Ghrelin and Insulin Secretion in Humans: Not a Tale of Two Hormones?

Failure of pancreatic β-cells to secrete adequate amounts of insulin is a fundamental defect in type 1 and type 2 diabetes, and the search for innovative strategies to improve β-cell mass and function is a major priority in diabetes research. Ghrelin, a 28-amino acid peptide hormone predominantly secreted by the stomach, was identified as ligand of the growth hormone secretagogue receptor type-1a (GHSR-1a) (1). The Ser3-octanoylated ghrelin form (acylated ghrelin [AG]) also was soon recognized to act as a hypothalamic orexigenic signal (2) and to modulate tissue pathways and functions as a potential contributor to metabolic adaptation to low nutrient availability. Experimental AG administration commonly causes weight gain and hyperglycemia by enhancing food intake, fat deposition, and hepatic gluconeogenesis (3–5). A more comprehensive understanding of the metabolic impact of ghrelin has been recently allowed by the increasing appreciation of the independent, and generally more favorable, effects of its unacylated form (UAG), which does not increase food intake or circulating glucose in vivo (3,4,6). Although no specific UAG receptor has been yet identified, UAG coadministration may counteract the glucogenic effects of AG as well as AG-induced hyperglycemia (3,4,7), and positive or negative associations have been respectively reported in humans between AG or UAG and markers of whole-body insulin resistance (8). Modulating the AG–UAG balance by inhibiting the acylating enzyme ghrelin O-acyltransferase (9) or by

A Clinically Relevant Diagnosis Code for “Malnutrition in Adults” Is Needed in ICD-11

Introduction: Loss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases) and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of a universally established SO definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes. Aims and Methods: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into stage I in the absence of clinical complications or stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction. Conclusions: ESPEN and EASO, as well as the expert international panel, advocate that the proposed SO definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing data sets, to study the predictive value, treatment efficacy and clinical impact of this SO definition

Defining and diagnosing sarcopenia: Is the glass now half full?

Low muscle mass and function exert a substantial negative impact on quality of life, health and ultimately survival, but their definition, identification and combination to define sarcopenia have suffered from lack of universal consensus. Methodological issues have also contributed to incomplete agreement, as different approaches, techniques and potential surrogate measures inevitably lead to partly different conclusions. As a consequence: 1) awareness of sarcopenia and implementation of diagnostic procedures in clinical practice have been limited; 2) patient identification and evaluation of therapeutic strategies is largely incomplete. Significant progress has however recently occurred after major diagnostic algorithms have been developed, with common features and promising perspectives for growing consensus. At the same time, the need for further refinement of the sarcopenia concept has emerged, to address its increasingly recognized clinical heterogeneity. This includes potential differential underlying mechanisms and clinical features for age- and disease-driven sarcopenia, and the emerging challenge of sarcopenia in persons with obesity. Here, we will review existing algorithms to diagnose sarcopenia, and major open methodological issues to assess skeletal muscle mass and function under different clinical conditions, in order to highlight similarities and differences. Potential for consensus on sarcopenia diagnosis as well as emerging new challenges will be discussed

High-Fat Diet with Acyl-Ghrelin Treatment Leads to Weight Gain with Low Inflammation, High Oxidative Capacity and Normal Triglycerides in Rat Muscle

Obesity is associated with muscle lipid accumulation. Experimental models suggest that inflammatory cytokines, low mitochondrial oxidative capacity and paradoxically high insulin signaling activation favor this alteration. The gastric orexigenic hormone acylated ghrelin (A-Ghr) has antiinflammatory effects in vitro and it lowers muscle triglycerides while modulating mitochondrial oxidative capacity in lean rodents. We tested the hypothesis that A-Ghr treatment in high-fat feeding results in a model of weight gain characterized by low muscle inflammation and triglycerides with high muscle mitochondrial oxidative capacity. A-Ghr at a non-orexigenic dose (HFG: twice-daily 200-µg s.c.) or saline (HF) were administered for 4 days to rats fed a high-fat diet for one month. Compared to lean control (C) HF had higher body weight and plasma free fatty acids (FFA), and HFG partially prevented FFA elevation (P<0.05). HFG also had the lowest muscle inflammation (nuclear NFkB, tissue TNF-alpha) with mitochondrial enzyme activities higher than C (P<0.05 vs C, P = NS vs HF). Under these conditions HFG prevented the HF-associated muscle triglyceride accumulation (P<0.05). The above effects were independent of changes in redox state (total-oxidized glutathione, glutathione peroxidase activity) and were not associated with changes in phosphorylation of AKT and selected AKT targets. Ghrelin administration following high-fat feeding results in a novel model of weight gain with low inflammation, high mitochondrial enzyme activities and normalized triglycerides in skeletal muscle. These effects are independent of changes in tissue redox state and insulin signaling, and they suggest a potential positive metabolic impact of ghrelin in fat-induced obesity

