The association between autoimmune diseases and type 1 diabetes (T1D) is mostly based on studies among people with T1D at baseline. We assessed the risk of incident T1D among adolescents with other au Show more
The association between autoimmune diseases and type 1 diabetes (T1D) is mostly based on studies among people with T1D at baseline. We assessed the risk of incident T1D among adolescents with other autoimmune diseases. Included were all Israeli adolescents without a history of dysglycemia, aged 16-19 years, undergoing medical evaluation before mandatory military service between January 1996 and December 2016. Data were linked with information on adult-onset T1D from the Israeli National Diabetes Registry. The cohort was dichotomized by the presence of any autoimmune disease. Cox proportional hazards modeling was applied. A total of 1,426,362 people were included, of whom 38,766 (2.7%) had a history of autoimmunity at study entry (10,333 with autoimmune thyroid disease [AITD] and 9,603 with celiac disease). Over 15,810,751 person-years of follow-up, there were 37 and 740 incident cases of T1D among people with and without autoimmunity, respectively, and a crude incident rate of 9.6 and 4.8 cases per 105 person-years, respectively. In a multivariable model adjusted for sex, birth year, and sociodemographic variables, the hazard ratio (HR) for incident T1D among people with autoimmunity was 2.19 (95% CI 1.57-3.04) versus those without. Results persisted when islet autoantibody data were used as mandatory criteria for T1D case definition (HR 2.22, 95% CI 1.13-4.35). The HRs among people with AITD and celiac disease were 3.99 (2.5-6.4) and 2.82 (1.46-5.45), respectively. Autoimmune diseases in late adolescence were associated with an increased risk of T1D in adulthood in both sexes, especially among those with AITD and celiac disease. Show less
Apolipoprotein A-V plays an important role in reducing plasma triglyceride levels. We hypothesized that expression of apoA-V would inhibit atherogenesis in apoE(-/-) mice fed chow diet which is a know Show more
Apolipoprotein A-V plays an important role in reducing plasma triglyceride levels. We hypothesized that expression of apoA-V would inhibit atherogenesis in apoE(-/-) mice fed chow diet which is a known model of hypercholesterolemia. Our aim was to study this protective effect and to explore possible mechanisms. ApoA-V(+/+)ApoE(-/-) mice expressing human apolipoprotein A-V (hapoA-V) were generated and compared to apoE(-/-) mice. Atherosclerotic aortic sinus lesion area was 70% smaller in hapoA-V(+/+)apoE(-/-). This was accompanied by a 58% reduction in lesion macrophage content. Furthermore, advanced atherosclerotic lesions in hapoA-V(+/+)apoE(-/-) mice showed features of a more stable plaque, manifested by 59% and 37% higher collagen and α-actin content, respectively. Plasma triglyceride and cholesterol levels in hapoA-V(+/+)apoE(-/-) mice were 47% and 33% lower, respectively. These were associated with a 33% reduction in very low density lipoprotein triglyceride production and 2-fold acceleration in triglyceride-rich lipoprotein clearance in hapoA-V(+/+)apoE(-/-) mice. In addition, hapoA-V(+/+)apoE(-/-) mice showed enhanced insulin sensitivity (25% and 15% improvement in glucose tolerance and insulin responsiveness, respectively). Finally, hapoA-V(+/+)apoE(-/-) displayed a milder systemic inflammatory response compared to apoE(-/-) mice, manifested by 22%, 65% and 15% lower plasma levels of TNFα, IL-1β and IL-6, respectively. We showed that human apolipoprotein A-V is a potent modulator of atherosclerosis in mice through multiple modes of action. These findings may identify apoA-V as a potential therapeutic target for treatment of atherosclerosis. Show less