The role of preoperative glycemic control in decreasing surgical site infections in lower extremity fractures.

BACKGROUND: Postoperative surgical site infections (SSIs) are an important complication to prevent in surgical treatment. Patients with diabetes mellitus (DM) have a higher risk of SSIs. Preoperative glycemic control is required. For patients with orthopedic trauma, the duration of preoperative glycemic control is limited because delaying operative treatment is difficult. However, whether preoperative glycemic control would decrease the risk of SSIs in diabetic patients with lower extremity fractures is unclear. The first aim of this study was to investigate the rate of SSIs among patients with DM who had undergone preoperative glycemic control, compared with that of patients without DM. As the secondary aim, we sought to demonstrate among patients with DM whether preoperative glycemic control would affect the development of SSIs between patients with controlled DM and patients with poorly controlled DM. METHODS: In this retrospective cohort study, 1510 patients treated surgically for lower extremity fractures were enrolled. Data collected were patient age, sex, body mass index, history of DM, development of SSIs, tobacco use, the presence of an open fracture, the period between the day of injury and the operation, the length of surgery, and blood glucose levels on admission and on the day before surgery. RESULTS: The rate of total SSIs was 6.0% among patients with DM and 4.4% among patients without DM (p = 0.31). Multivariate logistic regression revealed a significant association between the development of SSIs and the presence of DM (odds ratio, 1.79; 95% confidence interval 1.01-3.19; p = 0.047). The results of the secondary study revealed that the rate of early SSIs was significantly higher in the poorly controlled DM group than in the controlled DM group (5.9% vs. 1.5%; p = 0.032). However, multivariate logistic regression revealed that control levels of DM were not significantly associated with the development of SSIs. CONCLUSIONS: Even though patients with DM had undergone preoperative glycemic control, SSIs were significantly associated with DM, especially when the patients had poorly controlled DM. This finding suggested that continuous glycemic control is important preoperatively and postoperatively to prevent SSIs.

A family with type A insulin resistance syndrome caused by a novel insulin receptor mutation.

Summary: A 17-year-old boy was referred to our endocrinology clinic for a clinical investigation of hyperinsulinemia. An oral glucose tolerance test showed plasma glucose concentrations in the normal range. However, insulin concentrations were considerably elevated (0 min: 71 µU/mL; 60 min: 953 µU/mL), suggesting severe insulin resistance. An insulin tolerance test confirmed that he had insulin resistance. There was no apparent hormonal or metabolic cause, including obesity. The patient had no outward features of hyperinsulinemia, including acanthosis nigricans or hirsutism. However, his mother and grandfather also had hyperinsulinemia. Genetic testing showed that the patient (proband), his mother, and his grandfather had a novel p.Val1086del heterozygous mutation in exon 17 of the insulin receptor gene (INSR). Although all three family members have the same mutation, their clinical courses have been different. The onset of the mother's diabetes was estimated at 50 years, whereas the grandfather developed diabetes at 77 years. Learning points: Type A insulin resistance syndrome is caused by mutations in the insulin receptor (INSR) gene and results in severe insulin resistance. Genetic evaluation should be considered in adolescents or young adults with dysglycemia when an atypical phenotype, such as severe insulin resistance, or a relevant family history is observed. Clinical courses may differ even if the same genetic mutation is found in a family.

Postprandial activation of protein kinase Cµ regulates the expression of adipocytokines via the transcription factor AP-2ß.

