The feasibility of point shear wave elastography (pSWE) in the assessment of pancreas stiffness in diabetic patients and healthy volunteers.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the dysfunctional metabolism of carbohydrates, fats, and proteins caused by impaired insulin secretion and insulin resistance. This study investigated the feasibility of using point shear wave elastography (pSWE) of the pancreas by comparing the shear wave velocity (SWV) measurements of three anatomical areas in patients with T1DM and healthy volunteers. This study included 30 patients with T1DM (9 male, 21 female) and 23 healthy controls (11 men, 12 women). Two experienced certified operators performed the examinations and took the SWV measurements. The mean SWV of the entire pancreas parenchyma differed significantly between patients and controls (1.1 ± 0.29 and 0.74 ± 0.19 m/s, respectively; p ≤ 0.001). Moreover, the SWVs of the pancreatic segments were significantly different in patients and controls; the mean SWV values of the pancreas head, body, and tail (respectively) in patients vs. controls were 0.99 ± 0.36 vs. 0.76 ± 0.26 m/s (p = 0.012), 1.1 ± 0.52 vs. 0.74 ± 0.23 (p ≤ 0.001), and 1.0 ± 0.34 vs. 0.73 ± 0.28 (p ≤ 0.001). This study confirmed the feasibility of quantifying pancreas tissue stiffness with pSWE and revealed that patients with T1DM had higher pancreas tissue stiffness than controls. Further studies are required to determine the potential value of pSWE as a screening tool in patients with prediabetes.

Insulin resistance may accelerate typical changes in heart function among type 1 diabetes patients, particularly in overweight patients: a preliminary study.

Introduction: Type 1 diabetes (T1D) is a metabolic disease characterized by insulin deficiency and subsequent hyperglycemia. Cardiovascular diseases are the prime cause of mortality and morbidity among patients with T1D. Accumulating metabolic disturbances and accelerated cardiac fibrosis fuel the development of heart dysfunction. As insulin resistance (IR) is a risk factor for the development and worsened course of heart failure, this study aimed to assess its impact on heart function in patients with T1D. Methods: Adult participants were recruited prospectively. The inclusion criteria included a diagnosis of T1D. The exclusion criteria were other types of diabetes, symptoms/treatment of heart failure, AST and/or ALT exceeding the upper reference limit by ≥2x, hepatitis, alcoholism, metformin treatment, and pregnancy. The participants underwent a medical interview, physical examination, biochemical test, and echocardiography. Results: The mean age in the study group was 38 ± 9.6 years, and the mean diabetes duration was 21.8 ± 11.3 years. The median BMI in the study cohort was 23.39 kg/m2. Patients with IR had significantly lower mitral E/A ratio and left ventricular and left atrial volume ratio (LVLAVR), higher LV mass index, and presented with altered mitral annular velocities. Conclusions: IR seems to accelerate the pattern of typical changes in heart function among patients with T1D, especially in the overweight subgroup.

The association of thyroid autoimmunity with ovarian reserve in women with type 1 diabetes with and without polycystic ovary syndrome.

The aim of the study was to investigate the relation between thyroid autoimmunity (TAI), reflected as the presence of thyroid peroxidase antibodies (TPOAb), and parameters of ovarian reserve in women with type 1 diabetes (T1DM) and polycystic ovary syndrome (PCOS). We studied 83 euthyroid women with T1DM (age - 26 ± 5 years, BMI - 24 ± 3 kg/m2) - 12 with PCOS and positive TPOAb (PCOS + TPOAb), 29 with PCOS with negative TPOAb (PCOS + noTPOAb), 18 without PCOS with positive TPOAb (noPCOS + TPOAb), 24 without PCOS with negative TPOAb (noPCOS + noTPOAb). Serum concentrations of anti-Müllerian hormone (AMH), sex hormones, TSH, thyroid hormones and TPOAb were assessed. The prevalence of TAI was comparable between PCOS and noPCOS. We did not observe differences in hormonal profile or AMH concentration between two PCOS groups-PCOS + TPOAb and PCOS + noTPOAb (p > 0.05). Women with PCOS + TPOAb had lower FSH concentration and higher LH/FSH index than noPCOS + noTPOAb (p = 0.027; p = 0.019, respectively). Moreover, PCOS + TPOAb had lower oestradiol level than noPCOS + TPOAb (p = 0.041). AMH concentration was higher in both groups with PCOS, independent of TPOAb presence, than in noPCOS + noTPOAb (both p < 0.001). The presence of positive TPOAb titre was not related to the studied parameters of ovarian reserve - AMH and ovarian follicle number. In multiple linear regression analysis, the only significant predictor of AMH in the whole studied group with T1DM was total daily insulin dose U/kg (ß = - 0.264; p = 0.022). The presence of TAI did not affect the hormonal profile or ovarian reserve in women with T1DM with and without PCOS.

Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice.

Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients lose insulin independence by 3 years after ITx due to early graft loss, such that multiple donors are required to achieve insulin independence. In the present study, we investigated whether skeletal myoblast cells could be beneficial for promoting angiogenesis and maintaining the differentiated phenotypes of islets. In vitro experiments showed that the myoblast cells secreted angiogenesis-related cytokines (vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and stromal-derived factor-1α (SDF-1α)), contributed to maintenance of differentiated islet phenotypes, and enhanced islet cell insulin secretion capacity. To verify these findings in vivo, we transplanted islets alone or with myoblast cells under the kidney capsule of streptozotocin-induced diabetic mice. Compared with islets alone, the group bearing islets with myoblast cells had a significantly lower average blood glucose level. Histological examination revealed that transplants with islets plus myoblast cells were associated with a significantly larger insulin-positive area and significantly higher number of CD31-positive microvessels compared to islets alone. Furthermore, islets cotransplanted with myoblast cells showed JAK-STAT signaling activation. Our results suggest two possible mechanisms underlying enhancement of islet graft function with myoblast cells cotransplantation: "indirect effects" mediated by angiogenesis and "direct effects" of myoblast cells on islets via the JAK-STAT cascade. Overall, these findings suggest that skeletal myoblast cells enhance the function of transplanted islets, implying clinical potential for a novel ITx procedure involving myoblast cells for patients with diabetes.

Abnormal vascular thickness and stiffness in young adults with type 1 diabetes: new insights from cutting-edge ultrasound modalities.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with Type 1 Diabetes (T1D). Early markers of CVD include increased carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), but these existing ultrasound technologies show limited spatial and temporal resolution in young adults. The purpose of this study is to evaluate the utility of high-resolution ultrasound modalities, including high frequency ultrasound CIMT (hfCIMT) and ultrafast ultrasound PWV (ufPWV), in young adults with Type 1 Diabetes. METHODS: This is a prospective single-center observational cohort study including 39 participants with T1D and 25 age and sex matched controls. All participants underwent hfCIMT and ufPWV measurements. hfCIMT and ufPWV measures of T1D were compared with controls and associations with age, sex, BMI, A1c, blood pressure, and lipids were studied. RESULTS: Mean age was 24.1 years old in both groups. T1D had a greater body mass index (27.7 [5.7] vs 23.1 [3.2] kg/m2), LDL Cholesterol, and estimated GFR, and had a mean A1c of 7.4 [1.0] % (57 mmol/mol) and diabetes duration of 16.1 [3.7] years with 56% using insulin pumps. In T1D, hfCIMT was significantly increased as compared to controls (0.435 ± 0.06 mm vs 0.379 ± 0.06 mm respectively, p < 0.01). ufPWV measures were significantly increased in T1D (systolic foot PWV: 5.29 ± 0.23 m/s vs 5.50 ± 0.37 m/s, p < 0.01; dicrotic notch PWV = 7.54 ± 0.46 m/s vs 7.92 ± 0.41 m/s, p < 0.01). Further, there was an impact of A1c-measured glycemia on hfCIMT, but this relationship was not seen with ufPWV. No significant statistical correlations between hfCIMT and ufPWV measures in either T1D or healthy controls were observed. CONCLUSION: Young adults with T1D present with differences in arterial thickness and stiffness when compared with controls. Use of novel high-resolution ultrasound measures describe important relationships between early structural and vascular pathophysiologic changes and are promising tools to evaluate pre-clinical CVD risk in youth with T1D. TRIAL REGISTRATION: ISRCTN91419926.

Are the variations in ECG morphology associated to different blood glucose levels? implications for non-invasive glucose monitoring for T1D paediatric patients.

