Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

Glucagon is secreted from pancreatic a cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in b cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion

Underpressure in the northern Barents shelf: Causes and implications for hydrocarbon exploration

The underexplored Barents shelf petroleum province is a globally unique example where naturally occurring underpressure is observed offshore and onshore. In the offshore parts of the northern Barents shelf, minor underpressure (up to 23 bar below hydrostatic pressure) is observed in the fault-bounded Mesozoic reservoirs of the Fingerdjupet subbasin. More severe (50 bar below hydrostatic pressure although irregular, occurrences of underpressure are encountered in the Triassic intervals of the neighboring Greater Hoop area. The abnormal pressures extend to the onshore archipelago of Svalbard, where pressures exceeding 60 bar below hydrostatic were encountered during drilling for a CO2 sequestration project. In Svalbard, reservoir pressures were constantly monitored over 3 yr, providing an insight into the reservoir behavior at unique time scales. The low-permeability (<2 md) reservoir in Svalbard is exposed some 15 km to the north of the drill site. Quantitative analysis with the apparent lack of a regional lateral seal suggests a geologically recent origin of underpressure. Evidence that the underpressure extends into the top seal provides further indication to the likely cause of underpressure. Similar to many global occurrences of underpressure in petroleum provinces, the Barents shelf has undergone severe uplift, most recently caused by deglaciation. Well data, outcrop observations, and isotope data combined with the area’s geological history indicate that glacial loading, unloading, and erosion, potentially with the aid of natural fractures, is the likely dominant underpressure-generating mechanism

Micro- and macrovascular complications and risk factors for foot ulceration and amputation in individuals receiving dialysis with and without diabetes

INTRODUCTION: This study examined the prevalence of microvascular and macrovascular complications in people receiving dialysis with and without diabetes and investigated independent risk factors for foot ulcers and lower‐extremity amputations. METHODS: We performed a cross‐sectional study of 119 individuals with diabetes and 219 individuals without diabetes receiving chronic dialysis during June 2019 at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Effects of diabetes and other risk factors were assessed by log‐binomial regression. Prevalence data were compared with a historical control group of 38 individuals with diabetes receiving dialysis examined in 2004 in the same department. RESULTS: We found that persons with diabetes had a twofold higher risk ratio of current (unadjusted risk ratio 2.2 [95% CI 1.1, 4.7]) and previous foot ulcer (2.5 [1.7, 3.7]) and a fourfold higher risk ratio of lower‐extremity amputation (4.2 [2.1, 8.6]) in comparison with persons without diabetes (all p < .05). Furthermore, persons with diabetes had a 70% increased risk ratio of myocardial infarction (1.7 [1.0–2.8], p = .041). In multivariable‐adjusted analysis, current foot ulcer was independently associated with previous foot ulcer (adjusted risk ratio 4.0 [95% CI 1.8, 8.9]), while lower‐extremity amputation was independently associated with diabetes (3.8 [1.8, 8.2]) and male sex (4.1 [1.5, 11.3]) (all p < .01). CONCLUSIONS: Individuals with diabetes receiving dialysis had a higher prevalence of foot ulcer, lower‐extremity amputation and myocardial infarction compared to individuals without diabetes. Previous foot ulcer was the most important risk factor for current foot ulcer, while diabetes and male sex were important risk factors for lower‐extremity amputation

Non-adherence, medication beliefs and symptom burden among patients receiving hemodialysis -a cross-sectional study

Abstract Background Non-adherence to medication is a common and complex issue faced by individuals undergoing hemodialysis (HD). However, more knowledge is needed about modifiable factors influence on non-adherence. This study investigated the prevalence of non-adherence, medication beliefs and symptom burden and severity among patients receiving HD in Denmark. Associations between non-adherence, medications beliefs and symptom burden and severity were also explored. Method A cross-sectional questionnaire-based multisite study, including 385 participants. We involved patient research consultants in the study design process and the following instruments were included: Medication Adherence Report Scale, Beliefs about Medication Questionnaire and Dialysis Symptom Index. Logistic regression analysis was performed. Results The prevalence of non-adherence was 32% (95% CI 27–37%) using a 23-point-cut-off. Just over one third reported being concerned about medication One third also believed physicians to overprescribe medication, which was associated with 18% increased odds of non-adherence. Symptom burden and severity were high, with the most common symptoms being tiredness/ lack of energy, itching, dry mouth, trouble sleeping and difficulties concentrating. A high symptom burden and/or symptom severity score was associated with an increased odd of non-adherence. Conclusion The study found significant associations between non-adherence and, beliefs about overuse, symptom burden and symptom severity. Our results suggest health care professionals (HCP) should prioritize discussion about medication adherence with patients with focus on addressing patient-HCP relationship, and patients’ symptom experience. Future research is recommended to explore the effects of systematically using validated adherence measures in clinical practice on medication adherence, patient-HCP communication and trust. Additionally, studies are warranted to further investigate the relationship between symptom experience and adherence in this population. Trial registration NCT03897231