High prevalence of diabetes in patients with rheumatoid arthritis: results from a questionnaire survey linked to claims data

High prevalence of diabetes in patients with rheumatoid arthritis: results from a questionnaire... Abstract Objectives To investigate the prevalence of diabetes in patients with RA and the impact of diabetes on self-reported outcomes and health care. Methods RA patients between the ages of 18 and 79 years were randomly selected from a nationwide statutory health insurance fund and were surveyed about rheumatological care and disease burden. Comorbid diabetes (E10–14) was analysed regarding age, sex, BMI and socioeconomic status. Disease burden, comorbidity and prescriptions were compared in RA patients with and without diabetes. Predictors of rheumatological care were identified by multivariate regression. Results Of the 2535 RA patients, 498 (20%) had diabetes. Diabetes was more frequent in males, in older patients, in patients with a higher BMI and in those with a lower socioeconomic status. All disease outcomes were poorer in RA–diabetes patients and were mainly attributable to a higher BMI. RA–diabetes patients received less DMARDs (40% vs 48%) and had more hospital stays (41% vs 30%) than patients without diabetes (all P < 0.05). Rates of cardiovascular disease (35% vs 15%), depression (39% vs 26%) and renal failure (23% vs 8%) were higher in RA–diabetes patients (all P < 0.0001). They were less frequently treated by rheumatology specialists: 57% vs 67%; odds ratio = 0.64 (95% CI: 0.45, 0.92), after controlling for confounders. Conclusion The prevalence of diabetes in patients with RA is high and is associated with known sociodemographic factors. More than 40% of patients with RA and diabetes were not under rheumatological care even though they reported a high disease burden, were frequently hospitalized and often presented with further comorbidities. rheumatoid arthritis, diabetes, comorbidities, health care Rheumatology key messages The prevalence of diabetes is higher in RA patients than in the general population. People with RA and diabetes present with a high disease burden and further comorbidities. People with RA and diabetes are treated by rheumatologists less often than those without diabetes. Introduction RA is associated with an increased incidence and prevalence of diabetes [1, 2]. Furthermore, the risk of undiagnosed diabetes is elevated in patients with RA, especially in those with long-standing disease [3]. Adjusted comparisons with the general population indicate that the higher incidence is mainly driven by obesity, lifestyle factors and comorbidity [4]. Certain DMARDs, including TNF-α inhibitors, seem to decrease the incidence of diabetes in patients with RA by improving the markers of glucose metabolism [5–7], while glucocorticoids and statins are likely associated with an increased risk [8]. The coexistence of RA and diabetes increases cardiovascular risk [9]. These facts indicate that high diabetes prevalence and the resulting complications in patients with RA may be reduced by increasing awareness of the risk factors for diabetes at the patient level and by providing adequate anti-inflammatory RA therapy at the health care level. To assess the impact of diabetes in patients with RA, reliable data on diabetes prevalence and RA-related outcomes are required. RA cohorts cover data on disease activity and socioeconomic factors, whereas diabetes, as a comorbid condition, is reported either by the rheumatologist or the patient [10–12]. Furthermore, RA cohorts mostly represent RA patients in rheumatological care. In health care databases, diabetes is assessed by diagnostic codes and specific medications, whereas data on RA disease activity are missing [1, 2, 4, 5]. We took advantage of claims data linked to self-reported patient outcomes from a questionnaire survey within the network Linking Patient-Reported Outcomes with CLAIms data for health services research in Rheumatology (PROCLAIR) [13]. This linkage enables an investigation of the prevalence of diabetes in patients with RA by socioeconomic factors in a population-based setting and enables the assessment of the impact of diabetes on self-reported RA outcomes and the health care status of these patients. Methods This study was conducted using a cross-sectional design. Using data from a nationwide statutory health insurance fund (BARMER), RA patients between the age of 18 and 79 years were identified based on a diagnostic code of RA (M05, M06), according to the German modification of the International Statistical Classification of Diseases (ICD-10-GM) in at least two quarters of 2013 [13]. In 2015, an age, sex and diagnosis (M05 and M06) stratified random sample of 6600 people was provided with a questionnaire covering RA diagnosis confirmation, access to rheumatological care, self-reported disease burden, lifestyle factors and RA impacts on social and working life [14]. Patients gave their written informed consent for the linking of information derived from the questionnaire to claims data. Ethical approval was obtained from the ethics committee of the Charité University Medicine in March of 2015 (EA1/051/15). This research was conducted in agreement with the Declaration of Helsinki. The study was performed within the research networks PROCLAIR and Metabolic Impact on Joint and Bone Diseases (METARTHROS) [14, 15]. Claims data Age, sex, postal code, insurance status and comorbidities were assessed in the claims data from 2015. We identified patients with diabetes mellitus who were coded with the diagnoses E10–E14 in outpatient care in at least two quarters of 2015. Additional cardiovascular, respiratory and other comorbidities were also assessed with the data from 2015, and at least one diagnosis had to be documented in outpatient care (ICD-10 codes are reported in Table 2). Drug prescriptions in 2015 were identified via the anatomical therapeutic chemical classification as follows: conventional synthetic DMARDs (L04AA13, L04AD01, L04AX01, L04AX03, M01C), biologics (L04AA24, L04AB, L04AC03, L04AC07, L01XC02), glucocorticoids (H02AB, H02BX), NSAIDs (M01A), oral antidiabetics (A10B), insulin (A10A), anti-hypertensive agents (C02, C08, C09), diuretics (C03), statins (C10AA), anti-depressants (N06A) and analgesics were assessed according to a previously used reference list of anatomical therapeutic chemical codes [16]. Questionnaire data RA diagnosis confirmation (what is your disease called by the physician?), disease duration and rheumatological care (current/ever) were covered in the questionnaire. Tender and swollen joints were assessed by 50 and 48 joint counts for tenderness and swelling in a patient-reported question/mannequin format [17, 18]. Disability was assessed by the physical Functional Questionnaire Hannover (FFbH, range 0–100: full functional capacity) [19]. The impact of RA disease was ascertained by the RA Impact of Disease score (RAID; range 0: no impact, to 10: highest impact) [20, 21]. The WHO’s Five-item Well-being Index (WHO-5; scores transformed to 0–100) was used to determine the depressive symptoms based on the last 2 weeks. The depressive symptoms were categorized as mild (29–50) or moderate to severe (0–28), whereas patients scoring above 50 were considered to have no depressive symptoms [16]. BMI (kg/m2), household income (<1500, 1500–3200 