Showing papers by "Anny H. Xiang published in 2009"

Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose

Abstract: OBJECTIVE Glucokinase ( GCK ) and glucose-6-phosphatase catalytic subunit 2 ( G6PC2 ) regulate the glucose-cycling step in pancreatic β-cells and may regulate insulin secretion. GCK rs1799884 and G6PC2 rs560887 have been independently associated with fasting glucose, but their interaction on glucose-insulin relationships is not well characterized. RESEARCH DESIGN AND METHODS We tested whether these variants are associated with diabetes-related quantitative traits in Mexican Americans from the BetaGene Study and attempted to replicate our findings in Finnish men from the METabolic Syndrome in Men (METSIM) Study. RESULTS rs1799884 was not associated with any quantitative trait (corrected P > 0.1), whereas rs560887 was significantly associated with the oral glucose tolerance test 30-min incremental insulin response (30′ Δinsulin, corrected P = 0.021). We found no association between quantitative traits and the multiplicative interaction between rs1799884 and rs560887 ( P > 0.26). However, the additive effect of these single nucleotide polymorphisms was associated with fasting glucose (corrected P = 0.03) and 30′ Δinsulin (corrected P = 0.027). This additive association was replicated in METSIM (fasting glucose, P = 3.5 × 10 −10 30′ Δinsulin, P = 0.028). When we examined the relationship between fasting glucose and 30′ Δinsulin stratified by GCK and G6PC2 , we noted divergent changes in these quantitative traits for GCK but parallel changes for G6PC2 . We observed a similar pattern in METSIM. CONCLUSIONS Our data suggest that variation in GCK and G6PC2 have additive effects on both fasting glucose and insulin secretion.

Variation in IGF2BP2 Interacts With Adiposity to Alter Insulin Sensitivity in Mexican Americans

Abstract: Genome-wide association studies showed variation in insulin-like growth factor-2 binding protein 2 (IGF2BP2) to be associated with type 2 diabetes mellitus (T2DM). We examined a 20-kb region of IGF2BP2 for association with T2DM-related quantitative traits in Mexican American families of a proband with gestational diabetes mellitus (GDM) from the BetaGene study. We genotyped 14 single-nucleotide polymorphisms (SNPs) in 717 individuals from 146 families phenotyped by oral glucose tolerance test (OGTT), intravenous glucose tolerance tests (IVGTTs) with minimal model analysis, and dual-energy X-ray absorptiometry scan for percent body fat. Three SNPs and one SNP combination that captured the majority of the variation in the region were tested for association with T2DM-related quantitative traits using a variance components framework. After correction for multiple testing, rs11705701 showed association with percent body fat (PACT = 0.041) with body fat decreasing ∼1.5–2% per copy of the A allele. We next tested whether the interaction between rs11705701 and body fat was associated with T2DM-relative quantitative traits. rs11705701 was significantly associated with insulin sensitivity (Bonferroni P = 0.028) and marginally associated with OGTT 2-h insulin (Bonferroni P = 0.066) and disposition index (DI) (Bonferroni P = 0.072). We conclude that rs11705701 in IGF2BP2 is associated with body fat and this effect on body fat influences insulin resistance which may contribute to T2DM risk.

Evidence for Sex-Specific Associations between Variation in Acid Phosphatase Locus 1 (ACP1) and Insulin Sensitivity in Mexican-Americans

Abstract: Context: Acid phosphatase locus 1 (ACP1) is a low molecular weight tyrosine phosphatase that has been shown to be an important regulator of insulin receptor signaling. Objective: We tested whether variation in ACP1 is associated with type 2 diabetes-related traits in 1035 individuals in 339 Mexican-American families of probands with or without a previous diagnosis of gestational diabetes mellitus (GDM). Design: Study participants were phenotyped by oral glucose tolerance test (for glucose and insulin level) and iv glucose tolerance test (for insulin sensitivity and acute insulin response) and had dual-energy x-ray absorptiometry scans to assess body composition. Six tag single nucleotide polymorphisms (SNPs) were identified from among 15 SNPs genotyped across the ACP1 region. SNPs were tested for association with phenotypes using a likelihood ratio test under a variance components framework. Results: After Bonferroni correction, none of the SNPs were associated with type 2 diabetes mellitus-related phenot...

The linear cutting stapler may reduce surgical time and blood loss with muscle transection: a pilot study.

Abstract: Because of skeletal muscle’s density and vascularity, its transection with standard electrocautery can be tedious. In a pilot study we asked whether a linear cutting stapling device decreased surgical time, blood loss, transfusion rates, and complications in patients undergoing above-knee amputation when compared to traditional electrocautery. We retrospectively reviewed 11 patients with above-knee amputation cases using a linear cutting stapling device over a 10-year period and compared those to 13 patients in whom we used electrocautery. The patients treated with the linear cutting stapling device had an average of 97 minutes of surgical time, 302 cc blood loss, and 1.55 units transfusion, compared to an average 119 minutes, 510 cc, and 2.15 units, respectively, with the electrocautery cases. Despite the trends, these parameters, as well as major complications, were similar in these two small groups. In skeletal muscle transection, we believe the linear cutting stapler is a reasonable and potentially cost-effective technical alternative to electrocautery, possibly resulting in less blood loss and shorter surgical time with similar rates of complications. Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

The Linear Cutting Stapler May Reduce Surgical Time and Blood Loss with Muscle Transection

Abstract: Because of skeletal muscle's density and vas- cularity, its transection with standard electrocautery can be tedious. In a pilot study we asked whether a linear cutting stapling device decreased surgical time, blood loss, trans- fusion rates, and complications in patients undergoing above-knee amputation when compared to traditional electrocautery. We retrospectively reviewed 11 patients with above-knee amputation cases using a linear cutting stapling device over a 10-year period and compared those to 13 patients in whom we used electrocautery. The patients treated with the linear cutting stapling device had an average of 97 minutes of surgical time, 302 cc blood loss, and 1.55 units transfusion, compared to an average 119 minutes, 510 cc, and 2.15 units, respectively, with the electrocautery cases. Despite the trends, these parameters, as well as major complications, were similar in these two small groups. In skeletal muscle transection, we believe the linear cutting stapler is a reasonable and potentially cost- effective technical alternative to electrocautery, possibly resulting in less blood loss and shorter surgical time with similar rates of complications. Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.