Fraser W. Gibb

Flash Glucose Monitoring Improves Outcomes in a Type 1 Diabetes Clinic

The Freestyle Libre flash glucose monitoring (FGM; Abbott Diabetes Care, Witney, UK) system was introduced in the United Kingdom in 2013. Although similar to conventional continuous glucose monitoring (CGM) systems, a few significant differences exist. FGM sensors are factory calibrated and therefore do not require calibration with blood glucose testing over their 14-day lifespan. FGM is also considerably cheaper than conventional CGM but lacks alarm features and connectivity with continuous subcutaneous insulin infusion (CSII) devices, such as low-glucose suspend. The accuracy and usability of FGM have been validated in patients with both type 1 and type 2 diabetes. We sought to prospectively assess the impact of introducing FGM to patients attending our type 1 diabetes clinic in a university teaching hospital, over a 16-week period. In particular, we assessed the impact on HbA1c, hypoglycemia (recorded and self-reported) and quality of life measures (Diabetes Distress Scale). The only inclusion criteria were a diagnosis of type 1 diabetes and a willingness to upload FGM data at least monthly. Data were analyzed as intention-to-treat. Of the 25 participants, 13 were men, and the mean age was 39.8 ± 2.0 years. Mean duration of diabetes was 19 ± 2 years. A total of 8 patients were treated with CSII, and 17 used multiple daily injections. Immediately prior to commencement of FGM, the mean HbA1c of participants was 8.0 ± 0.14%, which did not differ from the mean of the previous 4 clinic recorded HbA1c values (8.0 ± 0.2%, P = .833). Mean HbA1c fell from 8.0 ± 0.14% to 7.5 ± 0.14% (–0.48%, P = .001) following 16 weeks of FGM. The number of people with an HbA1c of 7.5% or below more than doubled after FGM use (Figure 1). The mean reduction in HbA1c was greater in those with a baseline HbA1c > 7.5%: –0.59 ± 0.15% compared to −0.2 ± 0.11% in those with HbA1c <7.5% at baseline (P = .005). Female participants had greater mean reduction in HbA1c (–0.74 ± 0.19%) compared to men (–0.23 ± 0.15%, P = .049) despite no significant difference in baseline HbA1c (8.2 ± 0.25% vs 7.8 ± 0.14%, P = .174). Of participants, 24% (6/25) achieved an HbA1c reduction of greater than 1.0%. Episodes of hypoglycemia (glucose <72 mg/dl), as determined from FGM glucose data, reduced from 17 (IQR 10-20) in the first 2 weeks of use to 12 (IQR 8.5-16) in the final 2 weeks (P = .019). Significant reductions were observed in the Diabetes Distress Scale mean score (P = .006), as well as emotional burden (P = .035) and regimen-related distress subscores (P = .005). FGM use was associated with a significant increase in delivering bolus insulin 15-20 minutes in advance of meals (compared to immediately before or after meals), from 16% to 44% (P = .026). In summary, these results support the wider use of FGM to improve outcomes in people with type 1 diabetes. Benefits are realized across a number of important domains including improved HbA1c, hypoglycemia, and quality of life. 661560 DSTXXX10.1177/1932296816661560Journal of Diabetes Science and TechnologyDover et al letter2016

Derivatization of estrogens enhances specificity and sensitivity of analysis of human plasma and serum by liquid chromatography tandem mass spectrometry

Estrogens circulate at concentrations less than 20 pg/mL in men and postmenopausal women, presenting analytical challenges. Quantitation by immunoassay is unreliable at these low concentrations. Liquid chromatography tandem mass spectrometry (LC–MS/MS) offers greater specificity and sometimes greater sensitivity, but ionization of estrogens is inefficient. Introduction of charged moieties may enhance ionization, but many such derivatives of estrogens generate non-specific product ions originating from the “reagent” group. Therefore an approach generating derivatives with product ions specific to individual estrogens was sought. Estrogens were extracted from human plasma and serum using solid phase extraction and derivatized using 2-fluoro-1-methylpyridinium-p-toluenesulfonate (FMP-TS). Electrospray in positive mode with multiple reaction monitoring using a QTrap 5500 mass spectrometer was used to quantify “FMP” derivatives of estrogens, following LC separation. Transitions for the FMP derivatives of estrone (E1) and estradiol (E2) were compound specific (m/z 362→238 and m/z 364→128, respectively). The limits of detection and quantitation were 0.2 pg on-column and the method was linear from 1–400 pg/sample. Measures of intra- and inter-assay variability, precision and accuracy were acceptable (<20%). The derivatives were stable over 24 h at 10 °C (7–9% degradation). Using this approach, E1 and E2, respectively were detected in human plasma and serum: pre-menopausal female serum (0.5 mL) 135–473, 193–722 pmol/L; male plasma (1 mL) 25–111, 60–180 pmol/L and post-menopausal female plasma (2 mL), 22–78, 29–50 pmol/L. Thus FMP derivatization, in conjunction with LC–MS/MS, is suitable for quantitative analysis of estrogens in low abundance in plasma and serum, offering advantages in specificity over immunoassay and existing MS techniques.

Aromatase Inhibition Reduces Insulin Sensitivity in Healthy Men

Context: Deficiency of aromatase, the enzyme that catalyzes the conversion of androgens to estrogens, is associated with insulin resistance in humans and mice. Objective: We hypothesized that pharmacological aromatase inhibition results in peripheral insulin resistance in humans. Design: This was a double-blind, randomized, controlled, crossover study. Setting: The study was conducted at a clinical research facility. Participants: Seventeen healthy male volunteers (18–50 y) participated in the study. Intervention: The intervention included oral anastrozole (1 mg daily) and placebo, each for 6 weeks with a 2-week washout period. Main Outcome Measure: Glucose disposal and rates of lipolysis were measured during a stepwise hyperinsulinemic euglycemic clamp. Data are mean (SEM). Results: Anastrozole therapy resulted in significant estradiol suppression (59.9 ± 3.6 vs 102.0 ± 5.7 pmol/L, P = < .001) and a more modest elevation of total T (25.8 ± 1.2 vs 21.4 ± 0.7 nmol/L, P = .003). Glucose infusion rate, during the low-dose insulin infusion, was lower after anastrozole administration (12.16 ± 1.33 vs 14.15 ± 1.55 μmol/kg·min, P = .024). No differences in hepatic glucose production or rate of lipolysis were observed. Conclusion: Aromatase inhibition reduces insulin sensitivity, with respect to peripheral glucose disposal, in healthy men. Local generation and action of estradiol, at the level of skeletal muscle, is likely to be an important determinant of insulin sensitivity.

Adrenal insufficiency in patients on long-term opioid analgesia

Opioid analgesia has been implicated as a cause of secondary adrenal insufficiency, but little is known of the prevalence of this potentially serious adverse effect in patients with chronic pain.

The prevalence of structural pituitary abnormalities by MRI scanning in men presenting with isolated hypogonadotrophic hypogonadism

Hypogonadotrophic hypogonadism (HH) is commonly associated with ageing, obesity and type 2 diabetes. The indications for pituitary imaging are controversial, and current guidelines are based on small case series.

Predicting outcomes and complications following radioiodine therapy in Graves’ thyrotoxicosis

Radioiodine (RAI) is an effective treatment for Graves’ thyrotoxicosis but is associated with a failure rate of 15% and may be a risk factor for thyroid eye disease (TED) and weight gain. We sought to examine predictors of RAI failure, weight gain, TED and patient satisfaction.