AIMS: Recent clinical trials and real-world studies highlighted those variations in ECG waveforms and HRV recurrently occurred during hypoglycemic and hyperglycemic events in patients with diabetes. However, while several studies have been carried out for adult age, there is lack of evidence for paediatric patients. The main aim of the study is to identify the correlations of variations in ECG Morphology waveforms with blood glucose levels in a paediatric population. METHODS: T1D paediatric patients who use CGM were enrolled. They wear an additional non-invasive wearable device for recording physiological data and respiratory rate. Glucose metrics, ECG parameters and HRV features were collected, and Wilcoxon rank-sum test and Spearman's correlation analysis were used to explore if different levels of blood glucose were associated to ECG morphological changes. RESULTS: Results showed that hypoglycaemic events in paediatric patients with T1D are strongly associated with variations in ECG morphology and HRV. CONCLUSIONS: Results showed the opportunity of using the ECG as a non-invasive adding instrument to monitor the hypoglycaemic events through the integration of the ECG continuous information with CGM data. This innovative approach represents a promising step forward in diabetes management, offering a more comprehensive and effective means of detecting and responding to critical changes in glucose levels.

Targeting skeletal muscle health with exercise in people with type 1 diabetes: A protocol for HOMET1D, a prospective observational trial with matched controls.

INTRODUCTION: Individuals with type 1 diabetes (T1D) experience a complex set of alterations to skeletal muscle metabolic, neuromuscular, and vascular health; collectively referred to as diabetic myopathy. While the full scope of diabetic myopathy is still being elucidated, evidence suggests that even when individuals with T1D are physically active, indices of myopathy still exist. As such, there is a question if adherence to current physical activity guidelines elicits improvements in skeletal muscle health indices similarly between individuals with and without T1D. The objectives of this trial are to: 1) compare baseline differences in skeletal muscle health between adults with and without T1D, 2) examine the association between participation in a home-based exercise program, detraining, and retraining, with changes in skeletal muscle health, and 3) examine the roles of age and sex on these associations. METHODS AND ANALYSIS: This will be a prospective interventional trial. Younger (18-30 years) and older (45-65 years) males and females with T1D and matched individuals without T1D will engage in a four-phase, 18-week study sequentially consisting of a one-week lead-in period, 12-week exercise training program, one-week detraining period, and four-week retraining period. The exercise program will consist of aerobic and resistance exercise based on current guidelines set by Diabetes Canada. Metabolic, neuromuscular, and vascular outcome measures will be assessed four times: at baseline, post-exercise program, post-detraining, and post-retraining. Differences in baseline metrics between those with and without T1D will be examined with independent sample t-tests, and with two-way analyses of variance for age- and sex-stratified analyses. Changes across the duration of the study will be examined using mixed-model analyses. DISSEMINATION: Findings from this research will be shared locally and internationally with research participants, clinicians, diabetes educators, and patient advocacy organizations via in-person presentations, social media, and scientific fora. TRIAL REGISTRATION NUMBER: NCT05740514.

Short, frequent, light-intensity walking activity improves postprandial vascular-inflammatory biomarkers in people with type 1 diabetes: The SIT-LESS randomized controlled trial.

AIM: To examine the effect of interrupting prolonged sitting with short, frequent, light-intensity activity on postprandial cardiovascular markers in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized crossover trial, 32 adults with T1D (mean ± SD age 28 ± 5 years, glycated haemoglobin 67.9 ± 12.6 mmol/mol, 17 women) completed two 7-h laboratory visits separated by >7 days. Participants either remained seated for 7 h (SIT) or interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals commencing 1 h after each meal (SIT-LESS). Physical activity, insulin regimen, experimental start times, and meal consumption were standardized during each arm. Plasma levels of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, plasminogen activator inhibitor (PAI)-1 and fibrinogen were sampled at baseline, 3.5 and 7 h, and assessed for within- and between-group effects using a repeated measures ANOVA. The estimated glucose disposal rate was used to determine the insulin resistance status. RESULTS: Vascular-inflammatory parameters were comparable between SIT and SIT-LESS at baseline (p > .05). TNF-α, IL-1ß, PAI-1 and fibrinogen increased over time under SIT, whereas these rises were attenuated under SIT-LESS (p < .001). Specifically, over the 7 h under SIT, postprandial increases were detected in TNF-α, IL-1ß, PAI-1 and fibrinogen (+67%, +49%, +49% and +62%, respectively; p < .001 for all). Conversely, the SIT-LESS group showed no change in IL-1ß (-9%; p > .50), whereas reductions were observed in TNF-α, PAI-1 and fibrinogen (-22%, -42% and -44%, respectively; p < .001 for all). The intervention showed enhanced effects in insulin-resistant individuals with T1D. CONCLUSIONS: Interrupting prolonged sitting with light-intensity activity ameliorates postprandial increases in vascular-inflammatory markers in T1D. TRIAL REGISTRATION: The trial was prospectively registered (ISRCTN13641847).

