No abstract

No abstract

Background: Some dietary factors have been associated with the risk of type 1 diabetes in childhood. Objective: We investigated relations between dietary energy from major food groups and incidence of childhood type 1 diabetes by using an ecologic study design. Design: We conducted univariate and multivariate regression analysis with incidence rates of type 1 diabetes in the late 1980s and early 1990s among children aged < 15 y in 40 countries as the dependent variable and average per capita daily intake of major food items and other socioeconomic, demographic, and geographic risk factors as the independent variables. Results: In the univariate regression model, per capita total energy intake was nonsignificantly associated with type 1 diabetes incidence (r = 0.31, NS), whereas energy from animal sources was associated (r = 0.61, P < 0.01) and energy from vegetal sources was inversely associated (r = Ϫ0.35, P < 0.05) with diabetes incidence. Among dietary items of animal origin, meat (r = 0.55, P < 0.001) and dairy products (r = 0.80, P < 0.0001) were predictors of elevated incidence rates, whereas among dietary items of vegetal origin, cereals (r = Ϫ0.64, P < 0.001) were inverse predictors. In the multivariate analysis, the inverse relation of diabetes incidence with energy from vegetables and the direct correlation with energy from animal sources explained the positive associations of type 1 diabetes incidence with geographic and socioeconomic covariates. Conclusion: The incidence of type 1 diabetes varied worldwide according to dietary patterns. In-depth exploration of dietary risk factors during pregnancy and early neonatal life is warranted to confirm whether and to what extent diet cooperates with genetic susceptibility in the early onset of type 1 diabetes.Am J Clin Nutr 2000;71:1525-9.

Thyroid hormones regulate cell growth, cell differentiation, and metabolic functions via interaction with the thyroid hormone nuclear receptors (TRs). Recently, a small class of halogen-free high-affinity thyroid hormone agonists has been developed that are highly selective for the TRbeta subtype. Because of the selective hyperthyroidism generated by one of these agonists, GC-1, this compound has the potential to be developed as a new therapeutic agent for the treatment of a variety of metabolic disturbances, including lipid disorders and obesity; thus, it becomes important to determine whether GC-1 has other unknown effects on potential target organs. The purpose of this study was to investigate the effect of GC-1 on cell proliferation in rat liver and pancreas. Rats treated with GC-1 (50 or 100 mug/100 g body weight) were killed at different time points. Hepatic and pancreatic cell proliferation was monitored by immunohistochemical determination of bromodeoxyuridine incorporation. The expression of cell cycle-related genes was analyzed by Northern and Western analysis. The results show that GC-1 strongly stimulates rat hepatocyte proliferation in the absence of tissue injury. Although GC-1-induced hepatocyte proliferation was associated with a rapid increase in cyclin D1 mRNA levels, no change in the expression of c-jun and c-fos was observed. GC-1 also induced massive pancreatic cell proliferation. The results indicate that the TRbeta-selective agonist GC-1 is a strong mitogen for hepatocytes and pancreatic acinar cells. Furthermore, they suggest that the TRbeta receptor is the mediator for the mitogenic activity of thyroid hormone and other thyromimetics.

Differences between Finland and Sardinia in the seasonal pattern for the incidence of newly diagnosed IDDM cannot be explained by differences in climate, temperature, a longer warm period in Sardinia, or other climatic phenomena. The results do not provide evidence in favor of a specific viral etiology of IDDM. It may be suggested that there are triggering events at certain times, but they are likely to be unspecific. Nevertheless, why the incidence of IDDM in these two populations is equally high despite differences in climate, environment, and genetic background remains an unsolved question.

After binding to its receptor and activating the β-subunit, insulin is faced with two divergent pathways: one is phosphatidylinositol 3-kinase (PI 3-K) dependent, while another is dependent upon activation of mitogen-activated protein kinase (MAP-K). The former is absolutely necessary for mediating most metabolic and antiapoptotic effects; the latter is linked to nonmetabolic, proliferative and mitogenic effects. In obese patients, especially with type 2 diabetes mellitus (DM2), only the PI 3-K, but not the MAP-K, is resistant to insulin stimulation: hence insulin resistance is better defined as metabolic insulin resistance. The resulting ‘compensatory hyperinsulinemia’ is an unsuccessful attempt to overcome the inhibition of the metabolic pathway at the price of unopposed stimulation of the MAP-K pathway, and the administration of exogenous insulin might worsen the metabolic dysfunction. As the preferential activation of the MAP-K pathway in insulin-resistant patients has atherogenic and mitogenic properties, this leads to atherosclerosis and cancer. Metformin may carry out direct protective action on human β cells, inasmuch as it improves both primary and secondary endpoints through selective inhibition of fatty acyl oxidation.

Despite intensive treatment, LDL-C in ARH patients remains far from targets, and this translates into a poor long-term cardiovascular prognosis. Our data highlight the importance of an early diagnosis and treatment and confirm the fact that an effective treatment protocol for ARH is still lacking.

Selective insulin resistance influences pathogenesis and treatment of type 2 diabetes and metabolic syndrome. Downregulation of the antiatherogenic pathway and maintained activity of the proatherogenic and cancerogenic pathways lead to atherosclerosis and cancer. Exogenous insulin added to "compensatory" hyperinsulinemia might worsen the primary end points, resulting in potential increase in cardiovascular and cancer events in spite of improvement of surrogate metabolic end points. Conversely, metformin can improve primary and surrogate end points.