Hypoglycaemia in type 2 diabetes treated with pre-mixed insulin

The burden of hypoglycaemia in type 2 diabetes is increasingly recognised, regardless of treatment regimen.1-3 However, time in hypoglycaemia for individuals with type 2 diabetes who use pre-mixed (biphasic) insulin remains unclear. The aim of our prospective, open-label, single arm, pilot, observational study was to determine the amount of time individuals in this cohort spent in hypoglycaemia (ISRCTN 10603608). The primary endpoint was sensor derived time in hypoglycaemia (TBR

Effects of CO2 on H2O band profiles and band strengths in mixed H2O:CO2 ices

H2O is the most abundant component of astrophysical ices. In most lines of sight it is not possible to fit both the H2O 3 um stretching, the 6 um bending and the 13 um libration band intensities with a single pure H2O spectrum. Recent Spitzer observations have revealed CO2 ice in high abundances and it has been suggested that CO2 mixed into H2O ice can affect relative strengths of the 3 um and 6 um bands. We used laboratory infrared transmission spectroscopy of H2O:CO2 ice mixtures to investigate the effects of CO2 on H2O ice spectral features at 15-135 K. We find that the H2O peak profiles and band strengths are significantly different in H2O:CO2 ice mixtures compared to pure H2O ice. In all H2O:CO2 mixtures, a strong free-OH stretching band appears around 2.73 um, which can be used to put an upper limit on the CO2 concentration in the H2O ice. The H2O bending mode profile also changes drastically with CO2 concentration; the broad pure H2O band gives way to two narrow bands as the CO2 concentration is increased. This makes it crucial to constrain the environment of H2O ice to enable correct assignments of other species contributing to the interstellar 6 um absorption band. The amount of CO2 present in the H2O ice of B5:IRS1 is estimated by simultaneously comparing the H2O stretching and bending regions and the CO2 bending mode to laboratory spectra of H2O, CO2, H2O:CO2 and HCOOH.Comment: 12 pages, 11 figures, accepted by A&

HbA1c response and hospital admissions following commencement of flash glucose monitoring in adults with type 1 diabetes

Introduction Our aim was to assess the effect of introducing flash monitoring in adults with type 1 diabetes with respect to change in hemoglobin A1c (HbA1c) and frequency of hospital admissions.Research design and methods Prospective observational study of adults with type 1 diabetes in our center, in whom a prescription for a flash monitoring sensor was collected. Primary outcome was change in HbA1c between 2016 and after flash monitoring. Rates of hospital admission were compared between the first year after flash monitoring and the corresponding 12-month period 2 years earlier.Results Approximately half of all adults with type 1 diabetes, attending our center, collected prescriptions for flash monitoring sensors (n=2216). Median fall in HbA1c was −1 (−0.1) mmol/mol (%) (p<0.001) and was greatest in those with baseline HbA1c >75 (9.0) mmol/mol (%): −10 (−0.9) mmol/mol (%), p<0.001. 43% of those with a baseline HbA1c >53 mmol/mol (7%) experienced a ≥5 mmol/mol (0.5%) fall in HbA1c. In addition to higher HbA1c, early commencement within 1 month of NHS-funded flash monitoring (p<0.001), and male gender (p=0.013) were associated with a fall in HbA1c of ≥5 (0.5) mmol/mol (%). Socioeconomic deprivation (p=0.009) and collecting fewer than 2 sensors per month (p=0.002) were associated with lack of response. Overall, hospital admissions did not change but an increase in admissions for hypoglycemia was observed (1.1% vs 0.3%, p=0.026).Conclusions Flash monitoring is associated with reduction in HbA1c in individuals with HbA1c >58 mmol/mol. Numerous clinical features are independently associated with HbA1c response. An increase in hypoglycemia admissions occurred following flash monitoring

