Type 1 Diabetes: Its Problems and Solutions
Formerly known as juvenile-onset diabetes, type 1 diabetes (T1D) is an endocrine disorder characterized by hyperglycemia due to insulin deficiency.
Formerly known as juvenile-onset diabetes, type 1 diabetes (T1D) is an endocrine disorder characterized by hyperglycemia due to insulin deficiency.1 Most cases of T1D are immune-mediated due to cellular-mediated autoimmune destruction of beta cells, resulting in inadequate insulin secretion and hyperglycemia via abnormal macronutrient metabolism.1,2 Acute hyperglycemia can cause metabolic emergencies such as diabetic ketoacidosis (DKA) and a hyperosmolar hyperglycemic state. Chronic hyperglycemia can cause vascular complications such as nephropathy, retinopathy, and cardiovascular disease.
According to the American Diabetes Association (ADA), immune-mediated T1D accounts for 5% to 10% of diabetes cases. Although T1D may occur at any age, 50% to 60% of patients with T1D present at 16 years and younger.3-5 In a population- based cross-sectional study of children and adolescents in 2009, the overall prevalence of newly diagnosed cases of T1D was 1.93 per 1000 patients (95% CI, 1.88-1.97), with whites having the highest incidence of newly diagnosed T1D.6
A patient’s genome is a significant risk factor for T1D, as a case-control study of approximately 8000 patients with T1D identified 7 genetic variants associated with an increased risk of T1D and celiac disease.7 Other possible risk factors associated with an increased risk of T1D include high birth weight, childhood obesity, and a higher maternal age at birth.8-11 Childhood immunizations, however, are not associated with an increased risk for T1D.12,13 Conditions complicated by T1D include celiac disease and increased risk of hip fracture.14,15
HISTORY AND PHYSICAL
Patients with T1D rarely present asymptomatically; the most common symptoms include polyuria and nocturia, enuresis, lethargy, fatigue, polyphagia, and abdominal pain.4 Approximately 30% of children and adolescents with newly diagnosed T1D may present with DKA.16 When obtaining a patient’s medical history, ask about autoimmune diseases and a family history of diabetes.3,5 If a patient presents with an autoimmune disease, evaluate whether associated symptoms are present.
It is important to document the patient’s weight, as recent sudden weight loss is common in T1D.1,4 Additionally, patients may present with skin conditions associated with T1D, such as diabetic blisters.17 In the extremities, patients may present with diabetic foot ulcers or loss of sensation and reflex.3
The 2016 ADA guidelines list the criteria for diagnosing diabetes, which include the presence of at least 1 of the following3:
- Fasting blood glucose level ≥126 mg/dL
- Two-hour blood glucose level ≥200 mg/dL during a 75-g oral glucose tolerance test
- Glycated hemoglobin (A1C) level ≥6.5%
- In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random blood glucose level ≥200 mg/dL
The ADA guidelines recommend that clinicians use blood glucose levels instead of A1C levels to diagnose acute T1D in individuals with hyperglycemia symptoms (ie, polydipsia, polyphagia, polyuria; ADA grade E).3 Additional parameters (eg, electrolytes, blood urea nitrogen, creatinine, arterial blood gas, serum or urine ketones) should be tested to determine DKA severity (Table 1).18 The ADA guidelines also recommend screening for thyroid disease and celiac disease soon after diagnosing T1D in children (ADA grade E). In patients 10 years and older, obtaining a fasting lipid profile after a T1D diagnosis is recommended (ADA grade E).3,5
Urine studies should also be performed. If DKA is suspected, urinalysis and urine ketone testing via the dipstick method are recommended; if an infection is suspected, urinalysis is recommended. The ADA and the National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommend conducting annual albuminuria screening starting 5 years after a T1D diagnosis.3,19
In pediatric patients with T1D, the mortality rates associated with DKA are 0.15% to 0.3% in national population-based studies.20 A prospective cohort study of 1243 children 19 years and younger with T1D noted that severe hypoglycemia occurs in 19 per 100 person-years.21
In addition to the microvascular complications of T1D (ie, retinopathy, nephropathy, and neuropathy), patients may be at risk for macrovascular complications.22-25 For example, a systematic review of patients with diabetes (but without acute foot ulcerations or previous history of amputation) noted that in patients with T1D, there was an 18% increased risk of amputation for each 1% increase in A1C level.26
T1D is associated with several infections, such as malignant otitis externa, hepatitis B, and hepatitis C (Table 2). Additionally, pediatric patients with T1D may be prone to vulvovaginal candidiasis, as observed in a case-control study of 35 girls. This study also identified that a higher mean A1C level was associated with a diagnosis of vulvovaginal candidiasis.27
In pediatric patients with T1D, early-onset diabetes and hypoglycemia were associated with poorer cognitive performance.28 In a study that compared 244 children with diabetes with 110 siblings and 209 classmates, T1D was associated with increased behavior concerns reported by parents, but not academic performance.29
