ß-Thalassemia and Diabetes Mellitus: Current State and Future Directions.

ß-Thalassemia major is a congenital hemoglobin disorder that requires regular blood transfusion. The disease is often associated with iron overload and diabetes mellitus, among other complications. Pancreatic iron overload in ß-thalassemia patients disrupts ß-cell function and insulin secretion and induces insulin resistance. Several risk factors, including family history of diabetes, sedentary lifestyle, obesity, gender, and advanced age increase the risk of diabetes in ß-thalassemia patients. Precautionary measures such as blood glucose monitoring, anti-diabetic medications, and healthy living in ß-thalassemia patients notwithstanding, the prevalence of diabetes in ß-thalassemia patients continues to rise. This review aims to address the relationship between ß-thalassemia and diabetes in an attempt to understand how the pathology and management of ß-thalassemia precipitate diabetes mellitus. The possible employment of surrogate biomarkers for early prediction and intervention is discussed. More work is still needed to better understand the molecular mechanism(s) underlying the link between ß-thalassemia and diabetes and to identify novel prognostic and therapeutic targets.

New device, 'old' allergens. Allergic contact dermatitis caused by the Dexcom G7 glucose sensor.

BACKGROUND: Allergic contact dermatitis (ACD) has been reported as an adverse effect from the use of several glucose sensors and insulin pumps from different manufacturers. Isobornyl acrylate (IBOA) has been identified as a major culprit sensitizer, but also other acrylates and (modified) colophonium have been reported as causes of ACD. OBJECTIVES: To report the two first cases diagnosed with ACD caused by the Dexcom G7 (DG7) glucose sensor. PATIENTS AND METHODS: Two children with suspected ACD from DG7 were patch tested with our medical device series with an addition of selected test preparations including two variants of modified colophonium - methyl hydrogenated rosinate (MHR) and glyceryl hydrogenated rosinate (GHR). Both patients were also tested with acetone extracts made from different parts of the DG7 sensor. The extracts were analysed by gas chromatography-mass spectrometry (GC-MS). RESULTS: Both patients tested positive to IBOA, hydroabietyl alcohol and GHR. In addition, patient 1 had a positive reaction to MHR and patient 2 had a positive reaction to colophonium. The GC-MS analyses showed the presence of IBOA and colophonium-related substances in the DG7 extracts. CONCLUSIONS: Both patients were diagnosed with contact allergy to well-known medical device-related sensitizers. The presence of IBOA and (modified) colophonium in a newly introduced (on the Swedish market in 2023) glucose sensor is remarkable and indicates an inadequate toxicological assessment of the materials used in the sensor.

Diabetes and prediabetes in children with cystic fibrosis.

PURPOSE OF REVIEW: Glucose metabolism alterations in cystic fibrosis range from the classic cystic fibrosis-related diabetes (CFRD) to forms of glucose intolerance and prediabetes. The aim of the present work is to review the most up-to-date novelties in terms of CFRD diagnosis and therapy. This review is timely and relevant because it allows an update for the early and correct classification of glucose abnormalities in cystic fibrosis and because it favours an appropriate therapeutic approach. RECENT FINDINGS: Confirm that Oral Glucose Tolerance Test is still the diagnostic gold standard despite the advent of continuous glucose monitoring (CGM) systems; this latter is spreading very rapidly, however, to date, there is still no strong evidence to hypothesize the use of CGM for diagnostic purposes. CGM has indeed proven to be very useful in managing and guiding CFRD therapy. SUMMARY: Tailored and personalized insulin therapy is still the recommended therapy for children and adolescents with CFRD, although nutritional intervention and oral hypoglycaemic treatment are equally important and efficacious. Finally CFTR modulators have allowed the increase of the life expectancy of cystic fibrosis patients and have proven effective not only in improving the pulmonary function and the nutritional status but also the glucose control.

Persistent post-bariatric-surgery hypoglycemia: A long-term follow-up reassessment.

