Barbara Piccini

Seasonality at the clinical onset of type 1 diabetes-Lessons from the SWEET database

Seasonality at the clinical onset of type 1 diabetes (T1D) has been suggested by different studies, however, the results are conflicting. This study aimed to evaluate the presence of seasonality at clinical onset of T1D based on the SWEET database comprising data from 32 different countries.

Continuous subcutaneous infusion of protein C concentrate using an insulin pump in a newborn with congenital protein C deficiency.

We describe the case of a newborn presenting with multicystic encephalomalacy, hydrocephalus and bilateral hemovitreous. An underlying coagulation disorder was suspected and laboratory tests revealed severe protein C deficiency. At 25 days of life, after the appearance of purpura fulminans, replacement therapy with intravenous protein C concentrate (Ceprotin; Baxter, Vienna, Austria) was started.Due to difficulties in getting peripheral venous access and to repeated loss of the venous access, continuous subcutaneous infusion of protein C was started with an insulin pump (VEO 754; Medtronic, Minneapolis, Minnesota, USA), normally adopted in patients with type 1 diabetes mellitus. Protein C values increased into the normal range and the resolution of the purpuric skin lesion was achieved. Chronic prophylaxis with low-molecular-weight heparin failed and, due to cutaneous and cerebral recrudescence, replacement therapy with the pump was started again. The insulin pump allowed us to reduce the number of injections per day and to deal with the difficulties in getting peripheral venous access, permitting medical and paramedical staff an easier management of the therapy. The dosing schedule could be easily adapted with the insulin pump and the continuous subcutaneous administration of small amounts of protein C concentrate prevented fluctuation in trough levels of protein C. This is the first reported case of a novel, successful use of an insulin pump in an extremely rare disease, to administer a drug different from insulin, which needs to be further analyzed, underlining the importance of a multidisciplinary team approach in order to provide effective and efficient care in high-complexity diseases.

Circulating Endothelial Progenitor Cells in Type 1 Diabetic Patients: Relation with Patients’ Age and Disease Duration

Objectives Circulating endothelial progenitor cells (cEPCs) have been reported to be dysfunctional in diabetes mellitus (DM) patients, accounting for the vascular damage and the ensuing high risk for cardiovascular disease (CVD) characteristic of this disease. The aim of the present study was to evaluate the number of circulating cEPCs in type 1 DM (T1DM) patients, without clinical vascular damage, of different ages and with different disease duration. Methods An observational, clinical-based prospective study was performed on T1DM patients enrolled in two clinical centers. cEPCs were determined by flow cytometry, determining the number of CD34/CD133/VEGFR2-positive cells within peripheral blood mononuclear cells (PBMCs). Results The number of cEPCs was lower in adult T1DM patients, whilst higher in childhood/young patients, compared to controls of the same age range. When patients were grouped into two age groups (≥ or <20 years) (and categorized on the basis of the duration of the disease), the number of cEPCs in young (<20 years) patients was higher compared with older subjects, regardless of disease duration. A subset of patients with very high cEPCs was identified in the <20 years group. Conclusion There is an association between the number of cEPCs and patients’ age: childhood/young T1DM patients have significantly higher levels of cEPCs, respect to adult T1DM patients. Such difference is maintained also when the disease lasts for more than 10 years. The very high levels of cEPCs, identified in a subset of childhood/young patients, might protect vessels against endothelial dysfunction and damage. Such protection would be less operative in older subjects, endowed with lower cEPC numbers, in which complications are known to develop more easily.

Type 1 diabetes, sport practiced, and ankle joint mobility in young patients: What is the relationship?

It is known that patients with diabetes can develop limited joint mobility (LJM) and that this can depend on the metabolic control maintained and the duration of the disease. The aims of this study were to verify the presence of ankle joint mobility (AJM) deficits in both plantar and dorsiflexion in young type 1 diabetic patients (T1D) considering also the possible role of sport practiced as a further factor, able to modify AJM.

A mathematical model of the effect of metabolic control on joint mobility in youngtype 1 diabetic subjects

Diabetes mellitus is a metabolic disorder representing one of the main problems for the global public health. The impairment of metabolic control can influence periarticular tissue and other major risk factors of limited joint mobility (LJM) also in young type 1 diabetic patients. LJM is a widespread phenomenon in diabetic patients and it is often characterized by ankle stiffness. In particular, a deficit of ankle joint mobility may occur with the onset of the disease; later, this deficit tends to deteriorate in presence of a poor glycemic control. We hypothesized a mathematical model of diabetes mellitus long-term effects, assuming that a reduced metabolic control affects joint mobility according with a Gaussian function: it requires some time for developing a reduction of joint mobility, that persists for a stable period, before fading out with time (in case metabolic control has been recovered). A non-linear optimization estimated the model parameters for obtaining the best fit over a set of patients. Results are in good accordance with empirical estimates: lack of control needs to persist for at least a few months before generating a sensible effect, that persists for up to one year.

