RESUMO
OBJECTIVE: The main goal of this study was to determine the effects of incretins on type 2 diabetes (T2D) remission after Roux-en-Y gastric bypass (RYGB) surgery for patients taking insulin. BACKGROUND: Type 2 diabetes is a chronic disease with potentially debilitating consequences. RYGB surgery is one of the few interventions that can remit T2D. Preoperative use of insulin, however, predisposes to significantly lower T2D remission rates. METHODS: A retrospective cohort of 690 T2D patients with at least 12 months follow-up and available electronic medical records was used to identify 37 T2D patients who were actively using a Glucagon-like peptide 1 (GLP-1) agonist in addition to another antidiabetic medication, during the preoperative period. RESULTS: Here, we report that use of insulin, along with other antidiabetic medications, significantly diminished overall T2D remission rates 14 months after RYGB surgery (9%) compared with patients not taking insulin (56%). Addition of the GLP-1 agonist, however, increased significantly T2D early remission rates (22%), compared with patients not taking the GLP-1 agonist (4%). Moreover, the 6-year remission rates were also significantly higher for the former group of patients. The GLP-1 agonist did not improve the remission rates of diabetic patients not taking insulin as part of their pharmacotherapy. CONCLUSIONS: Preoperative use of antidiabetic medication, coupled with an incretin agonist, could significantly improve the odds of T2D remission after RYGB surgery in patients also using insulin.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica , Peptídeo 1 Semelhante ao Glucagon/agonistas , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Insulina/uso terapêutico , Período Pré-Operatório , Humanos , Indução de Remissão , Estudos RetrospectivosRESUMO
To better understand the population substructure of African Americans living in coastal South Carolina, we used restriction site polymorphisms and an insertion/deletion in mitochondrial DNA (mtDNA) to construct seven-position haplotypes across 1,395 individuals from Sierra Leone, Africa, from U.S. European Americans, and from the New World African-derived populations of Jamaica, Gullah-speaking African Americans of the South Carolina Sea Islands (Gullahs), African Americans living in Charleston, South Carolina, and West Coast African Americans. Analyses showed a high degree of similarity within the New World African-derived populations, where haplotype frequencies and diversities were similar. Phi-statistics indicated that very little genetic differentiation has occurred within New World African-derived populations, but that there has been significant differentiation of these populations from Sierra Leoneans. Genetic distance estimates indicated a close relationship of Gullahs and Jamaicans with Sierra Leoneans, while African Americans living in Charleston and the West Coast were progressively more distantly related to the Sierra Leoneans. We observed low maternal European American admixture in the Jamaican and Gullah samples (m = 0.020 and 0.064, respectively) that increased sharply in a clinal pattern from Charleston African Americans to West Coast African Americans (m = 0.099 and 0.205, respectively). The appreciably reduced maternal European American admixture noted in the Gullah indicates that the Gullah may be uniquely situated to allow genetic epidemiology studies of complex diseases in African Americans with low European American admixture.
Assuntos
Negro ou Afro-Americano/genética , DNA Mitocondrial/genética , Heterogeneidade Genética , Genética Populacional , Haplótipos/genética , Padrões de Herança/genética , Negro ou Afro-Americano/estatística & dados numéricos , Antropologia Física , Feminino , Humanos , Jamaica/etnologia , Masculino , Estados do Pacífico/epidemiologia , Serra Leoa/etnologia , South Carolina/epidemiologia , População Branca/genética , População Branca/estatística & dados numéricosRESUMO
To develop informative tools for the study of population affinities in African Americans, we sequenced the hypervariable segments I and II (HVS I and HVS II) of mitochondrial DNA (mtDNA) from 96 Sierra Leoneans; European Americans; rural, Gullah-speaking African Americans; urban African Americans living in Charleston, South Carolina; and Jamaicans. We identified single nucleotide polymorphisms (SNPs) exhibiting ethnic affinities, and developed restriction endonuclease tools to screen these SNPs. Here we show that three HVS restriction site polymorphisms (RSPs), EcoRV, FokI, and MfeI, exhibit appreciable differences in frequency (average delta = 0.4165) between putative African American parental populations (i.e., extant Africans living in Sierra Leone and European Americans). Estimates of European American mtDNA admixture, calculated from haplotypes composed of these three novel RSPs, show a cline of increasing admixture from Gullah-speaking African American (m = 0.0300) to urban Charleston African American (m = 0.0689) to West Coast African American (m = 0.1769) populations. This haplotype admixture in the Gullahs is the lowest recorded to date among African Americans, consistent with previous studies using autosomal markers. These RSPs may become valuable new tools in the study of ancestral affinities and admixture dynamics of African Americans.
Assuntos
População Negra/genética , DNA Mitocondrial/genética , Polimorfismo Genético , África/etnologia , California , Europa (Continente)/etnologia , Feminino , Genética Populacional , Humanos , Jamaica , Análise dos Mínimos Quadrados , Masculino , Polimorfismo de Nucleotídeo Único , Dinâmica Populacional , South CarolinaRESUMO
Ancestry informative markers (AIMs) are genetic loci showing alleles with large frequency differences between populations. AIMs can be used to estimate biogeographical ancestry at the level of the population, subgroup (e.g. cases and controls) and individual. Ancestry estimates at both the subgroup and individual level can be directly instructive regarding the genetics of the phenotypes that differ qualitatively or in frequency between populations. These estimates can provide a compelling foundation for the use of admixture mapping (AM) methods to identify the genes underlying these traits. We present details of a panel of 34 AIMs and demonstrate how such studies can proceed, by using skin pigmentation as a model phenotype. We have genotyped these markers in two population samples with primarily African ancestry, viz. African Americans from Washington D.C. and an African Caribbean sample from Britain, and in a sample of European Americans from Pennsylvania. In the two African population samples, we observed significant correlations between estimates of individual ancestry and skin pigmentation as measured by reflectometry (R(2)=0.21, P<0.0001 for the African-American sample and R(2)=0.16, P<0.0001 for the British African-Caribbean sample). These correlations confirm the validity of the ancestry estimates and also indicate the high level of population structure related to admixture, a level that characterizes these populations and that is detectable by using other tests to identify genetic structure. We have also applied two methods of admixture mapping to test for the effects of three candidate genes (TYR, OCA2, MC1R) on pigmentation. We show that TYR and OCA2 have measurable effects on skin pigmentation differences between the west African and west European parental populations. This work indicates that it is possible to estimate the individual ancestry of a person based on DNA analysis with a reasonable number of well-defined genetic markers. The implications and applications of ancestry estimates in biomedical research are discussed.