BACKGROUND AND AIM: Post-bariatric-surgery hypoglycemia (PBH) is a serious complication of bariatric surgery (BS). In our previous study about three quarters of the patients developed PBH. However long-term follow-up data is lacking to determine whether this condition improves with time. The aim of the current study was to re-assess post-BS patients who participated in our previous study and determine whether there are changes in the frequency and/or severity of hypoglycemic events. METHODS AND RESULTS: Twenty-four post-BS, post Roux-en-Y gastric-bypass (RYGB = 10), post omega-loop gastric-bypass (OLGB = 9) and post sleeve-gastrectomy (SG = 5) individuals were reevaluated in a follow-up study 34.4 ± 4 months after their previous assessment and 67 ± 17 months since surgery. The evaluation included: a dietitian assessment, a questionnaire, meal-tolerance test (MTT) and a one-week masked continuous glucose monitoring (CGM). Hypoglycemia and severe hypoglycemia were defined by glucose levels ≤54 mg/dl and ≤40 mg/dl, respectively. Thirteen patients reported questionnaire meal-related complaints, mainly non-specific. During MTT, hypoglycemia occurred in 75% of the patients, and severe hypoglycemia in a third, but none was associated with specific complaints. During CGM, 66% of patients developed hypoglycemia and 37% had severe hypoglycemia. We did not observe significant improvements in hypoglycemic events compared to the previous assessment. Despite the high frequency of hypoglycemia, it did not necessitate hospitalizations or lead to death. CONCLUSIONS: PBH did not resolve within long-term follow-up. Intriguingly, most patient were unaware of these events which can lead to underestimation by the medical staff. Further studies are needed to determine possible long term sequela of repeated hypoglycemia.

Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic mucosal melanoma.

INTRODUCTION: Nivolumab is an immune checkpoint inhibitor used in the treatment of several malignancies. A number of immune-related endocrinopathies have been linked to its use. CASE REPORT: We report a unique case of a 74-year-old man with well-controlled diabetes mellitus type 2 and metastatic mucosal anorectal melanoma who presented with diabetic ketoacidosis after receiving his third cycle of nivolumab 240 mg intravenous (IV) every 2 weeks. He was found to have autoantibodies against glutamic acid decarboxylase 65. Genotyping for human leukocyte antigens showed the presence of DQB1*02:01 and DRB1*03:01. MANAGEMENT AND OUTCOME: His presentation was complicated by acute renal failure. He required aggressive fluid resuscitation and insulin supplementation to reverse severe acid-base disturbance and multiple electrolyte abnormalities. After an 8-week interruption, the patient restarted nivolumab without any further evidence of adverse events over the next 12 weeks. He continues to require insulin replacement therapy. DISCUSSION AND CONCLUSION: Development of type 1 diabetes with the use of immune checkpoint inhibitors has been increasingly reported in the literature. The exact mechanism for autoimmune diabetes precipitated by nivolumab is yet to be elucidated. Patient education about the symptoms of diabetes and regular glucose monitoring cannot be overemphasized. Testing for antibodies against glutamic acid decarboxylase 65, insulin receptors, and islet cells may also prove useful. Human leukocyte antigen DQ and DR haplotyping prior to immune checkpoint inhibitor treatment might help determine susceptibility toward developing type 1 diabetes, and provide opportunities for earlier recognition, intervention, and possibly prevention.

Impact of super energy-dense oral nutritional supplementation (SED ONS) on glycemic variability and food intake postoperatively in gastric cancer patients.

PURPOSE: Adherence to oral nutritional supplements (ONS) to prevent weight loss after gastrectomy is problematic. The present study evaluated the impact of super energy-dense ONS (SED ONS; 4 kcal/mL) on glycemic change and energy intake after gastrectomy. METHODS: Gastrectomy patients were placed on continuous glucose monitoring for a 3-day observation period after food intake had been stabilized postoperatively. In addition, they were given 0, 200, and 400 kcal/day of SED ONS on Days 1, 2, and 3, respectively. The primary outcome was the area under the curve < glucose 70 mg/dL (AUC < 70). The secondary outcomes were other indices of glucose fluctuation and the amount of food and SED ONS intake. RESULTS: Seventeen patients were enrolled. The AUC < 70 did not differ significantly with or without SED ONS over the observation period. SED ONS did not cause postprandial hypoglycemia and prevented nocturnal hypoglycemia. The mean dietary intake did not change significantly during the observation period, and the total energy intake increased significantly according to the amount of SED ONS provided. CONCLUSION: SED ONS after gastrectomy increased the total energy intake without dietary reduction and it did not result in hypoglycemia.

Impaired awareness of hypoglycaemia in women with type 1 diabetes in pregnancy: Hypoglycaemia fear, glycaemic and pregnancy outcomes.

