Genomic imprinting, gene inactivation during gametogenesis, causes maternal and paternal alleles of some genes to function unequally. We examined the possibility of imprinting in insulin genes because the human insulin gene (ins) and its mouse homologue (ins2) are adjacent to the known imprinted genes, igf2 and H19, and because imprinting has been implicated in the transmission of an ins linked risk for Type I diabetes. We show, by single strand conformational polymorphism (SSCP) analysis of cDNAs from parents and progeny of interspecies mouse crosses, that insulin genes are imprinted. While both alleles of the two mouse insulin genes were active in embryonic pancreas, only paternal alleles for both genes were active in the yolk sac.
OBJECTIVEIn the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, ∼4 years of intensive versus standard glycemic control in participants with type 2 diabetes and other cardiovascular risk factors had a neutral effect on the composite cardiovascular outcome, increased cardiovascular and total mortality, and reduced nonfatal myocardial infarction. Effects of the intervention during prolonged follow-up were analyzed.RESEARCH DESIGN AND METHODSAll surviving ACCORD participants were invited to participate in the ACCORD Follow-on (ACCORDION) study, during which participants were treated according to their health care provider’s judgment. Cardiovascular and other health-related outcomes were prospectively collected and analyzed using an intention-to-treat approach according to the group to which participants were originally allocated.RESULTSA total of 8,601 people, representing 98% of those who did not suffer a primary outcome or death during the ACCORD trial, were monitored for a median of 8.8 years and a mean of 7.7 years from randomization. Intensive glucose lowering for a mean of 3.7 years had a neutral long-term effect on the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), death from any cause, and an expanded composite outcome that included all-cause death. Moreover, the risk of cardiovascular mortality noted during the active phase (hazard ratio 1.49; 95% CI 1.19, 1.87; P < 0.0001) decreased (HR 1.20; 95% CI 1.03, 1.39; P = 0.02).CONCLUSIONSIn high-risk people with type 2 diabetes monitored for 9 years, a mean of 3.7 years of intensive glycemic control had a neutral effect on death and nonfatal cardiovascular events but increased cardiovascular-related death.
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