Associations of marrow fat fraction with MR imaging based trabecular bone microarchitecture in first-time diagnosed type 1 diabetes mellitus.

Purpose: To determine whether there are alterations in marrow fat content in individuals first-time diagnosed with type 1 diabetes mellitus (T1DM) and to explore the associations between marrow fat fraction and MRI-based findings in trabecular bone microarchitecture. Method: A case-control study was conducted, involving adults with first-time diagnosed T1DM (n=35) and age- and sex-matched healthy adults (n=46). Dual-energy X-ray absorptiometry and 3 Tesla-MRI of the proximal tibia were performed to assess trabecular microarchitecture and vertebral marrow fat fraction. Multiple linear regression analysis was used to test the associations of marrow fat fraction with trabecular microarchitecture and bone density while adjusting for potential confounding factors. Results: In individuals first-time diagnosed with T1DM, the marrow fat fraction was significantly higher (p < 0.001) compared to healthy controls. T1DM patients also exhibited higher trabecular separation [median (IQR): 2.19 (1.70, 2.68) vs 1.81 (1.62, 2.10), p < 0.001], lower trabecular volume [0.45 (0.30, 0.56) vs 0.53 (0.38, 0.60), p = 0.013], and lower trabecular number [0.37 (0.26, 0.44) vs 0.41 (0.32, 0.47), p = 0.020] compared to controls. However, bone density was similar between the two groups (p = 0.815). In individuals with T1DM, there was an inverse association between marrow fat fraction and trabecular volume (r = -0.69, p < 0.001) as well as trabecular number (r = -0.55, p < 0.001), and a positive association with trabecular separation (r = 0.75, p < 0.001). Marrow fat fraction was independently associated with total trabecular volume (standardized ß = -0.21), trabecular number (ß = -0.12), and trabecular separation (ß = 0.57) of the proximal tibia after adjusting for various factors including age, gender, body mass index, physical activity, smoking status, alcohol consumption, blood glucose, plasma glycated hemoglobin, lipid profile, and bone turnover biomarkers. Conclusions: Individuals first-time diagnosed with T1DM experience expansion of marrow adiposity, and elevated marrow fat content is associated with MRI-based trabecular microstructure.

Lower left atrial function in young individuals with type 1 diabetes mellitus compared to healthy controls: an echocardiographic study.

In adulthood, individuals with type 1 diabetes mellitus may develop a condition of heart failure with preserved ejection fraction. However, subclinical changes to the heart in diabetes are likely to occur prior to the clinical presentation. This cross-sectional study aimed to compare left atrial function by echocardiography between 43 individuals with type 1 diabetes and 43 healthy controls, aged 10-30 years. All participants underwent echocardiography and 2D speckle tracking measurements for left atrial phase function parameters. Physical capacity was assessed by exercise test on a bicycle. Results showed that participants with type 1 diabetes had significantly lower left atrial function parameters than healthy controls (p < 0.05). There was a significant negative correlation between HbA1c means and reservoir and conduit strain (p < 0.05) and individuals with BMI < 30 showed a lower left atrial stiffness (p < 0.05). Individuals with type 1 diabetes and a higher physical capacity did not differ from their healthy peers. Results indicate that lower HbA1c levels, BMI < 30 and a higher physical capacity are favourable in terms of left atrial function in children and young adults with type 1 diabetes mellitus. Left atrial strain by echocardiography might become a new important tool in assessing heart function in T1DM.

Magnetization transfer ratio of the sciatic nerve differs between patients in type 1 and type 2 diabetes.

