). Genetic background may affect a person’s risk for autoimmune diseases, and patients with T1D exhibit an increased risk of other autoimmune disorders. Young people with T1D are tested on a regular basis (once a year) for additional autoimmune disorders. Adults are tested when they present symptoms typical of an underlying autoimmune disorder. 11
Multimorbidity among patients with type 2 diabetes (T2D) is well established,12,13 but little is known about the comorbidities associated with T1D and the extent to which those comorbidities impact patients.
The aim of this study was to estimate the prevalence of different physical and psychiatric disorders as well as multimorbidity in outpatients with T1D in Germany.
Materials and Methods
Database
This study was based on data from the Disease Analyzer database (IQVIA), which compiles drug prescriptions, diagnoses, and basic medical and demographic data obtained directly and in anonymous format from computer systems used in the practices of general practitioners and specialists. 14 The database covers approximately 3% of all outpatient practices in Germany. Diagnoses (according to the International Classification of Diseases, 10th revision [ICD-10]), prescriptions (according to the Anatomical Therapeutic Chemical [ATC] classification system), and the quality of reported data are monitored by IQVIA. In Germany, the sampling methods used to select physicians’ practices are appropriate for obtaining a representative database of general and specialized practices. The sampling method for the Disease Analyzer database is based on summary statistics from all doctors in Germany published yearly by the German Medical Association. IQVIA uses these statistics to determine the panel design according to the following strata: specialist group, German federal state, community size category, and age of physician. Altogether, the database contains data from approximately 3000 private practices, including general and specialist practices, and has a coverage of approximately 3% of private practice in Germany. 14
Study Population
This retrospective cross-sectional study included patients aged 18 years or older with a T1D diagnosis (ICD-10: E10) plus at least one insulin prescription. Study participants were followed in 888 general and 70 diabetologist practices in Germany between January 2015 and December 2019. Patients had to have an observation time of at least one year prior to their last visit. Patients with a T2D diagnosis (ICD-10: E11) or prescriptions of noninsulin hypoglycemic drugs in the past were excluded in order to avoid misclassification of T1D diagnoses (Figure 1).
Figure 1.
Selection of study patients.
Study Outcomes and Covariates
The main outcome of the study was the prevalence of different diabetes-related and nondiabetes-related disorders within 12 months prior to the last outpatient visit. The number of different disorders was also estimated. We included all chronic physical and psychiatric disorders diagnosed in the year prior to the last visit that were found in at least 3% of patients with T1D.
These disorders included microvascular complications (ie, diabetic neuropathy [E10.4], diabetic retinopathy [E10.3], renal complications [E10.2, N18, N19]), endocrine, nutritional, and metabolic diseases (ie, other hypothyroidism [ICD-10: E03], nontoxic goiter [E04], hyperthyroidism [E05], thyroiditis [E06], vitamin D deficiency [E55], obesity [E66], and dyslipidemia [ICD-10: E78]), diseases of the respiratory system (ie, vasomotor and allergic rhinitis [J30], chronic sinusitis [J32], bronchitis, not specified as acute or chronic [J40], chronic obstructive pulmonary disease [COPD] [J44], and asthma [J45]), diseases of the digestive system (ie, gastroesophageal reflux disease [K21], gastritis and duodenitis [K29], and other functional intestinal disorders [K76]), diseases of the musculoskeletal system and connective tissue (ie, other intervertebral disc disorders [M51], dorsopathies not elsewhere classified [M53], dorsalgia [M54], shoulder lesions [M75], enthesopathies [M77], other soft tissue disorders not elsewhere classified [M79], biomechanical lesions not elsewhere classified [M99]), diseases of the circulatory system (ie, hypertension [I10], chronic ischemic heart disease [I25], peripheral vascular diseases [I73]), psychiatric conditions (ie, mental and behavioral disorders due to the use of tobacco [F17], depression [F32, F33], anxiety disorders [F41], reaction to severe stress and adjustment disorders [F43], somatoform disorders (F45]), and other diseases (ie, cancer [C00-C99], iron deficiency anemia [D50], chronic headache [G43, G44], sleep disorders [G47], dermatitis [L30], and urethritis and urethral syndrome [N39]).
The prevalence of these disorders and the number of different disorders per patient was estimated and stratified by age group (18-40, 41-60, >60 years), sex, and average HbA1c value in the whole observation time prior to the last visit (<6.5%, 6.5%-7.4%, 7.5%-8.9%, ≥9%). Additionally, the number of different disorders per patient, between patients with T1D and age-matched and sex-matched patients without diabetes taken from the same database.
