Effect of linagliptin plus insulin in comparison to insulin alone on metabolic control and prognosis in hospitalized patients with SARS-CoV-2 infection

To evaluate the effect of the combination of linagliptin and insulin on metabolic control and prognosis in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hyperglycemia. A parallel double-blind randomized clinical trial including hospitalized patients with SARS-CoV-2 infection and hyperglycemia, randomized to receive 5 mg linagliptin + insulin (LI group) or insulin alone (I group) was performed. The main outcomes were the need for assisted mechanical ventilation and glucose levels during hospitalization. Subjects were screened for eligibility at hospital admission if they were not with assisted mechanical ventilation and presented hyperglycemia, and a total of 73 patients with SARS-CoV-2 infection and hyperglycemia were randomized to the LI group (n = 35) or I group (n = 38). The average hospital stay was 12 ± 1 vs 10 ± 1 days for the I and LI groups, respectively (p = 0.343). There were no baseline clinical differences between the study groups, but the percentage of males was higher in the LI group (26 vs 18, p = 0.030). The improvements in fasting and postprandial glucose levels were better in the LI group that the I group (122 ± 7 vs 149 ± 10, p = 0.033; and 137 ± 7 vs 173 ± 12, p = 0.017, respectively), and insulin requirements tended to be lower in the LI group than the I group. Three patients in the LI group and 12 in the I group required assisted mechanical ventilation (HR 0.258, CI 95% 0.092–0.719, p = 0.009); 2 patients in the LI group and 6 in the I group died after a follow-up of 30 days (p = 0.139). No major side effects were observed. The combination of linagliptin and insulin in hospitalized patients with SARS-CoV-2 infection and hyperglycemia reduced the relative risk of assisted mechanical ventilation by 74% and improved better pre and postprandial glucose levels with lower insulin requirements, and no higher risk of hypoglycemia.This study is registered at clinicaltrials.gov, number NCT04542213 on 09/03/2020.

Coincidence of juvenile idiopathic arthritis and type 1 diabetes: a case-based review

The study was aimed to review a rare coexistence of type 1 diabetes (T1D) and juvenile idiopathic arthritis (JIA) regarding different clinical approaches to the management and treatment options. Medical complications of the two autoimmune disorders in children and adolescents have been evaluated, particularly in those treated with glucocorticosteroids (GCS) and insulin. A review of the literature regarding reports on concomitant T1D and JIA was conducted using resources available in Medline, Google Scholar, and Web of Science databases, with a specific focus on the combination of T1D and JIA in a pediatric population. The review was extended by our analysis of two patients treated in a single center for this comorbidity. Eligible reports of four cases were found, and including our two original records, a total of six pediatric patients (5 females) were analyzed, of which three had also other autoimmune diseases (thyroiditis, coeliac disease, autoimmune hepatitis), whereas four had been treated with a long-term GCS, and two were receiving biological therapy (etanercept or adalimumab). Only one of them had good metabolic control of diabetes. Diabetes in childhood may coexist with other autoimmune diseases, including rheumatologic conditions. Hyperglycemia can worsen JIA therapy by induction and maintaining inflammation. Using modern diabetes technologies (like personal insulin pumps and continuous glucose monitoring) helps to minimize the deteriorating effect of JIA exacerbations and the rheumatoid treatment on metabolic control of diabetes.

Metabolic Control of the FreeStyle Libre System in the Pediatric Population with Type 1 Diabetes Dependent on Sensor Adherence

Aims: To evaluate the relationship between daily sensor scan rates and changes in HbA1c and hypoglycemia in children. Methods: We enrolled 145 paediatric T1D patients into a prospective, interventional study of the impact of the FreeStyle Libre 1 system on measures of glycemic control. Results: HbA1c was higher at lower scan rates, and decreased as the scan rate increased to 15–20 scans, after which it rose at higher scan rates. An analysis of the change in hypoglycemia, based on the number of daily sensor scans, showed there was a significant correlation between daily scan rates and hypoglycemia. Subjects with higher daily scan rates reduced all levels of hypoglycaemia. Conclusions: HbA1c is higher at lower scan rates, and decreases as scan rate increases. Reductions in hypoglycemia were evident in subjects with higher daily scan rates.