BACKGROUND: Previous studies on magnetic resonance neurography (MRN) found different patterns of structural nerve damage in type 1 diabetes (T1D) and type 2 diabetes (T2D). Magnetization transfer ratio (MTR) is a quantitative technique to analyze the macromolecular tissue composition. We compared MTR values of the sciatic nerve in patients with T1D, T2D, and healthy controls (HC). METHODS: 3-T MRN of the right sciatic nerve at thigh level was performed in 14 HC, 10 patients with T1D (3 with diabetic neuropathy), and 28 patients with T2D (10 with diabetic neuropathy). Results were subsequently correlated with clinical and electrophysiological data. RESULTS: The sciatic nerve's MTR was lower in patients with T2D (0.211 ± 0.07, mean ± standard deviation) compared to patients with T1D (T1D 0.285 ± 0.03; p = 0.015) and HC (0.269 ± 0.05; p = 0.039). In patients with T1D, sciatic MTR correlated positively with tibial nerve conduction velocity (NCV; r = 0.71; p = 0.021) and negatively with hemoglobin A1c (r = - 0.63; p < 0.050). In patients with T2D, we found negative correlations of sciatic nerve's MTR peroneal NCV (r = - 0.44; p = 0.031) which remained significant after partial correlation analysis controlled for age and body mass index (r = 0.51; p = 0.016). CONCLUSIONS: Lower MTR values of the sciatic nerve in T2D compared to T1D and HC and diametrical correlations of MTR values with NCV in T1D and T2D indicate that there are different macromolecular changes and pathophysiological pathways underlying the development of neuropathic nerve damage in T1D and T2D. TRIAL REGISTRATION: https://classic. CLINICALTRIALS: gov/ct2/show/NCT03022721 . 16 January 2017. RELEVANCE STATEMENT: Magnetization transfer ratio imaging may serve as a non-invasive imaging method to monitor the diseases progress and to encode the pathophysiology of nerve damage in patients with type 1 and type 2 diabetes. KEY POINTS: • Magnetization transfer imaging detects distinct macromolecular nerve lesion patterns in diabetes patients. • Magnetization transfer ratio was lower in type 2 diabetes compared to type 1 diabetes. • Different pathophysiological mechanisms drive nerve damage in type 1 and 2 diabetes.

No correlation between carotid intima-media thickness and long-term glycemic control in individuals with type 1 diabetes.

AIMS: To determine whether carotid intima-media thickness (CIMT), a surrogate marker of cardiovascular disease (CVD), is associated with long-term blood glucose control in individuals with type 1 diabetes (T1D). METHODS: We recruited 508 individuals (43.4% men; median age 46.1, IQR 37.8-55.9 years) with T1D (median diabetes duration of 30.4, IQR 21.2-40.8 years) in a cross-sectional retrospective sub-study, part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Glycated hemoglobin (HbA1c) data were collected retrospectively over the course of ten years (HbA1c-meanoverall) prior to the clinical study visit that included a clinical examination, biochemical sampling, and ultrasound of the common carotid arteries. RESULTS: Individuals with T1D had a median CIMT of 606 µm (IQR 538-683 µm) and HbA1c of 8.0% (7.3-8.8%) during the study visit and HbA1c-meanoverall of 8.0% (IQR 7.3-8.8%). CIMT did not correlate with HbA1c (p = 0.228) at visit or HbA1c-meanoverall (p = 0.063). After controlling for relevant factors in multivariable linear regression analysis, only age was associated with CIMT (p < 0.001). After further dividing CIMT into quartiles, no correlation between long-term glucose control and CIMT (%, 1st 8.1 [IQR 7.2-8.9] vs 4th 7.9 [7.4-8.7], p = 0.730) was found. CONCLUSIONS: We observed no correlation between long-term blood glucose control and CIMT in individuals with T1D. This finding suggests that the development of early signs of macrovascular atherosclerosis is not strongly affected by the glycemic control in people with T1D.

Trust-based health decision-making recruits the neural interoceptive saliency network which relates to temporal trajectories of Hemoglobin A1C in Diabetes Type 1.

Experimental approaches in neuroeconomics generally involve monetary utility. Utility in the health domain is relevant in diabetes because constant daily life decisions are critical for self-consequential long-term outcomes. We used fMRI to investigate self-consequent decision-making in the health and economic domains in Type 1 Diabetes Mellitus and controls (N = 50). We focused on two critical phases of decision-making: Investment and Feedback (Positive or Negative). Patients showed larger BOLD activation of limbic, and reward/dopaminergic regions in particular in the health trust game. Importantly, the worse the trajectory of metabolic control (increasing HbA1C), the higher the BOLD activity in regions of the interoceptive saliency network. This was manifested by positive correlations between brain activity during investment in anterior cingulate cortex and insula and HbA1c blood level progression. We conclude that the neural correlates of health-consequent decision-making domain involve limbic and reward related dopaminergic regions in Type 1 Diabetes Mellitus. Furthermore, the temporal trajectory of HbA1C blood levels is correlated with neural risk processing in the saliency network. Evidence for differential risk processing in the health versus the neuroeconomic context, and the discovery of a role for the saliency interoceptive network in metabolic control trajectories suggests a new perspective on the development of personalized interventions.

