- Email: [email protected]
Is the Risk of Diabetic Ketoacidosis Modifiable?
Is the Risk of Diabetic Ketoacidosis Modifiable?
D
iabetic ketoacidosis (DKA), a most serious, life(used as a proxy for low socioeconomic status), and age threatening acute complication of type 1 diabetes $12 years were the most important (OR 2.40-1.97); fe(T1D) in children, occurs in approximately 25%male sex and mental health comorbidity also contributed 30% of patients with newly diagnosed diabetes.1,2 significantly (OR approximately 1.40). The hierarchy of Following the initial diagnosis, a small, yet important, subrisk factors was different at individual hospitals, and pagroup of patients will have 1 or more tients at some hospitals did substantially See related article, p recurrent admissions for DKA. The incibetter than others, in as much as they dence of recurrent DKA in the US has been estimated at had a low risk of readmission. This suggests that “local” 8 per 100 person-years,3 but may be twice as high.4 In a factors may significantly affect the outcome of patients with T1D. major pediatric diabetes center, 80% of recurrent DKA How relevant is the study by Malik et al to clinical pracoccurred in 20% of the patients, and 60% of DKA tice? The risk factors they describe for recurrent DKA are occurred in 5% of the patients.3 Given the morbidity, not new, and had already been characterized in previous low but definite mortality5 of complications of DKA studies.3,7,11-13 What is new is the fact that the study (mainly cerebral edema), possible adverse effects of DKA 6 on brain morphology and function, and the social burden showed clear variability in how hospitals “perform” in terms of readmission rates. Unfortunately, the study could and the economic cost of these admissions (estimated at not determine whether the variability was related to pa$90 million/year in the US7), several investigators have tient/population factors, hospital factors, or a combination tried to identify risk factors for recurrent DKA in order of the two. Specific characteristics of the populations gravto develop effective prevention strategies. Recurrent DKA itating around each hospital, pattern of diabetes education is almost always related to omission or insufficiency of inor treatment at each center, including diabetes educator/ sulin delivery,2 usually in association with inadequate diapatient ratio and strength of the support provided by sobetes self-care. It is probable that this condition is cial services or psychologist may have played a role, but completely preventable, as suggested by the fact that the this is speculative. Other limitations of the study stem majority of compliant patients never experience DKA from its retrospective nature, and the fact that data were again after the initial diagnosis of T1D, and by the much harvested from the Pediatric Health Information System, lower incidence in countries with better access to medical an information hub which provides anagraphical, rather care, such as Scandinavian countries.8,9 than clinical, data on patients. Thus, no information could In this issue of The Journal, Malik et al retrospectively be extracted on other potentially important risk factors, examined the readmission rates for recurrent DKA in such as diabetes duration, diabetes control, total insulin 12 449 children between age 2 and 18 years, followed at dose, adequacy of diabetes education at diagnosis, fre42 US Children’s Hospitals between 2004 and 2012.10 quency of outpatient visits, all of which were addressed They examined multiple rolling 365-day intervals during in previous studies,3,7,11-13 and some of which (elevated a 5-year follow-up timeframe for each patient. In simple terms, when a patient was admitted for DKA, the patient Hemoglobin A1c especially) are powerful predictors of rewas tracked for evidence of readmission to the same hosadmission. Finally, the low readmission rate in some of the pital in the following 365 days. The main outcome for “better-performing” hospitals could be explained in part their study was the maximum number of DKA admissions by a larger number of poorly compliant patients moving within any 365-day interval during a 5-year follow-up to, and/or being treated at, other hospitals in the area period for each patient. The objectives of the study for further episodes of DKA. Such a scenario would not were: (1) to determine risk factors predicting DKA readbe unlikely in an urban setting with more than a single mission; and (2) to identify differences in these factors children’s hospital or unit, especially if one