and >3200 €), smoking (current, ever), lack of exercise and changes in dietary habits were ascertained as socioeconomic and lifestyle variables. As education status is highly associated with household income, income was used as a proxy for socioeconomic status [14]. Statistical analysis The total number of people who returned the questionnaires was weighted according to the age, sex and diagnosis distribution (M05 or M06) of the source population. People with RA who confirmed their RA diagnosis were classified as having diabetes or not. Descriptive statistics [mean, standard error of the mean (s.e.m.), percentages] were used to compare persons with RA with or without diabetes. The s.e.m. is used instead of the s.d. due to the stratified nature of the study sample. To account for differences between both groups, the results of those without diabetes are reported unweighted and weighted according to the age, sex and diagnosis (M05 and M06) distribution of the patients with diabetes. The prevalence of diabetes in people with RA was analysed by age, sex, region of residence, household income and BMI. All analyses were conducted using procedures for complex survey designs performed with SAS, version 9.4 (SAS Institute Inc., Cary, NC, USA). The Rao–Scott chi-square test was used to study differences between RA patients with and without diabetes, and the weighted results were compared. A multivariate regression analysis was performed with PROC SURVEYLOGISTIC to study the influence of diabetes on being in rheumatological care, adjusting for age group (18–49, 50–64 and 65–79 years), sex (male and female), BMI (<25.0, 25.0 to < 30 and ⩾30.0 kg/m2), diagnosis (M05 and M06), household income (<1500, 1500–3200 and >3200 €), tobacco use (current/former and never) and functional status (FFbH; <50, 50–70 and >70–100). Results Patient characteristics From a total of 6600 randomly selected people with an RA diagnosis, 6193 patients were still insured in 2015 and received the questionnaire. Of those patients, a total of 3184 people responded, and 3140 gave their consent for linking the questionnaire data to claims data (51%). A total of 2535 people confirmed the RA diagnosis (80%). Of the 2535 people with confirmed RA, 498 (19.7%) had at least two diabetes diagnostic codes. In addition, 65% of people with RA and diabetes diagnosis received at least one prescription of oral antidiabetics (45%) and/or insulin (27%). Furthermore, the mean disease duration was comparably long (16 years), and people with RA and diabetes were, on average, 6.6 years older, more often male (28.8% vs 18.3%) and more often obese (34.7% vs 16.9%) than people with RA without diabetes. People with RA and diabetes were more frequently former smokers but were less often current smokers. They reported a lack of exercise significantly more often, reported less frequent diet changes and had a higher BMI (Table 1). Table 1 Characteristics of the study population Characteristic  RA and diabetes (n = 498; 19.7%)  RA without diabetes (n = 2037; 80.3%)  RA without diabetes, weighteda  P-value  Age, mean (s.e.m.), years  68.1 (0.5)  61.5 (0.1)  67.0 (0.1)        18–49, n (%)  20 (4.0)  348 (17.1)  81 (4.0)  1.0000      50–64, n (%)  132 (26.4)  767 (37.7)  538 (26.4)      65–79, n (%)  347 (69.6)  922 (45.3)  1418 (69.6)  Sex, female, n (%)  350 (70.2)  1.664 (81.7)  1429 (70.2)  1.0000  RA diagnosis, M05, n (%)  122 (24.5)  544 (26.7)  498 (24.5)  1.0000  Disease duration of RA, mean (s.e.m.), years  16.8 (0.4)  15.5 (0.2)  16.3 (0.2)    BMI, mean (s.e.m.), kg/m2  28.9 (0.7)  26.1 (0.4)  26.2 (0.5)        <25, n (%)  111 (23.4)  897 (45.2)  851 (42.9)  <0.0001      25 to < 30, n (%)  189 (40.0)  746 (37.6)  811 (40.9)      ≥30, n (%)  173 (36.5)  343 (17.3)  320 (16.2)  Lifestyle variables              Smoking, n (%)                  Current  32 (6.5)  269 (13.5)  203 (10.0)  0.0145          Former  153 (30.7)  428 (21.0)  468 (23.0)      Lack of exercise, n (%)  286 (59.4)  949 (47.8)  978 (49.4)  <0.0001      Change in diet, n (%)  277 (57.4)  1239 (62.5)  1201 (60.7)  0.3680  Monthly household income, n (%)              <1500 €  185 (40.8)  645 (34.0)  699 (36.8)  0.2327      1500–3200 €  239 (52.5)  984 (51.9)  1012 (53.3)      >3200 €  31 (6.7)  266 (14.0)  190 (10.0)  Postal code, n (%)              West Germany  288 (57.7)  1398 (68.7)  1378 (67.7)  0.0061      East Germany  211 (42.3)  638 (31.4)  659 (32.4)  Characteristic  RA and diabetes (n = 498; 19.7%)  RA without diabetes (n = 2037; 80.3%)  RA without diabetes, weighteda  P-value  Age, mean (s.e.m.), years  68.1 (0.5)  61.5 (0.1)  67.0 (0.1)        18–49, n (%)  20 (4.0)  348 (17.1)  81 (4.0)  1.0000      50–64, n (%)  132 (26.4)  767 (37.7)  538 (26.4)      65–79, n (%)  347 (69.6)  922 (45.3)  1418 (69.6)  Sex, female, n (%)  350 (70.2)  1.664 (81.7)  1429 (70.2)  1.0000  RA diagnosis, M05, n (%)  122 (24.5)  544 (26.7)  498 (24.5)  1.0000  Disease duration of RA, mean (s.e.m.), years  16.8 (0.4)  15.5 (0.2)  16.3 (0.2)    BMI, mean (s.e.m.), kg/m2  28.9 (0.7)  26.1 (0.4)  26.2 (0.5)        <25, n (%)  111 (23.4)  897 (45.2)  851 (42.9)  <0.0001      25 to < 30, n (%)  189 (40.0)  746 (37.6)  811 (40.9)      ≥30, n (%)  173 (36.5)  343 (17.3)  320 (16.2)  Lifestyle variables              Smoking, n (%)                  Current  32 (6.5)  269 (13.5)  203 (10.0)  0.0145          Former  153 (30.7)  428 (21.0)  468 (23.0)      Lack of exercise, n (%)  286 (59.4)  949 (47.8)  978 (49.4)  <0.0001      Change in diet, n (%)  277 (57.4)  1239 (62.5)  1201 (60.7)  0.3680  Monthly household income, n (%)              <1500 €  185 (40.8)  645 (34.0)  699 (36.8)  0.2327      1500–3200 €  239 (52.5)  984 (51.9)  1012 (53.3)      >3200 €  31 (6.7)  266 (14.0)  190 (10.0)  Postal code, n (%)              West Germany  288 (57.7)  1398 (68.7)  1378 (67.7)  0.0061      East Germany  211 (42.3)  638 (31.4)  659 (32.4)  a The results from patients without diabetes were weighted according to age and sex of the patients with RA and diabetes. P-values compare patients with and without diabetes (weighted results) and were assessed by the Rao–Scott chi-square test. M05: seropositive RA according to ICD-10. To account for the age and sex differences between groups, self-reported outcomes, further comorbidities and drug prescriptions were compared using the weighted results. To consider differences in obesity, self-reported outcomes were reported by BMI categories. Diabetes prevalence in RA Diabetes was more frequent in males, in older patients, in patients with a higher BMI and in patients with a lower socioeconomic status (Fig. 1). The prevalence of diabetes was slightly higher in males who use tobacco and was higher in the Eastern federal states of Germany that belonged to the German Democratic Republic until 1990. Prevalence and confidence intervals are reported in the Supplementary Appendix Table S1, available at Rheumatology Online. Fig. 1 View largeDownload slide Diabetes prevalence in patients with RA Diabetes prevalence was analysed by sex, age, BMI, region of residence and household income. Fig. 1 View largeDownload slide Diabetes prevalence in patients with RA Diabetes prevalence was analysed by sex, age, BMI, region of residence and household income. Self-reported RA outcomes Compared with patients without diabetes, patients with RA and diabetes had, on average, 