Metabolic dysfunction-associated steatotic liver disease is associated with worse time in ranges in type 1 diabetes.

AIM: To investigate the relationship between continuous glucose monitoring (CGM)-derived glucometrics and metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes (T1D). METHODS: A cross-sectional study collecting data on anthropometrics, glucometrics and MASLD in adults with T1D using a CGM device was conducted. MASLD was assessed by abdominal ultrasound and the presence of at least one cardiometabolic criterion. Backward multivariable logistic regression models were applied to define variables independently associated with MASLD. RESULTS: A total of 302 consecutive participants were included (median age 49 [34-61] years, male sex 58%, median diabetes duration 29 [17-38] years, mean time in range [TIR] 55% ± 16%). MASLD was present in 17% of cases, and 32% had metabolic syndrome (MetS). MetS was significantly more prevalent in the MASLD group (65% vs. 25%, P < .0001). TIR (P = .038) and time below range (TBR) (P = .032) were lower and time above range (TAR) was higher (P = .006), whereas HbA1c did not reach significance (P = .068). No differences were found for the glycaemia risk index. TIR (P = .028), TAR (P = .007), TBR (P = .036), waist circumference (P < .001) and systolic blood pressure (P = .029) were independently associated with MASLD, while sex, age, aspartate aminotransferase/alanine aminotransferase ratio, gamma-glutamyl transferase, high-density lipoprotein cholesterol and triglycerides were not. CONCLUSIONS: TIR, TAR, TBR, waist circumference and systolic blood pressure were independently associated with MASLD.

An accidental finding of a giant intra-abdominal mass.

INTRODUCTION: Mesenteric cysts are rare intra-abdominal tumours often found incidentally on imaging studies or during surgery. The clinical presentation is various with most subjects being asymptomatic, but complications can occur such as torsion, rupture, hemorrhage or obstruction of nearby structures. The etiology of mesenteric cysts remains uncertain. Complete surgical resection is preferred, although there are no specific guidelines concerning optimal treatment strategy. CASE REPORT: We present a 61-year-old male with type 2 diabetes mellitus who underwent a routine abdominal ultrasound examination which accidentally uncovered a large mass. The patient had no complaints nor any physical discomfort. Magnetic resonance imaging and computed tomography revealed a giant thin-walled cyst with multiple septa spanning 24 × 24 cm2 originating from the mesentery. The primary differential diagnosis included a mesenteric cyst, a hydatid cyst due to echinococcus or malignancy. After multidisciplinary team approach, open surgical exploration was preferred. Surgical drainage and cyst sac resection were performed without any peri- or postoperative complications. Histopathology confirmed the presence of a large mesenteric cyst, probably caused post-traumatically. The patient has made a full recovery. CONCLUSION: Mesenteric cysts can develop asymptomatically and reach enormous proportions. They are often found accidentally. Imaging studies aid in the differential diagnosis, but histopathology remains the diagnostic gold standard. Surgical resection prevails compared to a conservative approach due to the risk of complications. The choice between open or laparoscopic surgery should be determined based on the perioperative risk.

The evolution of PAs in the Canadian Armed Forces.

This study documents the growing role of the physician assistant (PA) in the Canadian Armed Forces. PAs have served as the backbone of the Royal Canadian Medical Services' frontline medical operations since 1984, on land, aboard ships and submarines, and domestically in garrison. Candidates begin as medical technicians and receive advanced training to become PAs at midcareer. The current rank of PAs as warrant officers is evolving and a commissioned status is under consideration.

Insulin resistance and CGM-derived parameters in people with type 1 diabetes: are they associated?

