Maddalena Macedoni

Long-lasting immunogenicity and safety of a 2009 pandemic influenza A(H1N1) MF59-adjuvanted vaccine when co-administered with a 2009–2010 seasonal influenza vaccine in young patients with Type 1 diabetes mellitus

Diabet. Med. 28, 1530–1536 (2011)

Alpha-Lipoic Acid and Antioxidant Diet Help to Improve Endothelial Dysfunction in Adolescents with Type 1 Diabetes: A Pilot Trial

After evaluating the prevalence of early endothelial dysfunction, as measured by means of reactive hyperemia in adolescents with type 1 diabetes, we started a 6-month, double-blind, randomized trial to test the efficacy of an antioxidant diet (± alpha-lipoic acid supplementation) to improve endothelial dysfunction. Seventy-one children and adolescents, ages 17 ± 3.9 yrs, with type 1 diabetes since 9.5 ± 5.3 yrs, using intensified insulin therapy, were randomized into 3 arms: (a) antioxidant diet 10.000 ORAC + alpha-lipoic acid; (b) antioxidant diet 10.000 ORAC + placebo; (c) controls. BMI, blood pressure, fasting lipid profile, HbA1c, insulin requirement, dietary habits, and body composition were determined in each patient. An antioxidant diet significantly improved endothelial dysfunction when supplemented with alpha-lipoic acid, unlike diet with placebo or controls. A significant reduction in bolus insulin was also observed. We speculate that alpha-lipoic acid might have an antioxidant effect in pediatric diabetes patients by reducing insulin.

Adolescents and young adults with type 1 diabetes display a high prevalence of endothelial dysfunction

Little is known about endothelial function in adolescents with type 1 diabetes, and we evaluated endothelial dysfunction, using reactive hyperaemia peripheral arterial tonometry (RH‐PAT).

Insulin Pump Therapy in Children with Type 1 Diabetes: The Dark Side of the Moon

It is well established that insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] has several advantages when compared with multiple daily injections (MDI) of insulin, especially the sensor-augmented pump.1 However, we do not know whether the improvement in technology is accompanied by a high or low frequency of pump breakdowns or pump malfunctions (PM) and whether this has an impact on metabolic control. During a survey, we extrapolated the answers concerning malfunctions of the pump itself or the infusion set. Patients were divided into two groups according to the presence or absence of PM. Age, disease duration, last glycated hemoglobin (HbA1c), mean HbA1c of the whole period using CSII, last insulin requirement, last body mass index z-score, and severe hypoglycemia and diabetic ketoacidosis were compared in the two groups of children with type 1 diabetes. The use of a bolus calculator, the number of boluses made with the bolus calculator, the use of different type of boluses, the use of temporary basal, and the number of self-monitoring of blood glucose were also evaluated. The primary end point was the change in HbA1c between patients with or without PM. Among the 280 patients at our center, 130 (46%) were using CSII, of which 41 (32%) had used it for 3 years or more (range, 3–8.7 years; mean ± standard deviation, 5.3 ± 1.5 years). Pump malfunctions were recorded in 19/41 patients (46.3%), including battery or drive mechanism failure (n = 9, 47.4%), pump breakdown (n = 4, 21%), or others, including one theft (n = 6, 32.7%). Interestingly, after analyzing data of the two groups (malfunction or not), we found a significantly higher HbA1c in the malfunction group, while no difference was observed for any other factor analyzed (Table 1). In addition, in the group without PM, there were significantly more patients with HbA1c < 7.5% (58 mmol/mol; International Society for Pediatric and Adolescent Diabetes recommendations) than those who had had PM (50% versus 21%; p = .004 by chi-square test). Moreover, although various types of infusion set defects have been reported in 27/41 patients (65.9%), this does not seem to affect glycemic control, neither at the last visit or as a mean of the whole period using CSII (p = .75 and p = .56, respectively). Table 1 Clinical Characteristics of the 41 Children with Type 1 Diabetes Using an Insulin Pump for More Than 3 Years, According to Pump Malfunction (n = 19) or Not (n = 22)a The high number of pump and set failures, similar to that reported elsewhere,2–4 did not affect the increase of acute complications, probably because current insulin pumps already incorporate systems to detect some types of fault. To the best of our knowledge, no one has investigated the possible relationship between PM and impairment in metabolic control, as observed here. In our opinion, it is not a problem due to an acute lack of insulin, the breakdown of the insulin pump, or the delay in patients’ support (in Italy, pump companies offer a 24/7 assistance service, and in each case, the replacement of the pump occurred in less than 36 h and patients were instructed to use MDI in the meantime), but rather a possible distrust of the machine. It is as if the patients who experienced PM have a lesser confidence in the instrument and its technology. Ours is just a pilot (and in some way not planned) experience that needs to be confirmed in larger groups of patients. In the meantime, this aspect should be a warning for companies that make insulin pumps. Having a Ferrari (a smart pump) may be pointless if you are afraid of being left on foot. If anyone is interested, we are available to run a multicenter study about the relationship between PM and glycemic control.