considers within hospitals and across hospitals. The results of the that only 28% of hospitalizations for DKA occurred at a study were notable because a high percentage (28%) of major children’s hospital in one study.13 patients admitted for DKA (first and repeat episodes not The finding that (recurrent) “DKA begets DKA” and determined) were readmitted within the next 365 days. that each hospital has a group of patients who get readmitThere was a “hierarchy” of factors associated with the ted every few weeks or few months is well known to pedirelative risk of readmission (expressed as OR) across all atric endocrinologists. The hospitals in the present study hospitals. Non-Hispanic Black race, public insurance
DKA T1D
Diabetic ketoacidosis Type 1 diabetes
The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2016.01.057
1
THE JOURNAL OF PEDIATRICS
were academic pediatric hospitals; thus one would expect each of them to have a diabetes education team and 24hour telephone access for emergencies. The fact that the risk of readmission was much higher in AfricanAmericans and children with public insurance suggests that a standard education curriculum does not fit everybody. The issues of low literacy, specifically low health literacy and cultural sensitivity,14 economic pressure requiring long work hours for parent(s) and limited time off, and the burden of single parenthood with minimal babysitting options for siblings, often impair the initial and subsequent educational efforts, make regular clinic follow-up visits difficult, and result in poor supervision of children with diabetes. The latter is particularly detrimental during the teenage years, and more so in girls, who are more prone to psychological disturbances, abnormal eating patterns, and depression, all important risk factors for recurrent DKA. What can be done? There is suggestion in minority adults with type 2 diabetes that culturally appropriate health education may work better than “standard” education,15 and similar, albeit limited, data are available in children with T1D.16 Unfortunately, more intensive or prolonged education is often not covered by insurance carriers. Psychological support groups, especially for teenagers, have been successful at our institution by increasing self-motivation and improving self-care—but, again, economically disadvantaged families may have more difficulties in attending these sessions. The best any pediatric diabetes center can do at this time is to reiterate that recurrent DKA is a failure on the part of the provider/family/patient unit and is usually preventable. Appropriate education for the family’s needs should be reinforced together with the provision of an adequate 24-hour telephone support system to lessen the risk of DKA.17 We need increased measures to strengthen the social and psychological support with an individualized approach to the care of high risk patients. In addition, the healthcare system needs to be restructured to mandate insurers to adequately reimburse diabetes education and psychological and social support for diabetes, especially for youth at-risk for recurrent DKA, as this would result in cost-savings in the long run. n Luigi Garibaldi, MD Dorothy Becker, MBBCh Division of Endocrinology and Diabetes Children’s Hospital of the University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Reprint requests: Dorothy Becker, MBBCh, Division of Endocrinology and Diabetes, Children’s Hospital of UPMC, 4401 Penn Ave, Pittsburgh, PA 15224. E-mail: [email protected]
2
Volume -
www.jpeds.com References
1. Pinkey JH, Bingley PJ, Sawtell PA, Dunger DB, Gale EA. Presentation and progress of childhood diabetes mellitus: a prospective populationbased study. The Bart’s-Oxford Study Group. Diabetologia 1994;37: 70-4. 2. Smith CP, Firth D, Bennett S, Howard C, Chisholm P. Ketoacidosis occurring in newly diagnosed and established diabetic children. Acta Paediatr 1998;87:537-41. 3. Rewers A, Chase HP, Mackenzie T, Walravens P, Roback M, Rewers M, et al. Predictors of acute complications in children with type 1 diabetes. JAMA 2002;287:2511-8. 4. Levine BS, Anderson BJ, Butler DA, Antisdel JE, Brackett J, Laffel LM. Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetes. J Pediatr 2001;139:197-203. 5. Laing SP, Swerdlow AJ, Slater SD, Botha JL, Burden AC, Waugh NR, et al. The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16:466-71. 6. Cameron FJ, Scratch SE, Nadebaum C, Northam EA, Koves I, Jennings J, et al. Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children. Diabetes Care 2014;37:1554-62. 