Impact of Insulin Degludec/Liraglutide Fixed Combination on the Gut Microbiomes of Elderly Patients With Type 2 Diabetes: Results From A Subanalysis of A Small Non-Randomised Single Arm Study.

In elderly Type 2 Diabetes (T2D) patients the relationship between the destabilization of gut microbiome and reversal of dysbiosis via glucose lowering drugs has not been explored. We investigated the effect of 6 months therapy with a fixed combination of Liraglutide and Degludec on the composition of the gut microbiome and its relationship with Quality of Life, glucose metabolism, depression, cognitive function, and markers of inflammation in a group of very old T2D subjects (n=24, 5 women, 19 men, mean age=82 years). While we observed no significant differences in microbiome biodiversity or community among study participants (N = 24, 19 men, mean age 82 years) who responded with decreased HbA1c (n=13) versus those who did not (n=11), our results revealed a significant increase in Gram-negative Alistipes among the former group (p=0.013). Among the responders, changes in the Alistipes content were associated directly with cognitive improvement (r=0.545, p=0.062) and inversely with TNFα levels (r=-0.608, p=0.036). Our results suggest that this combination drug may have a significant impact on both gastrointestinal microbes and cognitive function in elderly T2D individuals.

Effect of deprescribing in elderly patients with type 2 diabetes: iDegLira might improve quality of life.

Older people with type 2 diabetes (T2D) often have several comorbidities and take multiple drugs. This study tested a deprescribing strategy in older T2D patients, replacing a hypoglycemic therapeutic scheme with a single drug combination (iDegLira). In this 6-month, real-world, single-arm, open interventional study, we enrolled patients ≥ 75 years with T2D taking ≥ 2 medications for diabetes. Patients on a basal-bolus insulin regimen (n = 13), on a basal-insulin regimen plus oral glucose-lowering drugs (n = 9), and those on oral glucose-lowering drugs (n = 18) were switched to daily iDegLira. The primary clinical endpoint of the study was an improvement in CASP-19 and/or DTSQ score after 6 months. We also evaluated changes in glucose metabolism, depression, cognitive function, level of independence, and markers of inflammation. Thirty-five patients (12 women, mean age=81.4 y) completed the protocol. Results shown here are given as estimated mean difference (95%CI). DTSQ score improved [11.08 (7.13/15.02); p = 0.0001], whereas CASP-19 did not after 6 months of iDegLira treatment. We observed reductions in BMI [- 0.81 (- 1.27/0.35); p < 0.001], fasting glucose [- 52.07 (- 77.26/26.88); p < 0.001], HbA1c [- 0.58 (- 1.08/0.08); p < 0.05], and TNF-α [- 1.83 (- 3.12/- 0.54); p = 0.007]. Activities of daily living and cognitive function score increased [p = 0.006 and p = 0.02], whereas depression score significantly decreased [p = 0.02]. Notably, no patient reported episodes of severe hypoglycemia after initiation of iDegLira treatment. Among older patients with T2D, deprescribing using a single dose of iDegLira resulted in a greater likelihood of improving health and quality of life. Although our data indicate the effectiveness and safety of this approach, it must be confirmed in larger studies.

Carotid intimal medial thickness in rotating night shift is related to IL1ß/IL6 axis.

BACKGROUND AND AIMS: Sleep disturbances may promote glucose abnormalities and inflammatory burden among shift workers. Therefore, precocious subclinical atherosclerotic process might develop in healthy shift workers even without known metabolic and cardiovascular risk factors. METHODS AND RESULTS: We measured anthropometric parameters, glucose, lipids, inflammation and common carotid Intimal Medial Thickness (cIMT) in rotating-night shift workers (r-NSW, n = 88, age = 40.3 ± 7.8 y) in comparison with former-night shift workers (f-NSW, n = 35, age = 44.2 ± 6.4 y) and with day-only workers (DW, n = 64, age = 44.1 ± 8.9 y). R-NSW and f-NSW showed significantly higher cIMT and high sensitivity C-Reactive Protein (hs-CRP) respect to DW (p = 0.043 and p = 0.025, respectively). IL-1ß levels were higher in r-NSW than in DW and f-NSW (p = 0.043) and significantly correlated with IL6 (r = 0.365, p < 0.001). In addition, r-NSW and f-NSW had higher HbA1c levels in comparison with DW (p = 0.047). Carotid-IMT was significantly related to night shift work (p = 0.023), with age (p < 0.001), with HOMA IR (p = 0.009), with insulin (p = 0.006) with HbA1c (p = 0.002), with LDL cholesterol (p < 0.001), with diastolic BP (p < 0.001), with WBC (p = 0.002) and with IL6 (p = 0.004). After performing a multivariate analysis night shift work remained statistically related to cIMT (B = 2.633, 95%CI = 0.489-4.776, p = 0.016). CONCLUSIONS: Our result described a possible link bridging night shift work, inflammation and carotid Intimal Medial Thickness. Future studies are warranted to understand if carotid atherosclerosis process should be mainly driven by the IL1ß/IL6 citokine axis connected to sleep disturbances.

Radiofrequency ablation plus drug-eluting beads transcatheter arterial chemoembolization for the treatment of single large hepatocellular carcinoma.

BACKGROUND: Our aim was to evaluate the effectiveness of the single-step combined therapy with radiofrequency ablation and drug-eluting beads transarterial chemoembolization in single hepatocellular carcinoma (HCC) larger than 3cm. Secondary aim was to compare the results with those obtained in a matched population treated with drug-eluting beads transarterial chemoembolization alone. METHODS: 40 consecutive cirrhotic patients with single HCC were prospectively enrolled and treated. Twenty-three patients had tumours between 3 and 5cm (Group A), and 17 larger than 5cm (Group B). Twenty cirrhotic patients with single HCC treated only with chemoembolization formed the control group. RESULTS: Complete response at 1 month was achieved in 32/40 tumours (80%). During follow-up, complete response was maintained in 25 patients (25/40, 62.5%), and this rate was higher in Group A (69.6% vs 53%, p=0.008). The group treated with combined therapy showed a significantly lower 2-year recurrence (48.1% vs 78.2%, p<0.001) and significantly higher survival (91.1% vs 60.6%, p=0.004) than the group treated with chemoembolization alone. CONCLUSIONS: Balloon-occluded-radiofrequency ablation plus drug-eluting beads transarterial chemoembolization is an effective treatment of HCC larger than 3cm not amenable to surgical resection, providing better results than transarterial chemoembolization alone. The best results are achieved in tumours up to 5cm.