AIMS: To examine maternal fear of hypoglycaemia, glycaemia and pregnancy outcomes in women with impaired and normal awareness of hypoglycaemia. METHODS: A pre-planned sub-study of 214 pregnant women with type 1 diabetes who participated in the CONCEPTT trial. Participants completed hypoglycaemia fear surveys (HFS-II) at baseline. Logistic regression and Poisson regression analyses were used to obtain an adjusted estimate for the rate ratio relating awareness to the number of severe hypoglycaemic episodes, and for several neonatal outcomes in relation to the total HFS-II score. The role of continuous glucose monitoring (CGM) use was examined. RESULTS: Overall, 30% of participants reported impaired awareness of hypoglycaemia (n = 64). Women with impaired awareness of hypoglycaemia had more episodes of severe hypoglycaemia (mean 0.44 vs. 0.08, p < 0.001) (12-34 weeks gestation) and scored higher on the HFS-II scale (43.7 vs. 36.0, p 0.008), indicating more fear of hypoglycaemia. They spent more time below range (CGM <3.5 mmol/L) and exhibited more glycaemic variability at 12 weeks gestation. Higher overall HFS-II scores were associated with a higher risk of maternal severe hypoglycaemia episodes (Rate Ratio 1.78, 95% CI 1.39-2.27). Women with impaired awareness of hypoglycaemia had less maternal weight gain but there were no differences in neonatal outcomes between women with impaired awareness of hypoglycaemia and normal hypoglycaemia awareness. Higher HFS-II scores were associated with more nephropathy (Odds Ratio 1.91, 95% CI 1.06-3.4). CGM use after 12 weeks was not associated with the number of episodes of severe hypoglycaemia (RR 0.75, 95% CI 0.49-1.15; p = 0.18). CONCLUSIONS: In pregnant women with type 1 diabetes, impaired awareness of hypoglycaemia is associated with more maternal severe hypoglycaemia episodes and more fear of hypoglycaemia. Having impaired awareness of hypoglycaemia and/or fear of hypoglycaemia should alert clinicians to this increased risk. Reassuringly, there was no increase in adverse neonatal outcomes.

Allergic contact dermatitis caused by dipropylene glycol diacrylate in the Omnipod® insulin pump.

BACKGROUND: Cases of allergic contact dermatitis (ACD) caused by isobornyl acrylate (IBOA) in the Omnipod® insulin pump have previously been reported. OBJECTIVES: To present three cases of patients with ACD caused by a new allergen in the pump, and results from chemical analyses. METHODS: Omnipod pumps from different batches were analysed by gas chromatography-mass spectrometry. Aimed testing, with the department's medical device (MD) series and substances identified in the pump including dipropylene glycol diacrylate (DPGDA) at 0·01% and 0·1% in petrolatum (pet.), was performed. Patch testing also included extracts from the device, the adhesive patch as is, and allergens from baseline series. RESULTS: All patients tested positive to 0·1% DPGDA in pet., and two patients additionally to a 0·01% concentration. DPGDA was found in extracts of the Omnipod pumps brought by the patients. An Omnipod pump from an earlier batch contained tripropylene glycol diacrylate, IBOA, N,N-dimethylacrylamide, di(ethylene glycol)ethyl ether acrylate (DEGEA) but no DPGDA. One of the patients reacted positively to all of these allergens except DEGEA, which was not tested. CONCLUSIONS: When suspecting ACD to MDs, DPGDA at 0·1% in pet. should be tested. The contents of Omnipod have changed over time. Patch testing with updated test series and relevance assessment of positive reactions is a delicate task. Children, with lifelong use of MDs, risk contracting many allergies with potential cross-allergies. A question should be raised as to whether these low molecular weight acrylates should be used at all in devices constantly worn on the skin.

Update on glucose control during and after critical illness.

