Type 1 Diabetes

Type 1 diabetes is the most common chronic disease of childhood in the US and accounts for nearly 98% of cases of diabetes in children <10 years of age and over 87% of the cases in children 10-19 years of age.

The incidence of Type 1 diabetes among children <20 years of age in the US is about 2.2 per 1000 children, rising by 1.4% from 2002 to 2015, according to the SEARCH for Diabetes in Youth Study (SEARCH).

The increase in incidence was seen in almost all ages, sex, and race/ethnic groups. Incidence rates also vary substantially but overall are increasing across the globe. The lowest incidence of ~1 per 100,000 person-years is in China and parts of South America. In comparison, rates are much higher at 30 per 100,000 person-years in Caucasian populations of Sweden, Finland, and Sardinia.

Incidence of T1DM in the US is highest in non-Hispanic white children, although the change in incidence rates was higher in non-Hispanic blacks (2.7% per year), Hispanics (4% per year), and Asian/Pacific Islanders (4.4% per year). See Figure 3 for a comparison of incidence rates between Type 1 and Type 2 diabetes mellitus.

Assuming the current annual increase in incidence continues, the number of T1D and T2D could triple, or even quadruple, to 600, 000 and 85,000 US children, respectively by the year 2050 (Divers et al. 2020 and Lawrence et al., 2021).

In almost all cases, type 1 diabetes is caused by an autoimmune process leading to T-cell mediated destruction of the insulin-producing β-cells of the pancreatic islet cells.

The autoimmune process is thought to be due to an unknown environmental trigger in those with a concomitant genetic susceptibility conferred by specific major histocompatibility complex (MHC) HLA-subtypes (DR/DQ haplotypes) on chromosome 6. While there is a genetic component to T1DM risk, only 10-20% of individuals diagnosed with T1DM have a family member with T1DM. The environmental component is suggested by the results of monozygotic twin concordance studies in which only 30-40% of initially unaffected twins develop diabetes when followed to 20 or 30 years of age.

Studies conducted through TrialNet are aimed at the prevention of Type 1 diabetes. These studies have pushed for a further distinction of Type 1 diabetes by “stages” by where an individual is identified on the spectrum of disease progression (Chiang et al., 2018 and Besser et al., 2022). Explore Figure 1 for more information!

Figure 1 – Shows the progression and stages of Type 1 diabetes. This figure and the associated information are adapted from https://www.trialnet.org/t1d-facts.

Symptoms of diabetes mellitus were discussed previously and include polyuria, polydipsia, polyphagia, and weight loss.

In Type 1 diabetes, these symptoms usually present on acute (days) to subacute (weeks to a few months) timeframes.

Up to 40% of children with Type 1 diabetes present with varying degrees of DKA severity.

Physical exam finds are usually limited to complications of progressive dehydration and acidosis.

• While acanthosis nigricans (AN) is more likely to be absent in those with Type 1 diabetes, Calcaterra et al. (2021) show that the prevalence of acanthosis nigricans is greater in children with Type 1 diabetes compared to healthy controls and is associated with older age and presence of obesity. Yet another factor complicating the clinical differentiation of T1DM from T2DM.

The diagnostic criteria for diabetes were discussed previously. Additional second-tier laboratory testing should be obtained to further distinguish between Type 1 and Type 2 diabetes.

Laboratory results that help define the diagnosis of Type 1 diabetes include:

• Positive islet/β-cell autoimmune antibodies include:
  • Glutamic acid decarboxylase antibodies (GAD Ab)
  • IA-2 Antibodies
  • Insulin antibodies
  • Islet cell antibodies
  • +/- Zinc transporter antibodies
• Low or inappropriately normal levels of:
  • o C-peptide (the endogenous cleavage product of pro-insulin, secreted in a 1:1 ratio upon insulin release)
  • o Total insulin (a measure of endogenous insulin)
    • Note: Total insulin levels should not be obtained in individuals who have already been started on exogenous insulin via injections or continuous infusion (i.e. an insulin drip).

Optimal management of Type 1 diabetes requires:

As Type 1 diabetics have insulin deficiency, the mainstay of treatment is insulin replacement therapy by using basal/bolus insulin regimens AND close monitoring of glucose. The overall goal of treatment is to mimic the physiologic production of insulin by the pancreas.

Basal/Bolus insulin regimens:

Discussed in greater detail in Unit 2.

Different routes of insulin administration can be achieved by these regimens:

In the following matching game, match the pictures of the diabetes devices at the periphery with the correct label:

Whichever route of insulin administration is chosen, it is then combined with a method of glucose monitoring which can be achieved by:

As seen in the table below, each insulin delivery method can be combined with various glucose monitoring methods. This allows endocrinologists to customize insulin therapy and glucose monitoring to the needs of the individual patient and their family in a way that optimizes their ability to attain the goals of insulin therapy.

Glucose monitoring methods are discussed in greater detail in Unit 6.

1.  Besser, R. E. J., Bell, K. J., Couper, J. J., Ziegler, A.-G., Wherrett, D. K., Knip, M., . . . Haller, M. J. (2022). ISPAD Clinical Practice Consensus Guidelines 2022: Stages of type 1 diabetes in children and adolescents. Pediatric Diabetes, 23(8), 1175-1187. doi:https://doi.org/10.1111/pedi.13410
2. Calcaterra, V., De Silvestri, A., Schneider, L., Acunzo, M., Vittoni, V., Meraviglia, G., . . . Mameli, C. (2021). Acanthosis Nigricans in Children and Adolescents with Type 1 Diabetes or Obesity: The Potential Interplay Role between Insulin Resistance and Excess Weight. Children (Basel), 8(8). doi:10.3390/children8080710
3. 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;41(9):2026-2044. doi: 10.2337/dci18-0023. Epub 2018 Aug 9. PMID: 30093549; PMCID: PMC6105320.
4. Divers J, Mayer-Davis EJ, Lawrence JM, Isom S, Dabelea D, Dolan L, Imperatore G, Marcovina S, Pettitt DJ, Pihoker C, Hamman RF, Saydah S, Wagenknecht LE. Trends in Incidence of Type 1 and Type 2 Diabetes Among Youths – Selected Counties and Indian Reservations, United States, 2002-2015. MMWR Morb Mortal Wkly Rep. 2020 Feb 14;69(6):161-165. doi: 10.15585/mmwr.mm6906a3. PMID: 32053581; PMCID: PMC7017961.
5. Lawrence, J. M., Divers, J., Isom, S., Saydah, S., Imperatore, G., Pihoker, C., . . . Liese, A. D. (2021). Trends in Prevalence of Type 1 and Type 2 Diabetes in Children and Adolescents in the US, 2001-2017. JAMA, 326(8), 717-727. doi:10.1001/jama.2021.11165