Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial
Purpose Monogenic diabetes accounts for 1–2% of diabetes cases. It is often undiagnosed, which may lead to inappropriate treatment. This study was performed to estimate the prevalence of monogenic diabetes in a cohort of overweight/obese adolescents diagnosed with type 2 diabetes (T2D). Methods Sequ...
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Veröffentlicht in: | Genetics in medicine 2018-06, Vol.20 (6), p.583-590 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Purpose
Monogenic diabetes accounts for 1–2% of diabetes cases. It is often undiagnosed, which may lead to inappropriate treatment. This study was performed to estimate the prevalence of monogenic diabetes in a cohort of overweight/obese adolescents diagnosed with type 2 diabetes (T2D).
Methods
Sequencing using a custom monogenic diabetes gene panel was performed on a racially/ethnically diverse cohort of 488 overweight/obese adolescents with T2D in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial. Associations between having a monogenic diabetes variant and clinical characteristics and time to treatment failure were analyzed.
Results
More than 4% (22/488) had genetic variants causing monogenic diabetes (seven
GCK
, seven
HNF4A
, five
HNF1A
, two
INS
, and one
KLF11
). Patients with monogenic diabetes had a statistically, but not clinically, significant lower body mass index (BMI)
z
-score, lower fasting insulin, and higher fasting glucose. Most (6/7) patients with
HNF4A
variants rapidly failed TODAY treatment across study arms (hazard ratio = 5.03,
P
= 0.0002), while none with
GCK
variants failed treatment.
Conclusion
The finding of 4.5% of patients with monogenic diabetes in an overweight/obese cohort of children and adolescents with T2D suggests that monogenic diabetes diagnosis should be considered in children and adolescents without diabetes-associated autoantibodies and maintained C-peptide, regardless of BMI, as it may direct appropriate clinical management. |
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ISSN: | 1098-3600 1530-0366 1530-0366 |
DOI: | 10.1038/gim.2017.150 |