PURPOSE OF REVIEW: There is a complex bidirectional relationship between critical illness and disordered glucose metabolism. This review aims to provide a comprehensive summary of the recent evidence focused on the relationship between critical illness and disordered glucose metabolism through the distinct phases of prior to, during, and after an acute illness that requires admission to the intensive care unit (ICU). RECENT FINDINGS: Recent data suggest that preexisting glucose metabolism affects the optimal blood glucose target during critical illness, with preliminary data suggesting that glucose targets should be 'personalized' based on preexisting glycemia. Because of the close association between critical illness and disordered glucose metabolism, there is a need to optimize glucose monitoring in the ICU with rapid, precise, and cost-efficient measurements at the bedside. Recent studies have evaluated the use of various methodologies, with a focus on the use of near-continuous glucose monitoring. For those patients with preexisting diabetes who survive ICU, nocturnal hypoglycemia may be an unrecognized and important issue when discharged to the ward. There is increasing evidence that patients with high blood glucose during their acute illness, so called 'stress hyperglycemia', are at increased risk of developing diabetes in the years following recovery from the inciting event. Critically ill patients with COVID-19 appear at greater risk. SUMMARY: There have been important recent insights in the approach to glucose monitoring and glucose targets during critical illness, monitoring and administration of glucose-lowering drugs on discharge from the ICU, and longitudinal follow-up of patients with stress hyperglycemia.

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.

Implantable and transcutaneous continuous glucose monitoring system: a randomized cross over trial comparing accuracy, efficacy and acceptance.

AIM: To compare accuracy, efficacy and acceptance of implantable and transcutaneous continuous glucose monitoring (CGM) systems. METHODS: In a randomized crossover trial we compared 12 weeks with Eversense implantable sensor (EVS) and 12 weeks with Dexcom G5 transcutaneous sensor (DG5) in terms of accuracy, evaluated as Mean Absolute Relative Difference (MARD) vs capillary glucose (SMBG), time of CGM use, adverse events, efficacy (as HbA1c, time in range, time above and below range) and psychological outcomes evaluated with Diabetes Treatment Satisfaction Questionnaire (DTSQ), Glucose Monitoring Satisfaction Survey (GMSS), Hypoglycemia Fear Survey (HFS2), Diabetes Distress Scale (DDS). RESULTS: 16 subjects (13 males, 48.8 ± 10.1 years, HbA1c 55.8 ± 7.9 mmol/mol, mean ± SD) completed the study. DG5 was used more than EVS [percentage of use 95.7 ± 3.6% vs 93.5 ± 4.3% (p = 0.02)]. MARD was better with EVS (12.2 ± 11.5% vs. 13.1 ± 14.7%, p< 0.001). No differences were found in HbA1c. While using EVS time spent in range increased and time spent in hyperglycemia decreased, but these data were not confirmed by analysis of retrofitted data based on SMBG values. EVS reduced perceived distress, without significant changes in other psychological outcomes. CONCLUSIONS: CGM features may affect glycemic control and device acceptance.

Contact allergy to the Dexcom G6 glucose monitoring system-Role of 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate in the new adhesive.

BACKGROUND: Skin reactions to the glucose monitoring systems Dexcom G5 and G6 have been rare. In 2019, the components of the adhesive were exchanged for better skin fixation. Since then, more and more patients experienced severe skin reactions. A few months ago, 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) was identified as a new component in the adhesive of the G6 model. Furthermore, it was suspected that isobornyl acrylate (IBOA) was also a component of the exchanged adhesive. OBJECTIVES: Our objective was to investigate if MBPA plays a major role in the increasing skin problems of patients without a history of IBOA-sensitization. Furthermore, our aim was to examine whether IBOA is contained in the newer model adhesive and may also contribute to allergic contact dermatitis (ACD). PATIENTS AND METHODS: Five patients with a newly occurred ACD caused by the glucose monitoring system Dexcom G6 were investigated. Patch testing including MBPA in three different concentrations, as well as IBOA, were performed. Gas chromatography-mass spectrometry of the newer system Dexcom G6 was carried out. RESULTS: All patients were shown to be sensitized to MBPA, while MBPA 0,5% showed the strongest reaction. On the other hand, IBOA was tested negative. CONCLUSION: In our study group, MBPA was observed to be the triggering allergen of the recently changed adhesive.

Dynamics of glucose levels after Billroth I versus Roux-en-Y reconstruction in patients who undergo distal gastrectomy.

