Diabetes Mellitus Type 1 In Children


Article Author:
Evan Los


Article Editor:
Andrew Wilt


Editors In Chief:
Chaddie Doerr


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
2/24/2019 1:38:16 PM

Introduction

Type 1 diabetes occurs when there is the autoimmune destruction of pancreatic beta cells leading to insufficient insulin production and resulting hyperglycemia. With insulin replacement, type 1 diabetes is a chronic disease requiring intensive effort on the part of the person with diabetes and caregivers. There is an emphasis on reducing hyperglycemia while minimizing the risk of hypoglycemia. The complex balance of glucose is affected by food, insulin doses, body stresses, exercise, and dozens of other factors. Patient and family education is key, as is an acknowledgment of the normal developmental stages and the challenges this brings in the context of daily living with a chronic disease. With proper care and support, children and adolescents with type 1 diabetes can expect to lead long and fulfilling lives.[1][2]

Etiology

Both genetic and environmental contributions lead to immune-mediated loss of beta cell function resulting in hyperglycemia and life-long insulin dependence. In an individual at risk (human leukocyte antigen (HLA) haplotype accounts for 30% to 50% of their genetic risk. More than 50 other genes have been found through candidate gene and genome-wide association studies.  A "triggering" insult (e.g., maternal and intrauterine environment, exposure to viruses, host microbiome, diet and many other factors are thought to contribute to disease susceptibility) is suspected to initiate a process that recruits antigen-presenting cells to transport beta cell self-antigens to autoreactive T cells. Through failures of self-tolerance, these T cells mediate beta-cell killing and inflammation leading to insulinopenia and symptomatic diabetes. Recently, preclinical stages of type 1 diabetes have been recognized. Stage 1 is defined by the presence of beta cell autoimmunity, but normal glucose-handling, stage 2 is defined by abnormal glucose handling but no overt symptoms, and finally stage 3 is defined by clinically-apparent symptoms of insulinopenia. Progression through these stages may take years. Although the pre-clinical staging is not usually clinically relevant, research focusing on interventions in the pre-clinical groups may prove to delay or prevent the onset of type 1 diabetes.[3][2]

Epidemiology

Type 1 diabetes may be diagnosed at nearly any age, though peaks in presentation occur between ages 5 to 7 and around puberty. There appears to be seasonal variation with more cases diagnosed in fall and winter. Unlike most autoimmune disorders, type 1 diabetes is slightly more common in boys and men. In the past several decades, type 1 diabetes incidence and prevalence has increased in most age, sex, and race/ethnic groups with some of the fastest growth in young children. There is significant variability in incidence based on geography and ethnicity. For example, the incidence in Finland is 60 per 100,000 person-years, while in China it is 0.1 per 100,000. In the United States, there are approximately 20 to 30 new diagnoses per 100,000 person-years. These incidences have increased by 200% to 300% in the past several decades. In the United States, there are now more than 1.25 million people living with type 1 diabetes., and around 500,000 are children.[4]

If a child has type 1 diabetes, concordance in another sibling is around 5%. In fraternal twins, it is around 10% to 30%, and with identical twins, it is 40% to 50%. Children of adults with type 1 diabetes are at an approximately 5% to 8% risk. In the United States, the general population risk is approximately 0.3%.[5]

Pathophysiology

Insufficient endogenous insulin leads to hyperglycemia, hyperglucagonemia, glucosuria, and without treatment, eventually ketosis, acidosis, dehydration, and death. About one-third of patients with newly-diagnosed type 1 diabetes present with diabetic ketoacidosis (DKA) which has a mortality rate of around 0.3-0.5%, despite aggressive treatment.[6][2]

The Diabetes Control and Complications Trial was the pivotal study published in 1993 documenting the clear association of chronic hyperglycemia with long-term microvascular complications such retinopathy, neuropathy, and microalbuminuria (as a surrogate for nephropathy). [7] Follow-up studies have documented the association of chronic hyperglycemia with macrovascular complications as well as all-cause mortality.[8] Iatrogenic hypoglycemia, however, was identified as the major limiting factor to intensive glucose control.[9]

For the last several decades, therapies have focused on normalizing glucose while minimizing the risk of hypoglycemia while at the same time monitoring for chronic complications and acknowledging the important psychosocial factors that affect a growing and developing children with a chronic disease.

Toxicokinetics

Insufficient insulin and/or poor oral intake may lead to the development of ketosis. If not recognized and treated appropriately, ketoacids increase and cause acidosis which if severe, may require hospitalization. Rates of admission for diabetic ketoacidosis are low with most children never requiring admission, though approximately 5% of children are admitted per year, and approximately 1% are admitted multiple times each year.[6] Rates are highest among adolescents, females, and those with poor social support.[10]

History and Physical

At presentation, children usually have a history of polyuria, polydipsia and weight loss for days to months. If the diagnosis is delayed, there may be vomiting, lethargy, altered mental status, dehydration, and acidosis. After diagnosis, and initiation of insulin therapy, follow-up management is typically coordinated by a pediatric endocrinologist on approximately a quarterly basis.

