Abstract
This study uses diabetes registry data to compare the frequency of diabetic ketoacidosis (DKA) in children and adolescents at time of type 1 diabetes diagnosis in Germany during the first 2 months of the coronavirus disease 2019 (COVID-19) pandemic vs the same time period in 2018 and 2019.
During the coronavirus disease 2019 (COVID-19) pandemic, a significantly lower rate of health care use has been reported, potentially leading to delayed medical care.1 Diabetic ketoacidosis is an acute life-threatening complication of a delayed diagnosis of type 1 diabetes.2 We investigated the frequency of diabetic ketoacidosis in children and adolescents at diagnosis of type 1 diabetes in Germany during the first 2 months of the COVID-19 pandemic.
Methods
This study used data from the German Diabetes Prospective Follow-up Registry (DPV) of children and adolescents with the diagnosis of type 1 diabetes between March 13, 2020, when most kindergartens and schools were closed to reduce interpersonal contacts, through May 13, 2020. The DPV registry has a nationwide coverage of more than 90% of pediatric patients with type 1 diabetes.3 Since 2018, 217 diabetes centers (hospitals and medical practices) have transferred information from pediatric patients with newly diagnosed type 1 diabetes.
Diabetic ketoacidosis was defined as a pH level less than 7.3 and/or bicarbonate level less than 15 mmol/L, and severe diabetic ketoacidosis as a pH level less than 7.1 and/or bicarbonate level less than 5 mmol/L.2,3 The frequencies of diabetic ketoacidosis and severe diabetic ketoacidosis observed during the COVID-19 period were compared with the same periods in 2018 and 2019 using multivariable logistic regression, adjusting for age, sex, and immigrant background (defined as patient or at least 1 parent born outside Germany). Differences were presented as adjusted relative risks (aRRs) with 95% CIs. A 2-sided P < .05 was considered statistically significant. All analyses were performed with SAS version 9.4 (SAS Institute Inc). Informed consent for participation in the DPV registry was obtained from patients or their parents by verbal or written procedure, as approved by the responsible data protection officers at each center. The analysis of anonymized data was approved by the ethics committee of the University of Ulm.
Results
We obtained and analyzed data of 532 children and adolescents with newly diagnosed type 1 diabetes from March 13 through May 13, 2020, from 216 of 217 diabetes centers. The median age of the cohort was 9.9 years (interquartile range, 5.8-12.9 years; 61.5% male) (Table 1). Diabetic ketoacidosis was present in 238 patients (44.7%) and severe ketoacidosis in 103 patients (19.4%) (Table 1). During the COVID-19 period in 2020, the frequency of diabetic ketoacidosis was significantly higher compared with the 2 previous years (44.7% in 2020 vs 24.5% in 2019; aRR, 1.84 [95% CI, 1.54-2.21]; P < .001; vs 24.1% in 2018; aRR, 1.85 [95% CI, 1.54-2.24]; P < .001). The incidence of severe diabetic ketoacidosis was also significantly higher compared with the previous years (19.4% in 2020 vs 13.9% in 2019; aRR, 1.37 [95% CI, 1.04-1.81]; P = .03; vs 12.3% in 2018; aRR, 1.55 [95% CI, 1.15-2.10]; P = .004) (Table 2). Children younger than 6 years had the highest risk for diabetic ketoacidosis (51.9% in 2020 vs 18.4% in 2019; aRR, 2.75 [95% CI, 1.88-4.02]; P < .001; vs 24.2% in 2018; aRR, 2.12 [95% CI, 1.48-3.02]; P < .001) and severe diabetic ketoacidosis (24.4% in 2020 vs 12.2% in 2019; aRR, 1.90 [95% CI, 1.12-3.23]; P = .02; vs 11.7% in 2018; aRR, 2.06 [95% CI, 1.16-3.65]; P = .01) during the COVID-19 pandemic (Table 2).
Table 1. Characteristics of Pediatric Patients Newly Diagnosed With Type 1 Diabetes in Germany From March 13 Through May 13, 2020, During the COVID-19 Pandemic, and During the Same Period in 2019 and 2018.
| Characteristics | No. (%) | ||
|---|---|---|---|
| March 13 to May 13, 2020 (n = 532) | March 13 to May 13, 2019 (n = 503) | March 13 to May 13, 2018 (n = 456) | |
| Age at diagnosis, median (IQR), y | 9.9 (5.8-12.9) | 9.1 (5.5-12.6) | 9.7 (5.8-13.2) |
| Sex | |||
| Male | 327 (61.5) | 263 (52.3) | 254 (55.7) |
| Female | 205 (38.5) | 240 (47.7) | 202 (44.3) |
| Age groups, y | |||
| <6 | 135 (25.4) | 147 (29.2) | 120 (26.3) |
| 6-11 | 232 (43.6) | 211 (42.0) | 186 (40.8) |
| 12-18 | 165 (31.0) | 145 (28.8) | 150 (32.9) |
| Immigrant backgrounda | 147 (27.6) | 127 (25.2) | 115 (25.2) |
| Diabetic ketoacidosis by age group, yb | |||
| All | 238 (44.7) | 123 (24.5) | 110 (24.1) |
| <6 | 70 (51.9) | 27 (18.4) | 29 (24.2) |
| 6-11 | 94 (40.5) | 58 (27.5) | 50 (26.9) |
| 12-18 | 74 (44.8) | 38 (26.2) | 31 (20.7) |
| Severe diabetic ketoacidosis by age group, yb | |||
| All | 103 (19.4) | 70 (13.9) | 56 (12.3) |
| <6 | 33 (24.4) | 18 (12.2) | 14 (11.7) |
| 6-11 | 44 (19.0) | 30 (14.2) | 25 (13.4) |
| 12-18 | 26 (15.8) | 22 (15.2) | 17 (11.3) |
Abbreviations: COVID-19, coronavirus disease 2019; IQR, interquartile range.