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

Band profiles and band strengths in mixed H2O:CO ices

A laboratory study on the band profiles and band strengths of H2O in CO ice, and vice versa, is presented and interpreted in terms of two models. The results show that a mutual interaction takes place between the two species in the solid, which alters the band positions and band strengths. It is found that the band strengths of the H2O bulk stretch, bending and libration vibrational bands decrease linearly by a factor of up to 2 when the CO concentration is increased from 0 to 80%. By contrast, the band strength of the free OH stretch increases linearly. The results are compared to a recently performed quantitative study on H2O:CO2 ice mixtures. It is shown that for mixing ratios of 1:0.5 H2O:X and higher, the H2O bending mode offers a good tracer to distinguish between CO2 or CO in H2O ice. Additionally, it is found that the band strength of the CO fundamental remains constant when the water concentration is increased in the ice. The integrated absorbance of the 2152 cm-1 CO feature, with respect to the total integrated CO absorption feature, is found to be a good indicator of the degree of mixing of CO in the H2O:CO laboratory ice system. From the change in the H2O absorption band strength in laboratory ices upon mixing we conclude that astronomical water ice column densities on various lines of sight can be underestimated by up to 25% if significant amounts of CO and CO2 are mixed in.Comment: 9 pages, 10 figure

Ongoing burden and recent trends in severe hospitalised hypoglycaemia events in people with type 1 and type 2 diabetes in Scotland:A nationwide cohort study 2016–2022

Aims: We examined severe hospitalised hypoglycaemia (SHH) rates in people with type 1 and type 2 diabetes in Scotland during 2016–2022, stratifying by sociodemographics. Methods: Using the Scottish National diabetes register (SCI-Diabetes), we identified people with type 1 and type 2 diabetes alive anytime during 2016–2022. SHH events were determined through linkage to hospital admission and death registry data. We calculated annual SHH rates overall and by age, sex, and socioeconomic status. Summary estimates of time and stratum effects were obtained by fitting adjusted generalised additive models using R package mgcv. Results: Rates for those under 20 with type 1 diabetes reached their minimum at the 2020–2021 transition, 30% below the study period average. A gradual decline over time also occurred among 20–49-year-olds with type 1 diabetes. Overall, females had 15% higher rates than males with type 2 diabetes (rate ratio 1.15, 95% CI 1.08–1.22). People in the most versus least deprived quintile experienced 2.58 times higher rates (95% CI 2.27–2.93) in type 1 diabetes and 2.33 times higher (95% CI 2.08–2.62) in type 2 diabetes. Conclusions: Despite advances in care, SHH remains a significant problem in diabetes. Future efforts must address the large socioeconomic disparities in SHH risks.</p

Efficacy and safety of cotadutide, a dual glucagon-like peptide-1 and glucagon receptor agonist, in a randomized phase 2a study of patients with type 2 diabetes and chronic kidney disease

AIM: To assess the efficacy, safety and tolerability of cotadutide in patients with type 2 diabetes mellitus and chronic kidney disease. MATERIALS AND METHODS: In this phase 2a study (NCT03550378), patients with body mass index 25‐45 kg/m(2), estimated glomerular filtration rate 30‐59 ml/min/1.73 m(2) and type 2 diabetes [glycated haemoglobin 6.5‐10.5% (48‐91 mmol/mol)] controlled with insulin and/or oral therapy combination, were randomized 1:1 to once‐daily subcutaneous cotadutide (50‐300 μg) or placebo for 32 days. The primary endpoint was plasma glucose concentration assessed using a mixed‐meal tolerance test. RESULTS: Participants receiving cotadutide (n = 21) had significant reductions in the mixed‐meal tolerance test area under the glucose concentration‐time curve (–26.71% vs. +3.68%, p < .001), more time in target glucose range on continuous glucose monitoring (+14.79% vs. –21.23%, p = .001) and significant reductions in absolute bodyweight (–3.41 kg vs. –0.13 kg, p < .001) versus placebo (n = 20). In patients with baseline micro‐ or macroalbuminuria (n = 18), urinary albumin‐to‐creatinine ratios decreased by 51% at day 32 with cotadutide versus placebo (p = .0504). No statistically significant difference was observed in mean change in estimated glomerular filtration rate between treatments. Mild/moderate adverse events occurred in 71.4% of participants receiving cotadutide and 35.0% receiving placebo. CONCLUSIONS: We established the efficacy of cotadutide in this patient population, with significantly improved postprandial glucose control and reduced bodyweight versus placebo. Reductions in urinary albumin‐to‐creatinine ratios suggest potential benefits of cotadutide on kidney function, supporting further evaluation in larger, longer‐term clinical trials