7. Maahs DM, Hermann JM, Holman N, Foster NC, Kapellen TM, Allgrove J, et al. Rates of diabetic ketoacidosis: international comparison with 49,859 pediatric patients with type 1 diabetes from England, Wales, the U.S., Austria, and Germany. Diabetes Care 2015;38:1876-82. 8. Hanas R, Lindgren F, Lindblad B. A 2-year national population study of pediatric ketoacidosis in Sweden: predisposing conditions and insulin pump use. Pediatr Diabetes 2009;10:33-7. 9. de Beaufort CE, Lange K, Swift PG, Aman J, Cameron F, Castano L, et al. Metabolic outcomes in young children with type 1 diabetes differ between treatment centers: the Hvidoere Study in Young Children 2009. Pediatr Diabetes 2013;14:422-8. 10. Malik FS, Hall M, Mangione-Smith R, Keren R, Mahant S, Shah SS, et al. Patient characteristics associated with differences in admission frequency for diabetic ketoacidosis in US Children’s Hospitals. J Pediatr 2016. this issue. 11. Fritsch M, Rosenbauer J, Schober E, Neu A, Placzek K, Holl RW, et al. Predictors of diabetic ketoacidosis in children and adolescents with type 1 diabetes. Experience from a large multicenter database. Pediatr Diabetes 2011;12:307-12. 12. Karges B, Rosenbauer J, Holterhus PM, Beyer P, Seithe H, Vogel C, et al. Hospital admission for diabetic ketoacidosis or severe hypoglycemia in 31 330 young patients with type 1 diabetes. Eur J Endocrinol 2015; 173:341-50. 13. Smaldone A, Honig J, Stone PW, Arons R, Weinger K. Characteristics of California children with single versus multiple diabetic ketoacidosis hospitalizations (1998-2000). Diabetes Care 2005;28:2082-4. 14. Swavely D, Vorderstrasse A, Maldonado E, Eid S, Etchason J. Implementation and evaluation of a low health literacy and culturally sensitive diabetes education program. J Healthc Qual 2014;36:16-23. 15. Creamer J, Attridge M, Ramsden M, Cannings-John R, Hawthorne K. Culturally appropriate health education for Type 2 diabetes in ethnic minority groups: an updated Cochrane Review of randomized controlled trials. Diabet Med 2016;33:169-83. 16. Vanelli M, Cangelosi AM, Fanciullo L, Scarabello C, Monti G, Gkliati D, et al. Children with type 1-diabetes from ethnic minorities: vulnerable patients needing a tailored medical support. Acta Biomed 2012;83:30-5. 17. Bismuth E, Laffel L. Can we prevent diabetic ketoacidosis in children? Pediatr Diabetes 2007;8(Suppl 6):24-33.
D
iabetic ketoacidosis (DKA), a most serious, life(used as a proxy for low socioeconomic status), and age threatening acute complication of type 1 diabetes $12 years were the most important (OR 2.40-1.97); fe(T1D) in children, occurs in approximately 25%male sex and mental health comorbidity also contributed 30% of patients with newly diagnosed diabetes.1,2 significantly (OR approximately 1.40). The hierarchy of Following the initial diagnosis, a small, yet important, subrisk factors was different at individual hospitals, and pagroup of patients will have 1 or more tients at some hospitals did substantially See related article, p recurrent admissions for DKA. The incibetter than others, in as much as they dence of recurrent DKA in the US has been estimated at had a low risk of readmission. This suggests that “local” 8 per 100 person-years,3 but may be twice as high.4 In a factors may significantly affect the outcome of patients with T1D. major pediatric diabetes center, 80% of recurrent DKA How relevant is the study by Malik et al to clinical pracoccurred in 20% of the patients, and 60% of DKA tice? The risk factors they describe for recurrent DKA are occurred in 5% of the patients.3 Given the morbidity, not new, and had already been characterized in previous low but definite mortality5 of complications of DKA studies.3,7,11-13 What is new is the fact that the study (mainly cerebral edema), possible adverse effects of DKA 6 on brain morphology and function, and the social burden showed clear variability in how hospitals “perform” in terms of readmission rates. Unfortunately, the study could and the economic cost of these admissions (estimated at not determine whether the variability was related to pa$90 million/year in the US7), several investigators have tient/population factors, hospital factors, or a combination tried to identify risk factors for recurrent DKA in order of the two. Specific characteristics of the populations gravto develop effective prevention strategies. Recurrent DKA itating around each hospital, pattern of diabetes education is almost always related to omission or insufficiency of inor treatment at each center, including diabetes educator/ sulin delivery,2 usually in association