Glucose-independent racial disparity in HbA1c is evident at onset of type 1 diabetes

ObjectiveHigher levels of HbA1c, independent of blood glucose levels, have been described in Blacks compared to Whites patients with established diabetes. The goal of this study was to determine if glucose-independent racial disparity in HbA1C is evident at diabetes onset.Research design and methodsWe conducted a retrospective single-center chart review of 189 youth with new onset Type 1 diabetes (T1D) 60 % Whites and 40 % Blacks. HbA1c, glucose and other biochemistry measures were obtained at presentation in the Emergency Department before initiation of any therapy. HbA1c levels were adjusted for presenting glucose, self-identified race, age, gender, hematocrit, and RDW-CV.ResultsBlacks with T1D had statistically significant higher unadjusted HbA1c (11.9 ± 1.9 vs 11.04 ± 2.0 %, p = 0.004), initial glucose (530.6 ± 230.4 vs 442 ± 211.3 mg/dL, p = 0.0075) and lower pHs (7.28 ± 0.15 vs 7.33 ± 0.12, p = 0.02) compared to white patients. Least squares means of HbA1c remained higher in Black patients even after statistical adjustment for presenting glucose, age, gender, RDW-CV, and pH. In a multiple variable model (R² = 0.38, p < 0.0001) c-peptide was influenced by HCO₃ (p = 0.0035), gender (p = 0.0092), BMI (p < 0.0001), but not race or glucose.ConclusionsHbA1c at initial presentation of T1D is higher in young Black patients compared to Whites even after adjustment for glucose, age, gender, and RDW-CV. This racial disparity is consistent with other studies in individuals without diabetes and patients with long-standing diabetes under treatment.     

Fetuin-A to adiponectin ratio is an independent indicator of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes mellitus

AimsThe purpose of this research was to explore the associations of fetuin-A, adiponectin, and fetuin-A/adiponectin ratio (F/A ratio) with subclinical atherosclerosis as evaluated by carotid intima-media thickness (CIMT) in cases with newly diagnosed type 2 diabetes mellitus (T2DM).MethodsA total of 283 newly diagnosed T2DM patients were enrolled in this study. Serum fetuin-A and adiponectin levels were determined with an ELISA method. Other clinical and biochemical parameters were also collected.ResultsSignificant linear increases in waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure, homoeostasis model assessment of insulin resistance, C-reactive protein (CRP) and F/A ratio, and a significant linear decrease in adiponectin with increasing tertiles of CIMT were observed (P for trends <0.05). However, no significant correlation between fetuin-A and CIMT was detected (P > 0.05). In multivariate logistic regression models, WHR, SBP and F/A ratio were independently correlated with higher CIMT. Receiver operating characteristic curve analysis indicated that F/A ratio had a better predictive power for higher CIMT than adiponectin and fetuin-A, with an area under the curve of 0.802, 0.713 and 0.646, respectively.ConclusionF/A ratio is an independent indicator of subclinical atherosclerosis in patients with newly diagnosed T2DM.     

Skin advanced glycation end products as a screening tool of neuropathy in type 2 diabetes mellitus

Aim of the studyTo examine the diagnostic utility of skin advanced glycation end products (AGEs) as screening tool of neuropathy in type 2 diabetes mellitus (T2DM).Patients and methodsWe included 132 participants (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm and were interpreted as normal vs. elevated. Distal sensorimotor polyneuropathy (DSPN) was diagnosed by the Neuropathy Disability Score. Cardiovascular autonomic neuropathy (CAN), sympathetic and parasympathetic nervous system impairment were diagnosed by cardiovascular autonomic reflex tests.ResultsFor DSPN, AGEs yielded high sensitivity (82.8%) and NPV (80.4 %) with moderate specificity (55.4 %). For CAN, they yielded relatively high sensitivity (75.0 %) and NPV (74.5 %) with low specificity (48.7 %). For sympathetic nervous system impairment, AGEs yielded relatively high sensitivity (75.0 %) and high NPV (84.3 %) with low specificity (43.9 %). For parasympathetic nervous system impairment, they yielded high PPV (81.0 %) with moderately high sensitivity (66.7 %) and moderate specificity (55.9 %).ConclusionsIn a simplified approach, skin AGEs may be used as a screening tool of DSPN and CAN (including sympathetic and parasympathetic nervous system impairment) in T2DM.     