1.2 more swollen and 2.4 more tender joints, a worse functional status [FFbH 63.1 (22.5) vs 71.3 (21.7)], and poorer ratings on the RAID [5.0 (2.6) vs 4.8 (2.5)] and the WHO-5 [41.9 (23.6) vs 49.7 (23.6)]. These differences remained after weighting for age, sex and M05/M06 diagnosis but disappeared when the data were stratified by BMI categories. The only exception was the WHO-5, which was not dependent on BMI. Higher BMI values were associated with poorer RAID, FFbH, SJC, TJC and WHO-5 values, which were independent of diabetes comorbidity (Fig. 2). Fig. 2 View largeDownload slide Self-reported outcomes in patients with RA with or without diabetes Self-reported swollen joint counts (SJC, 0–48), tender joint counts (TJC, 0–50), RA Impact of Disease score (RAID; 0–10) and WHO’s Five-item Well-being Index (WHO-5; 0–100) are distributed by BMI category for people with RA and diabetes compared with those without diabetes. All results are weighted for age and sex differences. Fig. 2 View largeDownload slide Self-reported outcomes in patients with RA with or without diabetes Self-reported swollen joint counts (SJC, 0–48), tender joint counts (TJC, 0–50), RA Impact of Disease score (RAID; 0–10) and WHO’s Five-item Well-being Index (WHO-5; 0–100) are distributed by BMI category for people with RA and diabetes compared with those without diabetes. All results are weighted for age and sex differences. Comorbidity and drug prescriptions in RA patients with or without diabetes Patients with RA and diabetes more frequently had cardiovascular diseases (35% vs 15%), depression (39% vs 26%), renal failure (23% vs 8%), polyneuropathy (20% vs 0.8%), retinopathy (12% vs 0.8%, all P < 0.0001) and venous ulcer (5% vs 1.9%, P < 0.05). These differences remained when adjusting for BMI values. Compared with patients without diabetes, patients with RA and diabetes were treated more frequently with anti-hypertensive drugs (74% vs 50%), statins (37% vs 23%), diuretics (30% vs 17%) and antidepressants (30% vs 15%, all P < 0.0001) (Table 2). Table 2 Comorbidities and drug prescriptions of the RA patients with or without diabetes Comorbidity and treatment  RA and diabetes  RA without diabetes, weighteda  P-value  Comorbidities            Hypertension (I10), n (%)  436 (87.5)  1290 (63.3)  <0.0001      Hyperlipidaemia (E78), n (%)  302 (60.6)  922 (45.3)  <0.0001      Coronary artery disease (I25), n (%)  142 (28.6)  351 (17.2)  0.0002      Stroke (I63, I64), n (%)  26 (5.2)  38 (1.9)  0.0062      Carotid stenosis (I65.2), n (%)  25 (4.9)  102 (5.0)  0.9787      COPD (J44), n (%)  67 (13.4)  252 (12.4)  0.6681      Bronchial asthma (J45), n (%)  72 (14.5)  229 (11.2)  0.1872      Pneumonia (J13–J18), n (%)  17 (3.4)  34 (1.7)  0.0857      Depression (F32, F33), n (%)  193 (38.8)  524 (25.7)  0.0001      Chronic renal failure (N18), n (%)  114 (22.9)  166 (8.2)  <0.0001      Polyneuropathy (G63), n (%)  97 (20.0)  16 (0.8)  <0.0001      Retinopathy (H36), n (%)  58 (11.7)  16 (0.8)  <0.0001      Venous ulcer (L98), n (%)  26 (5.2)  39 (1.9)  0.0148  Drug prescriptions            DMARDs, n (%)  199 (40.0)  969 (47.6)  0.0338      Biologics, n (%)  58 (11.7)  259 (12.7)  0.6393      Glucocorticoids, n (%)  237 (47.8)  1043 (51.2)  0.3102      NSAIDs, n (%)  218 (43.8)  912 (44.8)  0.7910      Anti-hypertensive drugs, n (%)  367 (73.6)  1020 (50.1)  <0.0001      Diuretics, n (%)  150 (30.2)  342 (16.8)  <0.0001      Statins, n (%)  185 (37.1)  466 (22.9)  <0.0001      Antidepressants, n (%)  151 (30.3)  306 (15.0)  <0.0001  Comorbidity and treatment  RA and diabetes  RA without diabetes, weighteda  P-value  Comorbidities            Hypertension (I10), n (%)  436 (87.5)  1290 (63.3)  <0.0001      Hyperlipidaemia (E78), n (%)  302 (60.6)  922 (45.3)  <0.0001      Coronary artery disease (I25), n (%)  142 (28.6)  351 (17.2)  0.0002      Stroke (I63, I64), n (%)  26 (5.2)  38 (1.9)  0.0062      Carotid stenosis (I65.2), n (%)  25 (4.9)  102 (5.0)  0.9787      COPD (J44), n (%)  67 (13.4)  252 (12.4)  0.6681      Bronchial asthma (J45), n (%)  72 (14.5)  229 (11.2)  0.1872      Pneumonia (J13–J18), n (%)  17 (3.4)  34 (1.7)  0.0857      Depression (F32, F33), n (%)  193 (38.8)  524 (25.7)  0.0001      Chronic renal failure (N18), n (%)  114 (22.9)  166 (8.2)  <0.0001      Polyneuropathy (G63), n (%)  97 (20.0)  16 (0.8)  <0.0001      Retinopathy (H36), n (%)  58 (11.7)  16 (0.8)  <0.0001      Venous ulcer (L98), n (%)  26 (5.2)  39 (1.9)  0.0148  Drug prescriptions            DMARDs, n (%)  199 (40.0)  969 (47.6)  0.0338      Biologics, n (%)  58 (11.7)  259 (12.7)  0.6393      Glucocorticoids, n (%)  237 (47.8)  1043 (51.2)  0.3102      NSAIDs, n (%)  218 (43.8)  912 (44.8)  0.7910      Anti-hypertensive drugs, n (%)  367 (73.6)  1020 (50.1)  <0.0001      Diuretics, n (%)  150 (30.2)  342 (16.8)  <0.0001      Statins, n (%)  185 (37.1)  466 (22.9)  <0.0001      Antidepressants, n (%)  151 (30.3)  306 (15.0)  <0.0001  a The results from patients without diabetes were weighted according to the age and sex of the patients with RA and diabetes. P-values were assessed by the Rao–Scott chi-square test. COPD: chronic obstructive pulmonary disease. Rheumatological care for people with RA and diabetes Patients with RA and diabetes were less frequently under rheumatological care (57% vs 67%, P = 0.004) than those without diabetes. A total of 42% of the patients with diabetes (vs 33% without, P = 0.019) were hospitalized at least once in 2015. The mean duration of the hospital stay was, on average, 2 days longer than that of the patients without diabetes [15.2 (15.6) vs 13.4 (19.4)]. The patients with RA and diabetes less frequently received DMARDs (40% vs 48%, P = 0.034). Glucocorticoids (48% vs 51%), NSAIDs (44% vs 45%) and analgesics (78% vs 69%) were frequently prescribed, despite these patients having diabetes. There was no difference in the prescription of biologics (12% vs 13%, P = 0.64). In the univariate and multivariate regression analyses, the M05 diagnosis, a younger age and not having diabetes were associated with a higher chance of being treated by a rheumatologist. There was no association for socioeconomic factors and functional status (Table 3). Table 3 Factors associated with rheumatological care: results from univariate and multivariate logistic regression analyses     Odds ratio (95% CI)  Characteristic  Reference  Univariate  Multivariate  M05 (seropositive RA)  M06  3.54 (2.81, 4.47)  3.88 (2.99, 5.04)  Age, 18–49 years  65–79 years  1.91 (1.41, 2.60)  2.04 (1.40, 2.96)  Age, 50–64 years  65–79 years  1.41 (1.08, 1.85)  1.51 (1.10, 2.08)  Diabetes  No diabetes  0.56 (0.42, 0.76)  0.64 (0.45, 0.92)  Male sex  Female  0.87 (0.70, 1.09)  1.11 (0.85, 1.46)  BMI, <25  25 to < 30  1.29 (0.97, 1.71)  1.28 (0.93, 1.77)  BMI, ≥30  25 to < 30  1.24 (0.89, 1.72)  1.23 (0.84, 1.79)  Tobacco use, never  Current/former  1.07 (0.83, 1.37)  1.17 (0.88, 1.57)  FFbH, <50  >70–100  1.23 (0.88, 1.72)  1.44 (0.98, 2.11)  FFbH, 50–70  >70–100  1.00 (0.74, 1.37)  1.35 (0.94, 1.93)  Monthly income, <1500 €  >3200 €  0.75 (0.49, 1.12)  0.80 (0.50, 1.29)  Monthly income, 1500–3200 €  >3200 €  0.70 (0.47, 1.03)  0.75 (0.48, 1.16)      Odds ratio (95% CI)  Characteristic  Reference  Univariate  Multivariate  M05 (seropositive RA)  M06  3.54 (2.81, 4.47)  3.88 (2.99, 5.04)  Age, 18–49 years  65–79 years  1.91 (1.41, 