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- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 3. |
- Alam, M, et al.
(författare)
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Gastric bypass surgery, but not caloric restriction, decreases dipeptidyl peptidase 4 activity in obese patients with type 2 diabetes.
- 2011
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 13:4, s. 378-381
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism by which incretins and their effect on insulin secretion increase markedly following gastric bypass surgery (GBP) is not fully elucidated. We hypothesized that a decrease in the activity of dipeptidyl peptidase-4 (DPP-4), the enzyme which inactivates incretins, may explain the rise in incretin levels post-GBP. Fasting plasma DPP-4 activity was measured after 10 kg equivalent weight loss by GBP (n=16) or by caloric restriction (CR, n=14) in obese patients with type 2 diabetes. DPP-4 activity decreased after GBP by 11.6% (p=0.01), but not after CR. The increased peak GLP-1 and GIP response to oral glucose after GBP did not correlate with DPP-4 activity. The decrease in fasting plasma DPP-4 activity after GBP occurred by a mechanism independent of weight loss and did not relate to change in incretins concentrations. Whether the change in DPP-4 activity contributes to improved diabetes control after GBP remains therefore to be determined.
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- Cederholm, Tommy, et al.
(författare)
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Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition : A modified Delphi approach
- 2023
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Ingår i: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 43:5, s. 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND : The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. METHODS : A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. RESULTS : The final round of review was highly favorable, with 99% overall "agree" or "strongly agree" responses. Thepresence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. CONCLUSION : Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.
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| 5. |
- Jensen, Gordon L., et al.
(författare)
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Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition : A modified Delphi approach
- 2024
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Ingår i: JPEN - Journal of Parenteral and Enteral Nutrition. - : John Wiley & Sons. - 0148-6071 .- 1941-2444. ; 48:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation.MethodsA GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements.ResultsThe final round of review was highly favorable, with 99% overall “agree” or “strongly agree” responses. The presence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used.ConclusionConfirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.
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| 6. |
- Kim, N. R., et al.
(författare)
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Testosterone Reduces Body Fat in Male Mice by Stimulation of Physical Activity Via Extrahypothalamic ER alpha Signaling
- 2021
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 162:6
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Tidskriftsartikel (refereegranskat)abstract
- Testosterone (T) reduces male fat mass, but the underlying mechanisms remain elusive, limiting its clinical relevance in hypogonadism-associated obesity. Here, we subjected chemically castrated high-fat diet-induced adult obese male mice to supplementation with T or the nonaromatizable androgen dihydrotestosterone (DHT) for 20 weeks. Both hormones increased lean mass, thereby indirectly increasing oxygen consumption and energy expenditure. In addition,T but not DHT decreased fat mass and increased ambulatory activity, indicating a role for aromatization into estrogens. Investigation of the pattern of aromatase expression in various murine tissues revealed the absence of Cyp99a1 expression in adipose tissue while high levels were observed in brain and gonads. In obese hypogonadal male mice with extrahypothalamic neuronal estrogen receptor alpha deletion (N-ER alpha KO), T still increased lean mass but was unable to decrease fat mass. The stimulatory effect of T on ambulatory activity was also abolished in N-ER alpha KO males. In conclusion, our work demonstrates that the fat-burning action ofT is dependent on aromatization into estrogens and is at least partially mediated by the stimulation of physical activity via extrahypothalamic ER alpha signaling. In contrast, the increase in lean mass upon T supplementation is mediated through the androgen receptor and indirectly leads to an increase in energy expenditure, which might also contribute to the fat-burning effects of T.
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| 7. |
- Barker, A., et al.
(författare)
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Age-dependent decline of beta-cell function in type 1 diabetes after diagnosis: a multi-centre longitudinal study
- 2014
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Ingår i: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 16:3, s. 262-267
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Tidskriftsartikel (refereegranskat)abstract
- AimsC-peptide secretion is currently the only available clinical biomarker to measure residual -cell function in type 1 diabetes. However, the natural history of C-peptide decline after diagnosis can vary considerably dependent upon several variables. We investigated the shape of C-peptide decline over time from type 1 diabetes onset in relation to age at diagnosis, haemoglobin A1c (HbA1c) levels and insulin dose. MethodsWe analysed data from 3929 type 1 diabetes patients recruited from seven European centres representing all age groups at disease onset (childhood, adolescence and adulthood). The influence of the age at onset on -cell function was investigated in a longitudinal analysis at diagnosis and up to 5-years follow-up. ResultsFasting C-peptide (FCP) data at diagnosis were available in 3668 patients stratified according to age at diagnosis in four groups (less than5years, n=344; greater than5yearsless than10years, n=668; greater than10yearsless than18years, n=991; greater than18years, n=1655). FCP levels were positively correlated with age (pless than0.001); the subsequent decline in FCP over time was log-linear with a greater decline rate in younger age groups (pless than0.0001). ConclusionsThis study reveals a positive correlation between age at diagnosis of type 1 diabetes and FCP with a more rapid decline of -cell function in the very young patients. These data can inform the design of clinical trials using C-peptide values as an end-point for the effect of a given treatment.