Immigrant background was defined as patient or at least 1 parent born outside Germany.
Diabetic ketoacidosis: pH level <7.3 and/or serum bicarbonate level <15 mmol/L; severe diabetic ketoacidosis: pH level <7.1 and/or serum bicarbonate level <5 mmol/L.
Table 2. Adjusted Relative Risk of Diabetic Ketoacidosis and Severe Diabetic Ketoacidosis at Diabetes Diagnosis From March 13 Through May 13, 2020, During the COVID-19 Pandemic, Compared With the Same Periods in 2019 and 2018.
| COVID-19 period in 2020 vs same period | ||||
|---|---|---|---|---|
| 2019 | 2018 | |||
| aRR (95% CI) | P value | aRR (95% CI) | P value | |
| Diabetic ketoacidosisa | ||||
| All patientsb | 1.84 (1.54-2.21) | <.001 | 1.85 (1.54-2.24) | <.001 |
| Age group, yc | ||||
| <6 | 2.75 (1.88-4.02) | <.001 | 2.12 (1.48-3.02) | <.001 |
| 6-11 | 1.51 (1.16-1.98) | .003 | 1.54 (1.16-2.04) | .003 |
| 12-18 | 1.73 (1.25-2.38) | <.001 | 2.15 (1.51-3.08) | <.001 |
| Sexd | ||||
| Male | 1.70 (1.34-2.16) | <.001 | 2.11 (1.61-2.76) | <.001 |
| Female | 2.01 (1.52-2.64) | <.001 | 1.63 (1.25-2.12) | <.001 |
| Immigrant backgrounde | ||||
| Yes | 1.96 (1.42-2-71) | <.001 | 1.88 (1.36-2.60) | <.001 |
| No | 1.78 (1.43-2.22) | <.001 | 1.84 (1.46-2.31) | <.001 |
| Severe diabetic ketoacidosisa | ||||
| All patientsb | 1.37 (1.04-1.81) | .03 | 1.55 (1.15-2.10) | .004 |
| Age group, yc | ||||
| <6 | 1.90 (1.12-3.23) | .02 | 2.06 (1.16-3.65) | .01 |
| 6-11 | 1.30 (0.85-1.99) | .23 | 1.37 (0.87-2.15) | .17 |
| 12-18 | 1.03 (0.61-1.75) | .90 | 1.39 (0.79-2.47) | .25 |
| Sexd | ||||
| Male | 1.16 (0.83-1.64) | .38 | 1.79 (1.19-2.70) | .006 |
| Female | 1.77 (1.10-2.83) | .02 | 1.31 (0.84-2.06) | .24 |
| Immigrant backgrounde | ||||
| Yes | 1.57 (0.97-2.54) | .06 | 1.68 (1.01-2.77) | .04 |
| No | 1.26 (0.89-1.79) | .18 | 1.49 (1.03-2.17) | .04 |
Abbreviations: aRR, adjusted relative risk; COVID-19, coronavirus disease 2019.
aDiabetic ketoacidosis: pH level <7.3 and/or serum bicarbonate level <15 mmol/L; severe diabetic ketoacidosis: pH level <7.1 and/or serum bicarbonate level <5 mmol/L.
Adjusted for age at diabetes onset, sex, and immigrant background.
Adjusted for sex and immigrant background.
Adjusted for age at diabetes onset and immigrant background.
Adjusted for age at diabetes onset and sex. Immigrant background was defined as patient or at least 1 parent born outside Germany.
Discussion
This study found a significant increase in diabetic ketoacidosis and severe ketoacidosis at diabetes diagnosis in children and adolescents during the COVID-19 pandemic in Germany. Underlying causes may be multifactorial and reflect reduced medical services, fear of approaching the health care system, and more complex psychosocial factors.1,4
Limitations of this study include that the individual socioeconomic status and a family history of diabetes were not available.
Further research into the possible causes of the increase in diabetic ketoacidosis during the COVID-19 pandemic and interventions to reduce diabetic ketoacidosis, such as public and health care clinician education or β-cell antibody screening, is required.
Section Editor: Jody W. Zylke, MD, Deputy Editor.
References
- 1.Baum A, Schwartz MD. Admissions to Veterans Affairs hospitals for emergency conditions during the COVID-19 pandemic. JAMA. 2020;324(1):96-99. doi: 10.1001/jama.2020.9972 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Cherubini V, Grimsmann JM, Åkesson K, et al. . Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents. Diabetologia. 2020;63(8):1530-1541. doi: 10.1007/s00125-020-05152-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Karges B, Schwandt A, Heidtmann B, et al. . Association of insulin pump therapy vs insulin injection therapy with severe hypoglycemia, ketoacidosis, and glycemic control among children, adolescents, and young adults with type 1 diabetes. JAMA. 2017;318(14):1358-1366. doi: 10.1001/jama.2017.13994 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Lazzerini M, Barbi E, Apicella A, Marchetti F, Cardinale F, Trobia G. Delayed access or provision of care in Italy resulting from fear of COVID-19. Lancet Child Adolesc Health. 2020;4(5):e10-e11. doi: 10.1016/S2352-4642(20)30108-5 [DOI] [PMC free article] [PubMed] [Google Scholar]