Sleep duration and association with cardiometabolic health in adolescents and adults with type 1 diabetes: Results from the BCQR-T1D study.

AIM: Type 1 diabetes (T1D) increases the risk of morbidity and mortality from cardiovascular disease, and insufficient sleep is prevalent. Emerging evidence suggests a link between sleep and cardiometabolic health, but this has not been examined across the lifespan in individuals with T1D. We aimed to examine associations between sleep and cardiometabolic health in adolescents and adults with T1D in a secondary analysis of data from a 4-week double-blind, random-order, placebo-controlled crossover trial of bromocriptine quick release (BCQR) therapy with a 4-week washout in between conditions. MATERIALS AND METHODS: Forty-two adults (19-60 years) and 42 adolescents (12-18 years) with T1D >9 months completed 1 week of home monitoring with wrist-worn actigraphy to estimate sleep duration and continuous glucose monitoring, anthropometrics, arterial stiffness, magnetic resonance imaging (adolescents only), and fasting laboratory testing at each treatment phase. RESULTS: Sixty-two per cent of adolescents and 74% of adults obtained <7 h of sleep per night at baseline. After adjustment for age, sex and diabetes duration, baseline sleep <7 h per night was associated with a higher body mass index, a higher waist circumference, a higher systolic blood pressure, worse arterial stiffness and a lower estimated insulin sensitivity (all p < .05). When examined by age group, associations between sleep duration and cardiometabolic health outcomes remained significant, predominantly for adolescents. In adolescents only, wake time was significantly later (p = .027) and time in bed was significantly longer with BCQR versus placebo (p = .049). CONCLUSIONS: Objectively measured sleep <7 h per night was prevalent in adolescents and adults with T1D and associated with poorer cardiometabolic health markers. Small changes in sleep were seen following BCQR treatment in adolescents only. Sleep may be an important and novel target for improving cardiometabolic health in individuals with T1D.

Longitudinal associations of the alternative healthy eating index with coronary artery calcification and pericardial adiposity in US adults with and without type 1 diabetes.

BACKGROUND AND AIM: Long-term associations between the alternative healthy eating index (AHEI) score and two predictive indicators for CVD, pericardial adipose tissue (PAT) and coronary artery calcification (CAC) volume, are lacking. Our study aims to investigate the longitudinal associations of the AHEI score with measures of CAC and PAT in adults with and without type 1 diabetes (T1D). METHODS AND RESULTS: The prospective Coronary Artery Calcification in T1D (CACTI) study included 652 people with T1D and 764 people without diabetes (non-DM) (19-56 years old) and was conducted in 2000-2002, 2003-2004, and 2006-2007. At each visit, food frequency questionnaires were collected and PAT and CAC were measured using electron beam computed tomography. Two variables were used for CAC analyses: a continuous variable for the square-root tranformed volume (SRV) for each visit and a second variable identified CAC progression from baseline to visit 3. Mixed effect models and a logistic regression model were used to conduct statistical analyses. A one-point increase in the AHEI score was significantly associated with a -0.12 cm3 (95% CI: -0.17, -0.08; p-value<0.0001) decrease in PAT volume in combined analyses, a -0.16 cm3 (95% CI: -0.22, -0.09; p-value<0.0001) decrease in the non-DM group, a marginally significant -0.07 cm3 (95% CI: -0.14, 0.002; p-value = 0.0571) decrease in the T1D group, and was not associated with either CAC outcome. CONCLUSION: The AHEI score is inversely associated with PAT; the association revealed greater magnitude of PAT reduction in the non-DM group. The AHEI score did not associate with CAC progression.