Statistical Analyses
The prevalence of different physical and psychiatric conditions was compared between age groups, men and women, and HbA1c groups using Chi-squared tests. The average number of different disorders per patient was compared between age groups, men and women, and HbA1c groups using Wilcoxon tests. Finally, a multivariate logistic regression model was fitted with multimorbidity differently defined as >2, >3, >4, and >5 different disorders as a dependent variable and age, sex, HbA1c values, and insulin pump therapy as impact variables. P values <.05 were considered statistically significant. Analyses were carried out using SAS version 9.4 (SAS Institute, Cary, USA).
Results
Basic Characteristics of the Study Sample
The present study included 6967 patients. The basic characteristics of the study patients are listed in Table 1. Mean age (standard deviation [SD]) was 45.3 (16.7) years; 42.9% were women, the mean HbA1c was 7.9% (SD: 1.4%). As of the last insulin therapy in the study period, 30.8% were insulin pump users, and 69.2% injected basal and bolus insulins (intensified insulin therapy).
Table 1.
Basic Characteristics of the Study Sample.
| Variable | Mean (SD) or proportion (%), n = 6967 |
|---|---|
| Age (mean, SD) | 45.3 (16.7) |
| 18-40 | 39.6 |
| 41-60 | 38.5 |
| >60 | 21.9 |
| Women (%) | 42.9 |
| Mean (%) | 57.1 |
| Glycated hemoglobin (mean, SD) (n = 4740) | 7.9 (1.4) |
| <6.5 | 13.0 |
| 6.5-7.4 | 32.6 |
| 7.5-8.9 | 37.6 |
| ≥9 | 16.8 |
| Insulin pump therapy | 30.8 |
| Basal + bolus therapy | 69.2 |
Prevalence of Different Disorders
The prevalence of predefined chronic disorders is shown in Table 2. The most frequent disorder was hypertension (31.2%), followed by dyslipidemia (26.4%), dorsalgia (20.4%), diabetic neuropathy (17.3%), and depression (14.6%). The proportion of thyroid gland disorders, retinopathy, urethritis, iron deficiency anemia, and psychiatric disorders was higher in women than in men. Hypertension and mental and behavioral disorders due to the use of tobacco were higher in men (Table 2). The proportion of individuals with the most disorders increased with age (Table 3). Diabetic complications, stomach diseases, hypertension, depression, and reaction to severe stress and adjustment disorders were more frequent in patients with higher HbA1c values (Table 4).
Table 2.
Prevalence of Chronic Disorders Among Adult Outpatients With Type 1 Diabetes in Germany, Total and Stratified by Sex.
| Diagnosis | Proportion in total patients (%), n = 6967 | Proportion in male patients (%), n = 3960 | Proportion in female patients (%), n = 3007 | P value |
|---|---|---|---|---|
| Diabetic renal complications | 12.6 | 12.1 | 13.3 | .131 |