2.60)  2.04 (1.40, 2.96)  Age, 50–64 years  65–79 years  1.41 (1.08, 1.85)  1.51 (1.10, 2.08)  Diabetes  No diabetes  0.56 (0.42, 0.76)  0.64 (0.45, 0.92)  Male sex  Female  0.87 (0.70, 1.09)  1.11 (0.85, 1.46)  BMI, <25  25 to < 30  1.29 (0.97, 1.71)  1.28 (0.93, 1.77)  BMI, ≥30  25 to < 30  1.24 (0.89, 1.72)  1.23 (0.84, 1.79)  Tobacco use, never  Current/former  1.07 (0.83, 1.37)  1.17 (0.88, 1.57)  FFbH, <50  >70–100  1.23 (0.88, 1.72)  1.44 (0.98, 2.11)  FFbH, 50–70  >70–100  1.00 (0.74, 1.37)  1.35 (0.94, 1.93)  Monthly income, <1500 €  >3200 €  0.75 (0.49, 1.12)  0.80 (0.50, 1.29)  Monthly income, 1500–3200 €  >3200 €  0.70 (0.47, 1.03)  0.75 (0.48, 1.16)  Significant values are presented in bold. FFbH: Functional Questionnaire Hannover; M05: seropositive RA; M06: other RA according to ICD-10. Discussion In this population-based sample of people with RA, one-fifth had concomitant diabetes. Considering the sex- and age-specific estimates, the prevalence of diabetes diagnosis was 10–15% higher than that in the general German population, reported from a recent study using data of all German health insurance funds [22]. A previous age- and sex-matched comparison with non-RA patients confirmed a higher prevalence of diagnosed diabetes in 20.8% of patients with RA compared with 17% of patients without RA [23]. The global prevalence of diabetes among RA patients ranges between 6 and 14% [11, 24, 25]. The high rate in the present study is partly explained by the high average age of the sample. Analogous to the general German population, the prevalence of diabetes was higher in males, in those with a higher BMI, in those with a lower socioeconomic status and in those located in the former East Germany [26]. For diabetes in general, these regional differences can be explained by socioeconomic and environmental factors, as well as regional deprivation [27]. We found a very similar regional pattern in patients with RA. However, male sex and obesity had the highest impact. Obesity was also responsible for the apparently higher disease burden in patients with RA and diabetes. These differences disappeared once the results were viewed within the different BMI categories. This observation is comparable to data from a cohort study by Dubreuil et al. [4] in which a substantial part of the increased incidence rates of diabetes in RA patients were attributed to BMI, smoking and alcohol. Part of the worse outcome measures in patients with RA and diabetes may not be related to diabetes, but may account for persons with diabetes generally being in poorer health. This was confirmed by the high prevalence of comorbidities in patients with RA and diabetes, including cardiovascular disease, depression, renal failure, polyneuropathy and retinopathy. Type 2 diabetes increases cardiovascular risk in patients with RA [9]. The impact of diabetes in patients with RA on non-cardiovascular comorbidities is less often investigated. However, these comorbid conditions are also of concern because they complicate RA management. We found a high prevalence of depression in people with RA and diabetes. The reported prevalence of depression ranges from 7 to 33% in people with type 2 diabetes compared with 4–19% in people without diabetes [28]. In longitudinal data from general practices in Germany, 30% of people with diabetes had a diagnosis of depression within 10 years [29], and 22% of people with RA had a diagnosis of depression within 5 years [30]. In people with RA, depression is reported in 15–39% of patients, depending on the definition and age of the sample [31]. Thus, depression is highly prevalent in patients with both diseases. It was expected and confirmed by the present data that people with RA and diabetes are more frequently hospitalized than people without diabetes. However, it was surprising that only 57% of these people reported being under current rheumatological care. Possible reasons for insufficient specialty care include other specialty health care, for example, general internal or diabetes care, a higher tendency to avoid medical care (compliance), other comorbid conditions given priority or the substantial immobility of patients with diabetes. However, our data did not show that any of these factors were associated with a lack of rheumatological care. Therefore, reasons for the lack of specialty health care in this risk group require further investigation. Treatment with DMARDs is essential for patients with RA and in those who also have diabetes; it is even more important that they avoid treatment with glucocorticoids. Our observation that about half the patients with RA and diabetes received glucocorticoids and NSAIDs and three-quarters received analgesics but only 41% received DMARDs needs further attention since it may reflect suboptimal treatment strategies. Limitations This study is based on claims data; therefore, the diagnoses of RA and diabetes could not be confirmed by external clinical validation. We addressed this problem by using self-reported validation of RA diagnosis as an inclusion criterion and by reporting the proportions of patients under current diabetes therapy instead. To limit the risk of overestimation, at least two diagnostic codes in two quarters were required. The comparison with the general population within the claims data is not influenced by overestimation [23]. Uncertainty remains regarding undiagnosed diabetes that cannot be estimated without clinical examination. The main strength of the study is the linkage of the claims data to the survey results, enabling confirmation of RA diagnosis by patient reports and controlling for BMI, sociodemographic and lifestyle factors. In summary, the health care of people with RA and diabetes is important on the individual level, and the socioeconomic level because these people represent a risk group for high disease burden, morbidity and hospitalization. Reasons for insufficient specialized care need to be further explored. Obesity increases the disease burden of patients with RA and diabetes and should be considered for both preventing diabetes and improving RA outcomes. Acknowledgements The authors thank the BARMER for providing data for this study and all patients who took the time to complete the survey. Funding: This work was supported by the Federal Ministry of Education and Research within the networks PROCLAIR [01EC1405] and METARTHROS [01EC1407D]. Disclosure statement: The authors have declared no conflicts of interest. Supplementary data Supplementary data are available at Rheumatology Online. References 1 Jafri K, Bartels CM, Shin D, Gelfand JM, Ogdie A. Incidence and management of cardiovascular risk factors in psoriatic arthritis and rheumatoid arthritis: a population-based study. Arthritis Care Res  2017; 69: 51– 7. Google Scholar CrossRef Search ADS   2 Solomon DH, Love TJ, Canning C, Schneeweiss S. Risk of diabetes among patients with rheumatoid arthritis, psoriatic arthritis and psoriasis. Ann Rheum Dis  2010; 69: 2114– 7. 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The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology  2013; 52: 2136– 48. Google Scholar CrossRef Search ADS PubMed  © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Rheumatology Oxford University Press

High prevalence of diabetes in patients with rheumatoid arthritis: results from a questionnaire survey linked to claims data

