Eating habits and sleep quality in individuals with type 1 diabetes on continuous glucose monitoring and insulin pump.

BACKGROUND AND AIMS: Sleep disorders are bidirectionally linked with eating behaviors and glucose metabolism, which could be clinically relevant in type 1 diabetes (T1D). We investigated the relationship between dietary habits and sleep quality in individuals with T1D on insulin pumps and continuous glucose monitoring (CGM). METHODS AND RESULTS: In a cross-sectional study, dietary habits (7-day food diary, EPIC questionnaire) and sleep quality (Pittsburgh Sleep Quality Index questionnaire) were assessed in 59 men and 58 women with T1D, aged 19-79 years, using CGM and insulin pump. Differences in dietary habits and blood glucose after dinner (6 h) between participants differing in sleep quality, sleep duration, and sleep onset latency were evaluated. Bad Sleepers (n = 81) were twice as prevalent as Good Sleepers (n = 36) and had a significantly higher intake of fat than Good Sleepers (dinner: 30.7 ± 10.7 vs. 24.0 ± 10.5 g, p = 0.004). Short sleepers had a significantly higher usual intake (g/1000 kcal) of coffee and tea (90.4 ± 71.7 vs. 62.0 ± 35.6), alcoholic (47.8 ± 51.1 vs. 28.9 ± 31.5) and carbonated beverages (21.8 ± 38.1 vs. 9.3 ± 17.2) (p < 0.05 for all) than Long Sleepers. Long Sleep Onset Latency was associated with a significantly higher fat intake at dinner (41.8 ± 7.4 vs. 38.1 ± 9.1 % total energy, p = 0.029) than Short Sleep Onset Latency. No significant differences in post-dinner blood glucose levels were detected between participants with good or bad sleep quality. CONCLUSION: Sleep disruption is common in T1D and is associated with unhealthy dietary choices, especially at dinner, independently of post-dinner blood glucose control.

Volanesorsen to treat severe hypertriglyceridaemia: A pooled analysis of randomized controlled trials.

BACKGROUND: Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat subjects with sHTG. The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat sHTG. We performed a systematic review and meta-analysis of RCTs on the efficacy and safety of volanesorsen as compared to placebo treatment in patients with severe HTG. METHODS: Studies were systematically searched in the PubMed, Web of Science and Scopus databases according to PRISMA guidelines. The last search was performed on 7 February 2022. RESULTS: Four studies showed significant reduction in TG after 3 months of treatment with volanesorsen as compared with placebo (MD: -73.9%; 95%CI: -93.5%, -54.2; p < .001 I2  = 89.05%; p < .001); VLDL-C level (MD: -71.0%; 95%CI: -76.6%, -65.4%; p < .001 I2  = 94.1%; p < .001); Apo-B48 level (MD: -69.03%; 95%CI: -98.59.4%, -39.47%; p < .001, I2  = 93.51%; p < .001) and Apo-CIII level (MD: -80.0%; 95%CI: -97.5%, -62.5; p < .001 I2  = 94.1%; p < .001) with an increase in HDL-C level (MD: +45.92%, 95%CI: +37.24%, +54.60%; p < .001 I2  = 94.34%; p < .001) and in LDL-C level (MD: +68.6%, 95%CI: +7.0%, +130.1%; p < .001 I2  = 96.18%; p < .001) without a significant elevation of Apo-B100 level (MD: +4.58%, 95%CI: -5.64%, +14.79%; p = .380 I2  = 95.09%; p < .001) in 139 volanesorsen patients as compared to 100 placebo-treated controls. Most of adverse events were mild and related to local injection site reactions. CONCLUSIONS: In patients with severe HTG, volanesorsen is associated with a significant reduction in TG, VLDL-C, Apo-B48 and non-HDL-C and increment of HDL-C as compared to placebo. Documented efficacy is accompanied by an acceptable safety profile.

Uncooked cornstarch for the prevention of hypoglycemic events.