| Diabetic neuropathy | 17.3 | 17.5 | 17 | .561 |
| Diabetic retinopathy | 10.8 | 9.8 | 12.2 | .001 |
| Hypothyroidism | 11.0 | 6.6 | 16.9 | <.001 |
| Nontoxic goiter | 4.9 | 3.2 | 7.2 | <.001 |
| Hyperthyroidism | 3.3 | 2 | 5.1 | <.001 |
| Thyroiditis | 7.9 | 4.2 | 12.8 | <.001 |
| Vitamin D deficiency | 3.8 | 2.9 | 4.9 | <.001 |
| Obesity | 8.8 | 8.5 | 9.3 | .211 |
| Dyslipidemia | 26.4 | 27.5 | 25 | .023 |
| Bronchitis, not specified as acute or chronic | 4.4 | 4.5 | 4.2 | .549 |
| Chronic obstructive pulmonary disease | 6.2 | 5.8 | 6.8 | .077 |
| Asthma | 8.8 | 9 | 8.6 | .575 |
| Vasomotor and allergic rhinitis | 3.5 | 3.8 | 3.1 | .151 |
| Chronic sinusitis | 5.4 | 5.1 | 5.8 | .197 |
| Gastroesophageal reflux disease | 5.2 | 5.6 | 4.6 | .061 |
| Gastritis and duodenitis | 9.7 | 9.3 | 10.3 | .194 |
| Other functional intestinal disorders | 4.2 | 4.7 | 3.6 | .022 |
| Other intervertebral disc disorders | 4.2 | 4.3 | 4 | .467 |
| Dorsopathies not elsewhere classified | 4.9 | 4 | 6.2 | <.001 |
| Dorsalgia | 20.4 | 20.2 | 20.6 | .700 |
| Shoulder lesions | 5.9 | 5.9 | 5.9 | .9150 |
| Enthesopathies | 4.7 | 5 | 4.2 | .1070 |
| Other soft tissue disorders, not elsewhere classified | 5.9 | 5.7 | 6.2 | .4090 |
| Biomechanical lesions, not elsewhere classified | 5.9 | 5.9 | 5.9 | .992 |
| Hypertension | 31.2 | 33.6 | 28 | <.001 |
| Chronic ischemic heart disease | 7.1 | 7.7 | 6.2 | .015 |
| Peripheral vascular disease | 5.0 | 5.6 | 4.2 | .010 |
| Chronic headache | 3.8 | 3 | 4.8 | <.001 |
| Sleep disorders | 5.5 | 5.2 | 5.8 | .223 |
| Atopic dermatitis | 6.8 | 6.5 | 7.1 | .259 |
| Urethritis and urethral syndrome | 8.3 | 3.4 | 14.8 | <.001 |
| Cancer | 4.1 | 3.8 | 4.4 | .202 |
| Iron deficiency anemia | 3.4 | 1.5 | 5.9 | <.001 |
| Mental and behavioral disorders due to use of tobacco | 7.4 | 8.7 | 5.8 | <.001 |
| Depression | 14.6 | 11.8 | 18.4 | <.001 |
| Anxiety disorders | 4.3 | 3.1 | 5.8 | <.001 |
| Reaction to severe stress, and adjustment disorders | 12.2 | 10.4 | 14.6 | <.001 |
| Somatoform disorders | 6.9 | 5.6 | 8.5 | <.001 |
| Number of different disorders additionally to type 1 diabetes | ||||
| 0 | 18.2 | 19.9 | 15.9 | <.001 |
| 1 | 18.1 | 18.6 | 17.5 | .220 |
| 2 | 14.9 | 15.1 | 14.6 | .627 |
| 3 | 11.9 | 12.5 | 11.2 | .097 |
| 4 | 10.1 | 9.8 | 10.6 | .234 |
| 5 | 7.2 | 6.8 | 7.7 | .143 |
| >5 | 19.5 | 17.3 | 22.5 | <.001 |
| Average number of disorders (mean, SD) | 3.1 (3.2) | 3.0 (3.0) | 3.6 (3.4) | <.001 |
Table 3.
Prevalence of Chronic Disorders Among Adult Outpatients With Type 1 Diabetes in Germany, Stratified by Age Group.
| Diagnosis | Proportion in patients aged 18-40 (%), n = 2971 | Proportion in patients aged 41-60 (%), n = 2888 | Proportion in patients aged >60 (%), n = 1646 | P value |
