Plasma Lipidomics Profiles Highlight the Associations of the Dual Antioxidant/Pro-oxidant Molecules Sphingomyelin and Phosphatidylcholine with Subclinical Atherosclerosis in Patients with Type 1 Diabetes.

Here, we report on our study of plasma lipidomics profiles of patients with type 1 diabetes (T1DM) and explore potential associations. One hundred and seven patients with T1DM were consecutively recruited. Ultrasound imaging of peripheral arteries was performed using a high image resolution B-mode ultrasound system. Untargeted lipidomics analysis was performed using UHPLC coupled to qTOF/MS. The associations were evaluated using machine learning algorithms. SM(32:2) and ether lipid species (PC(O-30:1)/PC(P-30:0)) were significantly and positively associated with subclinical atherosclerosis (SA). This association was further confirmed in patients with overweight/obesity (specifically with SM(40:2)). A negative association between SA and lysophosphatidylcholine species was found among lean subjects. Phosphatidylcholines (PC(40:6) and PC(36:6)) and cholesterol esters (ChoE(20:5)) were associated positively with intima-media thickness both in subjects with and without overweight/obesity. In summary, the plasma antioxidant molecules SM and PC differed according to the presence of SA and/or overweight status in patients with T1DM. This is the first study showing the associations in T1DM, and the findings may be useful in the targeting of a personalized approach aimed at preventing cardiovascular disease in these patients.

Gut Microbiota Composition and Functionality Are Associated With REM Sleep Duration and Continuous Glucose Levels.

CONTEXT: Sleep disruption is associated with worse glucose metabolic control and altered gut microbiota in animal models. OBJECTIVE: We aimed to evaluate the possible links among rapid eye movement (REM) sleep duration, continuous glucose levels, and gut microbiota composition. METHODS: This observational, prospective, real-life, cross-sectional case-control study included 118 (60 with obesity), middle-aged (39.1-54.8 years) healthy volunteers recruited at a tertiary hospital. Glucose variability and REM sleep duration were assessed by 10-day continuous glucose monitoring (CGM) (Dexcom G6) and wrist actigraphy (Fitbit Charge 3), respectively. The coefficient of variation (CV), interquartile range (IQR), and SD of glucose variability was assessed and the percentage of time in range (% TIR), at 126-139 mg/dL (TIR2), and 140-199 mg/dL (TIR3) were calculated. Shotgun metagenomics sequencing was applied to study gut microbiota taxonomy and functionality. RESULTS: Increased glycemic variability (SD, CV, and IQR) was observed among subjects with obesity in parallel to increased % TIR2 and % TIR3. REM sleep duration was independently associated with % TIR3 (ß = -.339; P < .001) and glucose variability (SD, ß = -.350; P < .001). Microbial taxa from the Christensenellaceae family (Firmicutes phylum) were positively associated with REM sleep and negatively with CGM levels, while bacteria from Enterobacteriacea family and bacterial functions involved in iron metabolism showed opposite associations. CONCLUSION: Decreased REM sleep duration was independently associated with a worse glucose profile. The associations of species from Christensenellaceae and Enterobacteriaceae families with REM sleep duration and continuous glucose values suggest an integrated picture of metabolic health.

Assessing the quality of the evidence underlying recommendations in type 2 diabetes' commonly used clinical practice guidelines.

AIM: In a world of data overload, clinical practice recommendations are needed to help practitioners and patients to take evidence-based decisions. However, in the field of type 2 diabetes mellitus (T2DM) recommendations on glycemic goals and treatment choice are controversial in spite of being supported by a common body of evidence. We hypothesize that internal and external validity of this body of evidence might not be as sound as expected. The aim of the current study is to appraise the studies supporting recommendations developed by influential medical societies dealing with glycemic goals and the choice of pharmacological treatment in adults with T2DM. METHODS: Clinical practice recommendations and their references were extracted out of eight documents developed by influential scientific societies between 2016 and 2019. Internal and external validity of each study was then appraised with standard tools and in duplicate. RESULTS: A total of 114 recommendations and their underlying 233 citations were extracted. Out of these 233 citations 81 (35%) corresponded to randomized controlled trials (RCT) and 45 (20%) to systematic reviews. After systematical appraisal only four RCT (5%) and eight systematic reviews (17%) were considered to be unflawed. Indirectness (lack of generalizability) was the most common caveat identified in RCTs. Out of the 114 recommendations analyzed (32 dealing with glycemic goals and 82 with treatment choice), only 21 (18.4%) were supported by at least one high-quality study. CONCLUSION: Only one in five recommendations regarding glycemic goals or pharmacological treatment choice in T2DM is based on at least one high-quality study. Clinical practice recommendations dealing with areas of uncertainty should be formulated more transparently to enable real evidence-based decisions.

Safety and Feasibility of the PEPPER Adaptive Bolus Advisor and Safety System: A Randomized Control Study.