Compared with the general population, T1D was associated with increased all-cause and cardiovascular mortality.30 Additionally, a cohort study from Scotland found that after 20 years of age, life expectancy may decrease by about 12 years in patients with T1D compared with the general population.31 One retrospective cohort study that evaluated patients with a diagnosis of T1D during childhood found that an increased risk of death in early adulthood was associated with higher mean pediatric A1C levels and a history of severe hypoglycemia episodes.32
In a survey of 535 patients given a diagnosis of diabetes before 18 years of age, 46% of respondents reported rehospitalization.33
The ADA guidelines recommend treating T1D with daily subcutaneous insulin therapy consisting of 3 or 4 daily injections of basal and prandial insulin to counteract insulin depletion (ADA grade A); insulin formulations vary in their pharmacokinetic action (Table 3).3 The total daily insulin doses depend on age, weight, pubertal status, medical history, and physical activity.34 Insulin regimens for patients with T1D are either a split/mixed regimen or a basal/bolus regimen.3 The split/mixed regimen consists of 2 or 3 daily insulin injections given in combination with multiple insulins, whereas the basal/bolus regimen consists of a long-acting insulin and preprandial insulin injections.
Table 3. Insulin Types and Pharmacokinetic Parameters34
Onset of Action
Peak of Action
Duration of Action (hr)
Novolog (aspart insulin)
Humalog (lispro insulin)
Apidra (glulisine insulin)
Novolin-R (regular insulin)
Humulin-R (regular insulin)
Novolin-N (NPH insulin)
Humulin-N (NPH insulin)
Lantus (insulin glargine)
Levemir (insulin detemir)
Subcutaneous insulin can be injected in multiple sites (Figure). It is important to counsel patients and caregivers to ensure rotation of insulin injection sections. If a mixed regimen is used, instruct the patient/caregiver to draw up the regular-acting insulin first (clear appearance) in the syringe, followed by the intermediate-acting insulin (cloudy appearance).
The adverse effects of insulin include injection-site reactions, hypoglycemia, hypokalemia, and weight gain. It is important for patients with T1D and caregivers to identify signs and symptoms of hypoglycemia (eg, cognitive impairment, loss of consciousness, seizure, coma) and treatment options (eg, glucose/carbohydrate- containing foods, glucagon).3
Glycemic goals should be individualized to achieve proper glycemic control, minimize the risk of hypoglycemia, and maintain normal growth and development. In children, the recommended goals are A1C levels less than 7.5% (ADA grade E), preprandial glucose levels between 90 and 130 mg/dL, and bedtime or overnight glucose levels between 90 and 150 mg/dL.3 Lifestyle interventions include dietary recommendations (ADA grade A), physical activity for at least 60 minutes per day in children (ADA grade B), and individualized diabetes self-management education for patients and caregivers (ADA grade B).3
ROLE OF THE PHARMACIST
Pharmacists can administer immunizations to pediatric patients with T1D based on the recommended schedule set forth by the Advisory Committee on Immunization Practices guidelines (ADA grade C). 3,5 It is important to ensure that patients with T1D receive the influenza vaccine but to exercise caution if administering the live-attenuated influenza vaccine in pediatric patients with T1D and chronic conditions, because administration of the live vaccine may worsen a patient’s chronic conditions, including T1D.35
Patients and caregivers should receive appropriate, individualized diabetes self-management education and support (ADA grade B).3 Pharmacists may also play a key role in initial patient counseling, as initial diabetes education in outpatient settings, compared with inpatient education in children with new-onset T1D, is associated with long-term glycemic control and similar acute complication rates (level 2 evidence).36 All pediatric patients with T1D should be advised not to smoke or use tobacco products (ADA grade A); if patients/caregivers do smoke, smoking cessation should be included in therapy management (ADA grade B).3 The ADA also set forth quarterly and annual routine follow-up recommendations for pediatric patients with T1D (Table 4).5 A retrospective cohort study found that pediatric patients with T1D and a history of smoking had increased A1C levels, diastolic blood pressure, triglyceride levels, and total cholesterol levels.37 Transition of care from pediatric clinicians to adult clinicians decreased hospitalization risk.38
Brian J. Catton, PharmD, graduated from the Bernard J. Dunn School of Pharmacy at Shenandoah University in Winchester, Virginia, in 2010. He received the Distinguished Young Pharmacist Award from the New Jersey Pharmacists Association in 2014. He currently is a Pharmacist Communicator at Ashfield Healthcare in Ivyland, Pennsylvania. His areas of interest include pediatrics, immunizations, drug-therapy management, social media, patient counseling, and immuno-oncology.