Hypoglycemia is a pathological condition characterized by a low plasma glucose concentration associated with typical autonomic and/or neuroglycopenic symptoms, and resolution of these symptoms with carbohydrate consumption. Hypoglycemia is quite common in clinical practice, particularly in insulin-treated patients with diabetes and in other inherited or acquired conditions involving the regulation of glucose metabolism. Beyond symptoms that might strongly affect the quality of life, hypoglycemia can lead to short- and long-term detrimental consequences for health. Hypoglycemia can be prevented by appropriate changes in dietary habits or by relevant modifications of the drug treatment. Several dietary approaches based on the intake of various carbohydrate foods have been tested for hypoglycemia prevention; among them uncooked cornstarch (UCS) has demonstrated a great efficacy. In this narrative review, we have summarized the current evidence on the UCS usefulness in some conditions characterized by high hypoglycemic risk, focusing on some inherited diseases -i.e. glycogen storage diseases and other rare disorders - and acquired conditions such as type 1 diabetes, postprandial hypoglycemia consequent to esophageal-gastric or bariatric surgery, and insulin autoimmune syndrome. We also considered the possible role of UCS during endurance exercise performance. Lastly, we have discussed the dose requirement, the side effects, the limitations of UCS use, and the plausible mechanisms by which UCS could prevent hypoglycemia.

Clinical insights into management options for recurrent type 2 diabetes and cardiovascular risk after metabolic-bariatric surgery.

AIMS: Long-term clinical trials evaluating the effects of metabolic-bariatric surgery (MBS) on type 2 diabetes (T2D) demonstrate that a significant proportion of patients either fail to achieve remission or experience T2D recurrence over time. Furthermore, patients with recurrent T2D might require reinstitution of pharmacotherapy to control comorbidities (hypertension, dyslipidemia). This paper reviews therapeutic options in patients with T2D relapse. DATA SYNTHESIS: Although presently there is no recommended pharmacological strategy, the available data support GLP-1 analogues (GLP-1a) as the most suitable option to control hyperglycemia post-MBS. Beside their efficacy in lowering glycemia and body weight while preserving lean mass, GLP-1a exert cardiovascular/renal-protection and are also safe and well tolerated in surgical patients. In addition, the s.c. route of administration of these medications circumvents the problem of changes in oral drugs bioavailability following MBS. Of note, the available data refers to liraglutide and needs to be confirmed with weekly GLP-1a agents. Information regarding the impact of MBS on the pharmacokinetics of lipid lowering and anti-hypertensive drugs is scarce and inconclusive. The findings indicate that timing from intervention is particularly important because of adaptive intestinal mechanisms. CONCLUSIONS: The recurrence of T2D following MBS is a clinically relevant issue. GLP-1a therapy represents the best option to improve glycemic and weight control with good tolerability. Long-term clinical trials will clarify the impact of these drugs on cardiovascular outcomes. A close monitoring of MBS patients is advised to guide drug dosage adjustments and ensure the control of cardiovascular risk factors.

Rate of post-bariatric hypoglycemia using continuous glucose monitoring: A meta-analysis of literature studies.

AIMS: Hypoglycemia is a serious complication of bariatric surgery. The aim of the present meta-analysis was to evaluate the rate and the timing of post-bariatric hypoglycemia (PBH) with different bariatric procedures using reliable data from continuous glucose monitoring (CGM). DATA SYNTHESIS: Studies were systematically searched in the Web of Science, Scopus and PubMed databases according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of PBH was expressed as weighted mean prevalence (WMP) with pertinent 95% confidence intervals (95%CI). A total of 8 studies (16 datasets) enrolling 280 bariatric subjects were identified. The total WMP of PBH was 54.3% (95%CI: 44.5%-63.8%) while the WMP of nocturnal PBH was 16.4% (95%CI: 7.0%-34%). We found a comparable rate of PBH after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) (OR 1.62, 95%CI: 0.71-3.7; P = 0.248); likewise, the percent time spent in hypoglycemia was similar with the two procedures (mean difference 5.3%, 95%CI: -1.4%-12.0%; P = 0.122); however, RYGB was characterized by a higher glycemic variability than SG. Regression models showed that the time elapsed from surgical intervention was positively associated with a higher rate of both total PBH (Z-value: 3.32, P < 0.001) and nocturnal PBH (Z-value: 2.15, P = 0.013). CONCLUSIONS: PBH, both post-prandial and nocturnal, is more prevalent than currently believed. The rate of PBH increases at increasing time from surgery and is comparable after RYGB and SG with a higher glucose variability after RYGB.

Obstetric antiphospholipid syndrome is not associated with an increased risk of subclinical atherosclerosis.

