Meg Bensignor, MD, FAAP
With a 95 percent increase in type 2 diabetes (T2DM) incidence in youth aged 10-19 years from 2001 to 2017, T2DM clearly is not just a disease of adulthood anymore. (1) It is also apparent that T2DM is not the same disease in adolescents as it is for adults. Firstly, T2DM in adolescents is a much more aggressive disease than in adults, characterized by rapid impairment of insulin secretion with up to 80 percent pancreatic β-cell function loss at the time of diagnosis. (2-6) Additionally, medications that typically work well for adults are not as effective in adolescents. For example, despite treatment with metformin and lifestyle management, about half of adolescents with T2DM required insulin therapy in a median treatment time of 11.5 months, which is a much higher failure rate than adults. (7-11) Two other medications commonly used in adults (dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter-2 inhibitors) were recently found to not improve diabetes control in adolescents as they were with adults. (12, 13, 14) On top of this, diabetes-related comorbidities occur early in youth with about a 60 percent cumulative incidence of any microvascular complication (retinopathy, diabetic kidney disease, hypertension, dyslipidemia, or nerve disease) in a mean of diagnosis length of 13 years. (15)
The American Diabetes Association (ADA) recommends to start screening at age 10 years or the start of puberty, whichever is sooner. (16) Screening is typical done with a hemoglobin A1c (HbA1c), which can be quickly obtained in an office setting. Any patient should be screened annually if they have a BMI > 85th percentile for age and sex and have a maternal history of diabetes or gestational diabetes, a first or second degree relative with T2DM, or signs of insulin resistance (acanthosis nigricans, skin tags, hypertension, dyslipidemia, history of small-for-gestational-age status, and polycystic ovarian syndrome). (16) However, is important to note that diabetes type cannot be diagnosed by signs of insulin resistance or BMI alone as 35-50 percent of youth with type 1 diabetes can also have overweight or obesity. (17) Obtaining diabetes auto-antibodies to exclude type 1 diabetes is recommended for all suspected cases of youth with diabetes before labeling a patient as having T2DM. (16)
Once T2DM is diagnosed with an HbA1c > 6.5 percent, a fasting glucose > 126 mg/dL, or a random glucose > 200 mg/dL with symptoms of polyuria, polydipsia, or unintentional weight loss, treatment with metformin should be started immediately along with lifestyle management. (16) A trial of lifestyle treatment alone without anti-diabetes pharmacotherapy is not recommend. Furthermore, insulin therapy initiation and referral to a pediatric endocrinologists should be done if the HbA1c > 8.5 percent.16 Although still limited, there are expanding treatment options for pediatric T2DM, including two injectable glucagon-like peptide-1 receptor agonists recently FDA approved for the use of patients > 10 years (weekly exenatide extended-release and daily liraglutide 1.8mg). (18,19)
Staying vigilant of a T2DM diagnosis in youth is imperative as delayed diagnosis and treatment initiation can lead to diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome, and poor long-term glycemic control in an already remarkably aggressive disease. (20)
About the Author
Meg Bensignor, MD, FAAP, is an Assistant Professor in the Department of Pediatrics and in the Division of Endocrinology and Diabetes at the University of Minnesota as well as a Core Faculty in the University of Minnesota Center for Pediatric Obesity Medicine. She is a board-certified obesity medicine specialist and a pediatric endocrinologist, specializing in type 2 diabetes in youth. Dr. Bensignor’s area of research involves evaluating the effects of eating patterns on obesity risk and appetite, in addition to novel and effective treatments for youth with Type 2 Diabetes and obesity. She is part of the multidisciplinary team, which includes diabetes nurse educators, a dietician, and a social worker, that make up the Pediatric Type 2 Diabetes Clinic at the University of Minnesota/MHealth.
- Lawrence JM, Divers J, Isom S, et al. Trends in Prevalence of Type 1 and Type 2 Diabetes in Children and Adolescents in the US, 2001-2017. JAMA. 2021;326(8):717-727.
- Elder DA, Woo JG, D’Alessio DA. Impaired beta-cell sensitivity to glucose and maximal insulin secretory capacity in adolescents with type 2 diabetes. Pediatr Diabetes. 2010;11(5):314-321.
- Elder DA, Hornung LN, Herbers PM, Prigeon R, Woo JG, D’Alessio DA. Rapid deterioration of insulin secretion in obese adolescents preceding the onset of type 2 diabetes. J Pediatr. 2015;166(3):672-678.
- Bacha F, Pyle L, Nadeau K, et al. Determinants of glycemic control in youth with type 2 diabetes at randomization in the TODAY study. Pediatr Diabetes. 2012;13(5):376-383.
- Group TS. Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and β-cell function in TODAY. Diabetes Care. 2013;36(6):1749-1757.
- Michaliszyn SF, Mari A, Lee S, et al. β-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes. Diabetes. 2014;63(11):3846-3855.
- Brown JB, Conner C, Nichols GA. Secondary failure of metformin monotherapy in clinical practice. Diabetes Care. 2010;33(3):501-506.
- Consortium R. Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: II. Observations Using the Oral Glucose Tolerance Test. Diabetes Care. 2018;41(8):1707-1716.
- Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999;281(21):2005-2012.
- Barnes NS, White PC, Hutchison MR. Time to failure of oral therapy in children with type 2 diabetes: a single center retrospective chart review. Pediatr Diabetes. 2012;13(7):578-582.
- Zeitler P, Hirst K, Pyle L, et al. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med. 2012;366(24):2247-2256.
- Jalaludin MY, Deeb A, Zeitler P, et al. Efficacy and safety of the addition of sitagliptin to treatment of youth with type 2 diabetes and inadequate glycemic control on metformin without or with insulin. Pediatr Diabetes. 2022;23(2):183-193.
- Shankar RR, Zeitler P, Deeb A, et al. A randomized clinical trial of the efficacy and safety of sitagliptin as initial oral therapy in youth with type 2 diabetes. Pediatr Diabetes. 2022;23(2):173-182.
- Tamborlane WV, Laffel LM, Shehadeh N, et al. Efficacy and safety of dapagliflozin in children and young adults with type 2 diabetes: a prospective, multicentre, randomised, parallel group, phase 3 study. Lancet Diabetes Endocrinol. 2022;10(5):341-350.
- Bjornstad P, Drews KL, Caprio S, et al. Long-Term Complications in Youth-Onset Type 2 Diabetes. N Engl J Med. 2021;385(5):416-426.
- Draznin B, Aroda VR, Bakris G, et al. 14. Children and Adolescents: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(Supplement_1):S208-S231.
- Hamman RF, Bell RA, Dabelea D, et al. The SEARCH for Diabetes in Youth study: rationale, findings, and future directions. Diabetes Care. 2014;37(12):3336-3344.
- AstraZeneca. Bydureon BCise (exenatide extended-release) approved in the US for the treatment of type 2 diabetes in pediatric patients ages 10 years and older. 2021; ttps://www.astrazeneca-us.com/media/press-releases/2021/bydureon-bcise-exenatide-extended-release-approved-in-the-us-for-the-treatment-of-type-2-diabetes.html. Accessed November 24, 2021, 2021.
- Bacha F. FDA approval of GLP-1 receptor agonist (liraglutide) for use in children. Lancet Child Adolesc Health. 2019;3(9):595-597.
- Alemzadeh R, Ellis J, Calhoun M, Kichler J. Predictors of metabolic control at one year in a population of pediatric patients with type 2 diabetes mellitus: a retrospective study. J Pediatr Endocrinol Metab. 2006;19(9):1141-1149.