OBJECTIVE -The aim of the present study was to define heterogeneity of adult-onset autoimmune diabetes based on characterization of GAD antibodies (GADAs). RESEARCH DESIGN AND METHODS-Patients enrolled in a nationwide survey, the Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study, have been screened for GADAs and IA-2 antibodies (IA-2As) and further characterized for GADA titer, antibodies to thyroid peroxidase (TPO), and HLA DRB1-DQB1 polymorphisms.RESULTS -Of 4,250 consecutive type 2 diabetic patients, 4.5% had either GADAs and/or IA-2As. Patients with autoimmune diabetes showed a clinical phenotype significantly different from that of type 2 diabetes, including higher fasting glucose and A1C, lower BMI and uric acid, lower prevalence of metabolic syndrome and its components, and higher frequency of TPO antibodies. More interestingly, analysis of GADA titers showed a bimodal distribution that identified two subgroups of patients with high (Ͼ32 GADA arbitrary units) and low (Յ32 GADA arbitrary units) GADA titers. Compared with those with low GADA titers, patients with high GADA titers had more prominent traits of insulin deficiency and a profile of more severe autoimmunity resulting in higher A1C, lower BMI, a lower prevalence of metabolic syndrome and its components (P Ͻ 0.02 for all), a higher prevalence of IA-2As, TPO antibodies (P Ͻ 0.003 for both), and DRB1*03-DQB1*0201 (50 vs. 26.8%, P ϭ 0.001), and a decreasing frequency of DQB1*0602 and DRB1*0403 (from type 2 to low and to high GADA titer autoimmune diabetes; P Ͻ 0.001 for trend for both comparisons).CONCLUSIONS -GADA titers identify two subgroups of patients with adult-onset autoimmune diabetes having distinct clinical, autoimmune, and genetic features. Diabetes Care 30:932-938, 2007

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We studied the circadian rhythm of plasma melatonin, growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), and cortisol in 52 mentally healthy old subjects, 35 old demented patients, and 22 clinically healthy young controls. When compared to young controls, the circadian profile of plasma melatonin of old subjects, both demented or not, was clearly flattened, particularly during the night. The selective impairment of nocturnal melatonin secretion was significantly related to both the age and the severity of mental impairment (Mini Mental State Examination [MMSE] score). The PRL and GH circadian profiles were similar in the three groups during the day, but a significant lowering of the values recorded during the night occurred with aging. The impairment of the nocturnal secretion was related to the subjects' age and, for the GH secretory pattern only, also to the MMSE score. The ACTH circadian profile was similar in the three groups studied, even when old subjects exhibited higher ACTH levels throughout the 24 h cycle, compared to young controls. Significantly higher cortisol values at evening- and nighttime occurred in elderly subjects and particularly in the demented group. Both the mean levels and the nadir values of plasma cortisol were positively related to age and negatively to MMSE score. In order to verify the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to the steroid feedback, the circadian profile of plasma cortisol was evaluated also after dexamethasone (DXM) administration (1 mg at 23:00 h); the sensitivity of the HPA axis was significantly impaired in old subjects and particularly in the demented ones. These findings suggest that the neuroendocrine alterations already present in physiological aging, due to both anatomical damages and unbalanced central neurotransmitters, are enhanced in senile dementia.

Aims/hypothesis: Established autoimmune markers of type 1 diabetes, including islet cell autoantibodies (ICA) and autoantibodies to glutamic acid decarboxylase (GADA) have been used to screen people presenting with type 2 diabetes for latent autoimmune diabetes in adults. We have examined the prevalence of autoantibodies to protein tyrosine phosphatase isoforms IA-2 (IA-2A) and IA-2β/phogrin (IA-2βA) in a cohort of adult UKPDS patients thought to have type 2 diabetes, and investigated the possible role of these autoantibodies in predicting requirement for insulin therapy. Methods: IA-2A and IA-2βA were measured by a validated radioimmunoassay with human recombinant autoantigens in 4,169 white Caucasian patients aged 25-65 years and newly diagnosed with type 2 diabetes. The clinical requirement for insulin therapy within 6 years was examined in 2,556 patients not randomised to insulin. Results: IA-2A and IA-2βA were present in 2.2 and 1.4%, respectively, of these patients. IA-2A were more prevalent in younger patients (p for trend <0.00001), more often associated with the HLA-DR4 allele (26.3 vs 8.0%, p<0.0001), and their presence increased the likelihood of insulin therapy requirement within 6 years from diagnosis [relative risk (95%CI) 12.2 (9.8-15.3)]. The presence of IA-2A together with GADA increased the relative risk of requiring insulin therapy from 5.4 (4.1-7.1) for GADA alone to 8.3 (3.7-18.8) and the corresponding positive predictive value from 33 to 50%. Conclusions/interpretation: In type 2 diabetes, the presence of IA-2A is infrequent, associated with the HLA-DR4 haplotype, and highly predictive of future need for insulin therapy. The measurement of IA-2βA does not provide additional information.

Hepatic abnormalities in Turner syndrome are not progressive. Oestrogen should not be considered the main cause of increased liver enzymes in Turner syndrome since most of our patients with this finding had not been previously treated with oestrogens. An auto-immune pathogenesis might be considered in some cases, whereas the association with weight excess seems the most frequent cause of liver disorder in Turner syndrome.