On diabetic foot ulcer knowledge gaps,innovation, evaluation,prediction markers,and clinical needs

Diabetic foot ulcers (DFUs) remain a very prevalent and challenging complication of diabetes worldwide due to high morbidity, high risks of lower extremity amputation and associated mortality. Despite major advances in diabetes treatment in general, there is a paucity of FDA approved technologies and therapies to promote successful healing. Furthermore, accurate biomarkers to identify patients at risk of non-healing and monitor response-to-therapy are significantly lacking. To date, research has been slowed by a lack of coordinated efforts among basic scientists and clinical researchers and confounded by non-standardized heterogenous collection of biospecimen and patient associated data. Novel technologies, especially those in the single and ‘multiomics’ arena, are being used to advance the study of diabetic foot ulcers but require pragmatic study design to ensure broad adoption following validation. These high throughput analyses offer promise to investigate potential biomarkers across wound trajectories and may support information on wound healing and pathophysiology not previously well understood. Additionally, these biomarkers may be used at the point-of-care. In combination with national scalable research efforts, which seek to address the limitations and better inform clinical practice, coordinated and integrative insights may lead to improved limb salvage rates.     

Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review

BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease(IBD)patients,complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.AIM To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.METHODS We searched PubMed/MEDLINE,Embase,and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.RESULTS A total of 23 articles with 30 clinical studies and 1939 IBD patients were included.The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6μg/mL in IBD.Blood concentration of infliximab reaching 5.0-12.7μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease.Blood concentration of adalimumab reaching 7.2-16.2μg/mL or more could predict mucosal healing in IBD.The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8μg/mL in perianal fistulizing Crohn's disease.Blood concentration of vedolizumab surpassing 25.0μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9μg/mL.CONCLUSION Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies,whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.     

A clinical and canine experimental study in small-airway response to bronchial thermoplasty: Role of the neuronal effect

BackgroundThe effects of bronchial thermoplasty (BT) on smooth muscle (SM) and nerves in small airways are unclear.MethodsWe recruited 15 patients with severe refractory asthma, who received BT treatment. Endobronchial optical-coherence tomography (EB-OCT) was performed at baseline, 3 weeks' follow-up and 2 years' follow-up to evaluate the effect of BT on airway structure. In addition, we divided 12 healthy beagles into a sham group and a BT group, the latter receiving BT on large airways (inner diameter >3 mm) of the lower lobe. The dogs’ lung lobes were resected to evaluate histological and neuronal changes of the treated large airways and untreated small airways 12 weeks after BT.ResultsPatients receiving BT treatment had significant improvement in Asthma Control Questionnaire (ACQ) scores and significant reduction in asthma exacerbations. EB-OCT results demonstrated a notable increase in inner-airway area (Ai) and decrease in airway wall area percentage (Aw%) in both large (3rd-to 6th-generation) and small (7th-to 9th-generation) airways. Furthermore, the animal study showed a significant reduction in the amount of SM in BT-treated large airways but not in untreated small airways. Protein gene product 9.5 (PGP9.5)–positive nerves and muscarinic receptor 3 (M3 receptor) expression in large and small airways were both markedly decreased throughout the airway wall 12 weeks after BT treatment.ConclusionsBT significantly reduced nerves, but not SM, in small airways, which might shed light on the mechanism of lung denervation by BT.     