with inadequate diapatient ratio and strength of the support provided by sobetes self-care. It is probable that this condition is cial services or psychologist may have played a role, but completely preventable, as suggested by the fact that the this is speculative. Other limitations of the study stem majority of compliant patients never experience DKA from its retrospective nature, and the fact that data were again after the initial diagnosis of T1D, and by the much harvested from the Pediatric Health Information System, lower incidence in countries with better access to medical an information hub which provides anagraphical, rather care, such as Scandinavian countries.8,9 than clinical, data on patients. Thus, no information could In this issue of The Journal, Malik et al retrospectively be extracted on other potentially important risk factors, examined the readmission rates for recurrent DKA in such as diabetes duration, diabetes control, total insulin 12 449 children between age 2 and 18 years, followed at dose, adequacy of diabetes education at diagnosis, fre42 US Children’s Hospitals between 2004 and 2012.10 quency of outpatient visits, all of which were addressed They examined multiple rolling 365-day intervals during in previous studies,3,7,11-13 and some of which (elevated a 5-year follow-up timeframe for each patient. In simple terms, when a patient was admitted for DKA, the patient Hemoglobin A1c especially) are powerful predictors of rewas tracked for evidence of readmission to the same hosadmission. Finally, the low readmission rate in some of the pital in the following 365 days. The main outcome for “better-performing” hospitals could be explained in part their study was the maximum number of DKA admissions by a larger number of poorly compliant patients moving within any 365-day interval during a 5-year follow-up to, and/or being treated at, other hospitals in the area period for each patient. The objectives of the study for further episodes of DKA. Such a scenario would not were: (1) to determine risk factors predicting DKA readbe unlikely in an urban setting with more than a single mission; and (2) to identify differences in these factors children’s hospital or unit, especially if one considers within hospitals and across hospitals. The results of the that only 28% of hospitalizations for DKA occurred at a study were notable because a high percentage (28%) of major children’s hospital in one study.13 patients admitted for DKA (first and repeat episodes not The finding that (recurrent) “DKA begets DKA” and determined) were readmitted within the next 365 days. that each hospital has a group of patients who get readmitThere was a “hierarchy” of factors associated with the ted every few weeks or few months is well known to pedirelative risk of readmission (expressed as OR) across all atric endocrinologists. The hospitals in the present study hospitals. Non-Hispanic Black race, public insurance
DKA T1D
Diabetic ketoacidosis Type 1 diabetes
The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2016.01.057
1
THE JOURNAL OF PEDIATRICS
were academic pediatric hospitals; thus one would expect each of them to have a diabetes education team and 24hour telephone access for emergencies. The fact that the risk of readmission was much higher in AfricanAmericans and children with public insurance suggests that a standard education curriculum does not fit everybody. The issues of low literacy, specifically low health literacy and cultural sensitivity,14 economic pressure requiring long work hours for parent(s) and limited time off, and the burden of single parenthood with minimal babysitting options for siblings, often impair the initial and subsequent educational efforts, make regular clinic follow-up visits difficult, and result in poor supervision of children with diabetes. The latter is particularly detrimental during the teenage years, and more so in girls, who are more prone to psychological disturbances, abnormal eating patterns, and depression, all important risk factors for recurrent DKA. What can be done? There is suggestion in minority adults with type 2 diabetes that culturally appropriate health education may work better than “standard” education,15 and similar, albeit limited, data are available in children with T1D.16 Unfortunately, more intensive or prolonged education is often not covered by insurance carriers. Psychological support groups, especially for teenagers, have been successful at our institution by increasing self-motivation and improving self-care—but, again, economically disadvantaged families