Three months of melatonin treatment reduces insulin sensitivity in patients with type 2 diabetes - a randomized placebo-controlled crossover trial

TY - JOUR

T1 - Three months of melatonin treatment reduces insulin sensitivity in patients with type 2 diabetes - a randomized placebo-controlled crossover trial

AU - Lauritzen, Esben S

AU - Kampmann, Ulla

AU - Pedersen, Mette G B

AU - Christensen, Lise-Lotte

AU - Jessen, Niels

AU - Møller, Niels

AU - Støy, Julie

N1 - This article is protected by copyright. All rights reserved.

PY - 2022/8

Y1 - 2022/8

N2 - The use of the sleep-promoting hormone melatonin is rapidly increasing as an assumed safe sleep aid. During the last decade, accumulating observations suggest that melatonin affects glucose homeostasis, but the precise role remains to be defined. We investigated the metabolic effects of long-term melatonin treatment in patients with type 2 diabetes including determinations of insulin sensitivity and glucose-stimulated insulin secretion. We used a double-blinded, randomized, placebo-controlled, crossover design. Seventeen male participants with type 2 diabetes completed (1) 3 months of daily melatonin treatment (10 mg) 1 h before bedtime (M) and (2) 3 months of placebo treatment 1 h before bedtime (P). At the end of each treatment period, insulin secretion was assessed by an intravenous glucose tolerance test (0.3 g/kg) (IVGTT) and insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp (insulin infusion rate 1.5 mU/kg/min) (primary endpoints). Insulin sensitivity decreased after melatonin (3.6 [2.9–4.4] vs. 4.1 [3.2–5.2] mg/(kg × min), p =.016). During the IVGTT, the second-phase insulin response was increased after melatonin (p =.03). In conclusion, melatonin treatment of male patients with type 2 diabetes for 3 months decreased insulin sensitivity by 12%. Clinical use of melatonin treatment in dosages of 10 mg should be reserved for conditions where the benefits will outweigh the potential negative impact on insulin sensitivity.

AB - The use of the sleep-promoting hormone melatonin is rapidly increasing as an assumed safe sleep aid. During the last decade, accumulating observations suggest that melatonin affects glucose homeostasis, but the precise role remains to be defined. We investigated the metabolic effects of long-term melatonin treatment in patients with type 2 diabetes including determinations of insulin sensitivity and glucose-stimulated insulin secretion. We used a double-blinded, randomized, placebo-controlled, crossover design. Seventeen male participants with type 2 diabetes completed (1) 3 months of daily melatonin treatment (10 mg) 1 h before bedtime (M) and (2) 3 months of placebo treatment 1 h before bedtime (P). At the end of each treatment period, insulin secretion was assessed by an intravenous glucose tolerance test (0.3 g/kg) (IVGTT) and insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp (insulin infusion rate 1.5 mU/kg/min) (primary endpoints). Insulin sensitivity decreased after melatonin (3.6 [2.9–4.4] vs. 4.1 [3.2–5.2] mg/(kg × min), p =.016). During the IVGTT, the second-phase insulin response was increased after melatonin (p =.03). In conclusion, melatonin treatment of male patients with type 2 diabetes for 3 months decreased insulin sensitivity by 12%. Clinical use of melatonin treatment in dosages of 10 mg should be reserved for conditions where the benefits will outweigh the potential negative impact on insulin sensitivity.

KW - indirect calorimetry

KW - insulin secretion

KW - insulin sensitivity

KW - insulin signaling and rs10830963

KW - melatonin

KW - sleep

KW - SLEEP

KW - VARIANTS

KW - MUSCLE

KW - DISORDERS

KW - SUPPLEMENTATION

KW - RESISTANCE

KW - INDEX

KW - SECRETION

KW - GLUCOSE-TOLERANCE

KW - Melatonin/therapeutic use

KW - Humans

KW - Male

KW - Glucose

KW - Insulin/metabolism

KW - Double-Blind Method

KW - Blood Glucose/metabolism

KW - Insulin Resistance

KW - Cross-Over Studies

KW - Diabetes Mellitus, Type 2/drug therapy

U2 - 10.1111/jpi.12809

DO - 10.1111/jpi.12809

M3 - Journal article

C2 - 35619221

SN - 0742-3098

VL - 73

JO - Journal of Pineal Research

JF - Journal of Pineal Research

IS - 1

M1 - e12809

ER -