Ultra-rapid-acting insulins for adults with diabetes: A systematic review and meta-analysis

We performed a systematic review and meta-analysis of randomized controlled trials to assess the efficacy and safety of the novel, ultra-rapid-acting insulins aspart and lispro in adults with type 1 or type 2 diabetes. Our primary outcome was change in HbA1c from baseline. We additionally assessed eight efficacy and six safety endpoints. We calculated weighted mean differences (WMD) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, alongside 95% confidence intervals (CIs). We additionally assessed statistical heterogeneity among studies with the I² statistic, considering values greater than 60% as indicative of substantial heterogeneity. Nine studies comprising 5931 patients were included in the systematic review; eight active-controlled studies could be synthesized in terms of a meta-analysis. Treatment with ultra-rapid-acting insulins had a similar effect on change in HbA1c compared with rapid-acting insulins (WMD −0.02%, 95% CI −0.08 to 0.05, I² = 61% for patients with type 1 diabetes and −0.02%, 95% CI −0.09 to 0.04, I² = 19% for patients with type 2 diabetes). Similarly, no difference was evident in terms of change in fasting plasma glucose, self-measured plasma glucose, body weight, basal or bolus insulin dose, incidence of serious adverse events and hypoglycaemia. Compared with rapid-acting insulins, ultra-rapid-acting insulins reduced 1- and 2-hour postprandial glucose (PPG) increment based on a liquid meal test, both in patients with type 1 and type 2 diabetes (WMD −0.94 mmol/L, 95% CI −1.17 to −0.72, I² = 0% and −0.56 mmol/L, 95% CI −0.79 to −0.32, I² = 0%, respectively, for change in 1-hour PPG increment). In conclusion, ultra-rapid-acting insulins were as efficacious and safe as rapid-acting insulins, showing a favourable effect solely on PPG control.     

Association of familial Mediterranean fever–related MEFV variations with ankylosing spondylitis

Objective

The pathogenesis of ankylosing spondylitis (AS) has a strong genetic contribution. Familial Mediterranean fever (FMF) is an autosomal recessively inherited autoinflammatory disorder caused by MEFV gene missense variations, and a clinical association between FMF and AS has been reported previously. The aim of this study was to analyze the association of common MEFV variations (M694V, M680I, V726A, and E148Q) with AS in a group of Turkish patients.

Methods

The study group comprised 193 patients with AS and 103 matched healthy control subjects. All individuals were genotyped for 4 MEFV variations and HLA–B27 using genomic DNA, and association of the variations with the clinical and laboratory features of the patients was analyzed.

Results

The MEFV missense variations were significantly more frequent in patients with AS (22.3%) compared with healthy control subjects (9.7%; odds ratio [OR] 2.67, 95% confidence interval [95% CI] 1.28–5.56). This difference was more prominent for exon 10 variations (M694V, V726A, M680I) (OR 3.75, 95% CI 1.41–9.97), especially for the most‐penetrant variation M694V (OR 4.73, 95% CI 1.39–16.12). MEFV variations were more frequent in HLA–B27–negative patients with AS, and the difference was statistically significant in patients carrying exon 10 variants.

Conclusion

FMF‐related MEFV variations are associated with AS, and these variations may contribute to the pathogenesis of AS, especially in populations in which the prevalence of FMF is high.