BACKGROUND: Insulin resistance (IR) is increasingly more prevalent in people with type 1 diabetes (T1D). We investigated whether IR is associated with continuous glucose monitor (CGM)-derived parameters (glucometrics) such as time in range (TIR), time above range (TAR), time below range (TBR) and glycaemic variability (CV). METHODS: This is a retrospective analysis of two databases: IR was quantified according to the estimated glucose disposal rate (eGDR) (NCT04664036) and by performing a hyperinsulinaemic-euglycaemic clamp (HEC) (NCT04623320). All glucometrics were calculated over 28 days. RESULTS: A total of 287 subjects were included. Mean age was 46 ± 17 years, 55% were male, TIR was 57 ± 14% and eGDR was 7.6 (5.6 - 9.3) mg/kg min. The tertile of people with the lowest eGDR (highest level of IR) had a higher TAR compared to the tertile with the highest eGDR (39 ± 15% versus 33 ± 14, p = 0.043). Using logistic regression, a higher eGDR was associated with a higher chance to fall in a higher TIR- (OR 1.251, p < 0.001), a lower TAR- (OR 1.281, p < 0.001) and a higher TBR-tertile (OR 0.893, p = 0.039), adjusted for age, sex, diabetes duration, smoking status and alcohol intake. In the 48 people undergoing a HEC, no significant association between glucometrics and the HEC-determined glucose disposal rate (M-value) was observed. CONCLUSION: In people with T1D, an association between IR, measured by eGDR, and worse CGM profiles was observed.

The 13C glucose breath test accurately identifies insulin resistance in people with type 1 diabetes.

OBJECTIVE: This study investigated whether the delta-over-baseline of exhaled 13CO2 (Δ13CO2), generated from a 13C glucose breath test (13C-GBT), measured insulin resistance (IR) in people with type 1 diabetes, using the hyperinsulinemic-euglycemic clamp (HEC) as reference method. Secondary objective was to compare the 13C-GBT with the estimated glucose disposal rate (eGDR). METHODS: A 40 mU/m2/min HEC and two separate 13C-GBTs (euglycemic with insulin bolus and hyperglycemic without bolus) were consecutively performed in 44 adults with type 1 diabetes with varying body compositions. eGDR was calculated based on HbA1c, presence of hypertension and waist circumference. RESULTS: Mean M-value was 5.9 ± 3.1 mg/kg/min, mean euglycemic Δ13CO2 was 6.4 ± 2.1 δ‰, while median eGDR was 5.9 [4.3 - 9.8] mg/kg/min. The hyperglycemic Δ13CO2 did not correlate with the M-value, while the euglycemic Δ13CO2 and the M-value correlated strongly (r = 0.74, p < 0.001). Correlation between M-value and eGDR was more moderate (Spearman's rho = 0.63, p < 0.001). Linear regression showed an association between Δ13CO2 and M-value, adjusted for age, sex and HbA1c (adjusted R² = 0.52, B = 1.16, 95% CI 0.80 - 1.52, p < 0.001). The AUROC for Δ13CO2 to identify subjects with IR (M-value < 4.9 mg/kg/min) was 0.81 (95% CI 0.68 - 0.94, p < 0.001). The optimal cut-off for Δ13CO2 to identify subjects with IR was ≤ 5.8 δ‰. CONCLUSIONS: Under euglycemic conditions, the 13C-GBT accurately identified individuals with type 1 diabetes and concurrent IR, suggesting its potential as a valuable non-invasive index.

Prevalence, risk factors and diagnostic accuracy of non-invasive tests for NAFLD in people with type 1 diabetes.

