The association between baseline persistent pain and weight change in patients attending a specialist weight management service

To quantify the influence of baseline pain levels on weight change at one-year follow-up in patients attending a National Health Service specialist weight management programme.We compared one-year follow-up weight (body mass) change between patient sub-groups of none-to-mild, moderate, and severe pain at baseline. A mean sub-group difference in weight change of ≥5kg was considered clinically relevant.Of the 141 complete cases, n = 43 (30.5%) reported none-to-mild pain, n = 44 (31.2%) reported moderate pain, and n = 54 (38.3%) reported severe pain. Covariate-adjusted mean weight loss (95%CI) was similar for those with none-to-mild (8.1kg (4.2 to 12.0kg)) and moderate pain (8.3kg (4.9 to 11.7kg). The mean weight loss of 3.0kg (-0.4 to 6.4kg) for the severe pain group was 5.1kg (-0.6 to 10.7, p = 0.08) lower than the none-to-mild pain group and 5.3kg (0.4 to 10.2kg, p = 0.03) lower than the moderate pain group.Patients with severe pain upon entry to a specialist weight management service in England achieve a smaller mean weight loss at one-year follow-up than those with none-to-moderate pain. The magnitude of the difference in mean weight loss was clinically relevant, highlighting the importance of addressing severe persistent pain in obese patients undertaking weight management programmes

Exercise management in type 1 diabetes:a consensus statement

Type 1 diabetes is a challenging condition to manage for various physiological and behavioural reasons. Regular exercise is important, but management of different forms of physical activity is particularly difficult for both the individual with type 1 diabetes and the health-care provider. People with type 1 diabetes tend to be at least as inactive as the general population, with a large percentage of individuals not maintaining a healthy body mass nor achieving the minimum amount of moderate to vigorous aerobic activity per week. Regular exercise can improve health and wellbeing, and can help individuals to achieve their target lipid profile, body composition, and fitness and glycaemic goals. However, several additional barriers to exercise can exist for a person with diabetes, including fear of hypoglycaemia, loss of glycaemic control, and inadequate knowledge around exercise management. This Review provides an up-to-date consensus on exercise management for individuals with type 1 diabetes who exercise regularly, including glucose targets for safe and effective exercise, and nutritional and insulin dose adjustments to protect against exercise-related glucose excursions

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Postharvest Fruit Detachment in Oil Palm Bunches with Ethephon and Ethylene Gas Application

The processing of oil palm fresh fruit bunches (FFB), together with loose fruits, in the current mill operation contributes to oil loss and high free fatty acids (FFA), affecting crude palm oil quality. Fruit detachment induced by ethephon and ethylene may mitigate the current processing issues. This study shows that a 0.50% (v/v) ethephon application by the evaporation method induced the highest fruit detachment of 30.8 ± 1.1% after 24 h at room temperature, with the FFA content in the extracted crude palm oil at 0.34 ± 0.09%. Ethephon application was effective on bunches between 14 and 28 kg, and fruit detachment was higher in ripe and underripe bunches at 24.1 ± 0.9% and 23.2 ± 0.1%, respectively. A significant fruit detachment of 47.2 ± 2.4% was achieved when the bunches were also stripped mechanically, but the FFA content increased almost 4-fold, from 1.0 ± 0.2% to 3.8 ± 1.2%. The application of ethylene gas at 750 ppm yielded 29.4 ± 1.9% fruit detachment. The findings present the possibility of using ethylene as an indirect method for minimizing oil loss without increasing the FFA content in future crude palm oil production systems

Modified release terbutaline (SKP1052) for hypoglycaemia prevention: a proof-of-concept study in people with type 1 diabetes mellitus

Aims: In this randomized, single blind, cross-over study 2.5mg and 5mg of the modified-release terbutaline formulation (SKP-1052) were compared with conventional immediate-release terbutaline (IRT, 5mg) and placebo on overnight blood glucose (BG) and hypoglycaemia in 30 subjects with type 1 diabetes mellitus. Methods: Subjects received subcutaneous injections of insulin glargine (individualized doses) before dinner. SKP-1052, IRT or placebo was administered around 21:00 hours. BG and terbutaline concentrations were monitored overnight for 10 h post-dosing. Endpoints comprised of the nadir BG (BGn 0–10 h, primary endpoint), mean overnight BG (BGmean), morning BG (BGmorning) and hypoglycaemia rates as well as pharmacokinetic (PK) endpoints. Results: SKP-1052 delayed release of terbutaline by 2 h [PK-tmax (mean±SD) 5.0±2.1 h (2.5 mg) and 4.7±1.7 h (5 mg) vs. 2.6±1.3 h with IRT, p<0.01, respectively]. Compared with placebo, no significant differences were observed for BGn 0–10 h across treatments, but both 5 mg formulations showed less hypoglycaemic events [10 (IRT), 16 (SKP-1052) vs. 33], higher BGmean (120, 114 and 95mg/dl) and BGmorning (126, 126 and 101 mg/dl, all comparisons p<0.05 vs. placebo). Numerically higher BG-levels between 3 and 8 h post-dosing were observed with 2.5mg SKP-1052 vs. placebo. Conclusions: Compared with IRT SKP-1052 delays release of terbutaline. 2.5mg SKP-1052 led to numerically higher BG 3 to 8 h post-dose without fasting hyperglycaemia while 5 mg SKP-1052 resulted in fasting hyperglycaemia vs. placebo. Future studies will investigate optimized doses of SKP-1052 for nocturnal hypoglycaemia prevention

One-year weight loss separated by pain classification group.

<p>One-year weight loss separated by pain classification group.</p