Intelligent Insulin vs. Artificial Intelligence for Type 1 Diabetes: Will the Real Winner Please Stand Up?

Research in the treatment of type 1 diabetes has been addressed into two main areas: the development of "intelligent insulins" capable of auto-regulating their own levels according to glucose concentrations, or the exploitation of artificial intelligence (AI) and its learning capacity, to provide decision support systems to improve automated insulin therapy. This review aims to provide a synthetic overview of the current state of these two research areas, providing an outline of the latest development in the search for "intelligent insulins," and the results of new and promising advances in the use of artificial intelligence to regulate automated insulin infusion and glucose control. The future of insulin treatment in type 1 diabetes appears promising with AI, with research nearly reaching the possibility of finally having a "closed-loop" artificial pancreas.

Characterization of thyroglobulin epitopes in Sardinian adults and juveniles with Hashimoto's thyroiditis: evidence against a major effect of age and genetic background on B-cell epitopes.

BACKGROUND: Using recombinant human monoclonal thyroglobulin antibodies expressed as Fab molecules (TgAb-Fab), we have recently confirmed the restriction of Tg epitopes in Hashimoto's thyroiditis (HT). OBJECTIVE: To investigate Tg epitopes of serum TgAb in HT adults and HT juveniles from a geographically isolated area (Sardinia). DESIGN AND PATIENTS: Serum TgAb of 39 Sardinian HT adults, 53 Sardinian HT juveniles and 45 non-Sardinian HT adults were evaluated. The binding of serum TgAb to Tg in ELISA was inhibited by four recombinant human TgAb-Fab, identifying Tg epitopic regions A-D. The percentage of Tg binding inhibition was calculated comparing the binding of serum TgAb in presence of each TgAb-Fab with that in its absence. RESULTS: In the whole cohort of 137 patients, A region TgAb-Fab induced the highest levels of inhibition (55.3 +/- 17.8%) (mean +/- SD). Lower levels of inhibition were induced by TgAb-Fab of regions B (27.8 +/- 25.8%), C (26.8 +/- 24.6%) and D (17.5 +/- 18.4%). In Sardinian HT adults inhibition by TgAb-Fab of regions A, B and C were comparable to Sardinian HT juveniles; the marginal D region TgAb-Fab induced a slightly higher inhibition (22.1 vs. 13.8%; P = 0.034) in the former than in the latter group. In Sardinian and non-Sardinian HT adults inhibitions by the four TgAb-Fab were similar. CONCLUSIONS: In HT, the Tg epitope pattern of serum TgAb was similar in juveniles and adults from a geographically restricted area and in two adult populations from different geographical areas. Thus, in HT, neither age nor genetic background appear to influence B-cell epitopes.

Cardiovascular risk in elderly hypothyroid patients.

Overt hypothyroidism (OH) and subclinical hypothyroidism (SH) are frequently found in the elderly. OH is associated with several functional cardiovascular abnormalities and increased risk of atherosclerosis resulting from hypertension associated to atherogenic lipid profile. Other potential atherogenic factors involved in OH are increased circulating C-reactive protein and homocysteine, increased arterial stiffness, endothelial dysfunction, and altered coagulation parameters. Similar (although mild) cardiovascular abnormalities are present in SH. Since all these abnormalities regress with levothyroxine (L-T4) administration, the cardiovascular benefits of replacement therapy in OH are not questionable, independently from the patient's age or the presence of coexisting cardiovascular disease. On the other hand, in spite of a very large number of studies, no consensus has been reached so far about the actual cardiovascular and/or general health impact of SH, and different recommendations have been recently made about screening and treatment of this condition. Although divergent results have been obtained in several epidemiological studies, recent meta-analyses provide evidence for a slight but significant increase of coronary heart disease (CHD) risk in SH. However, no agreement has been reached in favor or against active screening and/or treatment of mild thyroid failure. Moreover, L-T4 therapy is discouraged in aged subjects, because the increased oxygen consumption consequent to thyroid hormone administration could be dangerous, especially in the presence of coexisting CHD. In keeping with this concept are recent data showing reduced mortality risk in untreated mild hypothyroid subjects aged >85 years, suggesting that some degree of decreased thyroid activity at the tissue level might have favorable effects in the oldest-old. However, the effects of subtle thyroid dysfunction may be different in different age ranges. Since the main studies supporting a role for SH as a risk factor for atherosclerosis, cardiovascular disease, and all-cause mortality have been carried out in populations aged > or =55-60 years, mild thyroid failure could concur to increased cardiovascular risk in middle-aged and "young elderly" subjects, while being devoid of detrimental effects and possibly protective in the oldest-old. Further studies are needed to confirm this hypothesis.

Association of FTO polymorphisms with early age of obesity in obese Italian subjects.

Obesity is recognized as a major health problem worldwide. Genetic factors play a major role in obesity, and genomewide association studies have provided evidence that several common variants within the fat mass- and obesity-associated (FTO) gene are significantly associated with obesity. Very limited data is available on FTO in the Italian population. Aims of our study are to investigate: (1) the association of FTO gene SNPs rs9939609 and rs9930506 with body mass index (BMI) and obesity-related parameters in a large cohort (n = 752) of Italian obese subjects; (2) the association between the two FTO SNPs and age of onset of obesity. Our results demonstrate a strong association between FTO SNPs rs9939609 (P < 0.043) and rs9930506 (P < 0.029) with BMI in the Italian population. FTO rs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI + 1.4 kg/m² per G allele). We also observed that the association with BMI of the two FTO variants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability in FTO on BMI in a large Italian population.