The exact contribution of daily glucose exposure to HbA1c in people with type 1 diabetes (T1D) remains controversial. We examined the contribution of pre- and postprandial glycaemia, nocturnal and early-morning glycaemia, and glycaemic variability to HbA1c levels in T1D. In this analysis, we used clinical data, namely age, BMI and HbA1c, as well as glycaemic metrics (24-h glycaemia, postprandial, nocturnal, early-morning glycaemia, wake-up glucose, and glycaemic variability) obtained over a four-week period of continuous glucose monitoring (CGM) wear in thirty-two males with T1D.The trapezoid method was used estimate the incremental area under the glucose curve (iAUC) for 24-h, postprandial (3-h period following breakfast, lunch, and dinner, respectively), nocturnal (between 24:00-04:00 AM), and early-morning (2-h period 2-h prior to wake-up) glycaemia. Linear regression analysis was employed whereby CGM-derived glycaemic metrics were explanatory variables and HbA1c was the outcome.Thirty-two T1D males (mean ± SD: age 29 ± 4 years; HbA1c 7.3 ± 0.9% [56 ± 13 mmol/mol]; BMI 25.80 ± 5.01 kg/m2) were included in this analysis. In linear models adjusted for age and BMI, HbA1c was associated with 24-h mean glucose (r2 = 0.735, p < 0.001), SD (r2 = 0.643, p = 0.039), and dinner iAUC (r2 = 0.711, p = 0.001). CGM-derived metrics and non-glycaemic factors explained 77% of the variance in HbA1c, in which postprandial glucose accounted for 32% of the variance explained. The single greatest contributor to HbA1c was dinner iAUC resulting in 0.6%-point (~7 mmol/mol) increase in HbA1c per SD increase in dinner iAUC.Using comprehensive CGM profiling, we show that postprandial glucose, specifically evening-time postprandial glucose, is the single largest contributing factor to HbA1c in T1D.NCT02204839 (July 30th 2014); NCT02595658 (November 3rd 2015).
A 25 year old Asian woman with a 11 year history of juvenile idiopathic arthritis (polyarthritis, rheumatoid factor positive) was referred from a peripheral hospital with poor disease control despite multiple disease modifying anti-rheumatic drugs (DMARDS). She was not a cigarette smoker and had been taking azathioprine 125 mg daily and prednisolone 5 mg daily for the past 10 months. Her past medical history included pulmonary tuberculosis diagnosed 14 months ago for which she had completed six months of antituberculous treatment. Details of her previous respiratory management including radiographs were not available. Physical examination revealed generalised synovitis with normal respiratory findings. She was treated with intra-articular corticosteroid injections into multiple joints and sulfasalazine was added to her above medications. Sulfasalazine was increased to a dose of 2 g daily over a four week period.
One month later, she re-presented with about two weeks history of dry cough and dyspnoea. Physical examination revealed that she was apyrexial with normal respiratory findings and persistent synovitis. Based on her chest radiograph (fig 1A) showing patchy consolidation in the right lung, more prominently in the right mid and upper zones, and left lower zone, the presumed diagnosis was pneumonia, possibly with an atypical microorganism and she was treated with a course of ampicillin and erythromycin while investigations were performed. The main differential diagnosis was the recurrence of pulmonary tuberculosis. Laboratory investigations were largely unchanged from the previous month, with a normochromic …
Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM.56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions.Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083).Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM. Trial registration EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB.
The objective was to determine the effect of rumen boluses containing 6800 mg iodine, 1000 mg selenium and 1000 mg cobalt given to dry dairy cows on the efficiency of colostral immunoglobulin G (IgG) absorption in calves. Thirteen cows received the bolus approximately 58 days before calving. A further 12 cows received no bolus and were used as controls. The cows were housed as one group. Calves were prevented from suckling for the first 24 h of life, and were given three feeds of a fixed quantity of colostrum. At 24 h, the average plasma concentrations of IgG in the calves were 15.5 and 13.4 g/L for the control and bolus groups, respectively; these were not significantly different (P = 0.212). Bolus treatment was associated with higher levels of free and total tri-iodothyronine (T3) and thyroxine (T4) in the dams (all P < 0.001), although it had no effect on thyroid hormone levels in the calves. There were nevertheless positive and negative relationships between the efficiency with which colostral IgG was absorbed at 24 h and, respectively, total T3 at 24 h (P < 0.05) and total T4 at 1 h of age (P < 0.05). The underlying basis for these relationships remains to be established.
We hypothesised that the detrimental effect of high glucose variability (GV) in people with type 1 diabetes is mainly evident in those with concomitant insulin resistance.We conducted secondary analyses on continuous glucose monitoring (CGM) using baseline observational data from three randomised controlled trials and assessed the relationship with established vascular markers. We used standard CGM summary statistics and principal component analysis to generate individual glucose variability signatures for each participant. Cluster analysis was then employed to establish three GV clusters (low, intermediate, or high GV, respectively). The relationship with thrombotic biomarkers was then investigated according to insulin resistance, assessed as estimated glucose disposal rate (eGDR).Of 107 patients, 45%, 37%, and 18% of patients were assigned into low, intermediate, and high GV clusters, respectively. Thrombosis biomarkers (including fibrinogen, plasminogen activator inhibitor-1, tissue factor activity, and tumour necrosis factor-alpha) increased in a stepwise fashion across all three GV clusters; this increase in thrombosis markers was evident in the presence of low but not high eGDR and at a threshold of eGDR <5.1 mg/kg/min.Higher GV is associated with increased thrombotic biomarkers in type 1 diabetes but only in those with concomitant insulin resistance.
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