Scans per day as predictors of optimal glycemic control in people with type 1 diabetes mellitus using flash glucose monitoring: what number of scans per day should raise a red flag?

AIMS: This study aimed to determine the minimum frequency of flash glucose monitoring (FGM) scans necessary for optimal glycemic control in patients with type 1 diabetes (T1D). METHODS: Data were collected from 692 patients (47.5% female, with a median age of 47.4 years) who used FGM systems daily and recorded their clinical variables and device data. RESULTS: Logistic regression models showed that performing more than 12 scans per day was associated with improved T1D control (OR = 4.22, p < 0.001) and a reduction in HbA1c (7.6 vs 7.0%, 60-53 mmol/mol p < 0.001). However, those performing less than 6 scans showed no improvement in HbA1c (7.9 vs 7.8%, 63-61 mmol/mol p = 0.514). Thirteen daily scans were determined as the optimal cutoff point for predicting optimal glycemic control using a maximally selected rank algorithm. Significant reductions were observed in mean glucose (< 0.001), coefficient of variation (< 0.001), HbA1c (< 0.001), and an increase in TIR (< 0.001) in patients who performed more than 12 daily scans. CONCLUSIONS: The results suggest that a higher frequency of daily scans by T1D patients using FGM systems leads to improved chronic glycemic control. The minimum recommended frequency for optimal control is 13 scans per day, and more than 6 daily scans are needed to improve HbA1c.

Ratio of transmitral early filling velocity to diastolic strain rate and prognosis in type-1 diabetes.

BACKGROUND: Impaired diastolic function is a hallmark of diabetic cardiomyopathy and a common feature in type 1 diabetes mellitus (T1DM). The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has in recent studies proved to have strong prognostic value. This study aimed to investigate the prognostic value of E/e'sr compared to E/e' in T1DM without known heart disease. METHODS: In this prospective cohort of T1DM patients, echocardiography was performed including two-dimensional speckle tracking. Follow-up was performed using nationwide registries. Outcomes were all-cause mortality and major cardiovascular events (MACE). RESULTS: In total 1079 patients (age: 49.6 ± 14.5 years, 52.5% male, duration of diabetes 25.8 ± 14.6 years) were included in the study. During follow-up (median 6.3 years, IQR:5.7-6.9) 13.2% experienced MACE and 5.8% died. Following multivariable adjustment, both E/e'sr and E/e' was significantly associated with both MACE (E/e'sr: HR 1.16 CI95%:[1.05-1.29], p = 0.005, per 10 cm increase) vs. (E/e': HR 1.09 CI95%:[1.03-1.15], p = 0.001, per 1 unit increase) and all-cause mortality (E/e'sr: HR 1.20 [1.03-1.40], p = 0.016) vs. (E/e': HR: 1.11 [1.02-1.20], p = 0.016). Sex modified the association between E/e'sr and MACE (p for interaction = 0.008) such that E/e'sr after multivariable adjustment only remained significantly associated with MACE in females (HR: 1.41 [1.19-1.67], p < 0.001) but not in males (HR: 1.06 [0.93-1.20], p = 0.42). In females, E/e'sr provided incremental information beyond the Steno T1 Risk Engine (Harrell's C-statistic: 0.78 (0.72-0.83) vs. 0.81 (0.75-0.86), p = 0.007). CONCLUSION: In patients with T1DM, both E/e'sr and E/e' provides independent prognostic information regarding prognosis. E/e'sr seems to have stronger prognostic value in females with T1DM.

Adaptation and validation of an artificial intelligence based digital radiogrammetry tool for assessing bone health of indian children and youth with type-1 diabetes.