Necrobiosis lipoidica diabeticorum

Necrobiosis lipoidica is a rare disorder that usually appears in the lower extremities and it is often related to diabetes mellitus. There are few reported cases of necrobiosis lipoidica in children. We present an interesting case in that the patient developed lesions on the abdomen, which is an unusual location.

Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes

Hematopoietic stem and progenitor cells (HSPCs) are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D) and remains the only “experimental therapy” that has achieved a satisfactory rate of remission (nearly 60%) in T1D. Patients with newly diagnosed T1D have been successfully reverted to normoglycemia by administration of autologous HSPCs in association with a non-myeloablative immunosuppressive regimen. However, this approach is hampered by a high incidence of adverse effects linked to immunosuppression. Herein, we report that while the use of autologous HSPCs is capable of improving C-peptide production in patients with T1D, ex vivo modulation of HSPCs with prostaglandins (PGs) increases their immunoregulatory properties by upregulating expression of the immune checkpoint-signaling molecule PD-L1. Surprisingly, CXCR4 was upregulated as well, which could enhance HSPC trafficking toward the inflamed pancreatic zone. When tested in murine and human in vitro autoimmune assays, PG-modulated HSPCs were shown to abrogate the autoreactive T cell response. The use of PG-modulated HSPCs may thus provide an attractive and novel treatment of autoimmune diabetes.

Performance of the Flash Glucose Monitoring System during Exercise in Youth with Type 1 Diabetes

AIM Metabolic changes during exercise may affect the accuracy of glucose sensors impacting on Type 1 diabetes (T1D) management. The present study aimed at assessing the performance of the Flash Glucose Monitoring system (isCGM) during exercise and in free-living condition in youth with T1D. METHODS Seventeen youth (53% male), aged 13.7 ± 3.8 years, with T1D for 5.4 ± 3.8 years, HbA1c 7.4 ± 1.0% (57 ± 11 mmol/mol), were enrolled. Paired isCGM, plasma (PG) and capillary (CG) glucose values (total of 136) were collected during an interval exercise (45 min at 55% VO2max load with 20 s sprints at 80% VO2max every 10 min). Paired isCGM and CG (total of 832) were collected during free-living condition. RESULTS During exercise, isCGM absolute relative difference (ARDs) means/medians were 12.5/9.4% versus PG and 15.4/10.8% versus CG. During rest, ARDs means/medians were 16.6/12.0%. The Consensus Error Grid analysis showed 98.4% of readings during exercise and 97.24% during rest in zones A + B. Percentage of readings meeting the ISO criteria for CG levels <5.55 mmol/L was 62.5% during exercise, 53.4% during rest; for CG levels ≥5.55 mmol/L was 64.0% during exercise, 60.4% during rest. CONCLUSIONS isCGM demonstrated similar clinical safety and performance during exercise and in everyday life; further studies are needed to confirm its accuracy during exercise.

Metabolic control, ApoE genotypes, and dyslipidemia in children, adolescents and young adults with type 1 diabetes

BACKGROUND AND AIMS Limited data is available on the factors influencing the lipid profiles and the prevalence of dyslipidemia in children, adolescents and young adults with type 1 diabetes. We aimed at assessing the influences of metabolic control and ApoE genotypes on lipid profiles and the prevalence of dyslipidemia in children, adolescents and young adults with type 1 diabetes. METHODS Children, adolescents and young adults with type 1 diabetes from our nationwide cohort attending the annual check-up were prospectively included. Data on metabolic control and expanded lipid profiles were collected, and ApoE genotyping performed. Test for homoscedasticity of continuous variables was followed by ANOVA and Welchs ANOVA tests, and Chi-square test was used for categorical variables with Kruskal-Wallis test as a control. RESULTS 467 patients were included in the data analysis: 226 female (48.4%), mean age 14.71 ± 5.09 years and diabetes duration 6.74 ± 4.54 years. Mean HbA1c was 61 ± 5 mmoL/mol (7.71 ± 1.22%), with no gender-related differences. Females had higher mean total cholesterol (p < 0.001), LDL-C (p = 0.005), HDL-C (p < 0.001), non-HDL-C (p = 0.003), and ApoB levels (p < 0.001). 26.3% of participants had LDL-C levels above the type 1 diabetes LDL-C-goal of 2.6 mmoL/L, and 19.5% had elevated/borderline-elevated lipoprotein(a) (Lp(a)). HbA1c levels were positively related to higher levels of LDL-C (p = 0.0070) and Lp(a) (p = 0.0020). Participants with ApoE4(e3/e4) allele had higher levels of LDL-C (p = 0.010), independently of HbA1c. CONCLUSIONS Females and subjects with suboptimal metabolic control had more adverse lipid profiles. ApoE4(e3/e4) alleles were associated with significantly higher LDL-C levels, independently of HbA1c.

Nutritional Aspects of Type 1 Diabetes: We Need to Keep Struggling Against Palaeolithic Diet (How Research Helps Us to Do the Right Thing)

For both type 1 and type 2 diabetes, eating healthy is key to blood glucose management [1]. Nowadays it is well recognised that, for each child and adolescent with type 1 diabetes, nutrition therapy is recommended. Implementation of an individualised meal plan with appropriate insulin adjustments can help to improve glycaemic control. The optimal macronutrient distribution varies depending on an individualised assessment [2].