In this population of patients with Type 2 diabetes who attended a diabetes clinic, there was some evidence for a role of endothelial dysfunction in the progression of retinopathy. We could not demonstrate a role for low-grade inflammation. Our study emphasizes the importance of glycaemic control in the development and progression of retinopathy.

Melatonin regulates circadian rhythm, but may also have effects on glucose homeostasis. A common G‐allele in the MTNR1B locus has been associated with an increased risk of type 2 diabetes (T2DM). We aimed to examine acute effects of high doses of melatonin on glucose metabolism with attention to MTNR1B genotype. Twenty men were examined in a double‐blinded, randomized crossover study on two nonconsecutive days with four doses of 10 mg oral melatonin or placebo. Insulin sensitivity and insulin secretion were assessed by an intravenous glucose tolerance test (IVGTT) and a hyperinsulinaemic‐euglycaemic clamp (HEC). Blood samples were drawn to determine the metabolic profile and MTNR1B rs10830963 genotype. Indirect calorimetry and blood pressure measurements were also performed. Insulin sensitivity index was significantly reduced on the melatonin day (P = .028) in the whole group and in homozygous carriers of the rs10830963 C‐allele (P = .041). Glucose during the IVGTT was unaffected, but there was a tendency towards lower insulin and C‐peptide levels in the first minutes after glucose administration in G‐allele carriers. Systolic blood pressure decreased and lipid oxidation increased significantly on the melatonin day in rs10830963 G‐allele carriers. Overall, our study reports that acute administration of melatonin in supra‐physiological doses may have a negative impact on insulin sensitivity. Clinical trial registration number (clinicaltrial.gov): NCT03204877.

ContextDuring the inflammatory acute phase response, plasma glucose and serum triglycerides are increased in humans. Fibroblast growth factor (FGF) 21 has plasma glucose and lipid-reducing actions, but its role in the acute inflammatory response in human is unknown.ObjectiveTo investigate circulating levels of FGF21 after lipopolysaccharide (LPS) infusion.DesignTwo randomized, single-blinded, placebo-controlled crossover trials were used.SettingThe studies were performed at a university hospital clinical research center.Patients and interventionsStudy 1 (LPS bolus): Eight young, healthy, lean males were investigated two times: (1) after isotonic saline injection and (2) after LPS injection (bolus of 1 ng/kg). Each study day lasted 4 h. Study 2 (continuous LPS infusion): Eight, healthy males were investigated two times: (1) during continuously isotonic saline infusion and (2) during continuous LPS infusion (0.06 ng/kg/h). Each study day lasted 4 h. Circulating FGF21 levels were quantified every second hour by an immunoassay.ResultsA LPS bolus resulted in a late suppression (t = 240 min) of serum FGF21 (P = 0.035). Continuous LPS infusion revealed no significant effects on FGF21 levels (P = 0.82).ConclusionsOur studies show that a bolus of LPS results in decreased FGF21 levels 4 h from exposure.