Bridging dose of U-100 glargine with first dose of insulin degludec improves glycaemia in the 48 h after transition in twice-daily glargine users.

AIMS: To study the effects of a bridging dose of U-100 glargine (U-100G) with the first dose of degludec in type 1 diabetes (T1D) patients transitioning from glargine to degludec, by comparing the glucose metrics 48 h before and after the transition. MATERIALS AND METHODS: Patients with T1D on a stable U-100G regimen and with glycated haemoglobin concentration <75 mmol/mol were randomized (double-blind) to one dose of placebo or U-100G with first dose of degludec, administered at 9:00 pm. Patients on once-daily U-100G at baseline received 50% of total U-100G dose (bridging dose), while patients on twice-daily U-100G received 50% of the evening U-100G dose. Participants wore a continuous glucose monitor during the study. RESULTS: Forty participants were randomized, of whom 37 completed the study. The cohort was 65% male, the mean age was 47 years, duration of T1D 22 years, BMI 26 kg/m2, HbA1c 51 mmol/mol and total daily insulin dose 0.7 units/kg body weight. The bridging group included 19 participants (once-daily U-100G: n = 12; twice-daily U-100G: n = 7) and the placebo group included 18 participants (once-daily U-100G: n = 12; twice-daily U-100G: n = 6). Change in time in range (TIR) was not significantly different between the two treatment groups. In secondary analyses, among twice-daily U-100G users, TIR (3.9-10 mmol/L) increased 8% in the bridging group in the 48 h after first dose of degludec compared to the preceding 48 h, while participants in the placebo group had a 9.5% decrease (p = 0.027). CONCLUSIONS: A subgroup of well-controlled twice-daily U-100G users transitioning to degludec benefited from a 50% bridging dose of evening U-100G with the first dose of degludec in a small pilot study.

Associations of plasma miRNAs with waist circumference and insulin resistance among women with polycystic ovary syndrome - Pilot study.

BACKGROUND: Insulin resistance (IR) and central obesity are common in polycystic ovary syndrome (PCOS), but pathomechanisms for IR in PCOS are not established. Circulating microRNAs (miRNAs) are non-invasive biomarkers of epigenetic regulation that may contribute to the pathogenesis of IR and central adiposity in PCOS. METHODS: We conducted a pilot study to examine associations of circulating miRNAs with IR and central adiposity among women with PCOS (n = 11) using high-throughput miRNA sequencing. We fit generalized linear models examining associations of waist circumference and HOMA-IR with plasma miRNAs. We used false discovery rate (FDR)-adjusted cutoff p < 0.1 to correct for multiple testing. We used miRDB's Gene Ontology (GO) tool to identify predicted pathways for top hits. RESULTS: Mean age and BMI of participants were 27.9 years and 32.5 kg/m2, respectively. Lower levels of miR-1294 were associated with higher waist circumference (ß = -0.10, FDR = 0.095). While no miRNAs were associated with HOMA-IR at our FDR cut off <0.1, 11 miRNAs were associated with waist circumference and 14 miRNAs with HOMA-IR at unadjusted p < 0.01, including members of the highly conserved miR-17/92 cluster and miR-1294 (ß = -0.10, p < 0.001). The GO analysis of miR-1294 identified 54 overrepresented pathways, including "negative regulation of insulin receptor signaling" (FDR = 0.019), and 6 underrepresented pathways. CONCLUSIONS: Plasma miR-1294 along with members of the miR-17/92 cluster and miRNAs involved in insulin signaling may be associated with central obesity and insulin resistance in PCOS. Larger studies among women with and without PCOS are needed to validate these findings.

The Significance of Rapid Eye Movement Sleep Behavior Disorder in Neurodegenerative Diseases: An Updated Review.