BACKGROUND AND OBJECTIVES: BoneXpert (BX) is an artificial intelligence software used primarily for bone age assessment. Besides, it can also be used to screen for bone health using the digital radiogrammetry tool called bone health index (BHI) for which normative reference values available are calculated from healthy European children. Due to ethnic difference in bone geometry, in a previous study, we generated reference curves based on healthy Indian children. The objectives of this study were: 1) To assess and compare bone health of Indian children with Type 1 diabetes (T1D) using both European and Indian BHI SDS reference data and 2) To identify determinants of poor bone health in Indian children and youth with T1D by using BHI tool (based on BHI-SDS Indian reference data) of BX. METHOD: The BHI was assessed retrospectively in 1159 subjects with T1D using digitalised left-hand x-rays and SDS were computed using European and Indian data. The demographic, anthropometric, clinical, biochemistry, dual x-ray absorptiometry (DXA) data and peripheral quantitative computed tomography (pQCT) data collection were performed using standard protocols and were extracted from hospital records. RESULTS: The BHI correlated well with DXA and pQCT parameters in subjects with T1D. BHI-SDS calculated using Indian reference data had better correlation with height and DXA parameters. 8.6% study participants had low (less than -2) BHI-SDS (Indian), with height SDS having significant effect. Subjects with low BHI-SDS were older, shorter and had higher duration of diabetes. They also had lower IGF1 and vitamin D concentrations, bone mineral density, and trabecular density. Female gender, increased duration of illness, poor glycaemic control, and vitamin D deficiency/insufficiency were significant predictors of poor BHI-SDS. CONCLUSION: Our study highlights the utility of digital radiogrammetry AI tool to screen for bone health of children with T1D and demonstrates and highlights the necessity of interpretation using ethnicity specific normative data.

Interventional Radiology Approaches for Managing Postpancreatic Transplant Complications and Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-secreting beta cells in the pancreas, resulting in metabolic disturbances and long-term complications. While subcutaneous insulin remains the primary approach for achieving normoglycemia, pancreatic transplantation has emerged as an effective intervention for long-standing T1DM, providing insulin independence and normalized glycosylated hemoglobin levels. However, complications associated with pancreatic transplantation are frequent, necessitating thorough evaluation using diverse imaging modalities. This manuscript presents an overview of complications encountered with pancreatic transplantation, including vascular complications such as arterial and venous graft thrombosis, vessel stenosis, pseudoaneurysm, arterio-enteric fistula, and arteriovenous malformations. Additionally, the manuscript discusses other associated complications such as pancreatitis, pseudocyst formation, fistulas, pseudo-thrombosis of the iliac vein, post-transplantation lymphoproliferative disorder, and fluid collections. The integration of various imaging modalities plays a crucial role in diagnosing and managing these complications, with interventional radiologists assuming a vital role in employing image-guided procedures. Moreover, the manuscript explores pancreatic islet cell transplantation as a promising cellular-based therapy for T1DM, offering stable long-term glycemic control and decreased reliance on exogenous insulin in a significant proportion of recipients. This minimally invasive procedure involves the image-guided transcatheter infusion of islet cells obtained from deceased donors into the recipient's liver. The importance of interventional radiologists in managing complications related to pancreatic transplantation is underscored, with endovascular or image-guided approaches being utilized to address the diverse spectrum of encountered complications. Furthermore, the potential of islet cell transplantation as a minimally invasive alternative to traditional pancreatic transplantation is emphasized, as it offers the prospect of preventing many associated complications.

Prognostic value of myocardial performance index in individuals with type 1 and type 2 diabetes: Thousand&1 and Thousand&2 studies.

