Fasting glucose may be insufficient measure in pediatric pseudohypoparathyroidism 1a

BOSTON — Screening with fasting plasma glucose and HbA1c tests may miss impaired glucose tolerance in children with the rare monogenetic disorder pseudohypoparathyroidism type 1a, according to study results.

“In adult patients and in the mouse model, there’s some evidence that this disease causes early-onset insulin resistance and maybe an increased risk for type 2 diabetes,” presenter Ashley Hall Shoemaker, MD, MSCI, assistant professor of pediatrics at Vanderbilt University in Nashville, Tenessee, told Endocrine Today. “But when we previously studied this disease in children, we found normal fasting parameters; we didn’t see any evidence of early onset.”

Ashley Hall Shoemaker

Shoemaker and colleagues evaluated data from 13 patients with pseudohypoparathyroidism type 1a (PHP1a) aged 6 to 16 years (mean age, 11.2 years; 61.5% girls; all white; BMI z score 2.3, body fat 45.1%) and 25 controls (mean age 12.4 years; 57.7% girls; all white; BMI z score 2.3, body fat 48.1%). Researchers assessed insulin resistance with the homeostasis model assessment (HOMA) and insulin sensitivity with the quantitative insulin sensitivity check index (QUICKI). They administered the 75-g oral glucose tolerance test (OGTT) to 11 of the PHP1a participants and five controls.

Compared with controls, the PHP1a group had lower values for fasting glucose (90.3 vs. 77.2 mg/dL, P < .001), fasting insulin (21 vs. 13.9 mU/mL, P = .06) and HbA1c (5.4% vs. 5.2%, P = .10) as well as baseline insulin resistance (HOMA 4.6 vs. 2.6, P = .02). QUICKI insulin sensitivity was similar between groups. OGTT also indicated lower fasting glucose in the PHP1a subset (P < .001); however, the PHP1a subset had increased 2-hour glucose levels compared with controls (132.7 vs. 107.2 md/dL, P = .18). Type 2 diabetes was apparent in one patient with PHP1a (fasting glucose 82 mg/dL; 2-hour glucose 236 mg/dL; HbA1c 6.1%) and impaired glucose tolerance in three despite normal fasting glucose (range 77 – 78 mg/dL) and HbA1c (5.2% - 5.3%). All patients in the control group had normal glucose tolerance.

“It is important to evaluate patients with PHP1a for glucose intolerance, but typical screening labs — HbA1c, fasting glucose — may not be adequate. We recommend considering oral glucose tolerance testing in patients with PHP1a and obesity after onset of puberty,” Shoemaker said.

“We are finding glucose intolerance even in patients with normal fasting numbers in the 70s.” – by Jill Rollet

Reference :

Shoemaker AH, Perez KM. LBFri-18. Presented at: The Endocrine Society Annual Meeting; April 1-4, 2016; Boston.

Disclosure: Shoemaker reports serving on an advisory group for Zafgen, Inc.