- American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(suppl 1):S81-S90. doi: 10.2337/dc14-S014.
- Dabelea D, Pihoker C, Talton JW, et al; SEARCH for Diabetes in Youth Study. Etiological approach to characterization of diabetes type: the SEARCH for Diabetes in Youth Study. Diabetes Care. 2011;34(7):1628-1633. doi: 10.2337/dc10-2324.
- American Diabetes Association. Standards of medical care in diabetes-2016. Diabetes Care. 2016;39(suppl 1):S1-S112.
- Daneman D. Type 1 diabetes. Lancet. 2006;367(9513):847-858.
- Chiang JL, Kirkman MS, Laffel LM, Peters AL; Type 1 Diabetes Sourcebook Authors. Type 1 diabetes through the life span: a position statement of the American Diabetes Association. Diabetes Care. 2014;37(7):2034-2054. doi: 10.2337/dc14-1140.
- Dabelea D, Mayer-Davis EJ, Saydah S, et al. Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA. 2014;311(17):1778-1786. doi: 10.1001/jama.2014.3201.
- Smyth DJ, Plagnol V, Walker NM, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008;359(26):2767-2777. doi: 10.1056/NEJMoa0807917.
- Harder T, Roepke K, Diller N, Stechling Y, Dudenhausen JW, Plagemann A. Birth weight, early weight gain, and subsequent risk of type 1 diabetes: systematic review and meta-analysis. Am J Epidemiol. 2009;169(12):1428-1436. doi: 10.1093/aje/kwp065.
- Cardwell CR, Stene LC, Joner G, et al. Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data. Diabetologia. 2010;53(4):641-651. doi: 10.1007/s00125-009-1648-5.
- Verbeeten KC, Elks CE, Daneman D, Ong KK. Association between childhood obesity and subsequent Type 1 diabetes: a systematic review and meta-analysis. Diabet Med. 2011;28(1):10-18. doi: 10.1111/j.1464-5491.2010.03160.x.
- Cardwell CR, Stene LC, Joner G, et al. Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies. Diabetes. 2010;59(2):486-494. doi: 10.2337/db09-1166.
- DeStefano F, Mullooly JP, Okoro CA, et al; Vaccine Safety Datalink Team. Childhood vaccinations, vaccination timing, and risk of type 1 diabetes mellitus. Pediatrics. 2001;108(6):E112.
- Black SB, Lewis E, Shinefield HR, et al. Lack of association between receipt of conjugate haemophilus influenzae type B vaccine (HbOC) in infancy and risk of type 1 (juvenile onset) diabetes: long term follow-up of the HbOC efficacy trial cohort. Pediatr Infect Dis J. 2002;21(6):568-569.
- Pham-Short A, Donaghue KC, Ambler G, Phelan H, Twigg S, Craig ME. Screening for celiac disease in type 1 diabetes: a systematic review. Pediatrics. 2015;136(1):e170-e176. doi: 10.1542/peds.2014-2883.
- Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007;166(5):495-505.
- Dabelea D, Rewers A, Stafford JM, et al. Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study. Pediatrics. 2004;133(4):e938-e945. doi: 10.1542/peds.2013-2795.
- Van Hattem S, Bootsma AH, Thio HB. Skin manifestations of diabetes. Cleve Clin J Med. 2008;75(11):772-777.
- Westerberg DP. Diabetic ketoacidosis: evaluation and treatment. Am Fam Physician. 2013;87(5):337-346.