|---|---|---|---|---|
| Diabetic renal complications | 6.1 | 12.8 | 20 | <.001 |
| Diabetic neuropathy | 6.4 | 19.1 | 28.1 | <.001 |
| Diabetic retinopathy | 6 | 12.4 | 13.4 | <.001 |
| Hypothyroidism | 9.5 | 10.7 | 10.8 | <.001 |
| Nontoxic goiter | 2.4 | 5.3 | 7.4 | <.001 |
| Hyperthyroidism | 1.9 | 3.3 | 4.9 | <.001 |
| Thyroiditis | 8 | 8 | 5 | .0280 |
| Vitamin D deficiency | 2.5 | 4.2 | 4.1 | <.001 |
| Obesity | 6.6 | 9.7 | 8.6 | <.001 |
| Dyslipidemia | 12.1 | 30.2 | 37 | <.001 |
| Bronchitis, not specified as acute or chronic | 5.4 | 3.9 | 2 | <.001 |
| Chronic obstructive pulmonary disease | 6.5 | 6.4 | 3.5 | .005 |
| Asthma | 7.7 | 9.5 | 6.7 | .003 |
| Vasomotor and allergic rhinitis | 1.1 | 3.8 | 6.1 | <.001 |
| Chronic sinusitis | 4.7 | 5.3 | 4.9 | .102 |
| Gastroesophageal reflux disease | 2.9 | 5.8 | 6.3 | <.001 |
| Gastritis and duodenitis | 9.3 | 9.1 | 8.6 | .325 |
| Other functional intestinal disorders | 2.3 | 4.9 | 5.3 | <.001 |
| Other intervertebral disc disorders | 1.6 | 5.5 | 5.2 | <.001 |
| Dorsopathies not elsewhere classified | 3 | 6.3 | 4.6 | <.001 |
| Dorsalgia | 14.5 | 22.9 | 19.7 | <.001 |
| Shoulder lesions | 1.7 | 8.6 | 6.7 | <.001 |
| Enthesopathies | 2.4 | 6.3 | 4.2 | <.001 |
| Other soft tissue disorders, not elsewhere classified | 4.7 | 6.4 | 5.2 | .001 |
| Biomechanical lesions, not elsewhere classified | 5 | 6.4 | 4.5 | .016 |
| Hypertension | 10.8 | 35.3 | 50.5 | <.001 |
| Chronic ischemic heart disease | 0.6 | 6.4 | 17.4 | <.001 |
| Peripheral vascular disease | 0.8 | 5.1 | 10.8 | <.001 |
| Chronic headache | 4.7 | 3.4 | 1.6 | <.001 |
| Sleep disorders | 3.2 | 5.5 | 7.5 | <.001 |
| Atopic dermatitis | 4.9 | 6.1 | 8.9 | <.001 |
| Urethritis and urethral syndrome | 6.4 | 7.7 | 10.1 | <.001 |
| Cancer | 0.7 | 3.4 | 10 | <.001 |
| Iron deficiency anemia | 2.4 | 4 | 3 | <.001 |
| Mental and behavioral disorders due to use of tobacco | 5.7 | 9.1 | 5.2 | <.001 |
| Depression | 10.4 | 17 | 13.3 | <.001 |
| Anxiety disorders | 4.1 | 3.8 | 3.9 | .518 |
| Reaction to severe stress and adjustment disorders | 11.7 | 13.5 | 6.9 | <.001 |
| Somatoform disorders | 5.4 | 7 | 6.9 | <.001 |
| Number of different disorders additionally to type 1 diabetes | ||||
| 0 | 29.9 | 10.6 | 4.4 | <.001 |
| 1 | 23.5 | 15.3 | 7.5 | <.001 |
| 2 | 15.8 | 13.9 | 10.1 | .023 |
| 3 | 9.9 | 12.4 | 10.7 | <.001 |
| 4 | 7 | 11.1 | 10.8 | <.001 |
| 5 | 4.3 | 7.4 | 9.7 | <.001 |
| >5 | 9.3 | 22.3 | 26.9 | <.001 |
| Average number of disorders (mean, SD) | 2.1 (2.4) | 3.8 (3.3) | 4.8 (3.5) | <.001 |
Table 4.
Prevalence of Chronic Disorders Among Adult Outpatients With Type 1 Diabetes in Germany, Stratified by Glycated Hemoglobin (HbA1c) Group.