Abnormal secretion of adipocytokines promotes atherosclerosis, diabetes and insulin resistance, and is mainly induced by adipocyte hypertrophy. Recently, the circulating adipocytokine concentrations were reported to change in the postprandial period, as the levels of TNFα, IL-6 IL-8 and MCP-1 increased after a meal, whereas that of adiponectin decreased. These data suggest that prandial modulation of cytokines may be involved in the pathogenesis of atherosclerosis in type 2 diabetes. However, the regulatory mechanism of such change is still unclear. In the present study, we identified this mechanism with a special focus on the functions of protein kinase C (PKC) and of the transcription factor AP-2ß, both of which are associated with the pathophysiology of adipocytokine regulation. PKCµ was highly phosphorylated in the re-feeding condition compared to the fasting condition in mouse adipose tissue, while other PKC isoforms remained unchanged. Furthermore, overexpression of PKCµ in 3T3-L1 adipocytes, but not other PKC isoforms, positively regulated the mRNA expression and promoter activity of MCP-1 and IL-6, and negatively regulated those of adiponectin. AP-2ß had similar effects on the expression and promoter activity of these adipocytokines. Interestingly, overexpression of PKCµ enhanced the stimulatory and inhibitory effects of AP-2ß on the expression of these adipocytokines. Finally, PKCµ could not activate a mutant MCP-1 promoter lacking the AP-2ß binding domain. Our results suggest that postprandial activation of PKCµ plays a role in disordered postprandial adipocytokine expression through AP-2ß.

Effects of a fish-based diet on the serum adiponectin concentration in young, non-obese, healthy Japanese subjects.

AIM: Adiponectin has insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties, and researchers have recently reported that omega-3 polyunsaturated fatty acid (PUFA) can increase the serum adiponectin concentration, suggesting that dietary factors, such as fish intake, may have an influence on the serum adiponectin concentration. In general, Japanese subjects consume twice as much fish as people in other countries. We hypothesized that incremental change in serum omega-3 PUFA levels by fish intake is an important regulator of serum adiponectin even in Japanese subjects. The aim of this study was to explore the relationship among fish consumption, serum omega-3 PUFA, such as eicosapentaenoic acid (EPA), levels, and serum adiponectin levels. METHOD: We recruited 17 healthy Japanese volunteers (seven men and 10 women) for an 8-week fish-diet intervention (omega-3 PUFA 3.0 g/day) without affecting total energy intake, and measured serum adiponectin concentration and fatty acid profiles. RESULTS: Fish-diet intervention significantly increased the serum adiponectin concentration in women (from 13.5+/-4.6 to 15.8+/-5.2 microg/mL, p <0.01) but not in men (from 8.7+/-2.8 to 8.7+/-2.5 microg/mL). Serum omega-3 PUFA increased more in female subjects than male subjects after the fish-diet intervention (57.3+/-86.6 vs 150.9+/-46.7 microg/mL, p=0.011), suggesting that changes in omega-3 PUFA concentration may explain the different response between sexes. CONCLUSION: A fish-based diet intervention increased the serum adiponectin concentration in young, non-obese, healthy Japanese female subjects. The increment in serum omega-3 PUFA may regulate the serum adiponectin concentration.

Transcription factor AP-2beta: a negative regulator of IRS-1 gene expression.

Down-regulation of insulin receptor substrate-1 (IRS-1) expression could modify the ability of IRS-1 to fulfill its functions. It has been proposed that the phosphorylation of IRS-1 on serine residues could promote its degradation. However, few studies have investigated the transcriptional regulation of IRS-1 in the pathogenesis of insulin resistance. Genotyping for genome-wide single nucleotide polymorphisms revealed that the transcription factor activating enhancer-binding protein-2beta (AP-2beta) is a novel candidate gene for conferring susceptibility to obesity and type 2 diabetes. AP-2beta is expressed in adipose tissue and its expression is increased during the maturation of adipocytes. Overexpression of AP-2beta leads to adipocyte hypertrophy, directly inhibits adiponectin expression, and enhanced the expression of inflammatory adipokines such as IL-6 and MCP-1. In this study, we found that overexpression of AP-2beta in 3T3-L1 adipocytes impaired the promoter activity of IRS-1, and subsequently decreased mRNA and protein expression. Electrophoretic mobility shift assays showed that AP-2beta bound specifically to the IRS-1 promoter region. Furthermore, site-directed mutagenesis of the AP-2 binding site located at -362 to -351, relative to the transcription start site, markedly decreased AP-2-induced suppression of IRS-1 promoter activity, whereas other putative AP-2 binding sites did not. Our results clearly showed that AP-2beta directly decreased IRS-1 expression by binding to its promoter. Based on these findings, we speculate that the AP-2beta transcriptional factor is a unique regulator of IRS-1 and a candidate gene for insulin resistance.