AIMS: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in type 1 (T1D) and type 2 diabetes (T2D). Despite diabetes affects the myocardium, risk prediction models do not include myocardial function parameters. Myocardial performance index (MPI) reflects left ventricular function. The prognostic value of MPI has not been evaluated in large-scale diabetes populations. METHODS AND RESULTS: We evaluated two prospective cohort studies: Thousand&1 (1093 individuals with T1D) and Thousand&2 (1030 individuals with T2D). Clinical data, including echocardiography, were collected at baseline. We collected follow-up data from national registries. We defined major adverse cardiovascular events (MACE) as incident events of hospital admission for acute coronary syndrome, heart failure, stroke, or all-cause mortality. For included individuals (56% male, 54 ± 15 years, MPI 0.51 ± 0.1, 63% T1D), follow-up was 100% after median of 5.3 years (range: 4.8-6.3). MPI was associated with MACE (HR 1.2, 95%CI 1.0-1.3, P = 0.012, per 0.10-unit increase) and heart failure (HR 1.3, 95%CI 1.1-1.6, P = 0.005, per 0.10-unit increase) after adjusting for clinical and echocardiographic variables. MPI predicted MACE and heart failure better in T1D than T2D (P = 0.031 for interaction). MPI added discriminatory power to the Steno T1 Risk Engine, based on clinical characteristics, in predicting MACE [area under the curve (AUC) from 0.77 to 0.79, P = 0.030] and heart failure (AUC from 0.77 to 0.83, P = 0.009) in T1D. CONCLUSION: MPI is independently associated with MACE and heart failure in T1D but not T2D and improves prediction in T1D. Echocardiographic assessment in T1D may enhance risk prediction.

Comparison of Optical Coherence Tomography Angiography Findings between Healthy Children and Children with Type 1 Diabetes Mellitus and Autoimmune Thyroiditis

Objective: The aim of this study was to compare the development of early diabetic retinopathy (DR) findings, a microvascular complication, between patients with isolated type 1 diabetes mellitus (T1DM) (Group 1), concurrent T1DM and autoimmune thyroiditis (AT) (Group 2), and healthy controls (Group 3), who were matched for age, sex, number, and body mass index for comparison. Methods: This was a prospective observational study that included individuals aged 10-20 years, and patients in Groups 1 and 2 had been followed up for ≥5 years. None of them developed clinical DR during the follow-up period. Optical coherence tomography angiography (OCTA) was used to evaluate the foveal avascular zone (FAZ) and parafoveal vascular density (PVD) for the development of early DR. OCTA findings were compared between patients and healthy controls. Results: Thirty-five individuals were included in each of the groups. The mean FAZ and PVD differed significantly between the three groups (FAZ, p=0.016; PVD, p=0.006). The mean FAZ was higher in Groups 1 and 2 than in Group 3 (p=0.013 and p=0.119, respectively). The mean PVD was lower in Groups 1 and 2 than in Group 3 (p=0.007, respectively). No significant difference was found between Groups 1 and 2 in terms of the mean FAZ and PVD (p=0.832 and p=0.653, respectively). The mean glycated hemoglobin (HbA1c) level was significantly correlated with FAZ and PVD (FAZ: r=0.496, p<0.001; PVD: r=-0.36, p=0.001). Conclusion: In patients with T1DM who did not develop clinical DR, OCTA findings revealed an increase in FAZ, which was associated with higher HbA1c levels. The mean PVD was significantly lower in the group with coexisting AT and T1DM than in the control group. These results suggest that the coexistence of AT and T1DM can contribute to the development of microvascular complications. However, studies with larger patient series are required.

Patterns of Regional Brain Atrophy and Brain Aging in Middle- and Older-Aged Adults With Type 1 Diabetes.

Importance: Little is known about structural brain changes in type 1 diabetes (T1D) and whether there are early manifestations of a neurodegenerative condition like Alzheimer disease (AD) or evidence of premature brain aging. Objective: To evaluate neuroimaging markers of brain age and AD-like atrophy in participants with T1D in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, identify which brain regions are associated with the greatest changes in patients with T1D, and assess the association between cognition and brain aging indices. Design, Setting, and Participants: This cohort study leveraged data collected during the combined DCCT (randomized clinical trial, 1983-1993) and EDIC (observational study, 1994 to present) studies at 27 clinical centers in the US and Canada. A total of 416 eligible EDIC participants and 99 demographically similar adults without diabetes were enrolled in the magnetic resonance imaging (MRI) ancillary study, which reports cross-sectional data collected in 2018 to 2019 and relates it to factors measured longitudinally in DCCT/EDIC. Data analyses were performed between July 2020 and April 2022. Exposure: T1D diagnosis. Main Outcomes and Measures: Psychomotor and mental efficiency were evaluated using verbal fluency, digit symbol substitution test, trail making part B, and the grooved pegboard. Immediate memory scores were derived from the logical memory subtest of the Wechsler memory scale and the Wechsler digit symbol substitution test. MRI and machine learning indices were calculated to predict brain age and quantify AD-like atrophy. Results: This study included 416 EDIC participants with a median (range) age of 60 (44-74) years (87 of 416 [21%] were older than 65 years) and a median (range) diabetes duration of 37 (30-51) years. EDIC participants had consistently higher brain age values compared with controls without diabetes, indicative of approximately 6 additional years of brain aging (EDIC participants: ß, 6.16; SE, 0.71; control participants: ß, 1.04; SE, 0.04; P < .001). In contrast, AD regional atrophy was comparable between the 2 groups. Regions with atrophy in EDIC participants vs controls were observed mainly in the bilateral thalamus and putamen. Greater brain age was associated with lower psychomotor and mental efficiency among EDIC participants (ß, -0.04; SE, 0.01; P < .001), but not among controls. Conclusions and Relevance: The findings of this study suggest an increase in brain aging among individuals with T1D without any early signs of AD-related neurodegeneration. These increases were associated with reduced cognitive performance, but overall, the abnormal patterns seen in this sample were modest, even after a mean of 38 years with T1D.

