Disrupted Circadian Rhythm of Epinephrine in Males With Youth-Onset Type 2 Diabetes

Abstract

Context: Blood pressure and plasma catecholamines normally decline during sleep and rapidly increase in early morning. This is blunted in adults with type 2 diabetes (T2D).

Objective: We hypothesize that increased sympatho-adrenal activity during sleep differentiates youth with T2D from nondiabetic obese youth and lean youth.

Methods: Fasting spot morning and 24-hour urines were collected in obese adolescents with and without T2D, and normal-weight controls. Fractionated free urine catecholamines (epinephrine, norepinephrine, and dopamine) were measured, and the ratio of fasting spot morning to 24-hour catecholamines was calculated.

Results: Urinary 24-hour catecholamine levels were comparable across the 3 groups. Fasting morning epinephrine and the ratio of fasting morning/24-hour epinephrine were higher in youth with T2D (P = 0.004 and P = 0.035, respectively). In males, the ratio of fasting morning/24-hour epinephrine was also higher in youth with T2D (P = 0.005). In females, fasting morning norepinephrine and the ratio of fasting morning/24-hour dopamine were lower in obese youth with and without T2D (P = 0.013 and P = 0.005, respectively) compared with lean youth. Systolic blood pressure was higher in diabetic participants than other groups; males trended higher than females.

Conclusion: Circadian rhythm in catecholamines is disrupted in youth-onset T2D, with a blunted overnight fall in urinary epinephrine in males. Conversely, fasting morning norepinephrine and dopamine levels were lower in obese females with or without T2D. Higher nocturnal catecholamines in males with T2D might associate with, or predispose to, hypertension and cardiovascular complications. Lower catecholamine excretion in females with obesity might serve an adaptive, protective role.

Keywords: catecholamine; circadian rhythm; type 2 diabetes.

Figure 1.

A, Fasting spot morning epinephrine levels across the 3 groups (lean, obese, T2D). B, Ratio of fasting spot morning/24-hour epinephrine across the 3 groups (lean, obese, T2D).

Figure 2

. A, Fasting spot morning epinephrine levels in males across the 3 groups (lean, obese, T2D). B, Ratio of fasting spot morning/24-hour epinephrine in males across the 3 groups (lean, obese, T2D).

Figure 3.

A, Fasting spot morning norepinephrine levels in females across the 3 groups (lean, obese, T2D). B, Ratio of fasting spot morning/24-hour dopamine in females across the 3 groups (lean, obese, T2D).