At regular visits, the provider will assess changes in diabetes status and life circumstances affecting diabetes management, for example, school experience, changes in patterns of exercise and diet, the developmental stage of the child, their participation in diabetes care tasks, family and home life changes, and adherence to therapy. History and physical also focus on assessing issues related to glucose monitoring, insulin delivery (e.g., lipodystrophy, skin tolerance to medical adhesives on diabetes technology), and screening for symptoms of associated medical issues such as thyroid dysfunction or celiac disease. [2][11] As most children with type 1 diabetes are otherwise healthy, history and physical is usually limited to assessment of pertinent diabetes care.

Evaluation

Particular attention is paid to home glucose monitoring to learn the patterns of glucose variability and their relation to life circumstances such as school, exercise, and physical stresses such as illness and menses. Insulin dose adjustment is performed with child and family input, as appropriate.

Hemoglobin A1c is typically measured at clinic visits as a measure of average glucose over the prior two to three months. The American Diabetes Association recommends Hemoglobin A1c be less than 7.5%, although large population studies suggest only 20% to 25% of children and adolescents achieve this.[12] Diabetes organizations in other developed countries may suggest lower Hemoglobin A1c targets and are somewhat more successful at achieving these targets.[13]

Continuous glucose monitoring (CGM) has become more common in children and adolescents, and measures of "time in range" and glucose variability are likely to be even more valuable than Hemoglobin A1c, although insurance does not universally cover CGM and is not always desired by patients.

Screening for thyroid disorders is performed at regular intervals and screening for celiac disease is typically done as well, although frequency is not established. Regular screening for lipid disorders, microalbuminuria, and retinopathy are recommended based on the duration of diabetes. Assessment of mental health and psychosocial factors are also important.[2]

Treatment / Management

A diabetes healthcare team may include the medical provider, nurse, diabetes educator, dietician, social worker, and psychologist; However, not all specialties are always available, convenient, or covered by insurance. Contact between the child and family and medical team between in-office visits is frequent, at least initially, while treatment is adjusted and the family learns the daily management tasks of caring for a child with diabetes. The patient and family make long-term day to day treatment decisions.

Insulin delivery is by multiple daily injections (MDI) or an insulin pump to simulate endogenous insulin physiology. Multiple daily injections include basal insulin once or twice daily, and bolus insulin typically is given at meals three or more times daily and is based on carbohydrate content and current blood glucose. Insulin pumps deliver rapid-acting insulin only and provide a basal rate of insulin that is either programmed or automatically adjusted based on continuous glucose monitor input in some pumps, and mealtime insulin is typically calculated based on mealtime inputs of carbohydrate and current blood glucose.

The provider will also screen for associated disorders (e.g., thyroid disease, celiac disease, dyslipidemia), ensure screening for complications of chronic hyperglycemia (e.g., retinopathy, neuropathy, nephropathy), and ongoing healthcare maintenance such as influenza vaccine. A detailed description of diabetes care is documented in the American Diabetes Association Standards of Medical Care in Diabetes publication which is updated each January in the journal Diabetes Care.[2]

Pearls and Other Issues

Few other chronic diseases require as much vigilance by the patient and family for tasks as regular as eating, exercising, and going to school. The psychosocial impact of living with diabetes can be a challenge for any child and any family but is particularly burdensome to those with maladaptive coping skills. The result can sometimes be manifest as poor glucose control. In the United States, a study of almost 30,000 people with type 1 diabetes documented Hemoglobin A1c across the lifespan and showed a pronounced peak in adolescence and young adulthood.[12] Providers, families, and patients should all be aware of the developmental and psychosocial challenges in this age group and focus on patient-centered approaches to promote self-empowerment, decrease burdens and make diabetes more liveable.

Enhancing Healthcare Team Outcomes

The management of type 1 diabetes requires a diabetes healthcare team may include the medical provider, nurse, diabetes educator, dietician, social worker, and psychologist; However, not all specialties are always available, convenient, or covered by insurance. Contact between the child and family and medical team between in-office visits is frequent, at least initially, while treatment is adjusted and the family learns the daily management tasks of caring for a child with diabetes. The patient and family make long-term day to day treatment decisions.

All patients and their families need comprehensive education about the disease and its potential complications. In addition, all diabetics should be referred to an ophthalmologist, nephrologist, cardiologist and a neurologist for baseline workup of their respective organ systems.

