Summary Background The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity. Methods We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant’s body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2–11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220. Findings We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7–1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8–1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0–10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21–0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study. Interpretation Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas. Funding National Institute of Diabetes and Digestive and Kidney Diseases of the...

OBJECTIVE -We evaluated the role of a single measurement of HbA 1c in a diabetes case finding in hospitalized patients with random hyperglycemia at admission. RESEARCH DESIGN AND METHODS -From 20March to 31 July 2000, 508 patients admitted through the emergency department of one hospital were tested for random hyperglycemia (plasma glucose [PG] Ͼ125 mg/dl). Consenting patients with hyperglycemia (without preexisting diabetes or on corticosteroids) underwent testing for HbA 1c levels, two fasting PG levels, and an outpatient oral glucose tolerance test (OGTT) if necessary.RESULTS -Of the patients, 50 (9.8%) met the inclusion criteria. Of these, 70% (n ϭ 35) completed the study, and 60% (n ϭ 21) were diagnosed with diabetes. Patients with diabetes had higher HbA 1c levels than subjects without diabetes (6.8 Ϯ 0.4 vs. 5.3 Ϯ 0.1%, P ϭ 0.002). An HbA 1c level Ͼ6.0% was 100% specific (14/14) and 57% sensitive (12/21) for the diagnosis of diabetes. When a lower cutoff value of HbA 1c at 5.2% was used, specificity was 50% (10/21) and sensitivity was 100% (7/14). CONCLUSIONS -In acutely ill patients with random hyperglycemia at hospital admission, an HbA 1c Ͼ6.0% reliably diagnoses diabetes, and an HbA 1c level Ͻ5.2% reliably excludes it (paralleling the operating characteristics of the standard fasting glucose measurements); however, the rapidity of the HbA 1c level can be useful for diabetes case finding and treatment initiation early in the hospital course.

Until 2010 the diagnosis of diabetes mellitus was based solely on glucose concentration, but American Diabetes Association (ADA) recommendations now include a new criterion: hemoglobin A1C ≥6.5%. Because this change may have significant implications for diabetes diagnosis, we conducted a comprehensive literature review including peer-reviewed articles not referenced in the ADA report.We conclude that A1C and plasma glucose tests are frequently discordant for diagnosing diabetes. A1C ≥6.5% identifies fewer individuals as having diabetes than glucose-based criteria. Convenience of A1C test might increase the number of patients diagnosed, but this is unproven. Diagnostic cut-points for both glucose and A1C are based on consensus judgments regarding optimal sensitivity and specificity for the complications of hyperglycemia. A1C may not accurately reflect levels of glycemia in some situations, but in comparison with glucose measurements, it has greater analytic stability and less temporal variability. When choosing a diagnostic test for diabetes, the limitations of each choice must be understood. Clinical judgment and consideration of patient preference are required to appropriately select among the diagnostic alternatives.

No abstract

Aims/hypothesis Recent reports of decreased capillary density in the adipose tissue of obese individuals suggest that an imbalance of angiogenesis and adipogenesis may, in part, underlie insulin resistance. This study aimed to determine whether the insulin-sensitising peroxisome proliferator-activated receptor γ (PPARγ) activator rosiglitazone affects adipose tissue vascularisation in normal humans. Methods A randomised, parallel-group, investigator-blinded placebo-controlled trial was conducted with normoglycaemic volunteers with BMI 27–43, recruited from the community at the University of Massachusetts Medical School, Worcester, MA, USA. Peri-umbilical adipose tissue biopsies were obtained before and after treatment for 6 weeks with rosiglitazone (8 mg once daily) or placebo, which were randomly allocated from a sequentially numbered list. The primary outcomes were adipocyte size and capillary density measured by immunohistochemistry, and angiogenic potential assessed by capillary sprout formation in Matrigel. Secondary outcomes were serum adiponectin, glycaemic, lipid and liver function variables. Results A total of 35 individuals fulfilling the inclusion criteria were randomised, and complete before-vs-after analyses were achieved in 30 participants (13 and 17, placebo and rosiglitazone, respectively). Significant differences, assessed by paired two-tailed Student t tests, were seen in response to rosiglitazone for adipocyte size (3,458±202 vs 2,693±223 μm2, p=0.0049), capillary density (5.6±0.5 vs 7.5±0.5 lumens/field, p=0.0098), serum adiponectin (14.3±1.5 vs 28.6±3.0 ng/ml, p<0.0001) and alkaline phosphatase (1.04±0.07 vs 0.87±0.05 μkat/l, p=0.001). A difference in angiogenic potential before and after treatment between the placebo and rosiglitazone groups was also seen (−23.88±14 vs 13.42±13, p=0.029, two-tailed Mann–Whitney test). Conclusions/interpretation Significant effects on adipose tissue vascular architecture occur after a short period of treatment with rosiglitazone in individuals with normal glucose tolerance. Improved adipose tissue vascularisation may, in part, mediate the therapeutic actions of this class of drugs.