Authors found that prevalence of monogenic diabetes was higher at 6.3% then previously estimated among pediatric population (number one cause being diabetes type 1). MODY composed majority 87% of these cases. Proper genetic diagnosis is important as some children could be treated with sulfonyluria rather then daily insulin injections.
J C E M
Context: Cause of diabetes can affect the therapeutic strategy and prognosis of chronic complications.
Objective: The aim of the present study was to establish the relative percentage of different diabetes subtypes in patients attending Italian pediatric diabetes centers and the influence of an etiologic diagnosis on therapy.
Design, Setting, and Patients: This was a retrospective study. The clinical records of 3781 patients (age, 0-18 years) referred to 15 pediatric diabetes clinics with a diagnosis of diabetes or impaired fasting glucose from January 1, 2007 – December 31, 2012 were examined. The clinical features of the patients at their first referral to the centers, type 1 diabetes-related autoantibodies, molecular genetics records, and C-peptide measurements, if requested for the etiologic diagnosis, were acquired.
Main Outcome Measures: The primary outcome was to assess the percentage of each diabetes subtype in our sample.
Type 1 diabetes represented the main cause (92.4%) of diabetes in this group of patients.
Followed by MONOGENIC diabetes, which accounted for 6.3% of cases (5.5% MODY + 0.6% neonetal + 0.2% genetic syndromes).
Type 2 diabetes was diagnosed in 1% of the patients.
A genetic diagnosis prompted the transfer from insulin to sulphonylureas in 12 patients bearing mutations in the HNF1A or KCNJ11 genes.
Monogenic diabetes is highly prevalent in patients referred to Italian pediatric diabetes centers. A genetic diagnosis guided the therapeutic decisions, allowed the formulation of a prognosis regarding chronic diabetic complications for a relevant number of patients (i.e.,GCK / MODY), and helped to provide genetic counseling.
More from the publication:
Type 1 diabetes (T1D) is the most prevalent cause of diabetes in the youth in North America and Europe. In contrast, in other continents and countries (e.g., China), a much lower annual incidence has been reported. However, the relative percentage in the Western world of other forms of diabetes in children and adolescents, such as type 2 diabetes and monogenic diabetes, seems to vary greatly; this might be because of a number of reasons, including errors in clinical diagnosis. The identification of the exact etiologic cause of diabetes is important, because it can direct therapeutic decisions and influence genetic counseling.
The aim of the present study was to assess the prevalence of the different etiologies of diabetes mellitus in a large group of patients aged <18 years at diagnosis and referred to tertiary diabetes centers representative of peninsular Italy. Our data have shown that monogenic diabetes is the second prevailing cause of diabetes after T1D in Italian youth and that the correct etiologic diagnosis greatly affects the treatment and likely the prognosis of diabetic complications.
The present results show that monogenic diabetes accounts for ≥6.3% of all patients presenting to pediatric diabetes clinics for diabetes or IFG.
Also, MODY alone, at 5.5%, represents the second prevailing cause of hyperglycemia after T1D in Italian youth. The prevalence of MODY, the most common cause of monogenic diabetes, has currently been estimated at 1-2% of diabetes cases. If we exclude those patients classified with IFG, the MODY mutations represented about 1.85% of our data set, a percentage in line with the calculation of the MODY quota in patients with diabetes by Fajans and Bell. Nevertheless, it should be remembered that patients carrying GCK mutations, even if their fasting plasma glucose exceeds the threshold for diabetes, are almost invariably asymptomatic. Thus, decision making about genetic testing should not only rely on symptoms or signs of diabetes but also on careful clinical evaluation of any infant with a fasting plasma glucose level chronically >100 mg/dL.
In this context, the usefulness of T1D-related autoantibodies as a first step in the diagnostic process is shown by the results from the present study. The patients in our study presenting with IFG had no positive results from autoantibody testing. These findings have confirmed previous findings from the Italian Society of Pediatric Endocrinology and Diabetology diabetes study group showing that in a group of 748 patients with incidental hyperglycemia (>100 mg/dL; twice), 10%, 4.6%, and 4.9% tested positive for ICA, GADA, and IA-2A, respectively, some of whom developed full-blown T1D within 42 months.
MODY/NDM patients carrying mutations in specific genes (e.g.,HNF1A, HNF4A, KCNJ11, and ABCC8) can respond to SUs or mitiglinides. The switch to SUs was successful in all patients with HNF1A mutations identified in the present study, except for one. This result seems pertinent, considering that the guidelines from the International Society for Pediatric and Adolescent Diabetes promoting the switch from insulin to SU or mitiglinides in patients diagnosed with HNF1A/MODY are not always carefully followed.
In conclusion, in this large sample of patients referred to tertiary pediatric diabetes clinics scattered throughout Italy, the diagnosis of monogenic diabetes cases confirmed by genetic testing reached 6.3%, two full percentage points beyond the highest estimated data published to date.