Association of physical activity and sports participation with insulin resistance and non-alcoholic fatty liver disease in people with type 1 diabetes.

AIM: To evaluate the association between physical activity (PA) and sports participation with insulin resistance and non-alcoholic fatty liver disease (NAFLD) in people with type 1 diabetes (T1D). METHODS: People with T1D from a secondary and tertiary care centre were included. Questionnaire-derived PA was expressed in metabolic equivalent of task hours per week (METh/week). Insulin sensitivity was calculated with the estimated glucose disposal rate (eGDR). NAFLD was assessed by transient elastography (TE). Multivariate linear and logistic regression models were conducted, adjusted for age, sex, diabetes duration and BMI. RESULTS: In total, 254 participants were included (men 56%, age 44 ± 14 years, diabetes duration 24 ± 14 years, median BMI 24.8 kg/m2), of which 150 participants underwent TE. Total PA (median 50.7 METh/week) was not significantly associated with insulin resistance (median eGDR 7.31 mg/kg/min) (beta -0.00, 95% CI -0.01 to 0.00) or with NAFLD (OR 1.00, 95% CI 0.99-1.01). Participating in sports was significantly associated with eGDR (beta 0.94, 95% CI 0.48-1.41) and with NAFLD (OR 0.21, 95% CI 0.08-0.56). CONCLUSIONS: In our T1D population, we could not find any dose-dependent association between PA, insulin resistance and NAFLD. People participating in sports had a lower degree of insulin resistance and lower odds for NAFLD.

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.

Gastrointestinal symptom burden in diabetic autonomic and peripheral neuropathy - A Danes cohort study.

OBJECTIVE: We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately. RESULTS: We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group. CONCLUSIONS: A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.

The metabolome as a diagnostic for maximal aerobic capacity during exercise in type 1 diabetes.

AIMS/HYPOTHESIS: Our aim was to characterise the in-depth metabolic response to aerobic exercise and the impact of residual pancreatic beta cell function in type 1 diabetes. We also aimed to use the metabolome to distinguish individuals with type 1 diabetes with reduced maximal aerobic capacity in exercise defined by V ˙ O 2peak . METHODS: Thirty participants with type 1 diabetes (≥3 years duration) and 30 control participants were recruited. Groups did not differ in age or sex. After quantification of peak stimulated C-peptide, participants were categorised into those with undetectable (<3 pmol/l), low (3-200 pmol/l) or high (>200 pmol/l) residual beta cell function. Maximal aerobic capacity was assessed by V ˙ O 2peak test and did not differ between control and type 1 diabetes groups. All participants completed 45 min of incline treadmill walking (60% V ˙ O 2peak ) with venous blood taken prior to exercise, immediately post exercise and after 60 min recovery. Serum was analysed using targeted metabolomics. Metabolomic data were analysed by multivariate statistics to define the metabolic phenotype of exercise in type 1 diabetes. Receiver operating characteristic (ROC) curves were used to identify circulating metabolomic markers of maximal aerobic capacity ( V ˙ O 2peak ) during exercise in health and type 1 diabetes. RESULTS: Maximal aerobic capacity ( V ˙ O 2peak ) inversely correlated with HbA1c in the type 1 diabetes group (r2=0.17, p=0.024). Higher resting serum tricarboxylic acid cycle metabolites malic acid (fold change 1.4, p=0.001) and lactate (fold change 1.22, p=1.23×10-5) differentiated people with type 1 diabetes. Higher serum acylcarnitines (AC) (AC C14:1, F value=12.25, p=0.001345; AC C12, F value=11.055, p=0.0018) were unique to the metabolic response to exercise in people with type 1 diabetes. C-peptide status differentially affected metabolic responses in serum ACs during exercise (AC C18:1, leverage 0.066; squared prediction error 3.07). The malic acid/pyruvate ratio in rested serum was diagnostic for maximal aerobic capacity ( V ˙ O 2peak ) in people with type 1 diabetes (ROC curve AUC 0.867 [95% CI 0.716, 0.956]). CONCLUSIONS/INTERPRETATION: The serum metabolome distinguishes high and low maximal aerobic capacity and has diagnostic potential for facilitating personalised medicine approaches to manage aerobic exercise and fitness in type 1 diabetes.

Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents.

OBJECTIVES: Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters. METHODS: Twenty-three type 1 diabetic patients, aged 12-16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity. Proinflammatory cytokines' concentrations (TNF-α, IL-1ß, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. RESULTS: There were no statistically significant differences between the proinflammatory cytokines' concentrations in the two groups. PWV [6.63 (6.23-7.07) vs. 6.07 (5.15-6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=-0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA1c was negatively correlated with IL-10 (ρ=-0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. CONCLUSIONS: Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA1c might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.

Female Type 1 Diabetic Akita Mice Demonstrate Increased Bladder Contractility via FP Receptor Activation due to NLRP3-Mediated Inflammation.

BACKGROUND: Diabetic bladder dysfunction (DBD) is driven in part by inflammation which dysregulates prostaglandin release in the bladder. Precise inflammatory mechanisms responsible for such dysregulation have been elusive. Since prostaglandins impact bladder contractility, elucidating these mechanisms may yield potential therapeutic targets for DBD. In female Type 1 diabetic Akita mice, inflammation mediated by the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome is responsible for DBD. Here, we utilized female Akita mice crossbred with NLRP3 knock-out mice to determine how NLRP3-driven inflammation impacts prostaglandin release within the bladder and prostaglandin-mediated bladder contractions. METHODS: Akita mice were crossbred with NLRP3-⁣/- mice to yield four groups of non-diabetics and diabetics with and without the NLRP3 gene. Females were aged to 30 weeks when Akitas typically exhibit DBD. Urothelia and detrusors were stretched ex vivo to release prostaglandins. Prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) were quantified using enzyme linked immunosorbent assays (ELISA). In separate samples, ex vivo contractile force to PGE2 and PGF2α +/- the prostaglandin F (FP) receptor antagonist, AL8810, was measured. FP receptor protein expression was determined via western blotting. RESULTS: Stretch-induced PGE2 release increases in urothelia but decreases in detrusors of diabetics. However, PGE2-mediated bladder contractions are not impacted. Conversely, diabetics show no changes in PGF2α release, but PGF2α-mediated contractions increase significantly. This is likely due to signaling through the FP receptors as FP receptor antagonism prevents this increase and diabetics demonstrate a four-fold increase in FP receptor proteins. Without NLRP3-mediated inflammation, changes in prostaglandin release, contractility, and receptor expression do not occur. CONCLUSION: NLRP3-dependent inflammation dysregulates prostaglandin release and prostaglandin-mediated bladder contractions in diabetic female Akita mice via FP receptor upregulation.

Physical Activity Detection for Diabetes Mellitus Patients Using Recurrent Neural Networks.

Diabetes mellitus (DM) is a persistent metabolic disorder associated with the hormone insulin. The two main types of DM are type 1 (T1DM) and type 2 (T2DM). Physical activity plays a crucial role in the therapy of diabetes, benefiting both types of patients. The detection, recognition, and subsequent classification of physical activity based on type and intensity are integral components of DM treatment. The continuous glucose monitoring system (CGMS) signal provides the blood glucose (BG) level, and the combination of CGMS and heart rate (HR) signals are potential targets for detecting relevant physical activity from the BG variation point of view. The main objective of the present research is the developing of an artificial intelligence (AI) algorithm capable of detecting physical activity using these signals. Using multiple recurrent models, the best-achieved performance of the different classifiers is a 0.99 area under the receiver operating characteristic curve. The application of recurrent neural networks (RNNs) is shown to be a powerful and efficient solution for accurate detection and analysis of physical activity in patients with DM. This approach has great potential to improve our understanding of individual activity patterns, thus contributing to a more personalized and effective management of DM.

People with type 1 diabetes exhibit lower exercise capacity compared to a control population with similar physical activity levels.

