Risk of hypoglycemia in youth with type 2 diabetes on insulin
-
Madhia Shahid
,
Gabriel Q. Shaibi
Abstract
Background:
The objective of this study was to ascertain the risk of hypoglycemia among youth with type 2 diabetes (T2D) on insulin therapy.
Methods:
Twenty-two youth with T2D on insulin therapy (M=12, F=10, age=14.4±4.0 years) were enrolled from a single pediatric endocrine practice. They were followed-up for 3 months with weekly phone calls and monthly in-person visits to review blood glucose logs and document any signs or symptoms of hypoglycemia (defined as finger stick glucose of ≤70 mg/dL). Episodes of hypoglycemia were categorized into five categories: severe, documented symptomatic, asymptomatic, probable symptomatic and relative hypoglycemia. In addition to examining the risk of hypoglycemia, the degree to which hypoglycemia was associated with patient demographics (e.g. age, gender and body mass index [BMI]) or clinical factors (i.e. duration of diabetes, duration of insulin treatment, glycemic control or insulin dose and regimen) was determined.
Results:
Nine hypoglycemic events occurred during the study period in five patients with an incidence rate of nine events per 5.3 patient-years. Of the hypoglycemic events, five were symptomatic and four were asymptomatic. No severe hypoglycemic events occurred. Hypoglycemia was not associated with age, ethnicity, duration of insulin treatment, insulin dose or initial hemoglobin (HbA1c). However, a significant difference in BMI was noted, with T2D youth who experienced hypoglycemia having a lower BMI than those who did not experience hypoglycemia.
Conclusions:
The results of this study suggest that the risk of hypoglycemia in youth with T2D on insulin therapy is low.
Acknowledgments
We thank our patients who participated in the study, research staff and the faculty in the Division of Endocrinology at Phoenix Children’s Hospital. None of the authors have any relevant conflict of interest to disclose.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. MS collected/researched data and wrote the manuscript. GS reviewed and edited the manuscript. PG-F reviewed the manuscript. HB reviewed the manuscript. ZG reviewed the manuscript. MO reviewed the manuscript and contributed to discussion.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Pinhas-Hamiel O, Zeitler P. The global spread of type 2 diabetes mellitus in children and adolescents. J Pediatr 2005;146: 693–700.10.1016/j.jpeds.2004.12.042Search in Google Scholar
2. Kiess W, Gorski T, Penke M, Klamt S, Kapellen TM. Diabetes mellitus in children and adolescents – a global epidemic which has become neglected. J Pediatr Endocrinol Metab 2015;28:247–50.10.1515/jpem-2015-0900Search in Google Scholar
3. Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N Engl J Med 2017;376:1419–29.10.1056/NEJMoa1610187Search in Google Scholar
4. Pinhas-Hamiel O, Dolan LM, Daniels SR, Standiford D, Khoury PR, et al. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr 1996;128:608–15.10.1016/S0022-3476(96)80124-7Search in Google Scholar
5. Writing Group for the SEARCH for Diabetes in Youth Study Group, Dabelea D, Bell RA, D’Agostino RB Jr, Imperatore G, et al. Incidence of diabetes in youth in the United States. J Am Med Assoc 2007;297:2716–24.10.1001/jama.297.24.2716Search in Google Scholar PubMed
6. Kelsey MM, Geffner ME, Guandalini C, Pyle L, Tamborlane WV, et al. Presentation and effectiveness of early treatment of type 2 diabetes in youth: lessons from the TODAY study. Pediatr Diabetes 2016;17:212–21.10.1111/pedi.12264Search in Google Scholar PubMed PubMed Central
7. TODAY Study Group, Zeitler P, Hirst K, Pyle L, Linder B, et al. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med 2012;366:2247–56.10.1056/NEJMoa1109333Search in Google Scholar PubMed PubMed Central
8. TODAY Study Group, Lynch J, El L, Fisher L, Gidding SS, et al. Rapid rise in hypertension and nephropathy in youth with type 2 diabetes. Diabetes Care 2013;36:1735–41.10.2337/dc12-2420Search in Google Scholar PubMed PubMed Central
9. TODAY Study Group, Drews KL, Levitsky LL, Danis RP, Tamborlane WV, et al. Retinopathy in youth with type 2 diabetes participating in the TODAY clinical trial. Diabetes Care 2013;36:1772–4.10.2337/dc12-2387Search in Google Scholar PubMed PubMed Central
10. TODAY Study Group, Wienstock RS, Caprio S, Copeland KC, Hirst K, et al. Lipid and inflammatory cardiovascular risk worsens over 3 years with type 2 diabetes. Diabetes Care 2013;36:1758–64.10.2337/dc12-2388Search in Google Scholar PubMed PubMed Central
11. Owens DR. Clinical evidence for the earlier initiation of insulin therapy in type 2 diabetes. Diabetes Technol Ther 2013;15:776–85.10.1089/dia.2013.0081Search in Google Scholar