Background & Aims: The epidemiology of non-alcoholic fatty liver disease (NAFLD) in people with type 1 diabetes (T1D) is not yet elucidated. This study aimed to assess the diagnostic accuracy of non-invasive tests for NAFLD, to investigate the prevalence and severity of NAFLD, and to search for factors contributing to NAFLD in people with T1D. Methods: In this prospective cohort study, we consecutively screened 530 adults with T1D from a tertiary care hospital, using ultrasound (US), vibration-controlled transient elastography equipped with liver stiffness measurement (LSM) and controlled attenuation parameter, and the fatty liver index. Magnetic resonance spectroscopy (MRS) was performed in a representative subgroup of 132 individuals to validate the diagnostic accuracy of the non-invasive tests. Results: Based on MRS as reference standard, US identified individuals with NAFLD with an AUROC of 0.98 (95% CI 0.95-1.00, sensitivity: 1.00, specificity: 0.96). The controlled attenuation parameter was also accurate with an AUROC of 0.85 (95% CI 0.77-0.93). Youden cut-off was ≥270 dB/m (sensitivity: 0.90, specificity: 0.74). The fatty liver index yielded a similar AUROC of 0.83 (95% CI 0.74-0.91), but the conventional cut-off used to rule in (≥60) had low sensitivity and specificity (0.62, 0.78). The prevalence of NAFLD in the overall cohort was 16.2% based on US. Metabolic syndrome was associated with NAFLD (OR: 2.35 [1.08-5.12], p = 0.031). The overall prevalence of LSM ≥8.0 kPa indicating significant fibrosis was 3.8%, but reached 13.2% in people with NAFLD. Conclusions: NAFLD prevalence in individuals with T1D is 16.2%, with approximately one in 10 featuring elevated LSM. US-based screening could be considered in people with T1D and metabolic syndrome. Impact and Implications: We aimed to report on the prevalence, disease severity, and risk factors of NAFLD in type 1 diabetes (T1D), while also tackling which non-invasive test for NAFLD is the most accurate. We found that ultrasound is the best test to diagnose NAFLD. NAFLD prevalence is 16.2%, and is associated with metabolic syndrome and BMI. Elevated liver stiffness indicating fibrosis is overall not prevalent in people with T1D (3.8%), but it reaches 13.2% in those with T1D and NAFLD.

Artifactual hypoglycemia in a patient with systemic sclerosis.

Artifactual hypoglycemia, defined as a discrepancy between different laboratory measurements and actual blood glucose levels, can occur due to clinical conditions affecting the capillary microcirculation leading to falsely low blood glucose assessment. Systemic sclerosis, hallmarked by auto-immunity, fibrosis of the skin and/or internal organs and small vessel vasculopathy, can interfere with capillary point-of-care (POC) glycemia measurements, leading to the misdiagnosis of hypoglycemia. We report an 87-year-old woman with recurrent, asymptomatic hypoglycemia of unknown cause. Clinical examination revealed multiple features of limited cutaneous systemic sclerosis causing microvascular damage leading to artifactual hypoglycemia. Artifactual hypoglycemia is rarely considered by physicians and knowledge of its causes is generally lacking. Early identification of causes of inaccurate glycemia assessment can prevent unnecessary investigations and treatment. In the future, continuous glucose monitoring (CGM) could become a reliable alternative for inpatient glucose monitoring.

Therapeutic approaches for non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been reported as a novel worldwide epidemic, very often associated with obesity, metabolic syndrome, and type 2 diabetes. Both conditions have also been shown to be associated with a number of endocrine pathologies. Despite the epidemic, the complex pathophysiology and major complications, ranging from metabolic disturbances (diabetes and more) to cardiovascular disease, people with NASH are left with very few management options. The best and most approved therapeutic option is lifestyle intervention. Although pharmacotherapies based on pathophysiological background are in development, response rates appear modest, mainly for fibrosis treatment, which is the reason for lack of approved drug therapy. Previous drugs analyzed, such as pioglitazone and vitamin E, show weak efficacy. From different phase II trials, antidiabetic (injectable) drugs seem to be promising, both in mono- or bitherapy. Also, derivatives of peroxisome proliferator-activated receptors may have an interesting future, as well. For that reason, more focus should be given on prevention of this novel disease entity. In view of this booming epidemic, with a background of obesity and type 2 diabetes, and the important medical consequences, early recognition, prevention and intervention of NAFLD/NASH seems appropriate. In this review, we will focus on the different current and future therapeutic intervention options, taking into consideration the complex pathophysiology of this disease.

Hepatopathy Associated With Type 1 Diabetes: Distinguishing Non-alcoholic Fatty Liver Disease From Glycogenic Hepatopathy.

