Clinical, Genetic Characteristics in Neonatal Diabetes Cohort Similar to Previous Data

Previous data have reported a high incidence rate of neonatal diabetes mellitus (NDM), a rare form of monogenic diabetes, in countries in the Middle East, at a rate of 1 in 21,000 - 29,000 live births.

Accordingly, investigators led by Revital Nimri, MD, The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, set out to describe the clinical characteristics, molecular genetics, and long-term follow-up of 24 patients with NDM from a single pediatric endocrine center in Israel.

They observed their cohort had comparable clinical and genetic characteristics to other populations, finding patients with transient NDM (TNDM) to be taller and heavier compared to those diagnosed with permanent NDM (PNDM), but both cohorts showing rapid catch-up growth to normal growth parameters.

Methods

Nimri and colleagues noted most cases in TNDM are explained through 1 of 4 mutations, including UDP 6, 6q24, and activating mutations in ABCC8 and KCNJ11 genes.

Through a survey of all registered cases of neonatal diabetes diagnosed and followed-up between January 1975 - June 2020 in the diabetes clinic, a total 24 cases were found which met diagnostic criteria for NDM.

Information was collected from medical files, including demographic data, neonatal anthropometric data, auxological data, clinical presentation and laboratory data at diagnosis. Additionally, information on treatment, diabetes complications, DKA and severe hypoglycemic events, comorbidities, and data on genetic analysis was collected.

Furthermore, investigators collected data on weight, height, and body mass index (BMI), expressed as SDS for the age range of 2 - 20 years old.

Then, the assessment of new-onset diabetes at diagnosis was based on glucose levels, blood gases, electrolytes, pancreatic autoantibodies, and hemoglobin A1 or A1c levels (HbA1c). The assessment of glycemic control included capillary HbA1c values measured through an automated immunochemical technique. All patients underwent screening for mutations in ABCC8, KCNJ11, and INS.

Findings

Out of the 24-patient cohort, 54.2% (n = 13) were male, with a mean birth weight SDS at -1.72 ± 1.62 and a mean gestational age of 38.2 ± 2.72 weeks.

Data then show 9 patients had TNDM and 15 patients had PNDM, including 4 patients with syndromic features and 1 having IPEX syndrome.

Additionally, Investigators observed the median height SDS of the TNDM cohort was significantly taller, in comparison to the PNDM cohort (-0.52, -0.67 to -0.09 versus. -0.9, -1.42 to -0.3; P = .035).

On the other hand, the mean weight SDS of the TNDM cohort was significantly heavier compared to the PNDM cohort (0.22 ± 0.69 versus -0.89 ± 1.22, P = .02). In terms of mean BMI, there was no difference found between the 2 cohorts, remaining within normal weight or lightweight categories.

Investigators observed 87.5% (n = 21) of the NDM patients had a specific gene mutation, with the compost common being ABCC8 in the TNDM subgroup. In the PNDM subgroup, all cases had a genetic etiology, with the most common being a mutation in the KCNJ11 and insulin genes.

In the management of the condition, data show the switch from insulin was successful for 5 of 9 patients (56%) of qualifying candidates for the transfer to off-label sulfonylurea therapy.

They observed severe hypoglycemia and diabetes ketoacidosis occurred in 8% (n = 2) of patients and chronic diabetes complications occurred in 21% (n = 5) patients were more than 10 years of NDM.

Takeaways

“NDM patients show rapid catch-up growth, normal childhood growth, and attainment of normal near adult height and weight,” investigators wrote. “Larger scale studies are needed to assess growth patterns in NDM and its subcategories.”

The study, “Clinical characteristics, growth patterns, and long-term diabetes complications of 24 patients with neonatal diabetes mellitus: a single center experience,” was published in Pediatric Diabetes.