The Association between Treatment Modality, Lipid Profile, Metabolic Control in Children with Type 1 Diabetes and Celiac Disease—Data from the International Sweet Registry

Background and Aims: A higher frequency of dyslipidemia is reported in children with type 1 diabetes (T1D) and celiac disease (CD). Recently, continuous subcutaneous insulin infusion (CSII) has been associated with better lipid profiles in patients with T1D. The aim of this study was to investigate the association between treatment modality and lipid profile, metabolic control, and body mass index (BMI)-SDS in children with both T1D and CD. Methods: Cross-sectional study in children registered in the international SWEET database in November 2020. Inclusion criteria were children (2–18 years) with T1D and CD with available data on treatment modality (CSII and injections therapy, IT), triglyceride, total cholesterol, HDL, LDL, dyslipidemia, HbA1c, and BMI-SDS. Overweight/obesity was defined as > +1 BMI-SDS for age. Data were analyzed by linear and logistical regression models with adjustment for age, gender, and diabetes duration. Results: In total 1009 children with T1D and CD (female 54%, CSII 54%, age 13.9 years ±3.6, diabetes duration 7.2 years ±4.1, HbA1c 7.9% ±1.4) were included. Significant differences between children treated with CSII vs. IT were respectively found; HDL 60.0 mg/dL vs. 57.8 mg/dL, LDL 89.4 mg/dL vs. 94.2 mg/dL, HbA1c 7.7 vs. 8.1%, BMI-SDS 0.4 vs. 0.6, overweight and obesity 17% vs. 26% (all p < 0.05). Conclusions: CSII is associated with higher HDL and lower LDL, HbA1c, BMI-SDS, and percentage of overweight and obesity compared with IT in this study. Further prospective studies are required to determine whether CSII improves lipid profile, metabolic control and normalize body weight in children with both T1D and CD.

Assessment of Subclinical Left Ventricular Systolic and Diastolic Dysfunction in Patients with Type 1 DM with and without Good Metabolic Control

Background: Diabetic patients with normal left ventricular ejection fraction (LVEF)are frequently associated with diastolic dysfunction. However, LVEF is known not to be a sensitive marker for the detection of subclinical LV systolic dysfunction. This study aimed to assess left ventricular systolic and diastolic function in asymptomatic type 1 diabetic patients by conventional, tissue Doppler and two-dimensional speckle tracking echocardiography to assess subclinical left ventricular systolic and diastolic dysfunction. Methods: Case-control study was conducted at 150 patients aged 15-35 y were subdivided into three equal groups: Group A: with type 1 diabetes mellitus (T1DM) with good metabolic control (Hb A1C <7.0), Group B: T1DM with poor metabolic control (Hb A1C>7.0), and Group C: Control group: included 50 normal healthy subjects. Results: Tissue Doppler, diastolic function and strain parameters, AP4C LS, AP2C LS, AP3C LS, and GLS were significantly impaired among the three groups. AP4C LS, AP2C LS, AP3C LS, and GLS were significantly lower in group B than group A and group C and was significantly lower in group A than group C, A velocity was significantly impaired among the three groups. A velocity was significantly higher in group B than group A and group C and was insignificantly impaired in group A than group C. Conclusion: Conventional echocardiography parameters were insignificantly different between the study groups. 2D speckle tracking and tissue Doppler echocardiography showed that subclinical left ventricular systolic function may be affected even before affection of diastolic function. Longer duration and poor glycemic control of diabetes significantly affect GLS.

Optical Coherence Tomography to Assess Neurodegeneration in Phenylalanine Hydroxylase Deficiency

In phenylalanine hydroxylase (PAH) deficiency, an easily feasible method to access the progression of neurodegeneration is warranted to contribute to current discussions on treatment indications and targets. The objective of the present study was to investigate whether optical coherence tomography (OCT) measures as markers of neurodegeneration differ between patients with PAH deficiency and healthy controls (HCs) according to phenotype and metabolic control. In this single-center cross-sectional study, 92 patients with different phenotypes of PAH deficiency [PAH deficiency not requiring treatment, early treated phenylketonuria (ETPKU), and late-diagnosed phenylketonuria (PKU)] compared with 76 HCs were examined using spectral-domain OCT. Indices of phenylalanine elevation and variability were correlated with OCT parameters. Late-diagnosed PKU patients showed reduced peripapillary retinal nerve fiber layer (pRNFL) thickness and combined ganglion cell and inner plexiform layer (GCIPL) volume. Adult ETPKU patients were found to have lower GCIPL volume (p = 0.016), which correlated with the indices of phenylalanine control. In pediatric ETPKU patients with poor metabolic control, pRNFL was significantly reduced (p = 0.004). Patients with PAH deficiency not requiring treatment did not exhibit retinal degeneration. Inner nuclear layer (INL) was significantly increased in the pediatric ETPKU patients, driven by those with current poor metabolic control (p = 0.006). Our data provide evidence of retinal neuroaxonal degeneration and INL swelling, depending on the phenotype, current age, and metabolic control. These findings suggest that OCT is suitable to investigate neurodegeneration in PKU and we propose OCT as a sensitive, reliable, safe, low-burden, and low-cost examination for future multicenter studies.

