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How Are Familial and Sporadic Type 1 Diabetes Different?

  • Authors: News Author: Mitchel L. Zoler, PhD; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 6/6/2022
  • Valid for credit through: 6/6/2023
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

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Target Audience and Goal Statement

This activity is intended for diabetologists/endocrinologists, family medicine, primary care clinicians, nurses/nurse practitioners, physician assistants, pediatricians, pharmacists and other members of the health care team for patients with type 1 diabetes (T1D).

The goal of this activity is for learners to be better able to describe differences in course, prevalence of comorbidities and diabetes-related complications, treatment, and outcomes in familial vs sporadic T1D (T1D), according to an analysis of a US cohort enrolled in the T1D Exchange Clinic Registry and of a European population-based cohort.

Upon completion of this activity, participants will:

  • Describe demographic and phenotypic factors and comorbid conditions associated with familial or sporadic T1D according to data from a large US cohort enrolled in the T1D Exchange Clinic Registry
  • Determine the natural course, treatment, and outcomes in familial vs sporadic T1D, according to findings of a population-based cohort from Germany, Austria, Switzerland, and Luxembourg
  • Outline implications for the healthcare team


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News Author

  • Mitchel L. Zoler, PhD

    Freelance writer, Medscape


    Disclosure: Mitchel L. Zoler, PhD, has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC


    Disclosure: Laurie Barclay, MD, has disclosed the following relevant financial relationships:
    Stocks, stock options, or bonds: AbbVie Inc. (former)

Editor/Compliance Reviewer

  • Lisa Simani, APRN, MS, ACNP

    Associate Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Lisa Simani, APRN, MS, ACNP, has disclosed no relevant financial relationships.

Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

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This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.

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In support of improving patient care, Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

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How Are Familial and Sporadic Type 1 Diabetes Different?

Authors: News Author: Mitchel L. Zoler, PhD; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 6/6/2022

Valid for credit through: 6/6/2023


Clinical Context

Estimated prevalence of familial type 1 diabetes (T1D) varies from 5% to 12.2%, according to a recent report comparing familial and sporadic T1D among young patients, published in May 2021 in Diabetes Care.[1] First-degree relatives are ideal candidates for T1D prevention strategies because of high lifetime diabetes risk and easy identification.

Study Synopsis and Perspective

Evidence is accumulating that for patients with T1D who have a family history of it -- defined as having at least 1 first-degree relative with T1D -- the disease is often substantially different from that of people with sporadic T1D who have no family background.

The most striking difference: Familial cases are associated with many more comorbidities.

Researchers hope that a better understanding how familial and sporadic diabetes differ will yield new insights into how to best tailor treatments for patients with T1D in the future.

Among persons with familial disease, prevalence rates of hypertension, hyperlipidemia, atherosclerosis, retinopathy/maculopathy/vitreopathy (RMV), erectile and sexual dysfunction, gastroesophageal reflux disease (GERD), neuropathy, and nephropathy were significantly higher, as were rates of several other comorbidities.

In contrast, people with sporadic cases of T1D were significantly more likely to have no comorbidities. Several of the comorbidities among the familial patients clustered in groups of 2 or 3 in the studied cohort. The researchers identified these prevalence patterns using a specially designed analytic, data-mining algorithm.

7% of Type 1 Diabetes Cases Are Familial: Differences in Autoimmune Disease

The findings open a new dimension in the growing appreciation of how sporadic and familial cases differ. A 2021 report from Europe that involved assessment of a population-based registry with more than 57,000 children and teenagers with T1D from Germany, Austria, Switzerland, and Luxembourg[1] documented a familial prevalence of approximately 7% of the entire pediatric cohort.

The 2021 report also showed that familial disease showed up earlier. The average age of children with familial disease was 7.9 years compared with 9.7 years among children with sporadic disease. Among the patients with familial disease, there was a higher prevalence of associated autoimmune comorbidity and indications of more aggressive autoimmunity.

The researchers found that autoimmune diseases occurred in 16.7% of patients with familial T1D compared with 13.6% of patients with sporadic disease, a significant, 23% relative difference. Among the autoimmune diseases assessed, celiac disease showed the largest between-group difference, with a 6.2% prevalence among patients with familial T1D compared with a 4.2% prevalence among patients with sporadic disease.

The results in these 2 reports plus other findings suggest that the differences in risk profiles among patients with sporadic disease and patients with familial T1D are related to the "pathways of autoimmunity and inflammation" that help determine the "glycemic trajectory of the disease" and also influence "complications of abnormal glycemic control" in patients with familial disease, said Mark A. Clements, MD, PhD, a pediatric endocrinologist at Children's Mercy Hospital in Kansas City, Missouri, who co-authored the more recent US report.

Beyond One Size-Fits-All Type 1 Diabetes Care

Although Clements stressed that his group's findings are preliminary and need confirmation and validation with other datasets, they pointed toward an eventual end to the current practice of "applying the same care paradigm to all patients with [T1D]," he said in an interview.