OBJECTIVES: The persistent positivity of aPLs, either isolated or associated with thrombotic and/or obstetric events (APS), has been associated with the increase of intima-media thickness (IMT) and carotid plaques. Despite the fact that aPLs can promote both thrombotic and obstetric complications, some pathogenic differences have been documented between the two entities. This study aimed to evaluate whether the atherosclerotic risk differs between subjects with obstetric and thrombotic APS. METHODS: A total of 167 APS women (36 obstetric and 131 thrombotic) were compared with 250 aPLs negative controls. IMT of the common carotid artery (CCA) and of the bulb and the prevalence of carotid plaques were assessed. RESULTS: CCA- and bulb-IMT were significantly higher in women with thrombotic APS, while being similar between the obstetric APS and the controls [CCA-IMT: mean (s.d.) 0.97 (0.49), 0.78 (0.22) and 0.81 (0.12) mm for the thrombotic, obstetric and control groups, respectively, P < 0.001 between thrombotic and controls, P = 0.002 between thrombotic and obstetric; bulb-IMT: mean (s.d.) 1.38 (0.79), 0.96 (0.27) and 0.96 (0.51) mm for the thrombotic, obstetric and control groups, P < 0.001]. Women with thrombotic APS had significantly increased risk of presenting carotid plaques. This risk was significantly lower in obstetric APS. CONCLUSION: Unlike thrombotic APS, obstetric APS is not associated with an increase of markers of subclinical atherosclerosis. If confirmed on wider populations, these results could suggest different pathogenetic role of aPLs in promoting atherosclerosis in vascular and obstetric APS, and raise questions on the risk-benefit profile of thromboprophylaxis in obstetric APS outside pregnancy periods.

Evaluation of cardiovascular risk in adults with type 1 diabetes: poor concordance between the 2019 ESC risk classification and 10-year cardiovascular risk prediction according to the Steno Type 1 Risk Engine.

BACKGROUND: Patients with type 1 diabetes (T1D) have higher mortality risk compared to the general population; this is largely due to increased rates of cardiovascular disease (CVD). As accurate CVD risk stratification is essential for an appropriate preventive strategy, we aimed to evaluate the concordance between 2019 European Society of Cardiology (ESC) CVD risk classification and the 10-year CVD risk prediction according to the Steno Type 1 Risk Engine (ST1RE) in adults with T1D. METHODS: A cohort of 575 adults with T1D (272F/303M, mean age 36 ± 12 years) were studied. Patients were stratified in different CVD risk categories according to ESC criteria and the 10-year CVD risk prediction was estimated with ST1RE within each category. RESULTS: Men had higher BMI, WC, SBP than women, while no difference was found in HbA1c levels between genders. According to the ESC classification, 92.5% of patients aged < 35 years and 100% of patients ≥ 35 years were at very high/high risk. Conversely, using ST1RE to predict the 10-year CVD risk within each ESC category, among patients at very high risk according to ESC, almost all (99%) had a moderate CVD risk according to ST1RE if age < 35 years; among patients aged ≥35 years, the majority (59.1%) was at moderate risk and only 12% had a predicted very high risk by ST1RE. The presence of target organ damage or three o more CV risk factors, or early onset T1D of long duration (> 20 years) alone identified few patients (< 30%) among those aged ≥35 years, who were at very high risk according to ESC, in whom this condition was confirmed by ST1RE; conversely, the coexistence of two or more of these criteria identified about half of the patients at high/very high risk also according to this predicting algorithm. When only patients aged ≥ 50 years were considered, there was greater concordance between ESC classification and ST1RE prediction, since as many as 78% of those at high/very high risk according to ESC were confirmed as such also by ST1RE. CONCLUSIONS: Using ESC criteria, a large proportion (45%) of T1D patients without CVD are classified at very high CVD risk; however, among them, none of those < 35 years and only 12% of those ≥ 35 years could be confirmed at very high CVD risk by the ST1RE predicting algorithm. More studies are needed to characterize the clinical and metabolic features of T1D patients that identify those at very high CVD risk, in whom a very aggressive cardioprotective treatment would be justified.

Continuous glucose monitoring in subjects undergoing bariatric surgery: Diurnal and nocturnal glycemic patterns.

