Beta cells are partially replaced in neonatal rodents after deletion with streptozotocin (STZ). Exposure of pregnant rats to a low protein (LP) diet impairs endocrine pancreas development in the offspring, leading to glucose intolerance in adulthood. Our objective was to determine whether protein restriction has a similar effect on the offspring in mice, and if this alters the capacity for beta cell regeneration after STZ. Pregnant Balb/c mice were fed a control (C) (20% protein) or an isocaloric LP (8% protein) diet during gestation. Pups were given 35 mg/kg STZ (or vehicle) from d 1 to 5 for each dietary treatment. Histologic analysis showed that C-fed offspring had largely replaced beta cell mass (BCM) after STZ by d 30, but this was not sustained over time. Female LP-fed offspring showed an initial increase in BCM by d 14 but developed glucose intolerance by d 130. In contrast, male LP offspring showed no changes in BCM or glucose tolerance. However, LP exposure limited the capacity for recovery of BCM in both genders after STZ treatment. (Pediatr Res 68: 16-22, 2010) P oor fetal growth and low birth weight are associated with increased risk of impaired glucose tolerance (1), type 2 diabetes (2), the metabolic syndrome (3), and cardiovascular disease (4) in adult life. Animal models that have been developed to understand the role of the intrauterine environment in susceptibility to postnatal disease have included maternal dietary calorie restriction (5), nutritional imbalance (6), and pharmacological (7) or surgical intervention (8). Administration of a low protein (LP) diet to rats during pregnancy results in reduced birth weight (6), impaired islet cell development, deficient insulin release (9), an increased islet apoptotic rate (10,11), and decreased beta cell mass (BCM) in the offspring (9 -11). Offspring of LP-fed dams were glucose intolerant at 130 d of age (12). Our first objective was to characterize an LP model in mice, to facilitate future exploration into the mechanisms, whereby nutritional insult can predispose to adult disease by using genetic manipulation.Pancreatic beta cells have a significant capacity to regenerate after injury in early life. Subtotal deletion of beta cells with streptozotocin (STZ) is followed by their partial regeneration and remission of hyperglycemia in young rodents (13,14). However, this regenerative ability decreases with age (15).New beta cells have been postulated to be generated through three possible mechanisms: 1) beta cell replication (16), 2) pancreatic duct progenitor cell differentiation (17), and 3) acinar cell transdifferentiation (18). It remains to be determined, which mechanism is most important for beta cell regeneration and could be exploited for beta cell therapy. It is not known if administration of an LP diet to the pregnant rodent will alter beta cell renewal, or by which mechanism, in the offspring after an STZ insult, which constitutes our second objective in this study. Understanding how the intrauterine environment alters plasticity ...

Laboratory test overutilization increases health care costs, leads to unwarranted investigations, and may have a negative impact on health outcomes. The American Society of Clinical Pathology, in its Choosing Wisely Campaign, advocates that inflammation be investigated with C-reactive protein (CRP) instead of Erythrocyte Sedimentation Rate (ESR). London Health Sciences Centre (LHSC), a tertiary care hospital organization in Ontario, Canada, set a goal to reduce inappropriate ESR orders by 50%. After developing appropriateness criteria for ESR, we used a series of PDSA cycles to reduce inappropriate ESR ordering and analyzed our results with an interrupted time series design. Our intervention began with an educational bulletin and moved to city-wide implementation of computerized Clinical Decision Support (CDS). After implementation, ESR orders decreased by 40% from 386 orders per week to 241 orders per week. Our results are supported by previous literature on the effectiveness of CDS in reducing overutilization and suggest that provider habit is a significant contributor to inappropriate ordering.

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