| Diagnosis | Proportion in patients with average HbA1c <6.5% (%), n = 615 | Proportion in patients with average HbA1c 6.5-7.4 (%), n = 1,546 | Proportion in patients with average HbA1c 7.5-8.9 (%), n = 1,780 | Proportion in patients with average HbA1c ≥9 (%), n = 799 | P value |
|---|---|---|---|---|---|
| Diabetic renal complications | 10.7 | 14 | 15.5 | 13 | .024 |
| Diabetic neuropathy | 13 | 19 | 20.6 | 16.4 | <.001 |
| Diabetic retinopathy | 7.2 | 11.5 | 13 | 8.8 | <.001 |
| Hypothyroidism | 9.3 | 11.8 | 12.5 | 10.1 | .098 |
| Nontoxic goiter | 5.9 | 6.5 | 5.1 | 4 | .069 |
| Hyperthyroidism | 3.4 | 4.3 | 3 | 3.1 | .212 |
| Thyroiditis | 9.6 | 8 | 8.4 | 7 | .342 |
| Vitamin D deficiency | 4.9 | 4.9 | 5.3 | 3.6 | .320 |
| Obesity | 7.3 | 9.2 | 10.1 | 8.5 | .184 |
| Dyslipidemia | 25.9 | 27.8 | 29.9 | 25.8 | .082 |
| Bronchitis, not specified as acute or chronic | 4.9 | 4.7 | 3.7 | 4.8 | .393 |
| Chronic obstructive pulmonary disease | 6.5 | 5.1 | 5.6 | 9 | .001 |
| Asthma | 6 | 7.8 | 7.6 | 10.5 | .014 |
| Vasomotor and allergic rhinitis | 3.9 | 3.4 | 3.8 | 4.8 | .465 |
| Chronic sinusitis | 4.6 | 4.9 | 5.4 | 6.4 | .386 |
| Gastroesophageal reflux disease | 3.3 | 4.3 | 6.7 | 5.9 | .001 |
| Gastritis and duodenitis | 9.1 | 7.2 | 11.3 | 13.9 | <.001 |
| Other functional intestinal disorders | 4.7 | 3.9 | 3.6 | 5.1 | .251 |
| Other intervertebral disc disorders | 3.9 | 4.7 | 4.8 | 4 | .666 |
| Dorsopathies not elsewhere classified | 4.4 | 5.5 | 5.4 | 5.6 | .719 |
| Dorsalgia | 17.7 | 20.6 | 21.2 | 23.9 | .042 |
| Shoulder lesions | 4.4 | 6.9 | 6.5 | 6.1 | .187 |
| Enthesopathies | 3.7 | 4.9 | 5.7 | 3.5 | .050 |
| Other soft tissue disorders, not elsewhere classified | 4.1 | 6.1 | 6.3 | 7.9 | .032 |
| Biomechanical lesions, not elsewhere classified | 6.7 | 5.6 | 5.4 | 6 | .667 |
| Hypertension | 31.7 | 34.4 | 35.5 | 28.5 | .004 |
| Chronic ischemic heart disease | 6.7 | 7.3 | 8.5 | 7.6 | .426 |
| Peripheral vascular disease | 3.3 | 5.4 | 6.1 | 3.4 | .004 |
| Chronic headache | 4.4 | 2.7 | 3.1 | 5 | .016 |
| Sleep disorders | 3.3 | 5.5 | 5.8 | 6.5 | .047 |
| Atopic dermatitis | 7.3 | 7.8 | 6.2 | 7.3 | .343 |
| Urethritis and urethral syndrome | 6.8 | 8.5 | 8.4 | 10.3 | .143 |
| Cancer | 3.4 | 5.8 | 4.2 | 2.6 | .002 |
| Iron deficiency anemia | 3.9 | 4.6 | 3.3 | 4.3 | .289 |
| Mental and behavioral disorders due to use of tobacco | 6.7 | 5.7 | 7.6 | 11.3 | <.001 |
| Depression | 10.9 | 14.1 | 16.2 | 19.4 | <.001 |
| Anxiety disorders | 4.1 | 3.9 | 5.3 | 5.5 | .173 |
| Reaction to severe stress, and adjustment disorders | 10.6 | 10.4 | 13.5 | 18.5 | <.001 |
| Somatoform disorders | 6.3 | 5.2 | 7.4 | 6.4 | .088 |
| Number of different disorders additionally to type 1 diabetes | |||||
| 0 | 19.8 | 16.9 | 13.8 | 14.9 | .002 |
| 1 | 23.7 | 17.9 | 18.1 | 14.3 | <.001 |
| 2 | 15 | 15.7 | 14.8 | 16.6 | .669 |
| 3 | 9.3 | 12.4 | 12.3 | 13.9 | .068 |
| 4 | 9.9 | 10.1 | 10.7 | 11.8 | .598 |
| 5 | 5.9 | 8 | 7.7 | 6 | .140 |
| >5 | 16.4 | 19.1 | 22.6 | 22.5 | .002 |
| Average number of disorders (mean, SD) | 2.9 (3.2) | 3.3 (3.2) | 3.6 (3.3) | 3.5 (3.2) | <.001 |
Number of Different Disorders
On average, each patient was diagnosed with 3.1 different disorders. The mean number of disorders was slightly higher in women than in men (Table 2). Also, the number of disorders per patient increased with age from 2.1 in the 18-40 age group to 4.8 in the >60 age group (Table 3). The average number of disorders increased only slightly with HbA1c value, from 2.9 in patients with an HbA1c <6.5% to 3.5 in patients with an HbA1c ≥9% (Table 4). Compared with T1D patients, age-matched and sex-matched patients without diabetes had a significantly lower number of diagnoses (2.5, P < .001) (Table 5).