The influence of treatment, age at onset, and metabolic control on height in children and adolescents with type 1 diabetes-A SWEET collaborative study

To describe the association between height, demographics, and treatment in youths with type 1 diabetes participating in an international network for pediatric diabetes centers (SWEET).

Glycemic Control Maintained over Time and Joint Stiffness in Young Type 1 Patients: What Is the Mathematical Relationship?

Background: It is widely known that diabetes can induce stiffness and adversely affect joint mobility even in young patients with type 1 diabetes mellitus (T1D). The aim of this study was to identify a mathematical model of diabetes mellitus long-term effects on young T1D patients. Methods: Ankle joint mobility (AJM) was evaluated using an inclinometer in 48 patients and 146 healthy, sex- BMI-, and age-matched controls. Assuming time invariance and linear superposition of the effects of hyperglycemia, the influence of T1D on AJM was formalized as an impulse response putting into relationship past supernormal HbA1c concentrations with the ankle total range of motion. The proposed model was identified by means of a nonlinear evolutionary optimization algorithm. Results: AJM was significantly reduced in young T1D patients (P < .001). AJM in both plantar and dorsiflexion was significantly lower in subjects with diabetes than in controls (P < .001). The identified impulse response indicates that impaired metabolic control requires 3 months to bring out its maximum effect on the reduction of AJM, while the following long-lasting decay phase with the expected AJM recovery times, normally depends on the slow turnover of collagen. HbA1c concentration levels above 7.2% are sufficient to produce a reduction of ankle ROM. Conclusions: In young patients with T1D the lack of glycemic control over time affects AJM. HbA1c levels can serve as a relevant prognostic factor for assessing the progression of LJM in subjects with diabetes.

A mathematical model appraising the effect of metabolic control on joint mobility in young diabetic patients: a preliminary study

Objective. The impairment of glycemic control can induce limited joint mobility even in young type 1 diabetic (T1DM) patients. The aims of this study were to verify the presence of ankle joint mobility (AJM) deficits in young T1DM subjects and define a mathematical model of diabetes mellitus long-term effects on AJM. Methods. AJM was evaluated using an inclinometer in 37 patients and 53 healthy, sex- BMI- and age-matched controls. To set up the mathematical model, we assumed that reduced metabolic control affects AJM according to a lognormal function: requiring some time for development of a reduction of joint mobility, which then persists for a long period, before fading out over time (if glycemic control has been recovered). A non-linear optimization determined the model parameters to achieve the best fit for a series of patients. Results. Both plantar and dorsiflexion AJM was significantly lower in diabetic subjects than in controls (plantarflexion: 28.5°±7.5 vs 35.2°±6.5; dorsiflexion: 93.9°±16.0 vs 104.7±12.8; p<0.01). The defined model approximates the experimental data with good accuracy; after optimization, the lognormal curve obtained is in line with empirical estimates: lack of glycemic control needs to persist for at least a few months before producing a significant effect, that lasts up until one year. The fitting procedure indicated the optimal solution is p = (37; 30; 3:5; 6:7; 137); thus, the optimal _im(t) corresponds to the curve reported. Conclusion. AJM was significantly reduced in young T1DM patients. The mathematical model represents the experimental data accurately.

Transient Neonatal Diabetes Mellitus in a Very Preterm Infant due to ABCC8 Mutation

Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes occurring within 6 months from birth. NDM can be permanent or transient (TNDM). We report the case of a preterm infant with TNDM due to an ABCC8 mutation identified by next-generation sequencing. The pancreatic adenosine triphosphate (ATP)-sensitive K+ (K-ATP) channel is a key regulator of insulin secretion. Gain-of-function mutations in the genes encoding the Kir6.2 (KCNJ11) and SUR1 (ABCC8) subunits of the channel cause neonatal diabetes. The patient was successfully managed with insulin lispro at a 1:100 dilution, drawn up in an insulin pen injector with a 4-mm needle. The insulin lispro dilution allowed administration of the exact insulin doses, obtaining a good glycemic control and minimizing the burden of injections. At 2 months, corrected age insulin doses were progressively decreased until discontinuation.