Background: Rapid eye movement (REM) sleep behavior disorder (RBD), a parasomnia, after being diagnosed, can predict the emergence of an alpha-synuclein-associated neurodegenerative disease (NDD) in 20-45% and 92% of patients within 5 and 14 years, respectively. RBD is less common in tauopathies, and the studies to evaluate its association with polyglutamine diseases have been very few. Objective: To revisit our knowledge on the significance of RBD in the emergence of NDDs and to review the recent updates in the potential biomarkers, which can help predict the risk of phenconversion into NDDs in idiopathic RBD (iRBD) patients. We also aimed to look at the potential neuroprotective therapies that can potentially be used earlier in iRBD patients. Methods: We conducted a review of the papers, after selecting them from the PubMed database. After a thorough screening, 51 articles were chosen to be included in this review. Results and Conclusion: The prospective studies showed that the risk of phenoconversion of iRBD into overt NDDs increased over the longer duration of follow up. Magnetic resonance imaging (MRI) findings, Electroencephalographic findings along with subtle motor signs, autonomic dysfunction, impaired olfaction, and color vision, among others, can be used to predict the onset of an NDD in iRBD. Phytocannabinoids showed a possible neuroprotective effect in animal studies. Considering how RBD is the antecedent of NDDs, there is a need for additional studies to better understand the utility of the aforementioned biomarkers and institute potential neuroprotective therapies early in the process.

Diabetes Mellitus in the Middle-Aged and Elderly Population (>45 Years) and Its Association With Pancreatic Cancer: An Updated Review.

Diabetes mellitus (DM) and pancreatic cancer (PC) in the elderly are widely considered to be interrelated. New-onset diabetes (NOD) patients are considered a high-risk group for the development of PC within three years of diagnosis. We reviewed the literature to determine the pathophysiological association between DM and PC, which can help in the development of screening tests for early PC diagnosis in the elderly with NOD. We also studied the potential associations between them after pancreaticoduodenectomy (PD) or pancreatic resection. We collected studies published in the last five years in PubMed that are relevant to DM and PC in the elderly. We mainly focused on the pathophysiology and intracellular mechanisms involved between NOD and PC. We illustrated the clinical signs and immunological and metabolic biomarkers that can be used to diagnose early PC in the elderly with NOD. In the 34 studies we reviewed, five showed that long-term diabetes mellitus (LTDM) increases the risk of PC. Six studies showed that NOD in the elderly is an early sign of PC. Fourteen studies proposed that clinical signs and biomarker levels should be used to determine the high-risk risk group for PC among NOD patients. Six studies reported that NOD is associated with the worst outcomes postoperatively, and three studies showed that patients developed DM after pancreatic resection. LTDM is considered an independent risk factor for PC development in the elderly. NOD is a consequence and maybe the only early presenting sign of PC. Screening protocols and tests should be used in clinical practice to determine the proportion of NOD patients who should undergo further testing for early diagnosis of PC. DM and PC are also co-related postoperatively and patients should be monitored for impaired glucose levels, overall survival, and mortality.

The Association of Anti-Ganglioside Antibodies in the Pathogenesis and Development of Zika-Associated Guillain-Barré Syndrome.

Zika virus (ZIKV) has created major outbreaks all over the Americas and has caused severe neurological complications. The main neurological complications linked to ZIKV are Guillain-Barré syndrome (GBS), encephalitis, myelitis, and microcephaly. We thoroughly searched for published literature on PubMed and found evidence supporting the relationship between ZIKV and GBS. Through April 1, 2020, 429 publications were available on PubMed using the words "Zika associated GBS." Among these, only four results linked anti-ganglioside antibodies to Zika-associated GBS. So, we expanded our search to other platforms like PubMed Central® (PMC), Google Scholar, and Cochrane, after which we shortlisted 28 studies. These studies include review articles, observational studies, case series, and case reports. The information collected from these articles were mainly based on the outbreaks in Latin America and the results that these patients showed in the course of the disease. It took a lag time of 7-10 days for the patients to develop Zika-associated GBS. We used all the evidence regarding the epidemiology, clinical manifestations, neurological complications, and diagnostic criteria that supported the findings of anti-ganglioside antibodies to ZIKV-associated GBS. Patients were detected with the presence of these antibodies in their urine through the enzyme-linked immunosorbent assay (ELISA) test. But the mechanism by which the ZIKV causes other complications like myelitis and encephalitis is still unknown and yet to be explored to develop treatment and management strategies.