Repurposing of Empagliflozin as a Possible Treatment for Neutropenia and Inflammatory Bowel Disease in Glycogen Storage Disease Type Ib: A Case Report.

Glycogen storage disease type Ib (GSD-Ib) is an autosomal-recessive inborn error of carbohydrate metabolism, where severe fasting hypoglycemia is associated (among other manifestations) with neutropenia and neutrophil dysfunction (predisposing to recurrent, potentially life-threatening infections) and inflammatory bowel disease (IBD). Granulocyte colony-stimulating factors (G-CSFs) are commonly used for its treatment. Although they have improved the prognosis of the disease, these medicines have also led to concerns about complications associated with their use (namely splenomegaly and hematopoietic malignancies), not to mention their increased cost. Recently, a novel new treatment for neutropenia associated with this disease was discovered. It was found that sodium-glucose cotransporter type 2 (SGLT-2) inhibitors, usually used for the treatment of diabetes mellitus, can ameliorate both neutropenia and IBD-related symptoms and improve the quality of life in patients suffering from these diseases. They do it by inhibiting the renal reabsorption of 1,5-anhydroglucitol, a dietary analog of glucose, whose accumulation due to the specific enzyme deficiency leads to toxic effects on granulocytes. Herein we report the treatment of an adult patient suffering from GSD-Ib with empagliflozin, an SGLT-2 inhibitor.

Wheat Biscuits Enriched with Plant-Based Protein Contribute to Weight Loss and Beneficial Metabolic Effects in Subjects with Overweight/Obesity.

The present study aimed to assess the impact of daily consumption of a snack fortified with plant proteins with high content in amino acids with appetite regulating properties (BCAAs and L-arginine), as part of a dietary intervention, on weight loss. Seventy adults without diabetes (26 male, 44 female) and with overweight/obesity participated in a 12-week restricted dietary intervention and were randomized to either a control or an intervention group, consuming daily 70 g of conventional wheat biscuits (CB) or an isocaloric amount of wheat biscuits enriched with plant proteins (PB) originating from legumes and seeds, respectively. Anthropometric characteristics were measured and venous blood samples were collected at baseline and at the end of the intervention. Decreases in body weight, body fat mass and waist circumference were observed in both groups. Participants in the intervention group experienced greater weight loss (7.6 ± 2.7 vs. 6.2 ± 2.7%, p = 0.025) and marginally significant larger decrease in body fat mass (4.9 ± 2.2 vs. 3.9 ± 2.4 kg, p = 0.059). A moderate reduction in IL-1ß levels (p = 0.081), a significantly higher decrease in TNF-α levels (p < 0.001) and a marginally significant greater leptin decrease (p = 0.066) in subjects of the PB group were noticed. Greater reductions in caloric and carbohydrate intake and a trend towards a higher decrease in fat intake were also observed in participants of this group. Incorporation of plant-based proteins with high content in amino acids with appetite-regulating properties in wheat biscuits may contribute to greater weight loss and improvement of metabolic parameters in subjects who are overweight or obese. Protein enrichment of snacks offers a beneficial qualitative manipulation that could be successfully incorporated in a diet plan.

The association of insulin resistance measured through the estimated glucose disposal rate with predictors of micro-and macrovascular complications in patients with type 1 diabetes.

BACKGROUND AND AIM: Insulin resistance (IR) is associated with a higher rate of type 1 diabetes (T1D) complications. We aimed to examine the relationship between estimated glucose disposal rate (eGDR), a readily available marker of IR in clinical practice and early predictor biomarkers of macrovascular and microvascular complications in patients with T1D. DESIGN: A cross-sectional study. METHODS: A total of 165 consecutive patients with T1D free of cardiovascular, eye, and renal complications were included in the study from 2016 to 2020. Participants were characterized as insulin resistant if their eGDR value was ≤ 8 mg/kg/min. Pulse wave velocity (PWV) and global longitudinal strain (GLS) were used as surrogates for subclinical atherosclerosis and left ventricular systolic dysfunction (LVSD), respectively. Four previously standardized tests based on the calculation of heart rate variability (HRV) were used to evaluate subclinical cardiac autonomic neuropathy (CAN). Early nephropathy was assessed by assessing urinary albumin to creatinine ratio (ACR). RESULTS: The population sample (n = 165) included a majority of female patients (63%) and had a median age of 32 years (24-43), median disease duration of 14 years ( ± 9.5-21.5), a median BMI value of 23.7 kg/m2 (21.4-26.6), an HbA1C of 7.2% (6.7-8.2) and median eGDR (lower values indicate higher insulin resistance) of 9.2 mg/kg/min (8.2-9.9), while 21.8% (n = 36) of the participants were characterized as insulin resistant. After adjustment for age, gender, and the duration of diabetes, the presence of IR was significantly associated with higher prevalence of subclinical atherosclerosis (OR:2.59, 95% CI: 1.06-6.30, p = 0.036), CAN (OR:3.07, 95% CI: 1.02-9.32, p = 0.047) and subclinical LVSD (OR: 4.9, 95% CI: 1.94-12.79, p = 0.001). No association was shown with ACR. CONCLUSIONS: In patients with T1D, insulin resistance, as measured by eGDR, correlates well with early CVD predictors and CAN. These associations appear independent of the effects of gender, aging, and disease duration.

