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Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

Introduction: Necrobiosis lipoidica (NL) is a rare chronic granulomatous dermatitis that usually appears in the lower extremities. It affects about 0.3–1.2% of diabetic patients, the majority of whom have type 1 diabetes. The etiology and pathogenesis of this disorder are still unclear. NL is characterized by skin rash that usually affects the shins. The average onset is 30 years, with females being affected more commonly. There are very few reported cases of necrobiosis lipoidica in children. Case report: We report a case of a 16 year old girl affected by type 1 diabetes mellitus (15 years disease duration) who developed an erythematous nodular rash on the lower extremities and interscapular area. In the suspect of necrobiosis lipoidica, a skin biopsy was performed (lower extremities and interscapular area). The microscopic evaluation of the pretibial lesions was suggestive of necrobiosis lipoidica. The smaller lesions in the interscapular area showed signs of perivascular dermatitis which could be consistent with early stages of necrobiosis lipoidica. Local treatment with tacrolimus determined a progressive improvement of the lesions. Conclusion: In patients with T1DM, diagnosis of NL of the lower legs is usually unequivocal. However, diagnosis may be more challenging in the presence of lesions with recent onset and/or atypical clinical presentation and unusual site. In these cases, NL must always be taken in consideration in order to avoid misdiagnosis, wrong/late treatment decisions and progression to ulceration.

Biallelic insulin receptor (INSR) gene mutations cause congenital syndromes of severe insulin resistance (SIR) known as Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). At presentation, DS and RMS are difficult to differentiate since they share many clinical features; however, while patients with DS usually die within 1 year of birth, individuals classified as RMS can reach adult age. INSR mutations can be also found in pubertal females with hyperinsulinism, hyperandrogenism, and acanthosis nigricans (type A SIR). We studied the INSR gene in five subjects with congenital SIR and in a patient with type A SIR. Nine biallelic INSR gene mutations (eight novels, including an in-frame deletion of INSR signal peptide) were identified in patients with congenital SIR; a heterozygous, spontaneous INSR mutation was detected in the patient with type A SIR. Two probands, presenting severe hirsutism at birth, died at the age of 3 months and were classified as DS, while other 2, currently 2 and 3 years old, were diagnosed with RMS (patients 3 and 4). The fifth patient with congenital SIR died when 14 months old. Nephrocalcinosis, hyperaldosteronism, hyperreninemia, and hypokalemia, in the absence of hypertension, were discovered in patients 3 and 5 when 24 and 4 months old, respectively. Patient 3, now 3 years/3 months old, still shows hyperreninemic hyperaldosteronism requiring potassium supplementation. We conclude that renal abnormalities resembling antenatal Bartter's syndrome type II, recently reported also by others, is a common observation in patients with congenital SIR.

Background: Efficacy and feasibility of sensor-augmented pump (SAP) therapy were evaluated in very young children with type 1 diabetes (T1D). Subjects and Methods: SAP (Dexcom [San Diego, CA] Seven Plus™ usage combined with insulin pump) therapy was retrospectively evaluated in 28 children (15 boys) younger than 7 years (mean age, 5.8±1.2 years; range, 3–7 years), with T1D. Glycosylated hemoglobin (HbA1c) was evaluated at baseline and at the end of the study, as were efficacy and feasibility of the system, using a rating scale (with 3 being the most positive). Results: SAP has been used for at least 6 months by 85% of patients, with an overall good satisfaction (92%). The greatest perceived benefit was the reduced fear of hypoglycemia (score of 3, 81%). HbA1c significantly improved only in patients with baseline HbA1c >7.5% (P=0.026). Conclusions: SAP therapy is effective and feasible in preschool children with T1D. In patients with high HbA1c at baseline it provide a 0.9% decrease, sustained for...

The prevalence of diabetes is increasing. Improved glucose control is fundamental to reduce both long-term micro- and macrovascular complications and short-term complications, such as diabetic ketoacidosis and severe hypoglycemia. Frequent blood glucose monitoring is an essential part of diabetes management. However, almost all available blood glucose monitoring devices are invasive. This determines a reduced patient compliance, which in turn reflects negatively on glucose control. Therefore, there is a need to develop noninvasive glucose monitoring devices that will reduce the need of invasive procedures, thus increasing patient compliance and consequently improving quality of life and health of patients with diabetes.