BACKGROUND AND AIMS: Although the use of Continuous Glucose Monitoring (CGM) is rapidly extending, little evidence is currently available on daily glycemic excursions after different bariatric procedures. We assessed glycemic patterns after sleeve gastrectomy (SG) and roux-en-Y gastric bypass (RYGB) using CGM. METHODS AND RESULTS: Cross-sectional study in subjects who had undergone RYGB (n = 22) or SG (n = 29) since at least 1 year, without pre-surgery or in current diabetes (T2DM) remission. All subjects underwent 7 day-CGM (Dexcom G4 PLATINUM), which provides glucose variability (GV), number and time spent in hypoglycemia, hypoglycemia patterns (postprandial, nocturnal or mixed). All indexes of GV were higher after RYGB than after SG (p < 0.001). Twenty-eight (55%) subjects experienced hypoglycemia. The number of events was higher after RYGB than SG (p = 0.017) while it did not differ in subjects with or without pre-surgery T2DM (p = 0.129). Overall, 9 (32%) subjects presented hypoglycemia exclusively during the postprandial period, 8 (29%) an exclusively nocturnal pattern and 11 (39%) a mixed pattern. The nocturnal pattern was more frequent after SG than RYGB (53.8% vs 6.7%, p = 0.036) while no difference was observed in subjects with or without pre-surgery T2DM (p = 0.697). Hypoglycemia symptoms were more frequent in subjects with postprandial than in those with nocturnal pattern (77.8% vs 12.5%, p = 0.015). CONCLUSIONS: RYGB is characterized by a greater GV and a higher number of hypoglycemia events mostly post-prandial and symptomatic, while SG is associated with nocturnal and often asymptomatic hypoglycemia. These findings suggest that post-bariatric hypoglycemia is a more complex, not exclusively, postprandial phenomenon.

The risk of osteoporosis in patients with liver cirrhosis: a meta-analysis of literature studies.

OBJECTIVE: Data about the association between cirrhosis and osteoporosis are contrasting. Thus, we have performed a meta-analysis of literature studies on this topic. DESIGN: MEDLINE, Cochrane library, EMBASE, Scopus and Web of Science databases have been searched to retrieve all articles of interest. Data on prevalence of osteoporosis, bone mineral density (BMD) and bone turnover laboratory parameters were compared among cirrhotic patients and control subjects without cirrhosis. PATIENTS: Studies on patients with liver cirrhosis screened for the presence of osteoporosis were included. RESULTS: Six case-control studies (372 cirrhotic patients and 1579 controls) were included. The prevalence of osteoporosis was higher in cirrhotic patients than in controls (34·7% vs 12·8%, OR: 2·52, 95%CI: 1·11, 5·69; P = 0·03, I(2) = 81%; P = 0·005). Accordingly, a reduced lumbar spine BMD (MD: -0·13, 95%CI: -0·24, -0·02; P = 0·02, I(2) = 93%; P < 0·00001) and z-score (MD: -1·06, 95%CI: -1·79, -0·34; P = 0·004, I(2) = 95%; P < 0·00001) were found in cirrhotic patients as compared with controls. In contrast, no significant differences were reported in femoral neck BMD and z-score. Interestingly, bone turnover laboratory parameters widely confirmed these results showing higher levels of ALP and D-Pyr, accompanied by reduced levels of IGF-1, PTH and 25-OH-D in cirrhotic patients as compared with controls. CONCLUSIONS: Despite the high heterogeneity among studies, data showed an increased prevalence of osteoporosis in patients with cirrhosis. This information suggests the need of an accurate screening of bone mineral density in patients with liver cirrhosis to plan an adequate osteoporosis management.

Mild antithrombin deficiency and risk of recurrent venous thromboembolism: a prospective cohort study.