The glycemic status determines the direction of the relationship between red cell distribution width and HbA1c.

AIMS: Available studies conducted on heterogenous populations on the association between the erythrocyte distribution width (RDW) and HbA1c have reported a positive, negative or neutral relationship. The aim of the present study is to investigate the debated relationship between RDW and HbA1c among hematologically healthy individuals with and without type 2 diabetes mellitus (T2DM). METHODS: Paired measurements of RDW and HbA1c of 183 hematologically healthy individuals (100 without DM, 83 with T2DM) were obtained. The association of HbA1c with a) hematologic parameters (hemoglobin, log[ferritin], RDW) and b) factors related to glycemia (BMI, fructosamine, FPG) was examined within each group separately and in the sum of the study sample. RESULTS: There was a significant positive correlation of RDW with HbA1c among those without DM while the opposite was true among individuals with T2DM (r = 0.315, p = 0.001 and r = -0.275, p = 0.011). In the T2DM group a significant negative correlation with fructosamine was noted (r = -0.274, p = 0.012) which was absent among normoglycemic individuals. Among those without DM the association between HbA1c and RDW remained significant after adjustment for all tested parameters. In the population with T2DM the significance was attenuated after including glycemia-related factors values. In multivariable regression in the sum of the study sample, the interaction between diabetes status and RDW as regards HbA1c was significant [unstandardized correlation coefficient - 0.397 (-0.646 to -0.147), p = 0.002] and remained significant after adjustment for multiple potential confounders. CONCLUSIONS: Among individuals without DM, the RDW likely reflects the non-glycemic interference on HbA1c values, while in T2DM RDW may serve as an indirect index of glycemia and dysmetabolism.

Early left ventricular systolic dysfunction in asymptomatic patients with type 1 diabetes: a single-center, pilot study.

AIMS: Prevalence and risk factors of pre-symptomatic left ventricular systolic dysfunction (LVSD) in individuals with type 1 diabetes (T1D) have not been adequately studied. The present cross-sectional study assessed the prevalence of early LVSD in asymptomatic patients with type 1 diabetes and investigated potential risk factors. METHODS: Consecutive patients with T1D, free of cardiovascular disease and significant evident microvascular complications were examined. LVSD was assessed by speckle-tracking echocardiography and calculation of global longitudinal strain (GLS). Abnormal GLS was defined as a value>-18.7%. We looked for possible associations between the presence of LVSD and patient demographic, clinical and laboratory characteristics, as well as with autonomic nervous system (ANS) function and arterial stiffness. RESULTS: We enrolled 155 T1D patients (29.7% men, age 36.7 ±â€¯13.1 years, diabetes duration 19.1 ±â€¯10.0 years, HbA1c 7.5 ±â€¯1.4% [58 ±â€¯15 mmol/mol]). Early LVSD was prevalent in 53 (34.2%) patients. Multivariable analysis identified male gender (OR:4.14; 95% CI:1.39-12.31, p = 0.011), HbA1c (OR:1.59 per 1% increase; 95% CI:1.11-2.28, p = 0.011), glomerular filtration rate (GFR, OR:0.97; 95% CI:0.95-0.99, p = 0.010) and BMI (OR:1.19; 95% CI:1.06-1.34, p = 0.003) as independent predictors of LVSD presence. CONCLUSIONS: Early subclinical LVSD is a common finding in asymptomatic patients with T1D, free of macrovascular and significant microvascular complications. Apart from chronic hyperglycemia, increased adiposity may be implicated in its etiology. Further investigation is warranted to identify patients at high risk for whom early screening is required and to determine possible associations between risk markers identified in the present analysis and long-term outcomes.