Bone Mineral Density in Adult Patients with Type 1 Diabetes Mellitus Assessed by Both DXA and QCT.

Purpose: Bone mineral density (BMD) was measured in uncomplicated young adult patients with type 1 diabetes mellitus (T1DM) and sex- and age-matched controls, using both dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) to investigate their diagnostic ability in detecting abnormal values in these patients. Methods: 118 patients with T1DM (65 females, mean age 30.12 ± 8.78 years) and 94 sex- and age-matched controls were studied. BMD was assessed in all participants by DXA and QCT at lumbar spine (LS). Biochemical markers of bone metabolism were also measured. Results: T1DM was associated with lower BMD at L1-L3 vertebrae measured by both DXA and QCT and lower bone turnover compared to sex- and age-matched controls. In T1DM subjects, QCT detected more patients with abnormal BMD values compared to DXA. BMI and HbA1c levels were the only determinants of BMD. Bone turnover markers were lower in patients with longer duration of diabetes. Conclusion: QCT provides a higher sensitivity compared to DXA in detecting abnormal BMD values in patients with uncomplicated T1DM. In these patients, the diabetes-related decreased BMD may be present early, before it is detected by DXA, the clinical gold standard for BMD measurements, and before the presence of any other diabetes complications, stressing the importance of an early intervention for fracture prevention.

68 Ga-FAPI PET/CT Imaging of the Pancreas in a Patient With Fulminant Type 1 Diabetes.

ABSTRACT: Fulminant type 1 diabetes is a recently recognized diabetes subtype characterized by extremely rapid destruction of the pancreatic beta cells, leading to an absolute deficiency in insulin secretion. Fulminant type 1 diabetes is clinically characterized by the drastic onset of hyperglycemia and ketoacidosis within a few days, as well as near-normal glycated hemoglobin (HbA 1c ) levels despite remarkable hyperglycemia at initial presentation. A 41-year-old woman diagnosed with fulminant type 1 diabetes underwent 68 Ga-FAPI PET/CT, which showed intense FAPI uptake throughout the pancreas, especially in the pancreatic tail. Contrast-enhanced abdominal CT failed to reveal any pancreatic abnormalities. This case indicated that 68 Ga-FAPI PET/CT might be useful for evaluating patients with fulminant type 1 diabetes.

Monitoring ß-Cell Survival After Intrahepatic Islet Transplantation Using Dynamic Exendin PET Imaging: A Proof-of-Concept Study in Individuals With Type 1 Diabetes.