BACKGROUND: Antithrombin deficiency, defined by antithrombin levels of <70%, is a major thrombophilic condition associated with an increased risk of venous thromboembolism (VTE). No prospective data are available about the risk of recurrent VTE associated with mildly decreased antithrombin levels (70-80%). METHODS AND RESULTS: Consecutive patients with a first VTE were stratified according to functional antithrombin levels (<70%, 70-80%, >80%) and were followed up for a mean of 8.70 years to assess the incidence of VTE recurrence. A total of 823 patients (mean age, 48.3 years; 41.9% male) were enrolled. Recurrent VTE occurred in 253 patients (3.53% per patient-year). With stratification for antithrombin levels, VTE recurrence occurred in 19 patients with antithrombin levels <70% (5.90% per patient-year), in 20 patients with antithrombin levels 70% to 80% (5.35% per patient-year), and in 214 patients with antithrombin levels >80% (3.31% per patient-year). After adjustment for major VTE risk factors and for anticoagulation duration, the risk of VTE recurrence was significantly higher in patients with antithrombin levels <70% (hazard ratio, 3.48; 95% confidence interval, 2.16-5.61) and antithrombin levels 70% to 80% (hazard ratio, 2.40; 95% confidence interval, 1.51-3.80) compared with patients with antithrombin levels >80%. When the population was stratified according to the presence or absence of major risk factors for the index event, the association remained significant only in patients with unprovoked VTE. CONCLUSIONS: The presence of mild antithrombin deficiency (70-80% antithrombin) in patients with unprovoked VTE is associated with a significantly increased risk of recurrence and should be taken into account when the duration of secondary prevention is determined. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01382550.

Methylation reactions, the redox balance and atherothrombosis: the search for a link with hydrogen sulfide.

It is now clear that homocysteine (Hcy) is irreversibly degraded to hydrogen sulfide (H(2)S), an endogenous gasotransmitter that causes in vivo platelet activation via upregulation of phospholipase A2 and downstream boost of the arachidonate cascade. This mechanism involves a transsulfuration pathway. Based on these new data, clinical and experimental models on the relationships between Hcy and folate pathways in vascular disease and information on the Hcy controversy have been reanalyzed in the present review. Most interventional trials focused on Hcy lowering by folate administration did not exclude patients routinely taking the arachidonate inhibitor aspirin. This may have influenced the results of some of these trials. It is also clear that nutritional intake of folate affects several enzymatic reactions of the methionine-Hcy cycle and associated one-carbon metabolism and, thereby, both methylation reactions and redox balance. Hence, it is conceivable that the abnormally high Hcy levels seen in pathologic states reflect a poorly elucidated perturbation of such reactions and of such balance. While it is unknown whether there is an interplay between H2S, methylation reactions, and redox balance, measuring the sole reduction of blood Hcy that follows folate administration may well be an oversimplified approach to a complex biologic perturbation. The need to investigate this complex framework is thoroughly discussed in this article.

The impact of concomitant diffuse idiopathic skeletal hyperostosis on the achievement of minimal disease activity in subjects with psoriatic arthritis.

Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification of different entheses. Psoriatic arthritis (PsA) is a seronegative spondyloarthritis associated with psoriasis. Given the possible overlap of the two diseases, we assessed whether DISH presence may affect PsA clinical outcomes. Also, predictors of DISH presence in the cohort were investigated. Consecutive PsA patients from two Italian Rheumatology Research Units were enrolled. Subjects were splitted into two groups, according to the current treatment (TNF-α blockers or traditional DMARDs). All patients underwent a rheumatologic examination, blood sample collections and spine radiographs. Information about traditional vascular risk factors was recorded. In each patient, the presence of minimal disease activity was evaluated and the presence of DISH was established according to the Resnick and Niwayama criteria. Among the 80 enrolled subjects (57.5 % men, mean age 56.5 ± 11.1 years), the overall prevalence of DISH was 30.0 %. Patients with DISH were older, with higher BMI and waist circumference. DISH subjects showed worsen BASMI, HAQ and ESR. In a multivariate regression model, BASMI was a significant predictor of DISH presence (OR 3.027, 95 % CI 1.449-6.325, p = 0.003). The prevalence of MDA was lower in DISH patients than in no-DISH (16.7 vs 41.1 %, p = 0.041), and the presence of DISH was a predictor of not achieving MDA (OR 3.485, 95 % CI 1.051-11.550, p = 0.041). PsA subjects with DISH showed worsen indices of spine mobility and articular function and lower prevalence of minimal disease activity than no-DISH patients.

Weight loss and achievement of minimal disease activity in patients with psoriatic arthritis starting treatment with tumour necrosis factor α blockers.