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© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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Abstract

Abstract Objectives To investigate the prevalence of diabetes in patients with RA and the impact of diabetes on self-reported outcomes and health care. Methods RA patients between the ages of 18 and 79 years were randomly selected from a nationwide statutory health insurance fund and were surveyed about rheumatological care and disease burden. Comorbid diabetes (E10–14) was analysed regarding age, sex, BMI and socioeconomic status. Disease burden, comorbidity and prescriptions were compared in RA patients with and without diabetes. Predictors of rheumatological care were identified by multivariate regression. Results Of the 2535 RA patients, 498 (20%) had diabetes. Diabetes was more frequent in males, in older patients, in patients with a higher BMI and in those with a lower socioeconomic status. All disease outcomes were poorer in RA–diabetes patients and were mainly attributable to a higher BMI. RA–diabetes patients received less DMARDs (40% vs 48%) and had more hospital stays (41% vs 30%) than patients without diabetes (all P < 0.05). Rates of cardiovascular disease (35% vs 15%), depression (39% vs 26%) and renal failure (23% vs 8%) were higher in RA–diabetes patients (all P < 0.0001). They were less frequently treated by rheumatology specialists: 57% vs 67%; odds ratio = 0.64 (95% CI: 0.45, 0.92), after controlling for confounders. Conclusion The prevalence of diabetes in patients with RA is high and is associated with known sociodemographic factors. More than 40% of patients with RA and diabetes were not under rheumatological care even though they reported a high disease burden, were frequently hospitalized and often presented with further comorbidities. rheumatoid arthritis, diabetes, comorbidities, health care Rheumatology key messages The prevalence of diabetes is higher in RA patients than in the general population. People with RA and diabetes present with a high disease burden and further comorbidities. People with RA and diabetes are treated by rheumatologists less often than those without diabetes. Introduction RA is associated with an increased incidence and prevalence of diabetes [1, 2]. Furthermore, the risk of undiagnosed diabetes is elevated in patients with RA, especially in those with long-standing disease [3]. Adjusted comparisons with the general population indicate that the higher incidence is mainly driven by obesity, lifestyle factors and comorbidity [4]. Certain DMARDs, including TNF-α inhibitors, seem to decrease the incidence of diabetes in patients with RA by improving the markers of glucose metabolism [5–7], while glucocorticoids and statins are likely associated with an increased risk [8]. The coexistence of RA and diabetes increases cardiovascular risk [9]. These facts indicate that high diabetes prevalence and the resulting complications in patients with RA may be reduced by increasing awareness of the risk factors for diabetes at the patient level and by providing adequate anti-inflammatory RA therapy at the health care level. To assess the impact of diabetes in patients with RA, reliable data on diabetes prevalence and RA-related outcomes are required. RA cohorts cover data on disease activity and socioeconomic factors, whereas diabetes, as a comorbid condition, is reported either by the rheumatologist or the patient [10–12]. Furthermore, RA cohorts mostly represent RA patients in rheumatological care. In health care databases, diabetes is assessed by diagnostic codes and specific medications, whereas data on RA disease activity are missing [1, 2, 4, 5]. We took advantage of claims data linked to self-reported patient outcomes from a questionnaire survey within the network Linking Patient-Reported Outcomes with CLAIms data for health services research in Rheumatology (PROCLAIR) [13]. This linkage enables an investigation of the prevalence of diabetes in patients with RA by socioeconomic factors in a population-based setting and enables the assessment of the impact of diabetes on self-reported RA outcomes and the health care status of these patients. Methods This study was conducted using a cross-sectional design. Using data from a nationwide statutory health insurance fund (BARMER), RA patients between the age of 18 and 79 years were identified based on a diagnostic code of RA (M05, M06), according to the German modification of the International Statistical Classification of Diseases (ICD-10-GM) in at least two quarters of 2013 [13]. In 2015, an age, sex and diagnosis (M05 and M06) stratified random sample of 6600 people was provided with a questionnaire covering RA diagnosis confirmation, access to rheumatological care, self-reported disease burden, lifestyle factors and RA impacts on social and working life [14]. Patients gave their written informed consent for the linking of information derived from the questionnaire to claims data. Ethical approval was obtained from the ethics committee of the Charité University Medicine in March of 2015 (EA1/051/15). This research was conducted in agreement with the Declaration of Helsinki. The study was performed within the research networks PROCLAIR and Metabolic Impact on Joint and Bone Diseases (METARTHROS) [14, 15]. Claims data Age, sex, postal code, insurance status and comorbidities were assessed in the claims data from 2015. We identified patients with diabetes mellitus who were coded with the diagnoses E10–E14 in outpatient care in at least two quarters of 2015. Additional cardiovascular, respiratory and other comorbidities were also assessed with the data from 2015, and at least one diagnosis had to be documented in outpatient care (ICD-10 codes are reported in Table 2). Drug prescriptions in 2015 were identified via the anatomical therapeutic chemical classification as follows: conventional synthetic DMARDs (L04AA13, L04AD01, L04AX01, L04AX03, M01C), biologics (L04AA24, L04AB, L04AC03, L04AC07, L01XC02), glucocorticoids (H02AB, H02BX), NSAIDs (M01A), oral antidiabetics (A10B), insulin (A10A), anti-hypertensive agents (C02, C08, C09), diuretics (C03), statins (C10AA), anti-depressants (N06A) and analgesics were assessed according to a previously used reference list of anatomical therapeutic chemical codes [16]. Questionnaire data RA diagnosis confirmation (what is your disease called by the physician?), disease duration and rheumatological care (current/ever) were covered in the questionnaire. Tender and swollen joints were assessed by 50 and 48 joint counts for tenderness and swelling in a patient-reported question/mannequin format [17, 18]. Disability was assessed by the physical Functional Questionnaire Hannover (FFbH, range 0–100: full functional capacity) [19]. The impact of RA disease was ascertained by the RA Impact of Disease score (RAID; range 0: no impact, to 10: highest impact) [20, 21]. The WHO’s Five-item Well-being Index (WHO-5; scores transformed to 0–100) was used to determine the depressive symptoms based on the last 2 weeks. The depressive symptoms were categorized as mild (29–50) or moderate to severe (0–28), whereas patients scoring above 50 were considered to have no depressive symptoms [16]. BMI (kg/m2), household income (<1500, 1500–3200 and >3200 €), smoking (current, ever), lack of exercise and changes in dietary habits were ascertained as socioeconomic and lifestyle variables. As education status is highly associated with household income, income was used as a proxy for socioeconomic status [14]. Statistical analysis The total number of people who returned the questionnaires was weighted according to the age, sex and diagnosis distribution (M05 or M06) of the source population. People with RA who confirmed their RA diagnosis were classified as having diabetes or not. Descriptive statistics [mean, standard error of the mean (s.e.m.), percentages] were used to compare persons with RA with or without diabetes. The s.e.m. is used instead of the s.d. due to the stratified nature of the study sample. To account for differences between both groups, the results of those without diabetes are reported unweighted and weighted according to the age, sex and diagnosis (M05 and M06) distribution of the patients with diabetes. The prevalence of diabetes in people with RA was analysed by age, sex, region of residence, household income and BMI. All analyses were conducted using procedures for complex survey designs performed with SAS, version 9.4 (SAS Institute Inc., Cary, NC, USA). The Rao–Scott chi-square test was used to study differences between RA patients with and without diabetes, and the weighted results were compared. A multivariate regression analysis was performed with PROC SURVEYLOGISTIC to study the influence of diabetes on being in rheumatological care, adjusting for age group (18–49, 50–64 and 65–79 years), sex (male and female), BMI (<25.0, 25.0 to < 30 and ⩾30.0 kg/m2), diagnosis (M05 and M06), household income (<1500, 1500–3200 and >3200 €), tobacco use (current/former and never) and functional status (FFbH; <50, 50–70 and >70–100). Results Patient characteristics From a total of 6600 randomly selected people with an RA diagnosis, 6193 patients were still insured in 2015 and received the questionnaire. Of those patients, a total of 3184 people responded, and 3140 gave their consent for linking the questionnaire data to claims data (51%). A total of 2535 people confirmed the RA diagnosis (80%). Of the 2535 people with confirmed RA, 498 (19.7%) had at least two diabetes diagnostic codes. In addition, 65% of people with RA and diabetes diagnosis received at least one prescription of oral antidiabetics (45%) and/or insulin (27%). Furthermore, the mean disease duration was comparably long (16 years), and people with RA and diabetes were, on average, 6.6 years older, more often male (28.8% vs 18.3%) and more often obese (34.7% vs 16.9%) than people with RA without diabetes. People with RA and diabetes were more frequently former smokers but were less often current smokers. They reported a lack of exercise significantly more often, reported less frequent diet changes and had a higher BMI (Table 1). Table 1 Characteristics of the study population Characteristic  RA and diabetes (n = 498; 19.7%)  RA without diabetes (n = 2037; 80.3%)  RA without diabetes, weighteda  P-value  Age, mean (s.e.m.), years  68.1 (0.5)  61.5 (0.1)  67.0 (0.1)        18–49, n (%)  20 (4.0)  348 (17.1)  81 (4.0)  1.0000      50–64, n (%)  132 (26.4)  767 (37.7)  538 (26.4)      65–79, n (%)  347 (69.6)  922 (45.3)  1418 (69.6)  Sex, female, n (%)  350 (70.2)  1.664 (81.7)  1429 (70.2)  1.0000  RA diagnosis, M05, n (%)  122 (24.5)  544 (26.7)  498 (24.5)  1.0000  Disease duration of RA, mean (s.e.m.), years  16.8 (0.4)  15.5 (0.2)  16.3 (0.2)    BMI, mean (s.e.m.), kg/m2  28.9 (0.7)  26.1 (0.4)  26.2 (0.5)        <25, n (%)  111 (23.4)  897 (45.2)  851 (42.9)  <0.0001      25 to < 30, n (%)  189 (40.0)  746 (37.6)  811 (40.9)      ≥30, n (%)  173 (36.5)  343 (17.3)  320 (16.2)  Lifestyle variables              Smoking, n (%)                  Current  32 (6.5)  269 (13.5)  203 (10.0)  0.0145          Former  153 (30.7)  428 (21.0)  468 (23.0)      Lack of exercise, n (%)  286 (59.4)  949 (47.8)  978 (49.4)  <0.0001      Change in diet, n (%)  277 (57.4)  1239 (62.5)  1201 (60.7)  0.3680  Monthly household income, n (%)              <1500 €  185 (40.8)  645 (34.0)  699 (36.8)  0.2327      1500–3200 €  239 (52.5)  984 (51.9)  1012 (53.3)      >3200 €  31 (6.7)  266 (14.0)  190 (10.0)  Postal code, n (%)              West Germany  288 (57.7)  1398 (68.7)  1378 (67.7)  0.0061      East Germany  211 (42.3)  638 (31.4)  659 (32.4)  Characteristic  RA and diabetes (n = 498; 19.7%)  RA without diabetes (n = 2037; 80.3%)  RA without diabetes, weighteda  P-value  Age, mean (s.e.m.), years  68.1 (0.5)  61.5 (0.1)  67.0 (0.1)        18–49, n (%)  20 (4.0)  348 (17.1)  81 (4.0)  1.0000      50–64, n (%)  132 (26.4)  767 (37.7)  538 (26.4)      65–79, n (%)  347 (69.6)  922 (45.3)  1418 (69.6)  Sex, female, n (%)  350 (70.2)  1.664 (81.7)  1429 (70.2)  1.0000  RA diagnosis, M05, n (%)  122 (24.5)  544 (26.7)  498 (24.5)  1.0000  Disease duration of RA, mean (s.e.m.), years  16.8 (0.4)  15.5 (0.2)  16.3 (0.2)    BMI, mean (s.e.m.), kg/m2  28.9 (0.7)  26.1 (0.4)  26.2 (0.5)        <25, n (%)  111 (23.4)  897 (45.2)  851 (42.9)  <0.0001      25 to < 30, n (%)  189 (40.0)  746 (37.6)  811 (40.9)      ≥30, n (%)  173 (36.5)  343 (17.3)  320 (16.2)  Lifestyle variables              Smoking, n (%)                  Current  32 (6.5)  269 (13.5)  203 (10.0)  0.0145          Former  153 (30.7)  428 (21.0)  468 (23.0)      Lack of exercise, n (%)  286 (59.4)  949 (47.8)  978 (49.4)  <0.0001      Change in diet, n (%)  277 (57.4)  1239 (62.5)  1201 (60.7)  0.3680  Monthly household income, n (%)              <1500 €  185 (40.8)  645 (34.0)  699 (36.8)  0.2327      1500–3200 €  239 (52.5)  984 (51.9)  1012 (53.3)      >3200 €  31 (6.7)  266 (14.0)  190 (10.0)  Postal code, n (%)              West Germany  288 (57.7)  1398 (68.7)  1378 (67.7)  0.0061      East Germany  211 (42.3)  638 (31.4)  659 (32.4)  a The results from patients without diabetes were weighted according to age and sex of the patients with RA and diabetes. P-values compare patients with and without diabetes (weighted results) and were assessed by the Rao–Scott chi-square test. M05: seropositive RA according to ICD-10. To account for the age and sex differences between groups, self-reported outcomes, further comorbidities and drug prescriptions were compared using the weighted results. To consider differences in obesity, self-reported outcomes were reported by BMI categories. Diabetes prevalence in RA Diabetes was more frequent in males, in older patients, in patients with a higher BMI and in patients with a lower socioeconomic status (Fig. 1). The prevalence of diabetes was slightly higher in males who use tobacco and was higher in the Eastern federal states of Germany that belonged to the German Democratic Republic until 1990. Prevalence and confidence intervals are reported in the Supplementary Appendix Table S1, available at Rheumatology Online. Fig. 1 View largeDownload slide Diabetes prevalence in patients with RA Diabetes prevalence was analysed by sex, age, BMI, region of residence and household income. Fig. 1 View largeDownload slide Diabetes prevalence in patients with RA Diabetes prevalence was analysed by sex, age, BMI, region of residence and household income. Self-reported RA outcomes Compared with patients without diabetes, patients with RA and diabetes had, on average, 1.2 more swollen and 2.4 more