Diabetic complications are the major cause of morbidity and mortality in persons with diabetes. Chronic hyperglycemia is a major initiator of diabetic microvascular complications (eg, retinopathy, neuropathy, nephropathy). Glucose processing uses a variety of diverse metabolic pathways; hence, chronic hyperglycemia can induce multiple cellular changes leading to complications. Several predominant well-researched theories have been proposed to explain how hyperglycemia can produce the neural and vascular derangements that are hallmarks of diabetes. These theories can be separated into those that emphasize the toxic effects of hyperglycemia and its pathophysiological derivatives (such as oxidants, hyperosmolarity, or glycation products) on tissues directly and those that ascribe pathophysiological importance to a sustained alteration in cell signaling pathways (such as changes in phospholipids or kinases) induced by the products of glucose metabolism. This article summarizes these theories and the potential therapeutic interventions that may prevent diabetic complications in the presence of hyperglycemia, control of which is often difficult with current therapeutic options.

TGF- has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-1 activity with a TGF-1-specific, humanized, neutralizing monoclonal antibody (TGF-1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.3-3.3 mg/dl for women and 1.5-3.5 mg/dl for men (or eGFR of 20-60 ml/min per 1.73 m), and a 24-hour urine protein-to-creatinine ratio ≥800 mg/g to TGF-1 mAb (2-, 10-, or 50-mg monthly subcutaneous dosing for 12 months) or placebo. We assessed a change in SCr from baseline to 12 months as the primary efficacy variable. Although the Data Monitoring Committee did not identify safety issues, we terminated the trial 4 months early for futility on the basis of their recommendation. The placebo group had a mean±SD change in SCr from baseline to end of treatment of 0.33±0.67 mg/dl. Least squares mean percentage change in SCr from baseline to end of treatment did not differ between placebo (14%; 95% confidence interval [95% CI], 9.7% to 18.2%) and TGF-1 mAb treatments (20% [95% CI, 15.3% to 24.3%], 19% [95% CI, 14.2% to 23.0%], and 19% [95% CI, 14.0% to 23.3%] for 2-, 10-, and 50-mg doses, respectively). Thus, TGF-1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy.

RBX was well tolerated at doses up to 16 mg twice daily for 28 days in patients with diabetes. It ameliorated diabetes-induced RCT abnormalities. No serious safety problems were identified in this patient population. Compared with prior published data, these findings represent the first direct human evidence of both bioavailability of RBX to retinal vessels and amelioration of diabetes-induced retinal hemodynamic abnormalities by an oral PKC beta inhibitor.

This study determines the confidence levels of physicians in providing components of pediatric palliative care and identifies their willingness to obtain training and to make palliative care referrals. Surveys were mailed to all physicians at Primary Children's Medical Center. The survey instrument includes 3 demographic items, 9 items designed to assess physician confidence in core palliative care skills, and 4 items designed to assess what steps physicians would be likely to take to assure that patients receive palliative care. Physicians were asked to rate their confidence levels to provide palliative care components on a 4-point scale for each of the items. Five hundred ninety-seven surveys were mailed, with 323 usable surveys returned. The proportion of physicians who rate their ability to provide palliative care as "confident" or "very confident" ranges from 74% for giving difficult news to families to 23% for managing end-of-life symptoms. Thirty-six percent of the physicians say they would be "likely" or "very likely" to attend training to improve their ability to provide palliative care to children. Eighty-six percent would be "likely" or "very likely" to refer for a palliative care consult and 91% to a home health agency or hospice. There is wide variation in the confidence levels of physicians to provide the core components of palliative care. Few are interested in obtaining additional training, but most are willing to obtain consultation or to refer to a palliative care service. These results argue in favor of hospital-based palliative care teams and for specialty training and certification in pediatric palliative care.

Reports of family satisfaction with pediatric palliative care have been limited. This knowledge is critical for both program development and furthering understanding of needs. The purpose of this study was to assess parents' perceptions about whether a pediatric palliative care program was providing key elements of pediatric palliative care as described in the literature and to assess parental satisfaction with services. Data were collected from 65 parents, using a tool developed for the project, whose children died while receiving services from Rainbow Kids Palliative Care, a program of Primary Children's Medical Center, and the Department of Pediatrics, University of Utah, Salt Lake City, Utah. Respondents reported that the Rainbow Kids team had provided emotional support, helped with decision making and communication, and that their children's symptoms were managed. Furthermore, parent respondents expressed high levels of satisfaction with services from the Rainbow Kids team.