OBJECTIVES: To evaluate prospectively the effect of weight loss on the achievement of minimal disease activity (MDA) in overweight/obese patients with psoriatic arthritis (PsA) starting treatment with tumour necrosis factor α (TNFα) blockers. METHODS: Among subjects with PsA starting treatment with TNFα blockers, 138 overweight/obese patients received a concomitant dietary intervention (69 a hypocaloric diet (HD) and 69 a free-managed diet (FD)). Changes in metabolic variables were measured and a complete clinical rheumatological evaluation was made in all patients at baseline and after a 6-month follow-up to define the achievement of MDA. RESULTS: 126 subjects completed the study. MDA was more often achieved by HD than by FD subjects (HR=1.85, 95% CI 1.019 to 3.345, p=0.043). A diet was successful (≥5% weight loss) in 74 (58.7%) patients. Regardless of the type of diet, after 6 months of treatment with TNFα blockers, ≥5% of weight loss was a predictor of the achievement of MDA (OR=4.20, 95% CI 1.82 to 9.66, p<0.001). For increasing weight-loss categories (<5%, 5-10%, >10%), MDA was achieved by 23.1%, 44.8% and 59.5%, respectively. A higher rate of MDA achievement was found in subjects with 5-10% (OR=3.75, 95% CI 1.36 to 10.36, p=0.011) and in those with >10% (OR=6.67, 95% CI 2.41 to 18.41, p<0.001) weight loss in comparison with those with <5% weight loss. CONCLUSIONS: Regardless of the type of diet, a successful weight loss (≥5% from baseline values) is associated with a higher rate of achievement of MDA in overweight/obese patients with PsA who start treatment with TNFα blockers.

Wernicke encephalopathy in subjects undergoing restrictive weight loss surgery: a systematic review of literature data.

The use of weight loss surgery is progressively increasing, and in recent years, restrictive bariatric surgery procedures have been more often used. Although thought to be associated with a lower incidence of post-operative side effects than malabsorpitive surgery, some cases of micronutrients deficiency have been reported because of an acquired thiamine deficiency; in this clinical setting, some cases of Wernicke encephalopathy (WE) have been described. Major determinants and predictors of this major neurological complication are currently unknown. The aim of this systematic review was to analyse literature data in order to address this issue. The main result of our systematic review was that persistent vomiting is the major determinant of WE in patients undergoing restrictive weight loss surgery. In addition, early thiamine supplementation can rapidly improve the clinical conditions, avoiding permanent deficiencies. On the other hand, given the wide variability of clinical and demographic characteristics, definite prognostic factors of WE occurrence and of clinical outcome cannot be identified. In conclusion, although our results are suggestive, further ad hoc prospective studies evaluating changes in micronutrients levels according to different types of surgery are needed.

Delayed prandial insulin boluses are an important determinant of blood glucose control and relate to fear of hypoglycemia in people with type 1 diabetes on advanced technologies.

AIMS: Automated insulin delivery systems improve blood glucose control in patients with type 1 diabetes (T1D). However, optimizing their performance requires patient's proper compliance to meal insulin bolus administration. We explored real-life prevalence of delayed prandial boluses (DBs) in adults with T1D on advanced technologies, and their association with glycemic control and fear of hypoglycemia (FH). METHODS: In the last two-week web-based reports of 152 adults with T1D on Hybrid Closed Loop Systems (HCLS) or Sensor Augmented Pump (SAP), DBs were identified when a steep increase in blood glucose occurred at CGM before the prandial bolus, and CGM metrics were evaluated. All participants completed an online questionnaire on FH. RESULTS: Mean DBs over two weeks were 10.2 ± 4.7 (M ± SD, range 1-23) and more frequent in women than men (11.0 ± 4.6 vs. 9.4 ± 4.7, p = 0.036). Participants with more DBs (>12) showed significantly lower Time-In-Range (62.4 ± 13.8 vs. 76.6 ± 9.0 %) than those with less DBs (<7.7), along with higher Time-Above-Range, GMI, and Coefficient-of-Variation (ANOVA, p < 0.001 for all). Participants with higher FH score showed more DBs (11.6 ± 5.0) than those in lower tertiles (9.57 ± 4.59 and 9.47 ± 4.45, ANOVA p = 0.045). CONCLUSIONS: In patients on advanced technologies, delayed boluses are extremely common, and associate with significantly worse glycemic control. Utmost attention is needed to bolus timing, mainly tackling fear of hypoglycemia.

Postprandial Glucose Control With Different Hybrid Closed-Loop Systems According to Type of Meal in Adults With Type 1 Diabetes.

