Glucose Homeostasis and Energy Balance in Children With Pseudohypoparathyroidism

Abstract

Context: Pseudohypoparathyroidism (PHP) is a rare genetic disorder characterized by early-onset obesity and multihormone resistance. To treat abnormal weight gain and prevent complications such as diabetes, we must understand energy balance and glucose homeostasis in PHP types 1A and 1B.

Objective: The aim of this study was to evaluate food intake, energy expenditure, and glucose homeostasis in children with PHP.

Design: Assessments included resting energy expenditure (REE), physical activity, food intake, sucrose preference, questionnaires, endocrine status, and auxological status. All patients underwent an oral glucose tolerance test (OGTT).

Setting: Vanderbilt University Medical Center.

Patients: We assessed 16 children with PHP1A, three with PHP1B, and 15 healthy controls.

Main outcome measures: Food intake during an ad lib buffet meal and glucose at five time points during OGTT.

Results: PHP1A and control groups were well matched. Participants with PHP1A had significantly lower REE without concomitant change in food intake or physical activity. At baseline, participants with PHP1A had significantly lower fasting glucose and insulin resistance. During OGTT, participants with PHP1A had significantly delayed peak glucose and a slower rate of glucose decline despite similar oral glucose insulin sensitivity. Participants with PHP1A had 0.46% lower HbA1c levels than controls from a clinic database after adjustment for OGTT 2-hour glucose. The PHP1B group was similar to the PHP1A group.

Conclusions: In contrast to other monogenic obesity syndromes, our results support reduced energy expenditure, not severe hyperphagia, as the primary cause of abnormal weight gain in PHP. Patients with PHP are at high risk for dysglycemia without reduced insulin sensitivity.

Figures

Figure 1.

Results of a 75-g OGTT in children 8 to 18 y old. Circles and solid line: PHP1A. Squares and dashed line: matched controls. Results presented as mean ± SD. *P < 0.05 by repeated-measures ANOVA.

Figure 2.

Comparison of HbA1c and 2-h blood glucose after a 75-g OGTT. Circles and solid line: PHP1A. Squares and dashed line: controls from the Vanderbilt Prediabetes Clinic. Controlling for the 2-h blood glucose, on average the PHP1A group had an HbA1c 0.46 points lower than controls (95% CI −0.28 to −0.65, P < 0.001), and there was no difference in the slopes of the regression lines (P = 0.91).

Figure 3.

REE is lower in patients with PHP than in controls and is persistent over time. Open squares, triangles, and diamonds each represent a patient with PHP1A measured at two time points [during this study and 6 y earlier (10)]. Solid black circles and line represent the other 12 patients with PHP1A in this study. Open circles represent three patients with PHP1B. Solid gray diamonds and line represent control patients from both studies.