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.

Favorable course of previously undiagnosed Methylmalonic Aciduria with Homocystinuria (cblC type) presenting with pulmonary hypertension and aHUS in a young child: a case report.

BACKGROUND: Cobalamin C (cblC) defect is the most common inborn error of Vitamin B12 metabolism often causing severe neurological, renal, gastrointestinal and hematological symptoms. Onset with pulmonary hypertension (PAH) and atypical hemolytic-uremic syndrome (aHUS) is rare. CASE PRESENTATION: We describe the case of a 2-years old child, previously in good health, admitted to the hospital with severe respiratory symptoms, rapid worsening of clinical conditions, O2 desaturation and palmo-plantar edema. The patient showed PAH and laboratory findings compatible with aHUS. cblC defect, an inborn error of metabolism, was identified as the cause of all the symptoms described (cardiac, respiratory and renal involvement). Results of neonatal screening for inborn errors of metabolism had been negative. Administration of IM OHCbl (intramuscular hydroxocobalamin), oral betaine and symptomatic treatment with diuretics and anti-hypertensive systemic and pulmonary drugs induced dramatic improvement of both cardiac and systemic symptoms. CONCLUSIONS: In this case of cblC defect the metabolic treatment completely reverted symptoms of aHUS and PAH. The course was favorable, and the prognosis is what we foresee for the future.

Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM.

BACKGROUND: Treatments for childhood obesity are critically needed because of the risk of developing co-morbidities, although the interventions are frequently time-consuming, frustrating, difficult, and expensive. PATIENTS AND METHODS: We conducted a longitudinal, randomised, clinical study, based on a per protocol analysis, on 133 obese children and adolescents (n = 69 males and 64 females; median age, 11.3 years) with family history of obesity and type 2 diabetes mellitus (T2DM). The patients were divided into three arms: Arm A (n = 53 patients), Arm B (n = 45 patients), and Arm C (n = 35 patients) patients were treated with a low-glycaemic-index (LGI) diet and Policaptil Gel Retard, only a LGI diet, or only an energy-restricted diet (ERD), respectively. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda, insulinogenic and disposition indexes were calculated at T0 and after 1 year (T1). RESULTS: At T1, the BMI-SD scores were significantly reduced from 2.32 to 1.80 (p < 0.0001) in Arm A and from 2.23 to 1.99 (p < 0.05) in Arm B. Acanthosis nigricans was significantly reduced in Arm A (13.2% to 5.6%; p < 0.05), and glycosylated-haemoglobin levels were significantly reduced in Arms A (p < 0.005). The percentage of glucose-metabolism abnormalities was reduced, although not significantly. However, the HOMA-IR index was significantly reduced in Arms A (p < 0.0001) and B (p < 0.05), with Arm A showing a significant reduction in the insulinogenic index (p < 0.05). Finally, the disposition index was significantly improved in Arms A (p < 0.0001) and B (p < 0.05). CONCLUSIONS: A LGI diet, particularly associated with the use of Policaptil Gel Retard, may reduce weight gain and ameliorate the metabolic syndrome and insulin-resistance parameters in obese children and adolescents with family history of obesity and T2DM.

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.