Incidence of Hypoglycemia and Hospitalization Related to Chronic Diabetes Complications and Its Effect on Quality of Life Among Patients Initiating Second Line Therapy: DISCOVER Study

The management of patients with type 2 diabetes is a complex process that must be individualized and be patient centered. The aim of this study was to assess the metabolic control, the annual incidence and crude prevalence of hypoglycemia, hospitalization, and complications among patients with type 2 diabetes initiating second-line therapy. This study is an observational, longitudinal, prospective study as a part of the multinational DISCOVERing Treatment Reality of Type 2 Diabetes in Real World Settings (DISCOVER) study, that recruited 519 patients with type 2 diabetes who were non-insulin users, aged ≥18 years, and switching to second-line therapy. The cohort was clinically evaluated over three years of follow up. Fear of hypoglycemia was assessed using the Hypoglycemia Fear Survey (HFS II), while the quality of life was assessed using SF36v2 questionnaire. Using second-line therapy improved metabolic control but the annual incidence of microangiopathies were at 61/1000 patient-years, 47/1000 patient-years, and 4/1000 patient-years for neuropathy, retinopathy, and nephropathy, respectively. The incidence of hypoglycemia was 57/1000 patient-years, where 50% were recurrent during the three-years period. The HFS II showed a significant increase in patients’ worries related to hypoglycemia. The incidence of hospitalization was 31/1000 patient-years, out of which 8/1000 patient-years were related to cardiovascular events, mainly myocardial infarction. Moderate metabolic control was associated with lower incidence of macro angiopathy and an increased incidence and fear of hypoglycemia, while it was associated with improved mental component score when assessing the patients’ quality of life. The treating physician’s decision of treatment intensification should be individualized with consideration of befits of good glycemic control versus the risk of hypoglycemia, especially in elderly patients.

Sex differences over time for glycemic control, pump use and insulin dose in patients aged 10–40 years with type 1 diabetes: a diabetes registry study

IntroductionTo evaluate sex differences in people with type 1 diabetes concerning changes in glycemic control and trends in insulin pump use and insulin dose over two decades in adolescents and one-and-a-half decades in adults.Research design and methodsPeople aged 10–20 years (data years 1999–2018) and 21–40 years (data years 2004–2018) with type 1 diabetes were identified in the Diabetes Prospective Follow-up Registry (DPV). All available patients’ data sets of the respective period were used for linear regression analyses to investigate trends in HbA1c, pump use, insulin doses and body mass index SD scores (BMI-SDS) in females and males. In addition, stratification by migrant background was made for the adolescent group.ResultsIn the youth group (n=68 662), both boys and girls showed an HbA1c decrease over the period examined. After stratification for migrant background, an HbA1c convergence between boys and girls was seen in those without migrant background as of 2016. Usage of insulin pumps increased continuously from 3% (boys and girls) to 47% (boys) and 54% (girls), respectively. The daily insulin dose in units per kilogram body weight and day increased continuously from 1999 to 2018. An insulin dose leveling between boys and girls occurred. BMI-SDS consistently increased in girls whereas only slight variations were observed in boys.The adult group (n=15 380) showed constant HbA1c sex differences from 2004 to 2018 with lower HbA1c level in females. The use of insulin pump therapy rose from 18% to 35% (males) and 30% to 50% (females).ConclusionsThe gap in metabolic control between boys and girls with type 1 diabetes seems to close, but predominantly in adolescents without a migrant background. Improved HbA1c was associated with increased insulin pump use, especially in girls.In adult patients, sex differences in metabolic control and insulin pump use persist: women show constantly lower HbA1c values and higher insulin pump use.