Intrahepatic transplantation of islets of Langerhans (ITx) is a treatment option for individuals with complicated type 1 diabetes and profoundly unstable glycemic control, but its therapeutic success is hampered by deterioration of graft function over time. To improve ITx strategies, technologies to noninvasively monitor the fate and survival of transplanted islets over time are of great potential value. We used [68Ga]Ga-NODAGA-exendin-4 (68Ga-exendin) positron emission tomography (PET)/computed tomography (CT) imaging to demonstrate the feasibility of quantifying ß-cell mass in intrahepatic islet grafts in 13 individuals with type 1 diabetes, nine after ITx with functional islet grafts and four control patients not treated with ITx. ß-Cell function was measured by mixed-meal tolerance test. With dynamic 68Ga-exendin PET/CT images, we determined tracer accumulation in hepatic hotspots, and intrahepatic fat was assessed using MRI and spectroscopy. Quantification of hepatic hotspots showed a significantly higher uptake of 68Ga-exendin in the ITx group compared with the control group (median 0.55 [interquartile range 0.51-0.63] vs. 0.43 [0.42-0.45]). GLP-1 receptor expression was found in transplanted islets by immunohistochemistry. Intrahepatic fat was not detected in a majority of the individuals. Our study provides the first clinical evidence that radiolabeled exendin imaging can be used to monitor viable transplanted islets after intraportal ITx. ARTICLE HIGHLIGHTS: This clinical study researched the potential of radiolabeled exendin to follow the fate and survival of intrahepatic islet grafts. Is it feasible to quantitatively detect intrahepatic islet transplants with [68Ga]Ga-NODAGA-exendin-4 (68Ga-exendin) positron emission tomography (PET) imaging? Our study findings indicate that the imaging technique 68Ga-exendin PET can be used to monitor viable islet mass after intrahepatic islet transplantation in humans. Alongside functional measures, 68Ga-exendin PET imaging could significantly aid in the evaluation of strategies designed to improve islet engraftment, survival, and function.

Central nervous system microstructural alterations in Type 1 diabetes mellitus: A systematic review of diffusion Tensor imaging studies.

AIMS: Type 1 diabetes mellitus (T1DM) is a chronic childhood disease with potentially persistent CNS disruptions. In this study, we aimed to systematically review diffusion tensor imaging studies in patients with T1DM to understand the microstructural effects of this entity on individuals' brains METHODS: We performed a systematic search and reviewed the studies to include the DTI studies in individuals with T1DM. The data for the relevant studies were extracted and a qualitative synthesis was performed. RESULTS: A total of 19 studies were included, most of which showed reduced FA widespread in optic radiation, corona radiate, and corpus callosum, as well as other frontal, parietal, and temporal regions in the adult population, while most of the studies in the juvenile patients showed non-significant differences or a non-persistent pattern of changes. Also, reduced AD and MD in individuals with T1DM compared to controls and non-significant differences in RD were noted in the majority of studies. Microstructural alterations were associated with clinical profile, including age, hyperglycemia, diabetic ketoacidosis and cognitive performance. CONCLUSION: T1DM is associated with microstructural brain alterations including reduced FA, MD, and AD in widespread brain regions, especially in association with glycemic fluctuations and in adult age.

Relationship between risk factors for impaired bone health and HR-pQCT in young adults with type 1 diabetes.

Objective: In type 1 diabetes, risk factors associated with impaired bone health contribute to increased risk of fracture. The aim of this study was to (1): compare the high-resolution peripheral quantitative computed tomography (HR-pQCT) parameters of young adults with type 1 diabetes with those of healthy controls (2), identify sex differences, and (3) evaluate the association between diabetes and bone health risk factors, with HR-pQCT. Methods: This is a cross-sectional study in young Canadian adults with childhood onset type 1 diabetes. Z-scores were generated for HR-pQCT parameters using a large healthy control database. Diet, physical activity, BMI, hemoglobin A1C (A1C) and bone health measures were evaluated, and associations were analyzed using multivariate regression analysis. Results: Eighty-eight participants (age 21 ± 2.2 years; 40 males, 48 females, diabetes duration 13.9 ± 3.4 years) with type 1 diabetes were studied. Low trabecular thickness and elevated cortical geometry parameters were found suggesting impaired bone quality. There were no sex differences. Significant associations were found: Vitamin D (25(OH)D) with trabecular parameters with possible synergy with A1C, parathyroid hormone with cortical parameters, BMI with cortical bone and failure load, and diabetes duration with trabecular area. Conclusions: Our data suggests impairment of bone health as assessed by HR-pQCT in young adults with type 1 diabetes. Modifiable risk factors were associated with trabecular and cortical parameters. These findings imply that correction of vitamin D deficiency, prevention and treatment of secondary hyperparathyroidism, and optimization of metabolic control may reduce incident fractures.