BACKGROUND: Hybrid Closed-Loop Systems (HCLs) may not perform optimally on postprandial glucose control. We evaluated how first-generation and advanced HCLs manage meals varying in carbohydrates, fat, and protein. METHOD: According to a cross-sectional design, seven-day food records and HCLs reports from 120 adults with type 1 diabetes (MiniMed670G: n = 40, MiniMed780G: n = 49, Control-IQ [C-IQ]: n = 31) were analyzed. Breakfasts (n = 570), lunches (n = 658), and dinners (n = 619) were divided according to the median of their carbohydrate (g)/fat (g) plus protein (g) ratio (C/FP). After breakfast (4-hour), lunch (6-hour), and dinner (6-hour), continuous glucose monitoring (CGM) metrics and early and late glucose incremental area under the curves (iAUCs) and delivered insulin doses were evaluated. The association of C/FP and HCLs with postprandial glucose and insulin patterns was analyzed by univariate analysis of variance (ANOVA) with a two-factor design. RESULTS: Postprandial glucose time-in-range 70 to 180 mg/dL was optimal after breakfast (78.3 ± 26.9%), lunch (72.7 ± 26.1%), and dinner (70.8 ± 27.3%), with no significant differences between HCLs. Independent of C/FP, late glucose-iAUC after lunch was significantly lower in C-IQ users than 670G and 780G (P < .05), with no significant differences at breakfast and dinner. Postprandial insulin pattern (Ins3-6h minus Ins0-3h) differed by type of HCLs at lunch (P = .026) and dinner (P < .001), being the early insulin dose (Ins0-3h) higher than the late dose (Ins3-6h) in 670G and 780G users with an opposite pattern in C-IQ users. CONCLUSIONS: Independent of different proportions of dietary carbohydrates, fat, and protein, postprandial glucose response was similar in users of different HCLs, although obtained through different automatic insulin delivery patterns.

Clinical judgment when using coagulation tests during direct oral anticoagulant treatment: a concise review.

Because their anticoagulant effect is dose predictable, steady, and little influenced by diet and drugs, laboratory monitoring was deemed unnecessary in trials on venous and arterial thromboprophylaxis with the direct oral anticoagulant drugs (DOACs) rivaroxaban, apixaban, edoxaban, or dabigatran. However, there are special clinical settings in which measurement of their anticoagulant effect may be clinically desired. Because of lack of standardization between reagents employed and their global nature, the activated partial thromboplastin time (APTT) and the prothrombin time (PT) are not generally suitable for accurately assessing the anticoagulant effect of DOACs. The modified (diluted) PT reliably quantifies the anticoagulant effect of rivaroxaban or of apixaban. However, a higher intraindividual variability from one PT reagent to another is found when the data are compared with those obtained with standard PT. The HEMOCLOT (HYPHEN BioMed, France) assay is a modified (diluted) thrombin time (TT) provided with dabigatran calibrators. However, it is performed only in few specialized centers. Anti-factor Xa (anti-FXa) chromogenic assays employ routine automated coagulometers or manual spectrometers, and kits for anti-FIIa assays that measure dabigatran levels and kits for anti-Xa with rivaroxaban calibrators are commercially available. However, no correlation has been identified between any of these tests and clinical outcomes in patients taking any of the DOACs. Thus, currently, there are evidence gaps regarding the role of laboratory testing for surveillance and management of adverse events associated with DOACs. In view of this, in addition to standardization, validation of such assays is mandatory before they can be used to make clinical decisions.

Obesity and psoriatic arthritis: from pathogenesis to clinical outcome and management.

PsA is an axial and/or peripheral inflammatory arthritis associated with psoriasis, included in the group of spondylarthritides. It has been suggested that PsA could be a systemic disease, involving even coronary arteries and the heart. An increased prevalence of vascular risk factors has been found in PsA subjects as compared with the general population and psoriatic subjects. Moreover, PsA patients exhibit an increased prevalence of liver steatosis, a marker of metabolic syndrome, and of obesity. Interestingly, many reports demonstrate that adipose tissue is metabolically active, representing a source of inflammatory mediators, known as adipokines. The latter include TNF-α, macrophage chemoattractant protein-1, plasminogen activator inhibitor-1 (PAI-1), IL-6, leptin and adiponectin, leading to a pro-inflammatory status in obese subjects. This evidence supports the idea of obesity as a low-grade inflammatory disease. Accordingly, obesity might be associated with some rheumatic diseases. In particular, it seems to affect several features of PsA, such as its development, cardiovascular risk and clinical outcome. Recent data suggest that increased BMI in early adulthood increases the risk of PsA development in psoriatic patients, supporting a link between fat-mediated inflammation and joint involvement. Obesity may represent an additive cardio-metabolic risk factor in PsA subjects. Abdominal obesity may also determine an increased risk of not achieving minimal disease activity in PsA patients, highlighting the role of abdominal fat accumulation as a negative predictor of good clinical response to biologic agents. This review assesses the relationship between obesity and PsA according to the available literature.