PURPOSE: Recent studies have highlighted the importance of understanding trends in blood glucose levels. We examined the differences in blood glucose fluctuations according to the reconstruction method used after distal gastrectomy (DG) in patients with non-diabetic gastric cancer (GC). METHODS: Sixty-one patients who underwent DG followed by either Billroth 1 (B1) or Roux-en-Y (R-Y) reconstruction were enrolled in this study. We used flash continuous glucose monitoring (CGM), a new technique for assessing glycemic control, to document the post-gastrectomy glycemic profile. Immediately before discharge, a CGM sensor was placed subcutaneously to evaluate blood glucose trends for 2 weeks. RESULTS: The coefficient of variation of glucose levels was significantly higher in the Roux-en-Y (R-Y) group than in the Billroth I (B-I) group (p = 0.0260). The time below range (TBR, glucose levels of < 70 mg/dL) was also significantly higher in the R-Y group (p = 0.0115). Logistic regression analysis revealed that preoperative casual glucose levels of < 100 mg/dL and R-Y reconstruction were independently correlated with risk factors for a postoperative nocturnal TBR of > 30% (p = 0.006 and 0.042, respectively). CONCLUSION: Our findings provide new insights into the post-DG reconstruction method selected for patients with non-diabetic gastric cancer by assessing postoperative blood glucose fluctuations using flash CGM.

Real-world outcomes with different technology modalities in type 1 diabetes.

BACKGROUND AND AIMS: Several treatment modalities are available for type 1 diabetes (T1D), including continuous glucose monitoring (CGM) and flash glucose monitoring (FGM) with MDI, sensor-augmented pumps with predictive low-glucose suspend function (SAP-PLGS) and hybrid closed-loop systems (HCL). The aim of the study was to evaluate the real-world benefits obtained with these treatment modalities. METHODS AND RESULTS: A cross-sectional study was performed, selecting 4 groups of T1D subjects, regarding their treatment modalities, paired by age, sex and diabetes duration. A comparison was performed, concerning time in different glucose ranges in 2-week sensor downloads. Estimated HbA1c, glycaemic variability measures and sensor use were also compared. 302 T1D people were included (age: 39 ± 12 years, 47% male, diabetes duration: 21 ± 10 years, estimated HbA1c: 7.28 ± 0.84% (56 ± 9 mmol/mol), baseline HbA1c: 7.4 ± 1.0% (57 ± 11 mmol/mol), length of use of the device 8 [3-21] months). Group 1 (CGM + MDI) and 2 (FGM + MDI) showed no differences in time in different glucose ranges. Group 4 (HCL) showed a higher time 70-180 mg/dl and a lower time in hypoglycaemia than group 3 (SAP-PLGS). Group 1 and 2 showed lower time 70-180 mg/dl, higher time in hyperglycaemia and higher glycaemic variability measures than group 3. Group 4 was superior to groups 1 and 2 in all the outcomes. CONCLUSION: Real-life achievements in glycaemic control and glycaemic variability are described. HCL offer the maximum benefit in terms of time in range and hypoglycaemia protection, compared to CGM + MDI, FGM + MDI and SAP-PLGS.

Contact dermatitis from glucose sensors in Spain: A multicentric approach.

BACKGROUND: Allergic contact dermatitis from glucose sensors may interfere with their ongoing application. OBJECTIVE: To evaluate a series of Spanish patients with contact dermatitis to glucose sensors regarding former sources of contact allergens, patch test results, and outcomes from the ongoing use of the device. METHODS: A series of patients with contact dermatitis from glucose sensors was investigated in eight dermatology departments across Spain (epidemiological features, brands, latency time to develop dermatitis, the ability to continue using the devices as well as the patch test results). RESULTS: Thirty patients were evaluated (mean age 20.9 years). A total of 66.7% were children and 66.7% female. Ninety per cent used Freestyle Libre (FSL). Eight of 26 (30.8%) reacted to isobornyl acrylate (IBOA) and two of 20 (10.0%) to N,N dimethylacrylamide (DMAA). The mean latency time to develop dermatitis was 9 months. Sixteen of 29 (55.2%) patients continued using the same sensor causing the reaction. Thirteen of 29 (44.8%) patients were unable to continue using the sensor because of severe reactions. Of these, five were positive to IBOA, one to IBOA and DMAA, one to DMAA, one to colophony, and one to isopropyl alcohol wipes. In one patient, the outcome was unknown. CONCLUSION: The frequency of sensitisation to IBOA and DMAA, was lower than in other European series, but similar to a previously published Spanish article. Legislation requiring manufacturers to provide information regarding the composition of medical devices and cooperate with the investigations into contact dermatitis is urgently needed.

[Neural networks in the predictive diagnosis of cognitive impairment in type 1 and type 2 diabetes mellitus].