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| 8. |
- Lauria, A., et al.
(författare)
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BMI is an important driver of beta-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children
- 2015
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Ingår i: European Journal of Endocrinology. - : BioScientifica. - 0804-4643 .- 1479-683X. ; 172:2, s. 107-113
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Body weight-related insulin resistance probably plays a role in progression to type 1 diabetes, but has an uncertain impact following diagnosis. In this study, we investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis. Design: Multicentre longitudinal study carried out at diagnosis and up to 1-year follow-up. Methods: Data on C-peptide were collected from seven diabetes centres in Europe. Patients were grouped according to age at diagnosis (less than5 years, n = 126; greater than5 years less than10 years, n = 295; greater than10 years less than18 years, n = 421; greater than18 years, n = 410). Linear regression was used to investigate whether BMI was an independent predictor of change in fasting C-peptide over 1 year. Models were additionally adjusted for baseline insulin dose and HbA1c. Results: In individuals diagnosed between 0 and 5 years, 5 and 10 years and those diagnosed greater than18 years, we found no association between BMI and C-peptide decline. In patients aged 10-18 years, higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1 year with a decrease (beta 95% CI; P value) of 0.025 (0.010, 0.041) nM/kg per m(2) higher baseline BMI (P = 0.001). This association remained significant after adjusting for gender and differences in HbA1c and insulin dose (beta = 0.026, 95% CI = 0.0097, 0.042; P = 0.002). Conclusions: These observations indicate that increased body weight and increased insulin demand are associated with more rapid disease progression after diagnosis of type 1 diabetes in an age group 10-18 years. This should be considered in studies of beta-cell function in type 1 diabetes.
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| 9. |
- Ligthart-Melis, Gerdien C., et al.
(författare)
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Frailty, Sarcopenia, and Malnutrition Frequently (Co-)occur in Hospitalized Older Adults : A Systematic Review and Meta-analysis
- 2020
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Ingår i: Journal of the American Medical Directors Association. - : ELSEVIER SCIENCE INC. - 1525-8610 .- 1538-9375. ; 21:9, s. 1216-1228
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The purpose of this systematic review and meta-analysis was to summarize the prevalence of, and association between, physical frailty or sarcopenia and malnutrition in older hospitalized adults.Design: A systematic literature search was performed in 10 databases.Setting and Participants: Articles were selected that evaluated physical frailty or sarcopenia and malnutrition according to predefined criteria and cutoffs in older hospitalized patients.Measures: Data were pooled in a meta-analysis to evaluate the prevalence of prefrailty and frailty [together (pre-)frailty], sarcopenia, and risk of malnutrition and malnutrition [together (risk of) malnutrition], and the association between either (pre-)frailty or sarcopenia and (risk of) malnutrition.Results: Forty-seven articles with 18,039 patients (55% female) were included in the systematic review, and 39 articles (8868 patients, 62% female) were eligible for the meta-analysis. Pooling 11 studies (2725 patients) revealed that 84% [95% confidence interval (CI): 77%, 91%, I-2 = 98.4%] of patients were physically (pre-)frail. Pooling 15 studies (4014 patients) revealed that 37% (95% CI: 26%, 48%, I-2 = 98.6%) of patients had sarcopenia. Pooling 28 studies (7256 patients) revealed a prevalence of 66% (95% CI: 58%, 73%, I-2 = 98.6%) (risk of) malnutrition. Pooling 10 studies (2427 patients) revealed a high association [odds ratio (OR): 5.77 (95% CI: 3.88, 8.58), P < .0001, I-2 = 42.3%] and considerable overlap (49.7%) between physical (pre-)frailty and (risk of) malnutrition. Pooling 7 studies (2506 patients) revealed a high association [OR: 4.06 (95% CI: 2.43, 6.80), P < .0001, I-2 = 71.4%] and considerable overlap (41.6%) between sarcopenia and (risk of) malnutrition.Conclusions and Implications: The association between and prevalence of (pre-)frailty or sarcopenia and (risk of) malnutrition in older hospitalized adults is substantial. About half of the hospitalized older adults suffer from 2 and perhaps 3 of these debilitating conditions. Therefore, standardized screening for these conditions at hospital admission is highly warranted to guide targeted nutritional and physical interventions.
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