OR14-3 Disrupted circadian rhythm in catecholamines in youth-onset Type 2 Diabetes
Authors: Armstrong Sarah , Bain James R , Crawford Matthew , Freemark Michael , Grant Russell P , Gumus Balikcioglu Pinar , Hsia Daniel S , Jain Nina , Muehlbauer Michael , Ramaker Megan , Blew Kathryn 
Published: November 2022

Abstract

Objectives
In healthy, normal - weight adults there is a circadian rhythm in blood pressure (BP) and plasma catecholamines (epinephrine and norepinephrine): BP and the levels of norepinephrine and epinephrine decline during sleep, followed by a rapid increase during the early morning hours. Studies in adults with Type 2 diabetes (T2D) show blunted reductions in BP and plasma catecholamine levels during sleep that are associated with increased risks for heart failure, stroke, myocardial infarction, and sudden death. In this study, we explored if the circadian rhythm in catecholamines is disrupted in youth-onset T2D. We hypothesized that increased sympatho-adrenal activity during sleep differentiates youth with T2D from non-diabetic overweight/obese and lean youth of comparable age, pubertal status, and ethnicity. To that end, we measured urine catecholamines in fasting – morning-spot urines and 24-hour urine samples.

Methods
56 non-diabetic adolescents with overweight/obesity ("obese"), 42 adolescents with T2D ("T2D"), and 43 normal-weight controls ("lean"); aged 12-21 years, were studied. None was diagnosed with hypertension, and none was on antihypertensive treatment. Weight, height, BMI, BMI%, and BP were extracted from medical charts. Body fat percent (BF%) was measured by TANITA. Stress levels were assessed using PHQ-2 and PHQ-9 questionnaires. Fractionated free urine catecholamines (epinephrine, norepinephrine, and dopamine) were analyzed by liquid chromatography/tandem mass spectrometry (LC/MS-MS) in both spot and 24-hour urines, normalized to urinary creatinine. The ratio of fasting morning urine catecholamines to 24-hour urine catecholamines was calculated to assess circadian variation in catecholamines. Group differences were assessed by Kruskal-Wallis or ANOVA.

Results
Groups were comparable for age (obese 14.8 +/- 1.9; T2D 15.7 +/- 2.1 and lean 14.9 +/- 1.9-yr), pubertal status, and ethnicity. Obese youth with and without T2D were predominantly female (T2D, 28 F, 14 M; obese 33 F, 23 M; lean, 17 F, 26 M); those with T2D had highest BF% (obese 37.3 +/- 9.5; T2D 42.9 +/- 9.9; lean 20.1 +/- 6.3%; p=2.58e-22) and systolic blood pressure (obese 115.36 +/- 11.54; T2D 127.83 +/- 12.08 and lean 111.65 +/- 9.13 mmHg; p=5.49e-10). Fractionated free urine catecholamines (epinephrine, norepinephrine and dopamine) were comparable across groups in 24-hour urines. However, fasting morning epinephrine levels and the ratio of fasting morning/24-hour epinephrine were higher in T2D (p=0.0035, and p=0.035, respectively) than in either lean or nondiabetic youth with obesity. There were no differences in morning urine catecholamines between lean controls and non-diabetic youth with obesity.

Conclusions
Our results suggest a disrupted circadian rhythm in catecholamines in youth-onset T2D, with a blunted overnight fall in epinephrine levels. Higher levels of epinephrine levels at night in youth with T2D might be associated with, or predispose to, hypertension and long-term cardiovascular complications.
Presentation: Sunday, June 12, 2022 11:30 a.m. - 11:45 a.m.