tender joints, a worse functional status [FFbH 63.1 (22.5) vs 71.3 (21.7)], and poorer ratings on the RAID [5.0 (2.6) vs 4.8 (2.5)] and the WHO-5 [41.9 (23.6) vs 49.7 (23.6)]. These differences remained after weighting for age, sex and M05/M06 diagnosis but disappeared when the data were stratified by BMI categories. The only exception was the WHO-5, which was not dependent on BMI. Higher BMI values were associated with poorer RAID, FFbH, SJC, TJC and WHO-5 values, which were independent of diabetes comorbidity (Fig. 2). Fig. 2 View largeDownload slide Self-reported outcomes in patients with RA with or without diabetes Self-reported swollen joint counts (SJC, 0–48), tender joint counts (TJC, 0–50), RA Impact of Disease score (RAID; 0–10) and WHO’s Five-item Well-being Index (WHO-5; 0–100) are distributed by BMI category for people with RA and diabetes compared with those without diabetes. All results are weighted for age and sex differences. Fig. 2 View largeDownload slide Self-reported outcomes in patients with RA with or without diabetes Self-reported swollen joint counts (SJC, 0–48), tender joint counts (TJC, 0–50), RA Impact of Disease score (RAID; 0–10) and WHO’s Five-item Well-being Index (WHO-5; 0–100) are distributed by BMI category for people with RA and diabetes compared with those without diabetes. All results are weighted for age and sex differences. Comorbidity and drug prescriptions in RA patients with or without diabetes Patients with RA and diabetes more frequently had cardiovascular diseases (35% vs 15%), depression (39% vs 26%), renal failure (23% vs 8%), polyneuropathy (20% vs 0.8%), retinopathy (12% vs 0.8%, all P < 0.0001) and venous ulcer (5% vs 1.9%, P < 0.05). These differences remained when adjusting for BMI values. Compared with patients without diabetes, patients with RA and diabetes were treated more frequently with anti-hypertensive drugs (74% vs 50%), statins (37% vs 23%), diuretics (30% vs 17%) and antidepressants (30% vs 15%, all P < 0.0001) (Table 2). Table 2 Comorbidities and drug prescriptions of the RA patients with or without diabetes Comorbidity and treatment  RA and diabetes  RA without diabetes, weighteda  P-value  Comorbidities            Hypertension (I10), n (%)  436 (87.5)  1290 (63.3)  <0.0001      Hyperlipidaemia (E78), n (%)  302 (60.6)  922 (45.3)  <0.0001      Coronary artery disease (I25), n (%)  142 (28.6)  351 (17.2)  0.0002      Stroke (I63, I64), n (%)  26 (5.2)  38 (1.9)  0.0062      Carotid stenosis (I65.2), n (%)  25 (4.9)  102 (5.0)  0.9787      COPD (J44), n (%)  67 (13.4)  252 (12.4)  0.6681      Bronchial asthma (J45), n (%)  72 (14.5)  229 (11.2)  0.1872      Pneumonia (J13–J18), n (%)  17 (3.4)  34 (1.7)  0.0857      Depression (F32, F33), n (%)  193 (38.8)  524 (25.7)  0.0001      Chronic renal failure (N18), n (%)  114 (22.9)  166 (8.2)  <0.0001      Polyneuropathy (G63), n (%)  97 (20.0)  16 (0.8)  <0.0001      Retinopathy (H36), n (%)  58 (11.7)  16 (0.8)  <0.0001      Venous ulcer (L98), n (%)  26 (5.2)  39 (1.9)  0.0148  Drug prescriptions            DMARDs, n (%)  199 (40.0)  969 (47.6)  0.0338      Biologics, n (%)  58 (11.7)  259 (12.7)  0.6393      Glucocorticoids, n (%)  237 (47.8)  1043 (51.2)  0.3102      NSAIDs, n (%)  218 (43.8)  912 (44.8)  0.7910      Anti-hypertensive drugs, n (%)  367 (73.6)  1020 (50.1)  <0.0001      Diuretics, n (%)  150 (30.2)  342 (16.8)  <0.0001      Statins, n (%)  185 (37.1)  466 (22.9)  <0.0001      Antidepressants, n (%)  151 (30.3)  306 (15.0)  <0.0001  Comorbidity and treatment  RA and diabetes  RA without diabetes, weighteda  P-value  Comorbidities            Hypertension (I10), n (%)  436 (87.5)  1290 (63.3)  <0.0001      Hyperlipidaemia (E78), n (%)  302 (60.6)  922 (45.3)  <0.0001      Coronary artery disease (I25), n (%)  142 (28.6)  351 (17.2)  0.0002      Stroke (I63, I64), n (%)  26 (5.2)  38 (1.9)  0.0062      Carotid stenosis (I65.2), n (%)  25 (4.9)  102 (5.0)  0.9787      COPD (J44), n (%)  67 (13.4)  252 (12.4)  0.6681      Bronchial asthma (J45), n (%)  72 (14.5)  229 (11.2)  0.1872      Pneumonia (J13–J18), n (%)  17 (3.4)  34 (1.7)  0.0857      Depression (F32, F33), n (%)  193 (38.8)  524 (25.7)  0.0001      Chronic renal failure (N18), n (%)  114 (22.9)  166 (8.2)  <0.0001      Polyneuropathy (G63), n (%)  97 (20.0)  16 (0.8)  <0.0001      Retinopathy (H36), n (%)  58 (11.7)  16 (0.8)  <0.0001      Venous ulcer (L98), n (%)  26 (5.2)  39 (1.9)  0.0148  Drug prescriptions            DMARDs, n (%)  199 (40.0)  969 (47.6)  0.0338      Biologics, n (%)  58 (11.7)  259 (12.7)  0.6393      Glucocorticoids, n (%)  237 (47.8)  1043 (51.2)  0.3102      NSAIDs, n (%)  218 (43.8)  912 (44.8)  0.7910      Anti-hypertensive drugs, n (%)  367 (73.6)  1020 (50.1)  <0.0001      Diuretics, n (%)  150 (30.2)  342 (16.8)  <0.0001      Statins, n (%)  185 (37.1)  466 (22.9)  <0.0001      Antidepressants, n (%)  151 (30.3)  306 (15.0)  <0.0001  a The results from patients without diabetes were weighted according to the age and sex of the patients with RA and diabetes. P-values were assessed by the Rao–Scott chi-square test. COPD: chronic obstructive pulmonary disease. Rheumatological care for people with RA and diabetes Patients with RA and diabetes were less frequently under rheumatological care (57% vs 67%, P = 0.004) than those without diabetes. A total of 42% of the patients with diabetes (vs 33% without, P = 0.019) were hospitalized at least once in 2015. The mean duration of the hospital stay was, on average, 2 days longer than that of the patients without diabetes [15.2 (15.6) vs 13.4 (19.4)]. The patients with RA and diabetes less frequently received DMARDs (40% vs 48%, P = 0.034). Glucocorticoids (48% vs 51%), NSAIDs (44% vs 45%) and analgesics (78% vs 69%) were frequently prescribed, despite these patients having diabetes. There was no difference in the prescription of biologics (12% vs 13%, P = 0.64). In the univariate and multivariate regression analyses, the M05 diagnosis, a younger age and not having diabetes were associated with a higher chance of being treated by a rheumatologist. There was no association for socioeconomic factors and functional status (Table 3). Table 3 Factors associated with rheumatological care: results from univariate and multivariate logistic regression analyses     Odds ratio (95% CI)  Characteristic  Reference  Univariate  Multivariate  M05 (seropositive RA)  M06  3.54 (2.81, 4.47)  3.88 (2.99, 5.04)  Age, 18–49 years  65–79 years  1.91 (1.41, 2.60)  2.04 (1.40, 2.96)  Age, 50–64 years  65–79 years  1.41 (1.08, 1.85)  1.51 (1.10, 2.08)  Diabetes  No diabetes  0.56 (0.42, 0.76)  0.64 (0.45, 0.92)  Male sex  Female  0.87 (0.70, 1.09)  1.11 (0.85, 1.46)  BMI, <25  25 to < 30  1.29 (0.97, 1.71)  1.28 (0.93, 1.77)  BMI, ≥30  25 to < 30  1.24 (0.89, 1.72)  1.23 (0.84, 1.79)  Tobacco use, never  Current/former  1.07 (0.83, 1.37)  1.17 (0.88, 1.57)  FFbH, <50  >70–100  1.23 (0.88, 1.72)  1.44 (0.98, 2.11)  FFbH, 50–70  >70–100  1.00 (0.74, 1.37)  1.35 (0.94, 1.93)  Monthly income, <1500 €  >3200 €  0.75 (0.49, 1.12)  0.80 (0.50, 1.29)  Monthly income, 1500–3200 €  >3200 €  0.70 (0.47, 1.03)  0.75 (0.48, 1.16)      Odds ratio (95% CI)  Characteristic  Reference  Univariate  Multivariate  M05 (seropositive RA)  M06  3.54 (2.81, 4.47)  3.88 (2.99, 5.04)  Age, 18–49 years  65–79 years  1.91 (1.41, 2.60)  2.04 (1.40, 2.96)  Age, 