Table 5.
Prevalence of the Multimorbidity Among Adult Outpatients With Type 1 Diabetes (T1D) and Age-Matched and Sex-Matched Patients Without Diabetes in Germany.
| Diagnosis | Proportion in T1D patients (%), n = 6967 | Proportion in patients without diabetes (%), n = 6967 | P value |
|---|---|---|---|
| Number of different disorders (excluding T1D) | |||
| 0 | 18.2 | 17.5 | .320 |
| 1 | 18.1 | 22.0 | <.001 |
| 2 | 14.9 | 19.1 | <.001 |
| 3 | 11.9 | 14.0 | <.001 |
| 4 | 10.1 | 11.2 | .055 |
| 5 | 7.2 | 6.2 | .019 |
| >5 | 19.5 | 10.0 | <.001 |
| Average number of disorders (mean, SD) | 3.1 (3.2) | 2.5 (2.3) | <.001 |
Variables Associated With a Risk of Multimorbidity
The results of the multivariable regression analyses are shown in Table 6. Age had the strongest association with multimorbidity, followed by HbA1c value and female sex. Female sex had a stronger effect as more disorders were included in the multimorbidity definition. No association was found for insulin pump therapy compared with basal-bolus therapy, whereby only last insulin therapy was analyzed.
Table 6.
Association Between Age, Sex, Glycated Hemoglobin (HbA1c) Values, Insulin Pump Use, and the Risk of Multimorbidity in Patients With Type 1 Diabetes.
| Odds ratio (95% confidence limits) | ||||
|---|---|---|---|---|
| Variable | >2 disorders | >3 disorders | >4 disorders | >5 disorders |
| Age 41-60 versus 18-40 | 3.62 (3.15-4.16)* | 3.35 (2.89-3.89)* | 3.37 (2.86-3.98)* | 3.3 (2.78-4.05)* |
| Age >60 versus 18-40 | 8.13 (6.77-9.77)* | 7.01 (5.86-8.37)* | 6.21 (5.14-7.51)* | 5.44 (4.41-6.71)* |
| Women versus men | 1.23 (1.09-1.40)* | 1.34 (1.18-1.52)* | 1.36 (1.19-1.56)* | 1.42 (1.22-164)* |
| HbA1c 6.5-7.4 versus <6.5 | 1.25 (1.02-1.53)* | 1.11 (0.90-1.37) | 1.16 (0.92-1.46) | 1.07 (0.83-1.39) |
| HbA1c 7.5-8.9 versus <6.5 | 1.64 (1.34-2.00)* | 1.45 (1.18-1.78)* | 1.49 (1.19-1.86)* | 1.44 (1.12-1.84)* |
| HbA1c ≥9 versus <6.5 | 2.44 (1.93-3.08)* | 1.96 (1.55-2.49)* | 1.86 (1.44-2.41)* | 1.92 (1.45-2.56)* |
| Insulin pump therapy versus basal + bolus | 1.10 (0.92-1.32) | 0.97 (0.81-1.17) | 1.05 (0.86-1.28) | 0.92 (0.74-1.15) |
P < 0.05.
Discussion
The present study, which included patients with T1D from general and diabetologist practices in Germany, has shown that the most frequent disorder in combination with T1D was hypertension, followed by dyslipidemia, dorsalgia, diabetic neuropathy, and depression. The analysis found that the proportion of thyroid gland disorders, retinopathy, urethritis, iron deficiency anemia, and psychiatric disorders was higher in women than in men. In contrast, hypertension and mental and behavioral disorders due to the use of tobacco were more frequent in men. Finally, the number of disorders increases with age and slightly increases with the HbA1c level. To the best of our knowledge, this is the first study investigating multimorbidity in adult patients with T1D based on real-world data.