Clinical correlation of 2D shear wave elastography findings in children with type 1 diabetes mellitus without autoimmune thyroiditis.

OBJECTIVES: The aim of study was to evaluate the 2D shear wave sonoelastography (SWE) findings of the thyroid gland in children with type 1 diabetes mellitus (T1DM) with normal gray-scale findings and without thyroid autoimmunity (AIT) and obtain data that will be useful for the early detection of glandular involvement. METHODS: The study included 46 T1DM patients (mean age: 11.28 ± 3.3 years) and 46 healthy children (mean age: 12.01 ± 3.8 years) as the control group. The thyroid gland mean elasticity value was obtained as kPa and compared in groups. A correlation was investigated between elasticity values and age at diabetes, serum free T4, thyroid stimulating hormone (TSH), anti-thyroglobulin, anti-tissue peroxidase, and hemoglobin A1c values. RESULTS: No difference was found between T1DM patients and the control group in the thyroid 2D SWE evaluation (the median kPa value: 17.1 (10.2) in the study group and 16.8 (7.0) in the control group) (p=0.15). No significant correlation was found between 2D SWE kPa values and age at diagnosis, serum free T4, TSH, anti-thyroglobulin, anti-tissue peroxidase, and hemoglobin A1c levels in T1DM patients. CONCLUSIONS: Our study showed that the elasticity of the thyroid gland in T1DM patients without AIT was not affected differently from that of the normal population. If 2D SWE is used in routine follow-up in T1DM patients before the development of AIT, we think that it will be useful in the early detection of thyroid gland affections and AIT, and long-term comprehensive studies in this direction will contribute to the literature.

Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas.

OBJECTIVE: To determine the mechanism of reduced pancreas size in type 1 diabetes and the significance of islet-derived insulin in pancreatic growth. RESEARCH DESIGN AND METHODS: Using a validated and standardized MRI protocol, we measured pancreas volume and shape in a family with an autosomal-dominant insulin gene mutation that results in insulin deficiency similar in severity to that of type 1 diabetes but without autoimmunity. DNA sequencing confirmed the mutation in all four affected individuals and none of the four control family members. Insulin secretory capacity was determined by measuring postprandial urinary C-peptide. RESULTS: Family members with this form of monogenic diabetes had a markedly smaller pancreas and a severely impaired postprandial C-peptide level than family members without diabetes. CONCLUSIONS: These results suggest that severe insulin deficiency, rather than islet-directed autoimmunity, leads to reduced pancreas size in type 1 diabetes and that insulin is a major trophic factor for the exocrine pancreas.

Cognitive function and neuroimaging characteristics in patients with childhood-onset type 1 diabetes mellitus.

AIMS: In this study, we used neuropsychological tests and neuroimaging to examine the cognitive functions and neuroimaging characteristics to explore the brain mechanism of cognitive deficits in patients with childhood-onset type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: A total of 30 patients with childhood-onset T1DM and 28 healthy controls (HC) participated in the study. Neuropsychological tests were used to assess intelligence quotient, memory, and executive function. Voxel-based morphometry-diffeomorphic anatomical registration through exponential lie algebra analysis and amplitude of low-frequent fluctuation (ALFF) were performed to evaluate the brain grey matter volume and neural spontaneous activity for each participant. RESULTS: Compared with HC, patients with childhood-onset T1DM showed a significant decline in verbal memory (p = 0.001) and visual memory (p = 0.002). Patients with T1DM had smaller grey matter volumes at the midbrain, thalamus, and cerebellar culmen. They demonstrated an increased ALFF value in the left precentral gyrus, left postcentral gyrus, left insula, and left supramarginal gyrus and a decreased ALFF value in the basal ganglia (putamen nucleus), right insula, right superior temporal gyrus, and cerebellar posterior lobe than the healthy control group. In the T1DM group, the ALFF value in the right insula was positively related to the verbal memory scores (r = 0.423, p = 0.025). CONCLUSIONS: Childhood-onset T1DM was associated with cognitive deficits and changes in brain structure and function. These findings suggest that the brain structural and functional alterations in these regions may be the neuropathology of cognitive deficits in patients with T1DM.