Background: The Patient Empowerment through Predictive Personalized Decision Support (PEPPER) system provides personalized bolus advice for people with type 1 diabetes. The system incorporates an adaptive insulin recommender system (based on case-based reasoning, an artificial intelligence methodology), coupled with a safety system, which includes predictive glucose alerts and alarms, predictive low-glucose suspend, personalized carbohydrate recommendations, and dynamic bolus insulin constraint. We evaluated the safety and efficacy of the PEPPER system compared to a standard bolus calculator. Methods: This was an open-labeled multicenter randomized controlled crossover study. Following 4-week run-in, participants were randomized to PEPPER/Control or Control/PEPPER in a 1:1 ratio for 12 weeks. Participants then crossed over after a washout period. The primary end-point was percentage time in range (TIR, 3.9-10.0 mmol/L [70-180 mg/dL]). Secondary outcomes included glycemic variability, quality of life, and outcomes on the safety system and insulin recommender. Results: Fifty-four participants on multiple daily injections (MDI) or insulin pump completed the run-in period, making up the intention-to-treat analysis. Median (interquartile range) age was 41.5 (32.3-49.8) years, diabetes duration 21.0 (11.5-26.0) years, and HbA1c 61.0 (58.0-66.1) mmol/mol. No significant difference was observed for percentage TIR between the PEPPER and Control groups (62.5 [52.1-67.8] % vs. 58.4 [49.6-64.3] %, respectively, P = 0.27). For quality of life, participants reported higher perceived hypoglycemia with the PEPPER system despite no objective difference in time spent in hypoglycemia. Conclusions: The PEPPER system was safe, but did not change glycemic outcomes, compared to control. There is wide scope for integrating PEPPER into routine diabetes management for pump and MDI users. Further studies are required to confirm overall effectiveness. Clinical trial registration: ClinicalTrials.gov NCT03849755.

Decreased iron stores are associated with cardiovascular disease in patients with type 2 diabetes both cross-sectionally and longitudinally.

BACKGROUND AND AIMS: The possible contribution of iron to cardiovascular complications of type 2 diabetes (T2D) has been scarcely investigated. We aimed to study whether serum ferritin is linked to prevalent/incident cardiovascular disease (CVD) in T2D. METHODS: The prevalence of coronary heart disease (CHD), cerebrovascular disease (CEVD) and CVD was evaluated in the SIDIAP study (n = 38,617) and prevalence and 7-year incidence were analysed in the Edinburgh Type 2 Diabetes Study (ET2DS) (n = 821). Logistic and Cox regressions were used to describe associations between serum ferritin and CVD adjusting for confounding variables. RESULTS: Increase of 1 SD unit in log-ferritin was associated with lower CVD prevalence in fully-adjusted models (ET2DS odds ratio (OR) 95% confidence interval (CI): 0.81 (0.68-0.96), p = 0.018; SIDIAP study: 0.91 (0.88-0.94), p < 0.001). In ET2DS, ferritin in the highest (vs. the lowest) quintile was associated with lower incidence of CVD (fully adjusted HR 95% CI: 0.46 (0.26-0.83), p = 0.010). This association persisted after removing subjects with CVD at baseline (n = 536) (HR 95% CI: 0.34 (0.14-0.81), p = 0.016). CONCLUSIONS: Low iron status was associated with CVD risk in T2D. This pattern was consistent in populations at different cardiovascular risk. Low iron status seems to be harmful for cardiovascular health in T2D and it may be a target for intervention.

Glycemic control in type 2 diabetes: time for an evidence-based about-face?

Some diabetes guidelines set low glycemic control goals for patients with type 2 diabetes mellitus (such as a hemoglobin A(1c) level as low as 6.5% to 7.0%) to avoid or delay complications. Our review and critique of recent large randomized trials in patients with type 2 diabetes suggest that tight glycemic control burdens patients with complex treatment programs, hypoglycemia, weight gain, and costs and offers uncertain benefits in return. We believe clinicians should prioritize supporting well-being and healthy lifestyles, preventive care, and cardiovascular risk reduction in these patients. Glycemic control efforts should individualize hemoglobin A(1c) targets so that those targets and the actions necessary to achieve them reflect patients' personal and clinical context and their informed values and preferences.

Serum visfatin increases with progressive beta-cell deterioration.

Visfatin has shown to be increased in type 2 diabetes but to be unrelated to insulin sensitivity. We hypothesized that visfatin is associated with insulin secretion in humans. To this aim, a cross-sectional study was conducted in 118 nondiabetic men and 64 (35 men and 29 women) type 2 diabetic patients. Type 1 diabetic patients with long-standing disease (n = 58; 31 men and 27 women) were also studied. In nondiabetic subjects, circulating visfatin (enzyme immunoassay) was independently associated with insulin secretion (acute insulin response to glucose [AIRg] from intravenous glucose tolerance tests) but not with insulin sensitivity (Si) or other metabolic or anthropometric parameters, and AIRg alone explained 8% of visfatin variance (beta = -0.29, P = 0.001). Circulating visfatin was increased in type 2 diabetes (mean 18 [95% CI 16-21] vs. 15 ng/ml [13-17] for type 2 diabetic and nondiabetic subjects, respectively; P = 0.017, adjusted for sex, age, and BMI), although this association was largely attenuated after accounting for HbA1c (A1C). Finally, circulating visfatin was found to be increased in patients with long-standing type 1 diabetes, even after adjusting for A1C values (37 ng/ml [34-40]; P < 0.0001, adjusted for sex, age, BMI, and A1C compared with either type 2 diabetic or nondiabetic subjects). In summary, circulating visfatin is increased with progressive beta-cell deterioration. The study of the regulation and role of visfatin in diabetes merits further consideration.