BACKGROUND: Cognitive dysfunction, including mild cognitive impairment and dementia, is increasingly recognized as a serious complication of diabetes mellitus (DM) that affects patient well-being and disease management. Magnetic resonance imaging (MRI)-studies have shown varying degrees of cortical atrophy, cerebral infarcts, and deep white matter lesions. To explain the relationship between DM and cognitive decline, several hypotheses have been proposed, based on the variability of glycemia leading to morphometric changes in the brain. The ability to predict cognitive decline even before its clinical development will allow the early prevention of this pathology, as well as to predict the course of the existing pathology and to adjust medication regimens. AIM: To create a computer neural network model for predicting the development of cognitive impairment in DM on the basis of brain neuroimaging techniques. MATERIALS AND METHODS: The study was performed in accordance with the standards of good clinical practice; the protocol was approved by the Ethics Committee. The study included 85 patients with type 1 diabetes and 95 patients with type 2 diabetes, who were divided into a group of patients with normal cognitive function and a group with cognitive impairment. The patient groups were comparable in age and duration of disease. Cognitive impairment was screened using the Montreal Cognitive Assessment Scale. Data for glycemic variability were obtained using continuous glucose monitoring (iPro2, Libre). A standard MRI scan of the brain was performed axially, sagittally, and coronally on a Signa Creator E, GE Healthcare, 1.5 Tesla, China. For MRI data processing we used Free Surfer program (USA) for analysis and visualization of structural and functional neuroimaging data from cross-sectional or longitudinal studies, and for segmentation we used Recon-all batch program directly. All statistical analyses and data processing were performed using Statistica Statsofi software (version 10) on Windows 7/XP Pro operating systems. The IBM WATSON cognitive system was used to build a neural network model. RESULTS: As a result of the study, cognitive impairment in DM type 1was predominantly of mild degree 36.9% (n=24) and moderate degree 30.76% (n=20), and in DM type 2 mild degree 37% (n=30), moderate degree 49.4% (n=40) and severe degree 13.6% (n=11). Cognitive functions in DM type 1 were impaired in memory and attention, whereas in DM type 2 they were also impaired in tasks of visual-constructive skills, fluency, and abstraction (p0.001). The analysis revealed differences in glycemic variability indices in patients with type 1 and type 2 DM and cognitive impairment. Standard MRI of the brain recorded the presence of white and gray matter changes (gliosis and leukoareosis). General and regional cerebral atrophy is characteristic of type 1 and type 2 DM, which is associated with dysglycemia. When building neural network models for type 1 diabetes, the parameters of decreased volumes of the brain regions determine the development of cognitive impairment by 93.5%, whereas additionally, the coefficients of glycemic variability by 98.5%. The same peculiarity was revealed in type 2 DM 95.3% and 97.9%, respectively. CONCLUSION: In DM type 1 and type 2 with cognitive impairment, elevated coefficients of glycemic variability are more frequently recorded. This publication describes laboratory and instrumental parameters as potential diagnostic options for effective management of DM and prevention of cognitive impairment. Neural network models using glycemic variability coefficients and MR morphometry allow for predictive diagnosis of cognitive disorders in both types of diabetes.

Cutaneous adverse events in a randomized controlled trial of flash glucose monitoring among youth with type 1 diabetes mellitus.

BACKGROUND: The literature regarding flash glucose monitoring (FGM)-associated cutaneous adverse events (AE) is limited. OBJECTIVES: This study among youth participating in a 6 month randomized controlled trial aimed to compare cutaneous AE between FGM and self-monitored blood glucose (SMBG) use and evaluate premature FGM sensor loss. METHODS: Patients aged 13 to 20 years with type 1 diabetes were randomized to intervention (FGM and usual care) or control (SMBG and usual care). Participants self-reported cutaneous AEs electronically every 14 days. Reports were analyzed to determine frequency, type, and severity of cutaneous AEs, and evaluate premature sensor loss. RESULTS: Sixty-four participants were recruited; 33 randomized to FGM and 31 to control. In total, 80 cutaneous AEs were reported (40 in each group); however, the proportion of participants experiencing cutaneous AEs was greater in the FGM group compared to control (58% and 23% respectively, P = .004). FGM participants most frequently reported erythema (50% of AEs), while controls most commonly reported skin hardening (60% of AEs). For FGM users, 80.0% of cutaneous AEs were mild, 17.5% moderate, and 2.5% severe. Among controls, 82.5% of cutaneous AEs were mild and 17.5% moderate. One participant ceased using FGM due to recurring cutaneous AEs. Additionally, over 6 months, 82% of FGM participants experienced at least one premature sensor loss, largely unrelated to a cutaneous AE. CONCLUSIONS: Cutaneous FGM-associated AEs are common, and mostly rated as mild. However, the majority of users continued FGM despite cutaneous AEs. Awareness of cutaneous complications and mitigation measures may reduce cutaneous AEs and improve the overall experience of FGM.