An easy schedule for postsurgical radioiodine administration in newly diagnosed differentiated thyroid carcinoma patients.

OBJECTIVE: To validate the simplest approach to preparing patients with differentiated thyroid carcinoma (DTC) for (131) I-administration ((131) I-A), minimizing the impact of hypothyroidism. DESIGN: Panel study. PATIENTS: Ninety patients with DTC were enrolled in the study. Sixty (Group A) underwent total thyroidectomy (TT); L-T4 was not administered in preparation for (131) I-A planned for 3 weeks later. Thirty patients (Group B) with previous TT and (131) I-A stopped L-T4 in preparation for clinical evaluation, including whole-body scanning (WBS)/radioiodine therapy during thyrotrophin (TSH) stimulation planned for 3 weeks (or more) later. MEASUREMENTS: Thyrotrophin was measured the day before TT for group A, during L-T4 for group B (baseline-time 1) and then every week until it reached ≥ 30 mIU/l (time 2). Quality of life (QoL) was evaluated by Billewicz index. RESULTS: At week 3, 100% of patients in group A and 56.6% of group B exceeded TSH > 30 mIU/l. In group B, the cut-off was achieved in four patients at the fourth week (TSH 38.6 ± 8.7 mIU/l), in 3 at the fifth (53.2 ± 3) and in 6 at the sixth (42.3 ± 6.1). From time 1 to time 2, total QoL scores were less affected in group A (percentage decrease: 105%) than in group B (218%). At time 2, the total score was >+19 in group A in 46 patients and in 30 in group B. In group A, TSH levels in the higher tertile of QoL (61 ± 6 mIU/l) were not different from those in the lower tertile (62.3 ± 11.1)(P > 0.1); similar results were seen in group B (69.3 ± 13.3 vs 62.9 ± 13.1)(P > 0.1). There was a positive correlation between the time to obtain TSH ≥ 30 mIU/l and total QoL scores. CONCLUSIONS: Quality of life scores were not affected by thyrotrophin was measured the day before TT levels as absolute values. A longer time to obtain TSH ≥ 30 mIU/l was positively correlated with worse scores of QoL. We suggest 3 weeks without therapy can be used as an easy schedule in patients who undergo TT for DTC.

Nutritional management of glycogen storage disease type III: a case report and a critical appraisal of the literature.

Glycogen storage disease Type III (GSD III) is an autosomal recessive disease due to the deficiency of the debranching enzyme, which has two main consequences: a reduced availability of glucose due to the incomplete degradation of glycogen, and the accumulation of abnormal glycogen in liver and cardiac/skeletal muscle. The role of dietary lipid manipulations in the nutritional management of GSD III is still debated. A literature overview shows that low-carbohydrate (CHO) / high-fat diets may be beneficial in reducing muscle damage. We present a 24-year GSD IIIa patient with severe myopathy and cardiomyopathy in whom a gradual shift from a high-CHO diet (61% total energy intake), low-fat (18%), high-protein (21%) to a low-CHO (32 %) high-fat (45%) / high-protein (23%) diet was performed. CHO was mainly represented by high-fiber, low glycemic index food, and fat consisted prevalently of mono and polyunsaturated fatty acids. After a 2-year follow-up, all biomarkers of muscle and heart damage markedly decreased (by 50-75%), glucose levels remained within the normal range and lipid profile was unchanged. At echocardiography, there was an improvement in geometry and left ventricular function. A low -CHO, high-fat, high-protein diet seems to be safe, sustainable and effective in reducing muscle damage without worsening cardiometabolic profile in GSDIIIa. This dietary approach could be started as early as possible in GSD III displaying skeletal/cardiac muscle disease in order to prevent/minimize organ damage.