There are several studies that investigated the prevalence of defined comorbidities in patients with T1D but usually not a combination of different diseases. Since cardiovascular complications are considered to be related to T2D, a recent study pointed out that people with T1D 12 years and older have cardiac risk factors like hypertension and dyslipidemia, and many of these patients are not adequately treated for these disorders. The study also found that 30%-40% of patients with T1D do not achieve blood pressure and lipid target goals. This is similar to our results, as in our study, 30% of the patients with T1D had hypertension and 26% had dyslipidemia. The authors concluded that there is an urgent need not only to improve metabolic control but also to mitigate cardiovascular risk profiles by means of an adequate treatment strategy in people with T1D. 15 Subjects with T1D have decreased bone mineral density and an up to sixfold increased fracture risk, especially for recurrent vertebral fractures.16,17 Therefore, dorsalgia in patients with T1D may derive from a vertebral fracture, as the reason for dorsalgia is not specified. Diabetic neuropathy is a common long-term diabetes complication, and it is responsible for most of the lower limb amputations, reduced quality of life, and low-life expectancy. The reported prevalence of diabetic neuropathy among people with T1D is 11%. In our study, we found that 17% of the patients with T1D presented with diabetic neuropathy. Patients with neuropathy were older, had higher HbA1c levels, a longer duration of diabetes, were more likely to be female, and have cardiovascular diseases.18,19
Several studies have shown that T1D and depression is a common comorbidity that impairs diabetes management and glycemic control. Roy et al pointed out that the prevalence of depression is increased in people with T1D (twice as much), but the rates vary widely between studies (between 6% and 43%). This range may reflect differences in measurement methods, or differences in terms of country, socioeconomic factors, or other variables. 20 In our study, about 15% of the patients presented with depression, which was in line with the results of Roy et al’s study.
Rogers et al showed in their study that patients with T1D, particularly women, have a greater risk of developing concomitant autoimmune diseases (hypothyroidism, arthritis, and celiac disease) and a higher risk of renal failure, stroke, and myocardial infarction. The risk increases with the number of concomitant autoimmune diseases. 21 Patients exhibiting risky behavior have a higher rate of metabolic deterioration because of treatment disregard. 22
Our findings may have implications for the future care of patients with T1D. First, the focus should not only be on diabetes management but also on recognizing and treating additional comorbidities. Physical and psychiatric disorders are not always obvious but can negatively influence diabetes management. Second, treatment management should be more gender dependent, as women and men are susceptible to different comorbidities. Therefore, screening and treatment modalities should be geared toward gender. In this study, multimorbidity has a strong association with the female sex. This gender dependency is also important information for practitioners. Women are more susceptible to developing cardiovascular diseases than men.23,24 So, this work provides an information for the possible development of a “risk profile” and might be used to raise awareness of gender-based comorbidity.
Differences in diabetes-related distress and depression may play a crucial role in cardiovascular disease risk in women with T1D, 25 since women with T1D exhibit higher levels of diabetes distress than men.26,27
As patients with T1D age, the number of concomitant diseases may increase as well. Health care practitioners should keep this in mind when treating older patients with T1D or when treating younger patients with T1D over a long time period, especially those with poor metabolic control (high HbA1c).
Strengths and Limitations
The present study is based on real-world data from general practitioners and diabetologists with continuous documentation of several diagnoses. Moreover, the large number of patients available for analysis is one of the main strengths of this study. However, this study is also subject to several limitations. Diagnoses relied solely on ICD-10 codes, and no information on disease severity was available. For example, in this study, the prevalence of peripheral arterial disease was 5.0%, whereas, in the study of Mark et al, based on much more adult patients with T1D and The Digital Academic Archive register, the prevalence was 7.3%. 28 Furthermore, the data pertaining to several confounding factors (eg, education, income, smoking status, alcohol consumption) were lacking, potentially introducing a bias in our analyses. Furthermore, pre-existing psychiatric illness of mild severity might not be correctly coded resulting in no or incorrect documentation. HbA1c values may be collected in practices with different laboratory methods increasing the uncertainty related to the HbA1c result for the study population. Finally, the database contains no information on mortality and no hospital data.
Conclusion
In summary, patients with T1D are often multimorbid, and the multimorbidity is associated with higher gender, female sex, and high HbA1c values. Understanding all of these factors can help practitioners create a risk profile for every patient.
Footnotes
Abbreviations: ATC, Anatomical Therapeutic Chemical; IQVIA, Disease Analyzer database; MDI, multiple daily injection; T1D, Type 1 diabetes; HbA1c, hemoglobin A1c; SD, standard deviation, T2D, type 2 diabetes.
Author Contributions: KK was responsible for the study concept, study design, and data analysis. LVDB, MK, and GB interpreted the data. LVDB drafted the manuscript. All authors edited the drafts of the manuscript.
Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
ORCID iD: Karel Kostev 
https://orcid.org/0000-0002-2124-7227.
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