12. Ryan EA, Imes S, Wallace C. Short term intensive insulin therapy in newly diagnosed type 2 diabetics. Diabetes Care 2004;27:1028–32.10.2337/diacare.27.5.1028Search in Google Scholar
13. Weng J, Li Y, Xu W, Shi L, Zhang Q, et al. Effects of intensive insulin therapy on beta cell function and glycemic control in patients with newly diagnosed type 2 diabetes: a multicenter randomized parallel-group trial. Lancet 2008;371:1753–60.10.1016/S0140-6736(08)60762-XSearch in Google Scholar
14. Harrison LB, Adams-Huet B, Raskin P, Lingvay I. Beta cell function preservation after 3.5 years of intensive insulin therapy. Diabetes Care 2012;35:1406–12.10.2337/dc11-2170Search in Google Scholar PubMed PubMed Central
15. Cryer PE. Hypoglycemia: the limiting factor in glycemic management of type 1 and type 2 diabetes. N Engl J Med 2009;360:129–39.Search in Google Scholar
16. UK Hypoglycemia Study Group. Risk of hypoglycemia in type 1and type 2 diabetes: effects of treatment modalities and their duration. Diabetologia 2007;50:1140–7.10.1007/s00125-007-0599-ySearch in Google Scholar PubMed
17. TODAY Study Group. Safety and tolerability of the treatment of youth-onset type 2 diabetes. Diabetes Care 2013;36:1765–71.10.2337/dc12-2390Search in Google Scholar PubMed PubMed Central
18. Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013;36:1384–95.10.2337/dc12-2480Search in Google Scholar PubMed PubMed Central
19. American Diabetes Association Workgroup on Hypoglycemia. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 2005;28:1245–9.10.2337/diacare.28.5.1245Search in Google Scholar PubMed
20. Cryer PE. Hypoglycemia in diabetes: pathophysiology, prevalence and prevention. Alexandria, VA: American Diabetes Association, 2009.Search in Google Scholar
21. The Diabetes Prevention Program Research Group. Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin. Diabetes 2005;54:2404–14.10.2337/diabetes.54.8.2404Search in Google Scholar PubMed PubMed Central
22. Giannini C, Weiss R, Cali A, Bonadonna R, Santoro N, et al. Evidence for early defects in insulin sensitivity and secretion before the onset of glucose dysregulation in obese youths: a longitudinal study. Diabetes 2012;61:606–14.10.2337/db11-1111Search in Google Scholar PubMed PubMed Central
23. Defronzo RA. From triumvirate to ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009;58:773–95.10.2337/db09-9028Search in Google Scholar PubMed PubMed Central
24. Felszeghy E, Juhasz E, Kaposzta R, Ilyes I. Alterations of glucoregulation in childhood obesity–association with insulin resistance and hyperinsulinemia. J Pediatr Endocrinol Metab 2008;21:847–53.10.1515/JPEM.2008.21.9.847Search in Google Scholar PubMed
25. Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev 2008;29:351–66.10.1210/er.2007-0023Search in Google Scholar PubMed PubMed Central
26. Cerf ME. Beta cell dysfunction and insulin resistance. Front Endocrinol 2013;4:1–12.10.3389/fendo.2013.00037Search in Google Scholar PubMed PubMed Central
27. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10 year follow up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577–89.10.1056/NEJMoa0806470Search in Google Scholar PubMed
28. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. Br Med J 2000;321:405–12.10.1136/bmj.321.7258.405Search in Google Scholar PubMed PubMed Central
29. Mancia G, Grassi G. Protection of patients with diabetes, with or without HTN: implications of ADVANCE for clinical practice. J Hypertens Suppl 2009;27:S19–23.10.1097/01.hjh.0000354420.23557.e2Search in Google Scholar PubMed
30. Leese GP, Wang J, Broomhall J, Kelly P, Marsden A, et al. Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population–based study of health service resource use. Diabetes Care 2003;26: 1176–80.10.2337/diacare.26.4.1176Search in Google Scholar PubMed
31. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545–59.10.1056/NEJMoa0802743Search in Google Scholar PubMed PubMed Central
32. Henry RR, Gumbiner B, Ditzler T, Wallace P, Lyon R, et al. Intensive conventional insulin therapy for type II diabetes: metabolic effects during a 6-mo outpatient trial. Diabetes Care 1993;16:21–31.10.2337/diacare.16.1.21Search in Google Scholar PubMed
33. Donadon V, Balbi M, Ghersetti M, Grazioli S, Perciaccante A, et al. Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease. World J Gastroenterol 2009;15:2506–11.10.3748/wjg.15.2506Search in Google Scholar PubMed PubMed Central
34. Dib K, Whitehead JP, Humphreys PJ, Soos MA, Baynes KC, et al. Impaired activation of phosphoinositide 3-kinase by insulin in fibroblasts from patients with severe insulin resistance and pseudoacromegaly: a disorder characterized by selective postreceptor insulin resistance. J Clin Invest 1998;101:1111–20.10.1172/JCI119884Search in Google Scholar PubMed PubMed Central
35. Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology 2009;137:482–8.10.1053/j.gastro.2009.04.013Search in Google Scholar PubMed PubMed Central
36. Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006;29:254–8.10.2337/diacare.29.02.06.dc05-1558Search in Google Scholar PubMed
37. Yang X, Ko GT, So WY, Ma RC, Yu LW, et al. Associations of hyperglycemia and insulin usage with the risk of cancer in type 2 diabetes: the Hong Kong diabetes registry. Diabetes 2010;59:1254–60.10.2337/db09-1371Search in Google Scholar PubMed PubMed Central
38. RISE Consortium. Restoring Insulin Secretion (RISE): design of studies of β-cell preservation in prediabetes and early type 2 diabetes across the life span. Diabetes Care 2014;37:780–8.10.2337/dc13-1879Search in Google Scholar PubMed PubMed Central
39. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest 2000;106:473–81.10.1172/JCI10842Search in Google Scholar PubMed PubMed Central
40. Lu H, Castells S, Hagerty D, Quintos JB. Study of glucose profiles with continuous glucose monitoring in adolescents with poorly controlled type 2 diabetes mellitus. J Pediatr Endocrinol Metab 2008;21:729–36.10.1515/JPEM.2008.21.8.729Search in Google Scholar PubMed
41. Nadeau KJ, Anderson BJ, Berg EG, Chiang JL, Chou H, et al. Youth onset type 2 diabetes consensus report: current status, challenges and priorities. Diabetes Care 2016;39:1635–42.10.2337/dc16-1066Search in Google Scholar PubMed PubMed Central
©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Congenital hypothyroidism
- Original Articles
- Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?
- Incidence of congenital hypothyroidism in China: data from the national newborn screening program, 2013–2015
- The etiologies and incidences of congenital hypothyroidism before and after neonatal TSH screening program implementation: a study in southern Thailand
- Current status of the congenital hypothyroidism neonatal screening program in Adana Province, Turkey
- Risk of hypoglycemia in youth with type 2 diabetes on insulin
- Metabolic risk factors in adolescent girls with type 1 diabetes
- Definition of reference ranges for β-isomerized carboxy-terminal telopeptide collagen type I for children and adolescents
- Brown adipose tissue in young adults who were born preterm or small for gestational age
- Circulating soluble RAGE and cell surface RAGE on peripheral blood mononuclear cells in healthy children
- Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate
- Trends in the use of puberty blockers among transgender children in the United States
- Initial presentations and associated clinical findings in patients with classical congenital adrenal hyperplasia
- Cardiac examination in children with Laron syndrome undergoing mecasermin therapy
- Five novel ALMS1 gene mutations in six patients with Alström syndrome
- Case Reports
- Cutaneous mucormycosis as a presenting feature of type 1 diabetes in a boy – case report and review of the literature
- Severe lactic acidosis in an extremely low birth weight infant due to thiamine deficiency
- Exertional rhabdomyolysis in carbonic anhydrase 12 deficiency
Articles in the same Issue
- Frontmatter
- Editorial
- Congenital hypothyroidism
- Original Articles
- Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?
- Incidence of congenital hypothyroidism in China: data from the national newborn screening program, 2013–2015
- The etiologies and incidences of congenital hypothyroidism before and after neonatal TSH screening program implementation: a study in southern Thailand
- Current status of the congenital hypothyroidism neonatal screening program in Adana Province, Turkey
- Risk of hypoglycemia in youth with type 2 diabetes on insulin
- Metabolic risk factors in adolescent girls with type 1 diabetes
- Definition of reference ranges for β-isomerized carboxy-terminal telopeptide collagen type I for children and adolescents
- Brown adipose tissue in young adults who were born preterm or small for gestational age
- Circulating soluble RAGE and cell surface RAGE on peripheral blood mononuclear cells in healthy children
- Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate
- Trends in the use of puberty blockers among transgender children in the United States
- Initial presentations and associated clinical findings in patients with classical congenital adrenal hyperplasia
- Cardiac examination in children with Laron syndrome undergoing mecasermin therapy
- Five novel ALMS1 gene mutations in six patients with Alström syndrome
- Case Reports
- Cutaneous mucormycosis as a presenting feature of type 1 diabetes in a boy – case report and review of the literature
- Severe lactic acidosis in an extremely low birth weight infant due to thiamine deficiency
- Exertional rhabdomyolysis in carbonic anhydrase 12 deficiency
