Further evidence supporting a potential role for ADH1B in obesity.

Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with decreased ADH1B expression. Using established human subcutaneous pre-adipocyte cell lines derived from lean (BMI < 30 kg m-2) or obese (BMI ≥ 30 kg m-2) donors, we found that ADH1B protein expression increased substantially during differentiation, and overexpression of ADH1B inhibited fatty acid binding protein expression. Mature adipocytes from lean donors expressed ADH1B at higher levels than obese donors. Insulin further induced ADH1B protein expression as well as enzyme activity. Knockdown of ADH1B expression decreased insulin-stimulated glucose uptake. Our findings suggest that ADH1B is involved in the proper development and metabolic activity of adipose tissues and this function is suppressed by obesity.

Transcriptomic identification of ADH1B as a novel candidate gene for obesity and insulin resistance in human adipose tissue in Mexican Americans from the Veterans Administration Genetic Epidemiology Study (VAGES).

Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10(-4)) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10(-60)) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10(-9)), BMI (5.4 x 10(-6)), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits.

Retinol-binding protein 4 is associated with impaired glucose tolerance but not with whole body or hepatic insulin resistance in Mexican Americans.

Retinol-binding protein-4 (RBP4), a novel protein secreted mainly by adipose tissue, has been associated with insulin resistance in obese subjects and in individuals with type 2 diabetes mellitus (T2DM). We examined the relationship between plasma RBP4 levels, expression of RBP4 in skeletal muscle and adipose tissue, and insulin sensitivity in Mexican Americans with varying degrees of obesity and glucose tolerance. Seventy-two subjects [16 lean normal-glucose-tolerant (NGT), 17 obese NGT, and 39 subjects with impaired fasting glucose/impaired glucose tolerance/T2DM] received an oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Insulin secretion was measured as insulinogenic index during OGTT. In a subset of subjects, hepatic glucose production was measured by 3-[3H]glucose infusion, biopsies of the vastus lateralis muscle and subcutaneous adipose tissue were obtained under basal conditions, and quantitative RT-PCR was performed to measure the RBP4 mRNA gene expression. Plasma RBP4 was significantly elevated in impaired glucose tolerance/T2DM compared with NGT lean or obese subjects. Plasma RBP4 levels correlated with 2-h glucose, triglycerides, and hemoglobin A1c. There was no association between RBP4 levels and whole body insulin sensitivity measured with either the euglycemic insulin clamp or OGTT, basal hepatic glucose production rates, and the hepatic insulin resistance index. There was no correlation between plasma RBP4 levels and indexes of insulin secretion. RBP4 mRNA expression in skeletal muscle was similar in lean NGT subjects, obese NGT subjects, and T2DM subjects. There was no difference in RBP4 mRNA expression in adipose tissue between lean and obese NGT subjects or between NGT and T2DM individuals. Plasma RBP4 levels are elevated in T2DM and associated with impaired glucose tolerance, but not associated with obesity or insulin resistance or impaired insulin secretion in Mexican Americans.

Plastic surgery reconstruction of the diabetic foot.

Soft tissue reconstruction of the diabetic foot is a challenge for the perioperative team. Primary closure may not be an option and secondary healing may not be reliable. Therefore, surgery is vital and should be coordinated among a well-functioning multidisciplinary team that specializes in caring for patients with diabetes mellitus. Team members must have expertise in reconstructive surgery to ensure adequate wound healing. This article emphasizes the appropriate timing and staging of surgery, discusses the most common plastic surgery techniques, and underscores the importance of a team approach in the management of diabetic foot wounds.

Use of a muscle flap and a split-thickness skin graft for a calcaneal osteomyelitis after an open reduction and internal fixation.

Reconstruction of bone and soft-tissue defects after an open reduction and internal fixation of a severely comminuted calcaneal fracture presents a challenge to the treating surgeon. We present a case report in which an abductor digiti minimi muscle flap was used to cover a complicated wound with calcaneal osteomyelitis and wound dehisence at the surgical incision. This muscle flap provides an easy, reliable, and quick method to cover open wounds at the lateral aspect of the foot and ankle.

Utilizing a crossover reverse sural artery flap for soft tissue reconstruction of the plantar forefoot after a severe degloving injury.

Extensive soft tissue defects involving the weight-bearing areas of the plantar aspect of the foot often require coverage with flaps. The options often include free flaps, free muscle flaps with split-thickness skin grafting, or local flaps. When presented with high-energy-induced soft tissue injuries of the foot, choices become narrow, secondary to the associated zone of injury. Free flaps require a viable recipient vessel suitable for microvascular anastomosis. Split-thickness skin grafts applied to the plantar aspect of the foot are prone to persistent breakdown. Local flaps if available are useful for coverage of plantar soft tissue defects. However, when local flaps of the affected limb are compromised or extension is not sufficient for coverage, crossover leg and foot flaps become invaluable. The reported cases of crossover sural artery flaps are sparse. To the best of the authors' knowledge, the few reported cases of crossover leg and sural artery flaps were described to provide soft tissue coverage over the heel and leg. The authors report a case of a crossover reverse sural artery flap for soft tissue coverage to the plantar aspect of the forefoot after a high-energy-induced degloving injury.

Experience with railroad injuries at a major urban trauma center serving the United States-Mexico border.

BACKGROUND: In the United States (US), railroads are commonly used to transport humans and commerce, especially along the US-Mexico border. Some people will use freight trains to travel within the US. Some of these people will suffer a train-related injury with extensive soft tissue and bone trauma. There is little information about the demographics, injuries, or outcomes of these patients, and the financial expense of providing care for these individuals. We attempt to provide insight into some of these issues. METHODS: We performed a retrospective chart review of patients from the University of Texas Health Science Center at San Antonio from January 1996 to September 2003. Various demographic, total hospital costs, operative procedures, and outcomes were examined. RESULTS: Men were well represented (61 of 67 patients), and the overall mean age was 28.8 years. Hispanics (58 of 67 patients) were the main ethnic group and 61% were undocumented aliens (41 of 67 patients). Bony and soft tissue injuries were common, necessitating an amputation in 38 patients. The mean operative procedures per patient were 2.97. Follow-up was poor. Total hospital cost for all the patients was $2,468,004.47 with a mean of $36,835.89 ($1,305.00-$331, 452.74) per patient. CONCLUSION: Victims of train-related injuries were predominantly young and male. Many patients required an amputation. Multistaged and complex reconstructive procedures may not be realistic in a group of patients in whom follow-up is poor.