- National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI). KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis. 2007;49(2 suppl 2):S12-S154. doi: 10.1053/j.ajkd.2006.12.005.
- Wolfsdorf J, Glaser N, Sperling MA; American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(5):1150-1159.
- Rewers A, Chase HP, Mackenzie T, et al. Predictors of acute complications in children with type 1 diabetes. JAMA. 2002;287(19):2511-2518.
- Roy MS, Affouf M. Six-year progression of retinopathy and associated risk factors in African American patients with type 1 diabetes mellitus: the New Jersey 725. Arch Ophthalmol. 2006;124(9):1297-1306.
- Amin R, Widmer B, Dalton RN, Dunger DB. Unchanged incidence of microalbuminuria in children with type 1 diabetes since 1986: a UK based inception cohort. Arch Dis Child. 2009;94(4):258-262. doi: 10.1136/adc.2008.144337.
- Amin R, Widmer B, Prevost AT, et al. Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ. 2008;336(7646):697-701. doi: 10.1136/bmj.39478.378241.BE.
- Tesfaye S, Chaturvedi N, Eaton SE, et al. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005;352(4):341-350.
- Adler AI, Erqou S, Lima TA, Robinson AH. Association between glycated haemoglobin and the risk of lower extremity amputation in patients with diabetes mellitus-review and meta-analysis. Diabetologia. 2010;53(5):840-849. doi: 10.1007/s00125-009-1638-7.
- Kendirci M, Koç AN, Kurtoglu S, Keskin M, Kuyucu T. Vulvovaginal candidiasis in children and adolescents with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2004;17(11):1545-1549.
- Northam EA, Rankins D, Lin A, et al. Central nervous system function in youth with type 1 diabetes 12 years after disease onset. Diabetes Care. 2009;32(3):445-450. doi: 10.2337/dc08-1657.
- McCarthy AM, Lindgren S, Mengeling MA, Tsalikian E, Engvall JC. Effects of diabetes on learning in children. Pediatrics. 2002;109(1):e9.
- Lind M, Svensson AM, Kosiborod M, et al. Glycemic control and excess mortality in type 1 diabetes. N Engl J Med. 2014;371(21):1972-1982. doi: 10.1056/NEJMoa1408214.
- Livingstone SJ, Levin D, Looker HC, et al. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA. 2015;313(1):37-44. doi: 10.1001/jama.2014.16425.
- Cooper MN, de Klerk NH, Jones TW, Davis EA. Clinical and demographic risk factors associated with mortality during early adulthood in a population-based cohort of childhood-onset type 1 diabetes. Diabet Med. 2014;31(12):1550-1558. doi: 10.1111/dme.12522.
- Estrada CL, Danielson KK, Drum ML, Lipton RB. Hospitalization subsequent to diagnosis in young patients with diabetes in Chicago, Illinois. Pediatrics. 2009;124(3):926-934. doi: 10.1542/peds.2008-3826.
- Bangstad HJ, Danne T, Deeb L, Jarosz-Chobot P, Urakami T, Hanas R. Insulin treatment in children and adolescents with diabetes. Pediatr Diabetes. 2009;10(suppl 12):82-99. doi: 10.1111/j.1399-5448.2009.00578.x.
- Robinson CL; Advisory Committee on Immunization Practices (ACIP), ACIP Child/Adolescent Immunization Work Group. Advisory Committee on Immunization Practices Recommended Immunization Schedules for Persons Aged 0 Through 18 Years — United States, 2016. MMWR. 2016;65(4):86-87. doi: 10.15585/mmwr.mm6504a4.
- Smart CE, Annan F, Bruno LCP, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Nutritional management in children and adolescents with diabetes. Pediatr Diabetes. 2014;15(suppl 20):135-153. doi: 10.1111/pedi.12175.
- Hofer SE, Rosenbauer J, Grulich-Henn J, et al. Smoking and metabolic control in adolescents with type 1 diabetes. J Pediatr. 2009;154(1):20-23. doi: 10.1016/j.jpeds.2008.07.052.
- Nakhla M, Daneman D, To T, Paradis G, Guttmann A. Transition to adult care for youths with diabetes mellitus: findings from a Universal Health Care System. Pediatrics. 2009;124(6):e1134-e1141. doi: 10.1542/peds.2009-0041.