Laparoscopic versus open pancreatoduodenectomy: an individual participant data meta-analysis of randomized controlled trials

BackgroundRandomized trials have compared laparoscopic pancreatoduodenectomy (LPD) to open pancreatoduodenectomy (OPD) with conflicting results. An IPDMA may give more insight into the differences between LPD and OPD, and could identify high-risk subgroups.MethodsA systematic literature search was performed in the Pubmed, Embase, and the Cochrane library databases (October 2019). Out of 1410 studies, three randomized trials were identified. Primary outcome was major complications (Clavien-Dindo grade ≥ III). Subgroup analyses were performed for high-risk subgroups including patients with BMI of ≥25 kg/m2, pancreatic duct <3 mm, age ≥70 years, and malignancy.ResultsData from 224 patients were collected. After LPD, major complications occurred in 33/114 (29%) patients compared to 34/110 (31%) patients after OPD (adjusted odds ratio (OR) 0.62; 95% confidence interval (CI) 0.3–1.4, P = 0.257). No differences were seen for major complications and 90-day mortality LPD 8 (7%) vs OPD 4 (4%) (adjusted OR 0.2; 95% CI 0.02–1.3, P = 0.080). With LPD, operative time was longer (420 vs 318 min, p < 0.001) and hospital stay was shorter (mean difference ?6.97 days). Outcomes remained stable in the high-risk subgroups.ConclusionLPD did not reduce the rate of major postoperative complications as compared to OPD. LPD increased operative time and shortened hospital stay with 7 days.     

Recurrence hazard rate in patients with hepatocellular carcinoma and bile duct tumor thrombus: a multicenter observational study

BackgroundPatients with hepatocellular carcinoma (HCC) bile duct tumor thrombus (BDTT) have a high rate of postoperative recurrence. We aimed to describe the patterns and kinetics of recurrence in BDTT patients and provide management options accordingly.MethodsThis retrospective study included 311 HCC patients with BDTT who underwent surgery from 2009 to 2017 at five centers in China. The hazard rate of recurrence was calculated using the hazard function.ResultsThe hazard rate of intrahepatic recurrence was higher than that of extrahepatic recurrence (0.0588 vs. 0.0301), and both showed a decreasing trend, and the intrahepatic recurrence and extrahepatic recurrence risk decreased to a lower level after 40 and 20 months, respectively. Patients who underwent anatomic resection had a consistently lower hazard rate of recurrence than patients who underwent nonanatomic resection, whereas patients who received postoperative adjuvant transarterial chemoembolization (TACE) mainly had a lower hazard rate of recurrence in the first year than patients who did not.ConclusionThe follow-up of BDTT patients should be at least 40 months because of its high rate of recurrence, in parallel with the need for vigilance for extrahepatic recurrence within 20 months. Anatomic hepatectomy and adjuvant TACE are recommended to improve BDTT patient outcomes.     

Association of robotic approach with patient-reported outcomes after pancreatectomy: a prospective cohort study

BackgroundRobotic-assisted pancreatectomy continues to proliferate despite limited evidence supporting its benefits from the patient's perspective. We compared patient-reported outcomes (PROs) between patients undergoing robotic and open pancreatectomies.MethodsPROs, measured with the FACT-Hep, FACT-G, and HCS, were assessed in the immediate postoperative (i.e., preoperative to discharge) and recovery (i.e., discharge to three months postoperative) periods. Linear mixed models estimated the association of operative approach on PROs. Minimally important differences (MIDs) were also considered.ResultsAmong 139 patients, 105 (75.5%) underwent robotic pancreatectomies. Compared to those who underwent open operations, those who underwent robotic operations experienced worse FACT-Hep scores that were both statistically and clinically significant (mean difference [MD] 8.6 points, 95% CI 1.0–16.3). Declines in FACT-G (MD 4.3, 95% CI ?1.0 to 9.6) and HCS (MD 4.3, 95% CI 0.8–7.9) scores appeared to contribute equally in both operative approaches to the decline in total FACT-Hep score. Patients who underwent robotic versus open operations both statistically and clinically significantly improved due to improvements in HCS (MD 6.1, 95% CI 2.3–9.9) but not in FACT-G (MD 1.2, 95% CI ? 5.1-7.4).ConclusionThe robotic approach to pancreas surgery might offer, from the patient's perspective, greater improvement in symptoms over the open approach by three months postoperatively.