Relationships between thyroid function and autoimmunity with metabolic derangement at the onset of type 1 diabetes: a cross-sectional and longitudinal study.

BACKGROUND: Type 1 diabetes (T1DM) is an autoimmune disease often associated with thyroid abnormalities. PURPOSE: We investigated the correlation between thyroid function and metabolic derangement at onset and the influence of autoimmunity on thyroid function at onset and subsequently. METHODS: We evaluated 152 patients diagnosed with T1DM between 2000 and 2012 at onset and during a mean follow-up of 5.45 ± 2.8 years. Thyroid function at onset was correlated with metabolic derangement (degree of acidosis, metabolic control and adrenal function) and compared with that of 78 healthy children. Follow-up consisted of regular evaluation of thyroid function and autoimmunity. RESULTS: Thyroid hormonal pattern was not influenced at onset by thyroid autoimmunity, but only by metabolic derangement: pH and base excess in fact were significantly lower in patients with impaired thyroid function (p < 0.0001). Patients presenting normal thyroid function at onset showed a reduced conversion from FT4 to FT3 compared to nondiabetic children (FT3/FT4 0.3 ± 0.4 in the control group, 0.24 ± 0.4 in diabetic patients, p < 0.0001). Multiple regression analysis showed the highest correlation (negative) between FT3 levels at onset and base excess (p < 0.005). Thyroid abnormalities related to metabolic derangement disappeared during follow-up. Patients with thyroid antibodies at T1DM onset were at higher risk to require levothyroxine treatment during follow-up (p < 0.05). CONCLUSIONS: Thyroid function at T1DM onset is mainly influenced by metabolic derangement, irrespective of thyroid autoimmunity. Antithyroid antibodies evaluation at T1DM onset may be helpful to define which patients are at higher risk of developing hypothyroidism.

Transition from pediatric to adult care. eight years after the transition from pediatric to adult diabetes care: metabolic control, complications and associated diseases.

BACKGROUND: Transition from pediatric to adult care is a critical process in the life of patients with diabetes. AIM: Primary aim of the study was to compare the metabolic control between pediatric care and adult care at least 5 years in a group of patients with type 1 diabetes mellitus (T1DM). Secondary aim was to evaluate the presence of complications, associated diseases and psychological-psychiatric disorders. SUBJECTS AND METHODS: We obtained data from 73 % (69/94) patients (current mean age 34 years) transferred to local adult centers between 1985 and 2005 at a mean age of 23.8 years. Data were collected for HbA1c, diabetic complications and associated diseases. RESULTS: Mean HbA1c did not change during the pediatric, transition and adult period [8.4 ± 1.8 % (68 ± 18 mmol/mol), 8.3 ± 1.4 % (67 ± 15 mmol/mol) and 8.4 ± 1.3 % (68 ± 14 mmol/mol), respectively]. 13 patients dropped out, after 2-12 years since transition, and their HbA1c mean value at transition was 10.4 %. After a mean of 25.9 years of disease, 35/69 patients (50.7 %) showed retinopathy, and 12/69 patients (17.3 %) nephropathy. Thyroid diseases were the most frequent associated diseases (18.3 %), followed by depression (11.2 %) and benign neoplasms (9.8 %). Drug or alcohol addictions were present in four cases (5.6 %). CONCLUSIONS: After a mean follow-up of 8 years metabolic control after transition did not change significantly in patients constantly attending to adult care centre. Patients with diabetes onset between 20 and 40 years ago were free from complications in 50 % of cases when considering retinopathy and in more than 80 % considering nephropathy. Thyroid problems were the most common associated diseases. Poor metabolic control at transition is associated with higher risk of drop-out and psychosocial morbidity.

Severe hypoglycemic episodes: a persistent threat for children with Type 1 diabetes mellitus and their families.

BACKGROUND: As lowering glycated hemoglobin (HbA1c) levels is still the main goal of insulin treatment, severe hypoglycemia (SH) remains a common experience in children with Type 1 diabetes mellitus (T1DM) and their families. AIM: This study aims to evaluate the incidence and the clinical features of SH episodes in our Centre in the last 20 yr. SUBJECTS AND METHODS: We analyzed SH incidence in 269 patients (pts) diagnosed from 1990 to 2010 (total follow-up 2212.9 pts/yr). Inclusion criteria were at least 3 visits/yr and 1-yr follow- up. SH episode was defined as any condition of low blood glucose requiring third-party assistance. RESULTS: 50.2% of patients experienced at least 1 SH episode for a total of 345 episodes. Whole incidence was 15.6/100 pts/yr, slightly different between first and second decade (12.6 vs 16.5, p=0.047). HbA1c at the time of SH was lower in the non-basal bolus group (7.4±1.3 vs 8.2±1.4; p=0.0001) and worsened 3 months later (p=0.0001). Impaired awareness was the main or only symptom in 43.5%. SH occurred at night in 32% of patients; they were significantly younger than those with SH at other times. Five SH episodes or more occurred in 8.1% of patients who presented a lower HbA1c, a younger age and shorter disease duration than the other patients. HbA1c at first SH was negatively correlated with number of SH (r=-0.20; p=0.05). CONCLUSIONS: Despite the advent of new insulin regimens, we confirm that SH still represents a relevant risk and a current threat for patients with T1DM and their families.

Defective and nondefective adenovirus vectors for expressing foreign genes in vitro and in vivo.

We have constructed recombinant adenoviruses (Ad), with functional or defective E1a genes, which harbor either the hepatitis B (HB) virus s gene encoding the HB surface antigen, as well as the pre-S2 epitopes, or the bacterial gene encoding chloramphenicol acetyltransferase (CAT) under control of the Ad major late promoter (MLP). The recombinant viruses defective for E1a (Ad.MLP.S2 and Ad.CAT), which can be efficiently propagated only on 293 cells that complement this defect, and the nondefective (Ad.MLP.S2.E1A) recombinant were used to infect a wide spectrum of cells of different origin. The yields of HBs and CAT proteins obtained with these different recombinant viruses demonstrate no real advantage to using nondefective vectors, whatever the cell type infected. The injection into chimpanzees of Ad.MLP.S2 does not elicit the production of antibodies, but can immunologically prime the animals, resulting in a partial protection against HBV challenge.