Progressive Acceleration of Insulin Exposure Over 7 Days of Infusion Set Wear

Insulin exposure varies over 3 days of insulin infusion set (IIS) wear making day-to-day insulin dosing challenging for people with diabetes (PWD). Here we report insulin pharmacodynamic (PD) and pharmacokinetic (PK) data extending these observations to 7 days of IIS wear. PWD (A1C ≤8.5%, C-peptide tmax (P \u3c 0.001), Cmax (P \u3c 0.05), and mean residence time (P \u3c 0.0001). Area under the insulin concentration curve (AUC0–300) declined by ∼24% from days 0 to 7 (P \u3c 0.05). These results confirm/extend previous observations showing progressive acceleration of insulin exposure over IIS wear time. This may have implications for PWD and designers of closed-loop algorithms, although larger studies are necessary to confirm this. The study was registered in clinicaltrials.gov (NCT04398030)

Exploring the landscape of the National Forest : a walkers' guide to the landscape and natural environment of the National Forest

The National Forest offers a variety of landscape types, from extensive gently undulating clay lowlands dominated by mixed farming, to the hilly sandstone1 region in the central part. The coalfields, in Leicestershire and South Derbyshire, most notably demonstrate the great impact of man’s influence on the landscape. In the east Charnwood Forest, with its rolling hills and craggy knolls, presents us with a unique landscape that has been moulded over 600 million years. The rocks here date back to the Precambrian and contain some of the oldest known fossils. This book and map will help you to explore the region: its geology, landscape, biodiversity, archaeology and industrial and cultural heritage through a series of walks. You will have a fascinating glimpse of past variations in climate that show how England has moved around on the surface of the Earth by plate tectonics.There is evidence of a turbulent geological history that has included volcanoes, mountains, major earthquakes, rainforests, rivers, lakes, seas, deserts and glaciers. The book will also demonstrate how the geology of The National Forest has had a profound influence on the economy of the area, dating back over the centuries, with many industries largely dependent on the natural resources. Some are now no longer viable, such as coal mining, iron ore and lime, but others such as aggregate extraction, gypsum and brick clays, are still very prosperous. The effect of these industries has been to significantly change the landscape in many areas, most notably in the coalfields, but also the extensive aggregate extraction in Charnwood Forest

Effects of Dapagliflozin on 24-Hour Glycemic Control in Patients with Type 2 Diabetes: A Randomized Controlled Trial.

BackgroundGlycated hemoglobin (HbA1c) and measures of short-term glycemia do not fully capture daily patterns in plasma glucose dynamics. This study evaluated 24-h glycemic profiles in patients with type 2 diabetes (T2D) initiated on dapagliflozin treatment using continuous glucose monitoring (CGM).MethodsThis randomized double-blind placebo-controlled multicenter parallel-design 4-week study compared dapagliflozin (10 mg/d; n = 50) with placebo (n = 50) in adult patients with T2D uncontrolled (HbA1c 7.5%-10.5%) on either stable doses of metformin monotherapy (≥1500 mg/d) or insulin (≥30 U/d with or without up to two oral antidiabetes drugs). CGM was used to measure 24-h glycemic profiles for 7 days pretreatment and during week 4 of treatment. The primary outcome was change from baseline in 24-h mean glucose (MG) at week 4.ResultsThe 24-h MG decreased 18.2 mg/dL with dapagliflozin and increased 5.8 mg/dL with placebo (P < 0.001). The proportion of time spent in the target glucose range (70-180 mg/dL) increased significantly with dapagliflozin versus placebo (69.6% vs. 52.9%; P < 0.001), with a small (0.3%) increase in time spent in the hypoglycemic range (<70 mg/dL), driven by those on background insulin therapy. Dapagliflozin reduced postprandial glucose and significantly decreased overall glucose variability. Few events of symptomatic hypoglycemia occurred. The most common adverse event was urinary tract infection (6% in each treatment arm).ConclusionsCompared with placebo, dapagliflozin improved measures of glycemic control and variability as assessed by CGM. Glycemic improvements were more pronounced in the group on background metformin than those receiving basal insulin