Autoimmune destruction of pancreatic ß-cells results in the permanent loss of insulin production in type 1 diabetes (T1D). The daily necessity to inject exogenous insulin to treat hyperglycemia leads to a relative portal vein insulin deficiency and potentiates hypoglycemia which can induce weight gain, while daily fluctuations of blood sugar levels affect the hepatic glycogen storage and overall metabolic control. These, among others, fundamental characteristics of T1D are associated with the development of two distinct, but in part clinically similar hepatopathies, namely non-alcoholic fatty liver disease (NAFLD) and glycogen hepatopathy (GlyH). Recent studies suggest that NAFLD may be increasingly common in T1D because more people with T1D present with overweight and/or obesity, linked to the metabolic syndrome. GlyH is a rare but underdiagnosed complication hallmarked by extremely brittle metabolic control in, often young, individuals with T1D. Both hepatopathies share clinical similarities, troubling both diagnosis and differentiation. Since NAFLD is increasingly associated with cardiovascular and chronic kidney disease, whereas GlyH is considered self-limiting, awareness and differentiation between both condition is important in clinical care. The exact pathogenesis of both hepatopathies remains obscure, hence licensed pharmaceutical therapy is lacking and general awareness amongst physicians is low. This article aims to review the factors potentially contributing to fatty liver disease or glycogen storage disruption in T1D. It ends with a proposal for clinicians to approach patients with T1D and potential hepatopathy.

NAFLD in type 1 diabetes: overrated or underappreciated?

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries, affecting 25-30% of the general population and up to 65% in those with obesity and/or type 2 diabetes. Accumulation of visceral adipose tissue and insulin resistance (IR) contributes to NAFLD. NAFLD is not an innocent entity as it not only may cause nonalcoholic steatohepatitis and cirrhosis but also contribute to cardiovascular morbidity and mortality. More and more people with type 1 diabetes (T1D) are becoming overweight and present with features of IR, but the prevalence and impact of NAFLD in this population are still unclear. The utility of noninvasive screening tools for NAFLD in T1D is being explored. Recent data indicate that based upon ultrasonographic criteria NAFLD is present in 27% (ranging between 19% and 31%) of adults with T1D. Magnetic resonance imaging data indicate a prevalence rate of 8.6% (ranging between 2.1% and 18.6%). There are, however, multiple factors affecting these data, ranging from study design and referral bias to discrepancies in between diagnostic modalities. Individuals with T1D have a 7-fold higher risk of cardiovascular disease (CVD) and cardiovascular mortality is the most prominent cause of death in T1D. Patients with T1D and NALFD are also more prone to develop CVD, but the independent contribution of NAFLD to cardiovascular events has to be determined in this population. Furthermore, limited data in T1D also point towards a 2 to 3 times higher risk for microvascular complications in those with NAFLD. In this article, we will discuss epidemiological and diagnostic challenges of NAFLD in T1D, explore the link between IR and NAFLD and chronic complications, and examine the independent contribution of NAFLD to the presence of macro-, and microvascular complications.

A Case of Steroid-Responsive, COVID-19 Immune Reconstitution Inflammatory Syndrome Following the Use of Granulocyte Colony-Stimulating Factor.

We present a case report of a 54-year-old male with metastasized nasopharyngeal carcinoma presenting to the hospital with dyspnea, anorexia and fever. Examination revealed chemotherapy-induced pancytopenia. The patient tested positive for SARSCoV-2, but respiratory complications were mild. The patient was treated with granulocyte-colony stimulating factor (G-CSF) leading to amelioration of the neutropenia. However, severe acute respiratory distress syndrome (ARDS) occurred, prompting the diagnosis of immune reconstitution inflammatory syndrome (IRIS). GCSF is currently investigated as additional therapy in ARDS, but this case report emphasizes that risks and benefits must be carefully assessed. To our knowledge, this is the first case report of IRIS-induced ARDS in a COVID-19 patient.