Pediatric diabetes and skin disease (PeDiSkin): A cross-sectional study in 369 children, adolescents and young adults with type 1 diabetes.

BACKGROUND: The spectrum of skin disorders in children with type 1 diabetes (T1D) and their impact on affected persons are still incompletely understood. This study assessed the prevalence of skin diseases, cutaneous complications associated with T1D treatment and skin-related quality of life (QoL) in young T1D persons. METHODS: Participation in this interdisciplinary, single-center, cross-sectional, observational study was offered to all persons with T1D ≤20 years. Participants were characterized by a detailed medical history, routine laboratory workup, thorough clinical examinations and an established QoL questionnaire. RESULTS: Three hundred and sixty-nine persons were recruited (55% male; age 12.3 ± 4.4 years; HbA1c 7.4 ± 1.0%; mean ± SD). Continuous subcutaneous insulin infusion (CSII) was used by 72.4%, multiple daily injections (MDI) by 27.6% and continuous glucose monitoring (CGM) by 76%. Skin affections occurred in 91.8% of the study population. Device-associated lesions were most prevalent, including lipohypertrophy in 42.2% of MDI and 46.8% of CGM users and contact eczema associated with CSII or CGM in 14.2% and 18.3%, respectively. Diabetes-associated skin disorders and skin infections were rare or absent. Skin-related QoL impairment was low or absent in 95% of patients. CONCLUSIONS: Skin diseases have a high prevalence and a broad spectrum in young persons with T1D. Eczematous reactions to CSII and CGM devices represent the most frequent skin complications. This highlights the need for regular skin checkups as an integral part of pediatric diabetes consultations and interdisciplinary cooperation for classification and treatment options.

The implanted glucose monitoring system Eversense: An alternative for diabetes patients with isobornyl acrylate allergy.

BACKGROUND: Some patients with diabetes develop skin reactions when using systems for continuous glucose monitoring (CGM) or insulin pumps. Regular usage and long wearing periods lead not only to skin irritation, but also to allergic contact dermatitis. It has been shown that allergens such as isobornyl acrylate (IBOA) are present in the plastic housing and also in the adhesives of medical devices used for diabetes treatment. OBJECTIVES: To evaluate the IBOA content of all parts of a newly introduced, implanted CGM system (Eversense) to check whether this can be an alternative for IBOA-sensitized patients. METHODS: The IBOA content of the implanted sensor itself (n = 3), the transmitter (n = 3), and two different types of adhesive (white adhesive [n = 4] and clear adhesive [n = 4]) was measured by gas chromatography/mass spectrometry. RESULTS: No IBOA was found in any part of this CGM system. CONCLUSIONS: Patients with an IBOA allergy may be able to use this implanted CGM system.

Contact dermatitis caused by glucose sensors in diabetic children.

BACKGROUND: Allergic contact dermatitis caused by glucose sensors has been recently described in diabetics, mostly in adult patients. Isobornyl acrylate and N-N dimethylacrylamide are the potent causative agents. OBJECTIVES: To describe a child population with contact dermatitis caused by glucose sensors, determine the causative allergen, and assess the prevalence of isobornyl acrylate (IBOA) sensitization. PATIENTS AND METHODS: Overall, 12 children with a reaction to medical devices, either glucose sensors or insulin sets, were patch tested with the European baseline series, glues and rubber, (meth) acrylates series, and with piece of the adhesive part of the glucose sensor FreeStyle Libre. Isobornyl acrylate 0.1% pet. was patch tested in 11 patients, and N-N dimethylacrylamide in two. Some patients were tested with adhesive parts of the infusion set. RESULTS: Overall, 10 children reacted to the adhesive part of the sensor FreeStyle Libre, and 10 children were sensitized to IBOA. One patient turned out to be negative in all patch tests. CONCLUSION: Allergic contact dermatitis caused by glucose sensors is common in the pediatric diabetic patient population. Like in the adult patient population, IBOA was the culprit allergen, with 83.3% sensitization prevalence in children exhibiting adverse cutaneous reactions caused by FreeStyle Libre.