AIMS: We aimed to assess physical activity (PA) levels, adherence to PA guidelines, and fitness capacity in individuals with type 1 diabetes (T1D) and control population. METHODS: This cross-sectional study included 232 T1D and 248 controls. PA levels (IPAQ-SF questionnaire), adherence to guidelines (>150 min/week of moderate-to-vigorous PA), fitness capacity (VO2max, maximal incremental test on a cycle ergometer and 1RM test) were assessed, along with other clinical variables. RESULTS: Total PA levels (T1D 2202 ± 1839 vs. controls 2357 ± 2189 METs/min/week), adherence (T1D 53.1 % vs controls 53.2 %), and sedentariness (T1D 27.3 % vs. controls 25.1 %) were similar between groups. However, participants with T1D exhibited significantly lower levels of VO2max (29.1 ± 10.5 vs. 32.5 ± 11.5 mlO2/kg/min, p < 0.001), work capacity (2.73 ± 1.03 vs. 3 ± 10 W/kg of body weight, p = 0.004) and strength capacity (2.29 ± 0.53 vs. 2.41 ± 0.79 kg/kg body weight in 1RM, p = 0.01) than controls, after adjusting for sex and age. CONCLUSIONS: Individuals with T1D exhibit lower fitness capacity compared to a control population, regardless of age and sex, even when presenting similar levels of total physical activity and adherence to guidelines.

Evaluation of submandibular and parotid salivary glands by ultrasonography in patients with diabetes.

BACKGROUND: Microvascular complications of diabetes mellitus (DM) include oral manifestations and complications, including xerostomia, reduced salivary flow, susceptibility to infection, periodontal disease and salivary gland enlargement. OBJECTIVE: The present study aims to evaluate B-mode ultrasonography (USG) parameters such as size, volume and echogenicity of the submandibular and parotid salivary glands on both sides, shear-wave elastography (SWE) value and colour Doppler properties in patients with DM and healthy control groups. METHODS: In total, 160 right and left submandibular glands and 160 right and left parotid glands of 80 patients, 40 patients (20 type 1 DM, 20 type 2 DM) and 40 healthy control group, between the ages of 18-70 were examined by USG. Echogenicity, parenchyma internal structure, margin and dimensional measurements (antero-posterior length, supero-inferior length, medio-lateral length and volume) and colour Doppler with 'ML 6-15-D Matrix Array (4-15 MHz)' probe, shear-wave elastography '9L-D (2-8 MHz)' probe was investigated. RESULT: Statistically significant difference was observed in echogenicity in the right submandibular gland, echogenicity in the right parotid gland, margin characteristics, parenchymal homogeneity and colour Doppler characteristics between the type 1 DM, type 2 DM and control groups (p < .05). It was observed that the size, volume and SWE values of both submandibular and parotid glands were higher in the DM patient group than in the control group. Higher values were observed in type 2 DM compared to type 1 DM in the patient group. CONCLUSION: USG is an effective imaging technique in investigating the effects of diabetes on the submandibular and parotid salivary glands.

Long term clinical follow up of four patients with Wolfram syndrome and urodynamic abnormalities.

OBJECTIVES: Wolfram syndrome is characterised by insulin-dependent diabetes (IDDM), diabetes insipidus (DI), optic atrophy, sensorineural deafness and neurocognitive disorders. The DIDMOAD acronym has been recently modified to DIDMOAUD suggesting the rising awareness of the prevalence of urinary tract dysfunction (UD). End stage renal disease is the commonest cause of mortality in Wolfram syndrome. We present a case series with main objective of long term follow up in four children having Wolfram syndrome with evaluation of their urodynamic profile. METHODS: A prospective follow up of four genetically proven children with Wolfram syndrome presenting to a tertiary care pediatric diabetes clinic in Pune, India was conducted. Their clinical, and urodynamic parameters were reviewed. RESULTS: IDDM, in the first decade, was the initial presentation in all the four children (three male and one female). Three children had persistent polyuria and polydipsia despite having optimum glycemic control; hence were diagnosed to have DI and treated with desmopressin. All four patients entered spontaneous puberty. All patients had homozygous mutation in WFS1 gene; three with exon 8 and one with exon 6 novel mutations. These children with symptoms of lower urinary tract malfunction were further evaluated with urodynamic studies; two of them had hypocontractile detrusor and another had sphincter-detrusor dyssynergia. Patients with hypocontractile bladder were taught clean intermittent catheterization and the use of overnight drain. CONCLUSIONS: We report a novel homozygous deletion in exon 6 of WFS-1 gene. The importance of evaluation of lower urinary tract malfunction is highlighted by our case series. The final bladder outcome in our cases was a poorly contractile bladder in three patients.