A goal is to distinguish patients with familial and patients with sporadic forms with distinct multivariable risk models, he added. An attraction of the artificial intelligence method he and his associates applied is that it can potentially find "important patterns [of linked comorbidities] that people cannot see."

Stepped-Up Screening

The higher prevalence of autoimmune diseases in patients with familial disease suggests the potential for personalized screening for associated autoimmune diseases, Karges suggested in an interview.

"Regular screening for autoimmune thyroid and celiac disease may lead to earlier detection and treatment of comorbidities and improve patient care," Karges noted.

The study run by Clements and his associates (Tallon et al) used patients selected from the T1D Exchange Clinic Registry,[3] which enrolled more than 34,000 US residents with T1D during 2007 to 2018 at any of 83 US endocrinology practices. The researchers selected for their study a disproportionately high percentage of people with familial disease, 24% of the 16,232 individuals studied. Clements noted that the approximately 7% prevalence of familial T1D seen in the study led by Karges is a much better approximation of how often familial cases arise.

The Karges study used data compiled in the Diabetes Prospective Follow-up Registry,[4] based at Ulm University, Germany, with patients enrolled during 1995 to 2018.

A key difference between the US and European studies is that the US database included a significant minority of people with adult-onset T1D whereas the Karges' study exclusively focused on T1D in which onset occurred during childhood or adolescence.

Important differences in diet, activity, and other lifestyle and cultural factors also likely distinguish the US-based study and the one that involved patients from Central Europe, Clements noted.

Neither study received commercial funding. Clements is chief medical officer for Glooko and has received research support from Abbott Diabetes Care and Dexcom. Karges has disclosed no relevant financial relationships.

Study Highlights

  • Clements and colleagues (Tallon et al) applied an artificial intelligence algorithm to their T1D Exchange Clinic Registry cohort of 34,013 adult and pediatric participants receiving clinical care at 83 US-based endocrinology practices between July 2007 and April 2018.
  • Participants > 50 years were excluded to balance distribution of age and diabetes duration across subgroups.
  • Of 16,232 individuals meeting inclusion criteria, 3941 (24.3%) had familial and 12,291 sporadic T1D.
  • Conditions significantly enriched in familial vs sporadic T1D included hypertension, hyperlipidemia/dyslipidemia, atherosclerosis, RMV, erectile and sexual dysfunction, GERD, neuropathy, and nephropathy.
  • A higher proportion with familial vs sporadic T1D were non-Hispanic Black (6.3% vs 4.1%).
  • Sporadic vs familial T1D was more frequently associated with absence of comorbidities, Asian race, Hispanic ethnicity, and diagnosis at ages 5 to 9, 10 to 12, and 13 to 18 years.
  • Hyperlipidemia/dyslipidemia and hypertension co-occurred in 7% of familial T1D but only 4.4% of sporadic T1D; RMV and hyperlipidemia/dyslipidemia in 5% vs 3.1%, respectively.
  • Unlike most previous studies, this study did not exclude patients diagnosed with T1D as adults.
  • Karges’ population-based study compared patients (N = 57,371) with familial (6.6%) vs sporadic T1D (93.4%), onset age < 20 years, identified from the Diabetes Prospective Follow-up Registry between 1995 and 2018.
  • Familial vs. sporadic T1D was associated with younger age (median 7.9 vs. 9.7 years), lower ketoacidosis prevalence (11.9% vs. 20.4%), lower HbA1c levels (9.7% vs. 11.1%) at onset and higher prevalence of comorbid autoimmune disease (16.7% vs. 13.6%; P<.001 for all).
  • Celiac disease had the largest between-group difference (6.2% vs. 4.2%).
  • Over 10 years, patients with familial vs sporadic diabetes more often used insulin pumps (P < .001) and had a lower proportion with severe hypoglycemia (12.97 vs 14.44/100 patient-years; P < .001) but had similar HbA1c levels (P ≥ .08) and ketoacidosis rates (1.85 vs 2.06/100 patient-years; P = .11).
  • In familial and sporadic T1D, absence of ketoacidosis at onset predicted fewer events of severe hypoglycemia (hazard ratio [HR] 0.67, P<.001, and 0.91, P<.001, respectively) and of ketoacidosis (0.64, P=.007, and 0.66, P<.001, respectively) after 10 years.
  • Higher autoimmune disease prevalence in patients with familial T1D suggests the potential for regular screening for autoimmune thyroid and celiac disease, which could improve patient care by earlier detection and treatment.
  • After following an index-case diagnosis, clinicians for patients with T1D should recognize and potentially act on higher risk in close relatives.

Clinical Implications

  • In a large US cohort, sporadic vs familial T1D was more frequently associated with absence of comorbidities.
  • In a European study, familial vs sporadic T1D was characterized by earlier disease manifestation, higher autoimmune comorbidity, and less metabolic decompensation at onset.
  • Implications for the Healthcare Team: The results may affect generalizability of findings of diabetes prevention trials from patients with familial T1D to patients with sporadic T1D.


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