ContextDerangement of 11-β hydroxysteroid dehydrogenase type 1 and type 2 (11β-HSD1 and 11β-HSD2), which regulate intracellular cortisol production, has been suggested in both type 2 diabetes (T2D) and chronic kidney disease (CKD). However, activity of 11β-HSD enzymes in patients with T2D and CKD has never been assessed.ObjectivesTo compare 11β-HSD activities between patients with T2D and healthy controls, and assess whether in T2D, renal function is associated with 11β-HSD activities.DesignCross-sectional analysis in the Diabetes and Lifestyle Cohort Twente (DIALECT-1).SettingReferral center for T2D.PatientsPatient with T2D [n = 373, age 64 ± 9 years, 58% men, 26% of patients estimated glomerular filtration rate (eGFR) <60 mL/min·1.73 m2] and healthy controls (n = 275, age 53 ± 11 years, 48% men).Mean Outcome MeasureWe measured cortisol, cortisone, and metabolites [tetrahydrocortisol (THF), allo-THF (aTHF), and tetrahydrocortisone (THE)] in 24-hour urine samples. Whole body 11β-HSD and 11β-HSD2 activities were calculated as the urinary (THF + aTHF)/THE and cortisol/cortisone ratios, respectively.ResultsPatients with T2D had a higher (THF + aTHF)/THE ratio [1.02 (0.84 to 1.27) vs 0.94 (0.79 to 1.0), P < 0.001] and cortisol/cortisone ratio [0.70 (0.58 to 0.83) vs 0.63 (0.54 to 0.74), P < 0.001] than healthy controls. In T2D, lower eGFR was associated with a higher (THF + aTHF)/THE ratio (β = −0.35, P < 0.001), and a higher cortisol/cortisone ratio (β = −0.16, P = 0.001).ConclusionsIn this real-life secondary care setting of patients with T2D, 11β-HSD enzymes activities were shifted to higher intracellular cortisol production in T2D, which was further aggravated in patients with CKD. Prospective analyses are warranted to investigate causality of these associations.

Pharmacological treatment of narcolepsy is complex. We reported a case of recurrent episodes of polymorphic ventricular tachycardia attributed to the use of modafinil, a recently approved wake-promoting agent for narcolepsy and shift work sleep disorder. Modafinil is also approved as adjunctive treatment of obstructive sleep apnea/hypopnea syndrome. While the exact mechanism of action for modafinil is not known, central dopamine receptors seem to play an essential role. Adverse influences on the electrocardiogram (ECG) or drug-related cardiac arrhythmias are rarely reported, but are considered as clinically important.

A 72-year old woman on chronic hemodialysis developed cholesterol embolization syndrome after the discontinuation of statin therapy. Four months after starting hemodialysis, statin therapy had been discontinued because she developed aspecific abdominal complaints and wanted to reduce the daily amount of pills. Five months later she developed blue toe syndrome. After restarting lipid-lowering therapy (simvastatin/ezetimibe), the pain and skin lesions diminished and eventually disappeared. Many patients starting hemodialysis use a statin. However, the benefit of statins in patients on chronic hemodialysis is not completely clear. Discontinuation of statin treatment may confer so far unrecognized risks in hemodialysis patients with severe atherosclerosis. In this case, the blue toe syndrome disappeared after restarting cholesterol-lowering treatment