Background: Glycemic variability has been proposed as a contributing factor in the development of diabetes complications. Multiple measures exist to calculate the magnitude of glycemic variability, but normative ranges for subjects without diabetes have not been described. For treatment targets and clinical research we present normative ranges for published measures of glycemic variability. Methods: Seventy-eight subjects without diabetes having a fasting plasma glucose of < 120 mg/dL (6.7 mmol/L) underwent up to 72 h of continuous glucose monitoring (CGM) with a Medtronic Minimed (Northridge, CA) CGMS Ò Gold device. Glycemic variability was calculated using EasyGV ª software (available free for noncommercial use at www.easygv.co.uk), a custom program that calculates the SD, M-value, mean amplitude of glycemic excursions (MAGE), average daily risk ratio (ADRR), Lability Index (LI), J-Index, Low Blood Glucose Index (LBGI), High Blood Glucose Index (HBGI), continuous overlapping net glycemic action (CONGA), mean of daily differences (MODD), Glycemic Risk Assessment in Diabetes Equation (GRADE), and mean absolute glucose (MAG). Results: Eight CGM traces were excluded because there were inadequate data. From the remaining 70 traces, normative reference ranges (mean -2 SD) for glycemic variability were calculated: SD, 0-3.0; CONGA, 3.6-5.5; LI, LBGI, HBGI, GRADE, MODD, ADDR, and MAG,. Conclusions: We present normative ranges for measures of glycemic variability in adult subjects without diabetes for use in clinical care and academic research.

Problematic hypoglycemia, defined as two or more episodes per year of severe hypoglycemia or as one episode associated with impaired awareness of hypoglycemia, extreme glycemic lability, or major fear and maladaptive behavior, is a challenge, especially for patients with long-standing type 1 diabetes. Individualized therapy for such patients should include a composite target: optimal glucose control without problematic hypoglycemia. Therefore, we propose a tiered, four-stage algorithm based on evidence of efficacy given the limitations of educational, technological, and transplant interventions. All patients with problematic hypoglycemia should undergo structured or hypoglycemia-specific education programs (stage 1). Glycemic and hypoglycemia treatment targets should be individualized and reassessed every 3–6 months. If targets are not met, one diabetes technology—continuous subcutaneous insulin infusion or continuous glucose monitoring—should be added (stage 2). For patients with continued problematic hypoglycemia despite education (stage 1) and one diabetes technology (stage 2), sensor-augmented insulin pumps preferably with an automated low-glucose suspend feature and/or very frequent contact with a specialized hypoglycemia service can reduce hypoglycemia (stage 3). For patients whose problematic hypoglycemia persists, islet or pancreas transplant should be considered (stage 4). This algorithm provides an evidence-informed approach to resolving problematic hypoglycemia; it should be used as a guide, with individual patient circumstances directing suitability and acceptability to ensure the prudent use of technology and scarce transplant resources. Standardized reporting of hypoglycemia outcomes and inclusion of patients with problematic hypoglycemia in studies of new interventions may help to guide future therapeutic strategies.

Pingitore, A. et al. (2017) The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. Diabetes, Obesity and Metabolism, 19(2), pp. 257-265. (doi:10.1111/dom.12811) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/130703/ Accepted ArticleThe diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. This article is protected by copyright. All rights reserved.This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. propionate on β-cell function in humans and the direct effects of propionate on isolated human islets in vitro. Materials and Methods:For 24 weeks human subjects ingested an inulinpropionate ester that delivers propionate to the colon. Acute insulin, GLP-1 and nonesterified fatty acid (NEFA) levels were quantified pre-and post-supplementation in response to a mixed meal test. Expression of the SCFA receptor FFAR2 in human islets was determined by western blotting and immunohistochemistry. Dynamic insulin secretion from perifused human islets was quantified by radioimmunoassay and islet apoptosis was determined by quantification of caspase 3/7 activities.Results: Colonic propionate delivery in vivo was associated with improved β-cell function with increased insulin secretion that was independent of changes in GLP-1 levels. Human islet β-cells expressed FFAR2 and propionate potentiated dynamic glucose-stimulated insulin secretion in vitro, an effect that was dependent on signalling via protein kinase C. Propionate also protected human islets from apoptosis induced by the NEFA sodium palmitate and inflammatory cytokines. Conclusions:Our results indicate that propionate has beneficial effects on β-cell function in vivo, and in vitro analyses demonstrated that it has direct effects to potentiate glucose-stimulated insulin release and maintain β-cell mass through

Although there are now widely accepted diagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) there are few epidemiological data. A prevalence study was performed in the four Thames health regions, population 14 049 850. The prevalence date was 1 January 1995. Data were from a national consultant neurologist surveillance programme and the personal case series of two investigators. A diagnosis of CIDP was made according to definite, probable, possible, or suggestive diagnostic criteria. A wide diVerence in prevalence rates between the four health regions was noted, probably due to reporting bias. In the South East Thames Region, from which the data were most comprehensive the prevalence for definite and probable cases was 1.00/100 000; the highest total prevalence (if possible and suggestive cases were included) would have been 1.24/100 000. On the prevalence date 13% of patients required aid to walk and 54% were still receiving treatment. (J Neurol Neurosurg Psychiatry 1999;66:677-680)