may have more difficulties in attending these sessions. The best any pediatric diabetes center can do at this time is to reiterate that recurrent DKA is a failure on the part of the provider/family/patient unit and is usually preventable. Appropriate education for the family’s needs should be reinforced together with the provision of an adequate 24-hour telephone support system to lessen the risk of DKA.17 We need increased measures to strengthen the social and psychological support with an individualized approach to the care of high risk patients. In addition, the healthcare system needs to be restructured to mandate insurers to adequately reimburse diabetes education and psychological and social support for diabetes, especially for youth at-risk for recurrent DKA, as this would result in cost-savings in the long run. n Luigi Garibaldi, MD Dorothy Becker, MBBCh Division of Endocrinology and Diabetes Children’s Hospital of the University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Reprint requests: Dorothy Becker, MBBCh, Division of Endocrinology and Diabetes, Children’s Hospital of UPMC, 4401 Penn Ave, Pittsburgh, PA 15224. E-mail: [email protected]
2
Volume -
www.jpeds.com References
1. Pinkey JH, Bingley PJ, Sawtell PA, Dunger DB, Gale EA. Presentation and progress of childhood diabetes mellitus: a prospective populationbased study. The Bart’s-Oxford Study Group. Diabetologia 1994;37: 70-4. 2. Smith CP, Firth D, Bennett S, Howard C, Chisholm P. Ketoacidosis occurring in newly diagnosed and established diabetic children. Acta Paediatr 1998;87:537-41. 3. Rewers A, Chase HP, Mackenzie T, Walravens P, Roback M, Rewers M, et al. Predictors of acute complications in children with type 1 diabetes. JAMA 2002;287:2511-8. 4. Levine BS, Anderson BJ, Butler DA, Antisdel JE, Brackett J, Laffel LM. Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetes. J Pediatr 2001;139:197-203. 5. Laing SP, Swerdlow AJ, Slater SD, Botha JL, Burden AC, Waugh NR, et al. The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16:466-71. 6. Cameron FJ, Scratch SE, Nadebaum C, Northam EA, Koves I, Jennings J, et al. Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children. Diabetes Care 2014;37:1554-62. 7. Maahs DM, Hermann JM, Holman N, Foster NC, Kapellen TM, Allgrove J, et al. Rates of diabetic ketoacidosis: international comparison with 49,859 pediatric patients with type 1 diabetes from England, Wales, the U.S., Austria, and Germany. Diabetes Care 2015;38:1876-82. 8. Hanas R, Lindgren F, Lindblad B. A 2-year national population study of pediatric ketoacidosis in Sweden: predisposing conditions and insulin pump use. Pediatr Diabetes 2009;10:33-7. 9. de Beaufort CE, Lange K, Swift PG, Aman J, Cameron F, Castano L, et al. Metabolic outcomes in young children with type 1 diabetes differ between treatment centers: the Hvidoere Study in Young Children 2009. Pediatr Diabetes 2013;14:422-8. 10. Malik FS, Hall M, Mangione-Smith R, Keren R, Mahant S, Shah SS, et al. Patient characteristics associated with differences in admission frequency for diabetic ketoacidosis in US Children’s Hospitals. J Pediatr 2016. this issue. 11. Fritsch M, Rosenbauer J, Schober E, Neu A, Placzek K, Holl RW, et al. Predictors of diabetic ketoacidosis in children and adolescents with type 1 diabetes. Experience from a large multicenter database. Pediatr Diabetes 2011;12:307-12. 12. Karges B, Rosenbauer J, Holterhus PM, Beyer P, Seithe H, Vogel C, et al. Hospital admission for diabetic ketoacidosis or severe hypoglycemia in 31 330 young patients with type 1 diabetes. Eur J Endocrinol 2015; 173:341-50. 13. Smaldone A, Honig J, Stone PW, Arons R, Weinger K. Characteristics of California children with single versus multiple diabetic ketoacidosis hospitalizations (1998-2000). Diabetes Care 2005;28:2082-4. 14. Swavely D, Vorderstrasse A, Maldonado E, Eid S, Etchason J. Implementation and evaluation of a low health literacy and culturally sensitive diabetes education program. J Healthc Qual 2014;36:16-23. 15. Creamer J, Attridge M, Ramsden M, Cannings-John R, Hawthorne K. Culturally appropriate health education for Type 2 diabetes in ethnic minority groups: an updated Cochrane Review of randomized controlled trials. Diabet Med 2016;33:169-83. 16. Vanelli M, Cangelosi AM, Fanciullo L, Scarabello C, Monti G, Gkliati D, et al. Children with type 1-diabetes from ethnic minorities: vulnerable patients needing a tailored medical support. Acta Biomed 2012;83:30-5. 17. Bismuth E, Laffel L. Can we prevent diabetic ketoacidosis in children? Pediatr Diabetes 2007;8(Suppl 6):24-33.