ABSTRACT
Presentation A 20 year old female attended the Emergency Department by ambulance following a collapse at a concert. On arrival she was complaining of generalised muscular pain. She had not eaten for over 12 hours and had been dancing for approximately 6 hours. The patient was known to have Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD). She had a normal exam, and normal vital signs. Diagnosis A diagnosis of rhabdomyolysis was made after her creatinine kinase (CK) was found to be >100000 units/litre (Normal range < 170U/L). Her urine was dark brown with urinalysis positive for blood. Treatment The patient was admitted to the high dependency unit, where she was treated with intravenous fluids. Her urine output and renal function were closely monitored. She made a full recovery and was discharged home four days later. Conclusion (VLCAD) is an inherited, autosomal recessive, metabolic disorder caused by mutations in the ACADVL gene. Management includes treatment of manifestation, primary prevention of manifestation, and prevention of secondary complications.
Subject(s)
Lipid Metabolism, Inborn Errors , Rhabdomyolysis , Acyl-CoA Dehydrogenase, Long-Chain/genetics , Adult , Congenital Bone Marrow Failure Syndromes , Female , Humans , Lipid Metabolism, Inborn Errors/complications , Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/genetics , Mitochondrial Diseases , Muscular Diseases , Rhabdomyolysis/diagnosis , Rhabdomyolysis/etiology , Rhabdomyolysis/therapy , Young AdultABSTRACT
AIMS: To conduct a systematic review and meta-analysis to assess the efficacy, safety and tolerability of sodium-glucose co-transporter-2 inhibitors vs placebo as add-on therapy after metformin and dipeptidyl peptidase-4 inhibitor dual therapy in type 2 diabetes. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number: CRD42018099398). A search was conducted via PubMed, www.clinicaltrials.gov and Cochrane Central Register of Controlled Trials of relevant randomised controlled trials up until 14 August 2020 that compared sodium-glucose co-transporter-2 inhibitors vs placebo as add-on therapy after metformin and dipeptidyl peptidase-4 inhibitor therapy. A random-effects model was used. RESULTS: Six randomised controlled trials (1661 participants) met the inclusion criteria. Compared with placebo, sodium-glucose co-transporter-2 inhibitor treatment, as add-on to metformin and dipeptidyl peptidase-4 inhibitor therapy, was associated with a significant reduction in HbA1c level [mean difference -8 mmol/mol, 95% CI -10, -6 (-0.7%, 95% CI -0.9, -0.6); P < 0.00001], in fasting plasma glucose level [mean difference -1.70 mmol/l, 95% CI -1.91, -1.49; P < 0.00001], in weight (mean difference -1.76 kg, 95% CI -2.04, -1.48; P < 0.00001) and in blood pressure (systolic blood pressure: mean difference -3.6 mmHg, 95% CI -4.8, -2.4; P < 0.00001; diastolic blood pressure: mean difference -1.5 mmHg; 95% CI -2.4, -0.6; P = 0.002). Genital mycotic infections (odds ratio 7.37, 95% CI 3.06, 17.76; P < 0.00001) were more common with sodium-glucose co-transporter-2 inhibitors, but there was no significant statistical difference in urinary tract infections (odds ratio 1.16, 95% CI 0.63, 2.13; P = 0.64), in hypoglycaemia (odds ratio 1.36, 95% CI 0.61, 3.04; P = 0.45), or in discontinuation rates due to adverse events (odds ratio 1.52, 95% CI 0.78, 2.97; P = 0.22) between the two groups. CONCLUSIONS: In comparison with placebo, add-on therapy with a sodium-glucose co-transporter-2 inhibitor is significantly more efficacious in lowering HbA1c , fasting plasma glucose and weight in people with type 2 diabetes following inadequate glycaemic control with metformin and a dipeptidyl peptidase-4 inhibitor. The rate of discontinuation due to adverse events was similar despite higher risk of genital mycotic infections.
