Evidence suggests that insulin delivery to skeletal muscle interstitium is the rate-limiting step in insulin-stimulated muscle glucose uptake and that this process is impaired by insulin resistance. In this review we examine the basis for the hypothesis that insulin acts on the vasculature at three discrete steps to enhance its own delivery to muscle: (1) relaxation of resistance vessels to increase total blood flow; (2) relaxation of pre-capillary arterioles to increase the microvascular exchange surface perfused within skeletal muscle (microvascular recruitment); and (3) the trans-endothelial transport (TET) of insulin. Insulin can relax resistance vessels and increase blood flow to skeletal muscle. However, there is controversy as to whether this occurs at physiological concentrations of, and exposure times to, insulin. The microvasculature is recruited more quickly and at lower insulin concentrations than are needed to increase total blood flow, a finding consistent with a physiological role for insulin in muscle insulin delivery. Microvascular recruitment is impaired by obesity, diabetes and nitric oxide synthase inhibitors. Insulin TET is a third potential site for regulating insulin delivery. This is underscored by the consistent finding that steady-state insulin concentrations in plasma are approximately twice those in muscle interstitium. Recent in vivo and in vitro findings suggest that insulin traverses the vascular endothelium via a trans-cellular, receptor-mediated pathway, and emerging data indicate that insulin acts on the endothelium to facilitate its own TET. Thus, muscle insulin delivery, which is rate-limiting for its metabolic action, is itself regulated by insulin at multiple steps. These findings highlight the need to further understand the role of the vascular actions of insulin in metabolic regulation.

OBJECTIVETo create surveillance algorithms to detect diabetes and classify type 1 versus type 2 diabetes using structured electronic health record (EHR) data.RESEARCH DESIGN AND METHODSWe extracted 4 years of data from the EHR of a large, multisite, multispecialty ambulatory practice serving ∼700,000 patients. We flagged possible cases of diabetes using laboratory test results, diagnosis codes, and prescriptions. We assessed the sensitivity and positive predictive value of novel combinations of these data to classify type 1 versus type 2 diabetes among 210 individuals. We applied an optimized algorithm to a live, prospective, EHR-based surveillance system and reviewed 100 additional cases for validation.RESULTSThe diabetes algorithm flagged 43,177 patients. All criteria contributed unique cases: 78% had diabetes diagnosis codes, 66% fulfilled laboratory criteria, and 46% had suggestive prescriptions. The sensitivity and positive predictive value of ICD-9 codes for type 1 diabetes were 26% (95% CI 12–49) and 94% (83–100) for type 1 codes alone; 90% (81–95) and 57% (33–86) for two or more type 1 codes plus any number of type 2 codes. An optimized algorithm incorporating the ratio of type 1 versus type 2 codes, plasma C-peptide and autoantibody levels, and suggestive prescriptions flagged 66 of 66 (100% [96–100]) patients with type 1 diabetes. On validation, the optimized algorithm correctly classified 35 of 36 patients with type 1 diabetes (raw sensitivity, 97% [87–100], population-weighted sensitivity, 65% [36–100], and positive predictive value, 88% [78–98]).CONCLUSIONSAlgorithms applied to EHR data detect more cases of diabetes than claims codes and reasonably discriminate between type 1 and type 2 diabetes.

High-deductible health plans (HDHPs) have expanded under the Affordable Care Act and are expected to play a major role in the future of US health policy. The effects of modern HDHPs on chronically ill patients and adverse outcomes are unknown.OBJECTIVE To determine the association of HDHP with high-priority diabetes outpatient care and preventable acute complications.DESIGN, SETTING, AND PARTICIPANTS Controlled interrupted-time-series study using a large national health insurer database from January 1, 2003, to December 31, 2012. A total of 12 084 HDHP members with diabetes, aged 12 to 64 years, who were enrolled for 1 year in a low-deductible (Յ$500) plan followed by 2 years in an HDHP (Ն$1000) after an employer-mandated switch were included. Patients transitioning to HDHPs were propensity-score matched with contemporaneous patients whose employers offered only low-deductible coverage. Low-income (n = 4121) and health savings account (HSA)-eligible (n = 1899) patients with diabetes were subgroups of interest. Data analysis was performed from February 23, 2015, to September 11, 2016.EXPOSURES Employer-mandated HDHP transition.MAIN OUTCOMES AND MEASURES High-priority outpatient visits, disease monitoring tests, and outpatient and emergency department visits for preventable acute diabetes complications. RESULTSIn the 12 084 HDHP members included after the propensity score match, the mean (SD) age was 50.4 (10.0) years; 5410 of the group (44.8%) were women. The overall, low-income, and HSA-eligible diabetes HDHP groups experienced increases in out-of-pocket medical expenditures of 49.4% (95% CI, 40.3% to 58.4%), 51.7% (95% CI, 38.6% to 64.7%), and 67.8% (95% CI, 47.9% to 87.8%), respectively, compared with controls in the year after transitioning to HDHPs. High-priority primary care visits and disease monitoring tests did not change significantly in the overall HDHP cohort; however, high-priority specialist visits declined by 5.5% (95% CI, −9.6% to −1.5%) in follow-up year 1 and 7.1% (95% CI, −11.5% to −2.7%) in follow-up year 2 vs baseline. Outpatient acute diabetes complication visits were delayed in the overall and low-income HDHP cohorts at follow-up (adjusted hazard ratios, 0.94 [95% CI, 0.88 to 0.99] for the overall cohort and 0.89 [95% CI, 0.81 to 0.98] for the low-income cohort). Annual emergency department acute complication visits among HDHP members increased by 8.0% (95% CI, 4.6% to 11.4%) in the overall group, 21.7% (95% CI, 14.5% to 28.9%) in the low-income group, and 15.5% (95% CI, 10.5% to 20.6%) in the HSA-eligible group.CONCLUSIONS AND RELEVANCE Patients with diabetes experienced minimal changes in outpatient visits and disease monitoring after an HDHP switch, but low-income and HSA-eligible HDHP members experienced major increases in emergency department visits for preventable acute diabetes complications.