evidence for acute stimulation of fibrinogen production by glucagon in humans

Fibrinogen, an acute-phase protein, and glucagon, a stress hormone, are often elevated in many conditions of physical and metabolic stress, including uncontrolled diabetes. However, the possible mechanisms for this association are poorly known. We have studied the acute effects of selective hyperglucagonemia (raised from ∼200 to ∼350 pg/ml for 3 h) on fibrinogen fractional secretion rate (FSR) in eight normal subjects during infusion of somatostatin and replacement doses of insulin, glucagon, and growth hormone. Fibrinogen FSR was evaluated by precursor-product relationships using either Phe ( n = 8) or Leu ( n = 2) tracers. Hyperglucagonemia did not change either plasma Phe or Tyr specific activity. After hyperglucagonemia, fibrinogen FSR increased by ∼65% (from 12.9 ± 3.6 to 21.5 ± 6.1% per day, P < 0.025) using plasma Phe specific activity as the precursor pool. FSR increased by ∼80% (from 16.6 ± 4.8 to 29.4 ± 8.8% per day, P < 0.025) if plasma Phe specific activity was corrected for the ketoisocaproate/Leu enrichment (or specific activity) ratio to obtain an approximate estimate of intrahepatic Phe specific activity. FSR increased by ∼60% when using plasma Tyr specific activity as precursor pool ( n = 8) ( P < 0.05), as well as when using the Leu tracer precursorproduct relationship ( n = 2). In conclusion, selective hyperglucagonemia for ∼3 h acutely stimulated fibrinogen FSR using a Phe tracer method. Thus, glucagon may be involved in the increase of fibrinogen concentration and FSR observed under stressed or pathologic conditions

Tuberculosis and malnutrition: The European perspective

Tuberculosis (TB) is a leading infectious cause of death worldwide, despite ongoing efforts to limit its incidence and mortality. Although the European Region has made gains in TB incidence and mortality, it now contends with increasing numbers of multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). Malnutrition is a major contributor to the burden of TB and may also be directly caused or enhanced by the onset of TB. The presence of malnutrition may worsen TB and MDR/RR-TB related treatment outcomes and contribute to growing TB drug-resistance. Preventing and treating all forms of malnutrition is an important tool to limit the spread of TB worldwide and improve TB outcomes and treatment efficacy. We carried out a scoping review of the existing evidence that addresses malnutrition in the context of TB. Our review found malnutrition increased the risk of developing TB in high-burden settings and increased the likelihood of developing unfavorable treatment outcomes, including treatment failure, loss to follow-up, and death. The potential impact of nutritional care and improved nutritional status on patient prognosis was more difficult to evaluate due to heterogeneity of patient populations, treatment protocols, and treatment durations and goals. High-quality trials that consider malnutrition as a major risk factor and relevant treatment target when designing effective strategies to limit TB spread and mortality are needed to inform evidence-based practice. In TB patients, we suggest that widespread and regular nutritional screening, assessment, and counselling, has the potential to increase effectiveness of TB management strategies and improve patient quality of life, overall outcomes, and survival

Multidimensional prognostic index predicts short- and long-term mortality and rehospitalizations in older patients with hip fracture

Background: Multidimensional Prognostic Index (MPI), calculated on cognitive, functional, nutritional, social, pharmacological and comorbidity domains, strongly correlates with mortality in older patients. Hip fractures are a major health problem and are associated with adverse outcomes in those affected by frailty. Aim: We aimed at evaluating whether MPI is a predictor of mortality and rehospitalization in hip fracture older patients. Methods: We investigated the associations of MPI with all-cause 3- and 6-month mortality and rehospitalization in 1259 older patients admitted for hip fracture surgical treatment and managed by an orthogeriatric team [age 85 years (65–109); male gender: 22%]. Results: Overall mortality was 11,4%, 17% and 23,5% at 3, 6 and 12 months from surgery (rehospitalizations: 15, 24,5 and 35,7%). MPI was associated (p < 0.001) with 3-, 6- and 12- month mortality and readmissions; Kaplan–Meier estimate for rehospitalization and survival according to MPI risk classes confirmed these results. In multiple regression analyses these associations were independent (p < 0.05) of mortality and rehospitalization-associated factors not included in the MPI, such as gender, age and post-surgical complications. Similar MPI predictive value was observed in patients undergoing endoprosthesis or other surgeries. ROC analysis confirmed that MPI was a predictor (p < 0.001) of both 3- and 6- month mortality and rehospitalization. Conclusions: In hip fracture older patients, MPI is a strong predictor of 3-, 6- and 12- months mortality and rehospitalization, independently of surgical treatment and post-surgical complications. Therefore, MPI should be considered a valid pre-surgical tool to identify patients with higher clinical risk of adverse outcomes

Response to “Lean body mass should not be used as a surrogate measurement of muscle mass in malnourished men and women: Comment on Compher et al”

N/

Brief interventions to prevent NCDs and their nutritional complications in primary care setting

N/

Pédiatrie [News in paediatrics]

Every pediatrician will be confronted with newborns oryoung infants with skin lesions in proximity of the vertebral column. It is important not to miss a spinal dysraphism because of the risk of meningeal infection or of the possible presence of a tethered cord. A practical algorithm is presented. Non-accidental injury in young infants and toddlers is not rare but difficult to detect. Bruises and fractures are highly suspicious for non-accidental injury and should trigger specific investigations. Emergency departments and hospitals are switching from hypotonic to isotonic solutions as maintenance infusions of children. They reduce the risk of hyponatremia without increasing that of hypernatremia, and they should be used preferentially in the majority of pediatric clinical settings