In a 12 week double-blind, placebo-controlled randomized trial, 120 subjects with obesity
(BMI≥30 kg/m2) and pre-diabetes (HbA1c, 5.7-6.4%) will be randomly assigned 1:1 to receive
either placebo or 2 mg of controlled-release melatonin, taken orally every evening 1 hour
before bed. The investigators will assess melatonin's effect on insulin sensitivity by
performing a hyperinsulinemic euglycemic glucose clamp and β-islet cell function measured
using a hyperglycemic clamp, as a primary endpoint. The investigator will also evaluating
melatonin supplementation's effect on mean 24-hour ambulatory blood pressure, nocturnal blood
pressure, and potential intermediates including endothelial function using brachial
ultrasound, catecholamine production using 24-hour epinephrine and norepinephrine excretion,
and renin-angiotensin system activation using measurements of plasma renin activity,
angiotensin II, and urine aldosterone excretion. The final endpoint will be to evaluate
melatonin supplementation's effect on cellular cytokine and CC family chemokine expression as
well as high sensitivity C-reactive protein, IL-6, and TNF-α.
There will be a 24 week cohort phase as an extension of the trial. This will be an open-label
prospective study of 50 subjects recruited from the trial who will take 2 mg of
controlled-release melatonin nightly for 24 weeks after completion of the 12-week trial. At
the end of the cohort-phase (36 weeks after entry in the trial), the investigators will again
assess the extended use of melatonin supplementation on 24-hour BP, and glycemic control
(HbA1, fasting glucose).