The provider will also screen for associated disorders (e.g., thyroid disease, celiac disease, dyslipidemia), ensure screening for complications of chronic hyperglycemia (e.g., retinopathy, neuropathy, nephropathy), and ongoing healthcare maintenance such as influenza vaccine. A detailed description of diabetes care is documented in the American Diabetes Association Standards of Medical Care in Diabetes publication which is updated each January in the journal Diabetes Care.[2]


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Diabetes Mellitus Type 1 In Children - Questions

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A 15-year-old boy who was diagnosed with type 1 diabetes mellitus at age eight is being seen in follow-up. His hemoglobin A1c measurement has typically been 9% to 9.5% over the last year and his mean glucose has been in the low to mid 200s on glucose meter download. Today his glucose meter download demonstrates a mean glucose of 126 mg/dL with nearly all glucose levels being between 100-140 mg/dL except for two glucose in the 300s. On exam, he has few finger-poke sites visible on his fingertips. His hemoglobin A1c today is 10.8%. He asks for a refill of glucose meter control solution. What is the most likely explanation for the apparent difference in glycemia between home glucose monitoring and hemoglobin A1c measurement?



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A 9-year-old boy is diagnosed with type 1 diabetes mellitus. No one else in the extended family is known to have type 1 diabetes. The boy has an identical twin brother and a younger sister. What is the risk to each of his siblings to develop type 1 diabetes?



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A 15-year-old girl with type 1 diabetes diagnosed 4 years ago has been admitted for diabetic ketoacidosis 6 times in the previous 12 months. Her hemoglobin A1c (HbA1c) is 13.4%. Her reported insulin doses appear adequate for age and body weight. Her mother reports the patient has mostly been managing her diabetes independently and doesn't like talking about diabetes with anyone. Which intervention is most likely to be effective in improving glycemic control?



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What were the primary findings of the Diabetes Control and Complications Trial (DCCT) published in 1993?



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A 16-year-old child with type 1 diabetes mellitus diagnosed eight years ago. For which of the following conditions is regular laboratory screening recommended?



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Diabetes Mellitus Type 1 In Children - References

References

Chiang JL,Maahs DM,Garvey KC,Hood KK,Laffel LM,Weinzimer SA,Wolfsdorf JI,Schatz D, Type 1 Diabetes in Children and Adolescents: A Position Statement by the American Diabetes Association. Diabetes care. 2018 Sep;     [PubMed]
13. Children and Adolescents: {i}Standards of Medical Care in Diabetes-2019{/i}. Diabetes care. 2019 Jan;     [PubMed]
Insel RA,Dunne JL,Atkinson MA,Chiang JL,Dabelea D,Gottlieb PA,Greenbaum CJ,Herold KC,Krischer JP,Lernmark �,Ratner RE,Rewers MJ,Schatz DA,Skyler JS,Sosenko JM,Ziegler AG, Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes care. 2015 Oct;     [PubMed]
Atkinson MA,Eisenbarth GS,Michels AW, Type 1 diabetes. Lancet (London, England). 2014 Jan 4;     [PubMed]
Triolo TM,Fouts A,Pyle L,Yu L,Gottlieb PA,Steck AK, Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes. Diabetes care. 2019 Feb;     [PubMed]
Nathan DM,Genuth S,Lachin J,Cleary P,Crofford O,Davis M,Rand L,Siebert C, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The New England journal of medicine. 1993 Sep 30;     [PubMed]
Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes: The DCCT/EDIC Study 30-Year Follow-up. Diabetes care. 2016 May;     [PubMed]
Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group. Diabetes. 1997 Feb;     [PubMed]
Wolfsdorf JI,Glaser N,Agus M,Fritsch M,Hanas R,Rewers A,Sperling MA,Codner E, ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatric diabetes. 2018 Oct;     [PubMed]
Fritsch M,Rosenbauer J,Schober E,Neu A,Placzek K,Holl RW, Predictors of diabetic ketoacidosis in children and adolescents with type 1 diabetes. Experience from a large multicentre database. Pediatric diabetes. 2011 Jun;     [PubMed]
Phelan H,Lange K,Cengiz E,Gallego P,Majaliwa E,Pelicand J,Smart C,Hofer SE, ISPAD Clinical Practice Consensus Guidelines 2018: Diabetes education in children and adolescents. Pediatric diabetes. 2018 Oct;     [PubMed]
Miller KM,Foster NC,Beck RW,Bergenstal RM,DuBose SN,DiMeglio LA,Maahs DM,Tamborlane WV, Current state of type 1 diabetes treatment in the U.S.: updated data from the T1D Exchange clinic registry. Diabetes care. 2015 Jun;     [PubMed]
McKnight JA,Wild SH,Lamb MJ,Cooper MN,Jones TW,Davis EA,Hofer S,Fritsch M,Schober E,Svensson J,Almdal T,Young R,Warner JT,Delemer B,Souchon PF,Holl RW,Karges W,Kieninger DM,Tigas S,Bargiota A,Sampanis C,Cherubini V,Gesuita R,Strele I,Pildava S,Coppell KJ,Magee G,Cooper JG,Dinneen SF,Eeg-Olofsson K,Svensson AM,Gudbjornsdottir S,Veeze H,Aanstoot HJ,Khalangot M,Tamborlane WV,Miller KM, Glycaemic control of Type�1 diabetes in clinical practice early in the 21st century: an international comparison. Diabetic medicine : a journal of the British Diabetic Association. 2015 Aug;     [PubMed]

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