Endothelium, acting as a barrier, protects tissues against factors that provoke insulin resistance and type 2 diabetes and itself responds to the insult of insulin resistance inducers with altered function. Endothelial insulin resistance and vascular dysfunction occur early in the evolution of insulin resistance-related disease, can co-exist with and even contribute to the development of metabolic insulin resistance, and promote vascular complications in those affected. The impact of endothelial insulin resistance and vascular dysfunction varies depending on the blood vessel size and location, resulting in decreased arterial plasticity, increased atherosclerosis and vascular resistance, and decreased tissue perfusion. Women with insulin resistance and diabetes are disproportionately impacted by cardiovascular disease, likely related to differential sex-hormone endothelium effects. Thus, reducing endothelial insulin resistance and improving endothelial function in the conduit arteries may reduce atherosclerotic complications, in the resistance arteries lead to better blood pressure control, and in the microvasculature lead to less microvascular complications and more effective tissue perfusion. Multiple diabetes therapeutic modalities, including medications and exercise training, improve endothelial insulin action and vascular function. This action may delay the onset of type 2 diabetes and/or its complications, making the vascular endothelium an attractive therapeutic target for type 2 diabetes and potentially type 1 diabetes.

Background Many insurance companies have considerable pre-bariatric surgery requirements despite a lack of evidence for improved clinical outcomes. The hypothesis of this study is that insurance-specific requirements will be associated with a decreased progression to surgery and increased delay in time to surgery. Methods Retrospective data collection was performed for patients undergoing bariatric surgery evaluation from 2010–2015. Patients who underwent surgery (SGY; n= 827; mean BMI 49.1) were compared to those who did not (no-SGY; n= 648; mean BMI 49.4). Univariate and multivariate analysis were performed to identify specific comorbidity and insurance specific predictors of surgical dropout and time to surgery. Results A total of 1475 patients using 12 major insurance payers were included. Univariate analysis demonstrated insurance requirements associated with surgical drop out included longer median diet duration (no-SGY= 6 months; SGY=3 months; p< 0.001); PCP letter of necessity (p<0.0001); laboratory testing (p=0.019); and evaluation by cardiology (p<0.001), pulmonology (p<0.0001), or psychiatry (p=0.0003). Using logistic regression to control for comorbidities, longer diet requirement (OR 0.88, p<0.0001), PCP letter (OR 0.33, p<0.0001), cardiology evaluation (OR 0.22, p=0.038), and advanced laboratory testing (OR 5.75, p=0.019) independently predicted surgery dropout. Additionally, surgical patients had an average interval between initial visit and surgery of 5.8±4.6 months with significant weight gain (2.1 kg, p<0.0001). Conclusion Many pre-bariatric surgery insurance requirements were associated with lack of patient progression to surgery in this study. In addition, delays in surgery were associated with preoperative weight gain. Although prospective and multicenter studies are needed, these findings have major policy implications suggesting insurance requirements may need to be reconsidered to improve medical care.

Muscle microvasculature critically regulates skeletal and cardiac muscle health and function. It provides endothelial surface area for substrate exchange between the plasma compartment and the muscle interstitium. Insulin fine‐tunes muscle microvascular perfusion to regulate its own action in muscle and oxygen and nutrient supplies to muscle. Specifically, insulin increases muscle microvascular perfusion, which results in increased delivery of insulin to the capillaries that bathe the muscle cells and then facilitate its own transendothelial transport to reach the muscle interstitium. In type 2 diabetes, muscle microvascular responses to insulin are blunted and there is capillary rarefaction. Both loss of capillary density and decreased insulin‐mediated capillary recruitment contribute to a decreased endothelial surface area available for substrate exchange. Vasculature expresses abundant glucagon‐like peptide 1 (GLP‐1) receptors. GLP‐1, in addition to its well‐characterized glycemic actions, improves endothelial function, increases muscle microvascular perfusion, and stimulates angiogenesis. Importantly, these actions are preserved in the insulin resistant states. Thus, treatment of insulin resistant patients with GLP‐1 receptor agonists may improve skeletal and cardiac muscle microvascular perfusion and increase muscle capillarization, leading to improved delivery of oxygen, nutrients, and hormones such as insulin to the myocytes. These actions of GLP‐1 impact skeletal and cardiac muscle function and systems biology such as functional exercise capacity. Preclinical studies and clinical trials involving the use of GLP‐1 receptor agonists have shown salutary cardiovascular effects and improved cardiovascular outcomes in type 2 diabetes mellitus. Future studies should further examine the different roles of GLP‐1 in cardiac as well as skeletal muscle function.

Context Obesity and type 2 diabetes are associated with chronic hyperinsulinemia, elevated plasma levels of dipeptidyl peptidase-4 (DPP4), and a pro-atherosclerotic milieu. Evidence Acquisition PubMed search of the term “insulin and atherosclerosis”, “hyperinsulinemia”, “atherosclerosis” or “cardiovascular outcomes” cross-referenced with “DPP4”. Relevant research and review articles were reviewed. Conclusion DPP4 may represent a key link between central obesity, insulin resistance, and atherosclerosis. The gaps in knowledge in DPP4 function and discrepancy in cardiovascular outcomes observed in pre-clinical and large scale randomized controlled studies with DPP4 inhibitors warrant additional research.

Dandy-Walker syndrome (DWS), or Dandy-Walker complex, is a congenital brain malformation of the posterior fossa, typically resulting in developmental delay and cognitive disability. The co-occurrence of Down syndrome (DS) and DWS is relatively uncommon; thus, its impact on developmental outcomes has not been fully elucidated. Herein, we report a case of a 37-month-old child with DS and DWS, who is functioning at the following age-equivalent: gross motor at a 9-mo level, fine motor 6 mo, expressive language 14 mo, receptive language 9 mo. As such, it is important to determine how the DWS influences developmental outcomes, and appreciate the importance of early interventional therapy.