50–64 years  65–79 years  1.41 (1.08, 1.85)  1.51 (1.10, 2.08)  Diabetes  No diabetes  0.56 (0.42, 0.76)  0.64 (0.45, 0.92)  Male sex  Female  0.87 (0.70, 1.09)  1.11 (0.85, 1.46)  BMI, <25  25 to < 30  1.29 (0.97, 1.71)  1.28 (0.93, 1.77)  BMI, ≥30  25 to < 30  1.24 (0.89, 1.72)  1.23 (0.84, 1.79)  Tobacco use, never  Current/former  1.07 (0.83, 1.37)  1.17 (0.88, 1.57)  FFbH, <50  >70–100  1.23 (0.88, 1.72)  1.44 (0.98, 2.11)  FFbH, 50–70  >70–100  1.00 (0.74, 1.37)  1.35 (0.94, 1.93)  Monthly income, <1500 €  >3200 €  0.75 (0.49, 1.12)  0.80 (0.50, 1.29)  Monthly income, 1500–3200 €  >3200 €  0.70 (0.47, 1.03)  0.75 (0.48, 1.16)  Significant values are presented in bold. FFbH: Functional Questionnaire Hannover; M05: seropositive RA; M06: other RA according to ICD-10. Discussion In this population-based sample of people with RA, one-fifth had concomitant diabetes. Considering the sex- and age-specific estimates, the prevalence of diabetes diagnosis was 10–15% higher than that in the general German population, reported from a recent study using data of all German health insurance funds [22]. A previous age- and sex-matched comparison with non-RA patients confirmed a higher prevalence of diagnosed diabetes in 20.8% of patients with RA compared with 17% of patients without RA [23]. The global prevalence of diabetes among RA patients ranges between 6 and 14% [11, 24, 25]. The high rate in the present study is partly explained by the high average age of the sample. Analogous to the general German population, the prevalence of diabetes was higher in males, in those with a higher BMI, in those with a lower socioeconomic status and in those located in the former East Germany [26]. For diabetes in general, these regional differences can be explained by socioeconomic and environmental factors, as well as regional deprivation [27]. We found a very similar regional pattern in patients with RA. However, male sex and obesity had the highest impact. Obesity was also responsible for the apparently higher disease burden in patients with RA and diabetes. These differences disappeared once the results were viewed within the different BMI categories. This observation is comparable to data from a cohort study by Dubreuil et al. [4] in which a substantial part of the increased incidence rates of diabetes in RA patients were attributed to BMI, smoking and alcohol. Part of the worse outcome measures in patients with RA and diabetes may not be related to diabetes, but may account for persons with diabetes generally being in poorer health. This was confirmed by the high prevalence of comorbidities in patients with RA and diabetes, including cardiovascular disease, depression, renal failure, polyneuropathy and retinopathy. Type 2 diabetes increases cardiovascular risk in patients with RA [9]. The impact of diabetes in patients with RA on non-cardiovascular comorbidities is less often investigated. However, these comorbid conditions are also of concern because they complicate RA management. We found a high prevalence of depression in people with RA and diabetes. The reported prevalence of depression ranges from 7 to 33% in people with type 2 diabetes compared with 4–19% in people without diabetes [28]. In longitudinal data from general practices in Germany, 30% of people with diabetes had a diagnosis of depression within 10 years [29], and 22% of people with RA had a diagnosis of depression within 5 years [30]. In people with RA, depression is reported in 15–39% of patients, depending on the definition and age of the sample [31]. Thus, depression is highly prevalent in patients with both diseases. It was expected and confirmed by the present data that people with RA and diabetes are more frequently hospitalized than people without diabetes. However, it was surprising that only 57% of these people reported being under current rheumatological care. Possible reasons for insufficient specialty care include other specialty health care, for example, general internal or diabetes care, a higher tendency to avoid medical care (compliance), other comorbid conditions given priority or the substantial immobility of patients with diabetes. However, our data did not show that any of these factors were associated with a lack of rheumatological care. Therefore, reasons for the lack of specialty health care in this risk group require further investigation. Treatment with DMARDs is essential for patients with RA and in those who also have diabetes; it is even more important that they avoid treatment with glucocorticoids. Our observation that about half the patients with RA and diabetes received glucocorticoids and NSAIDs and three-quarters received analgesics but only 41% received DMARDs needs further attention since it may reflect suboptimal treatment strategies. Limitations This study is based on claims data; therefore, the diagnoses of RA and diabetes could not be confirmed by external clinical validation. We addressed this problem by using self-reported validation of RA diagnosis as an inclusion criterion and by reporting the proportions of patients under current diabetes therapy instead. To limit the risk of overestimation, at least two diagnostic codes in two quarters were required. The comparison with the general population within the claims data is not influenced by overestimation [23]. Uncertainty remains regarding undiagnosed diabetes that cannot be estimated without clinical examination. The main strength of the study is the linkage of the claims data to the survey results, enabling confirmation of RA diagnosis by patient reports and controlling for BMI, sociodemographic and lifestyle factors. In summary, the health care of people with RA and diabetes is important on the individual level, and the socioeconomic level because these people represent a risk group for high disease burden, morbidity and hospitalization. Reasons for insufficient specialized care need to be further explored. Obesity increases the disease burden of patients with RA and diabetes and should be considered for both preventing diabetes and improving RA outcomes. Acknowledgements The authors thank the BARMER for providing data for this study and all patients who took the time to complete the survey. Funding: This work was supported by the Federal Ministry of Education and Research within the networks PROCLAIR [01EC1405] and METARTHROS [01EC1407D]. Disclosure statement: The authors have declared no conflicts of interest. Supplementary data Supplementary data are available at Rheumatology Online. References 1 Jafri K, Bartels CM, Shin D, Gelfand JM, Ogdie A. Incidence and management of cardiovascular risk factors in psoriatic arthritis and rheumatoid arthritis: a population-based study. Arthritis Care Res  2017; 69: 51– 7. Google Scholar CrossRef Search ADS   2 Solomon DH, Love TJ, Canning C, Schneeweiss S. Risk of diabetes among patients with rheumatoid arthritis, psoriatic arthritis and psoriasis. Ann Rheum Dis  2010; 69: 2114– 7. 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The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology  2013; 52: 2136– 48. Google Scholar CrossRef Search ADS PubMed  © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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RheumatologyOxford University Press

Published: Feb 1, 2018

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