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| 32. |
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| 33. |
- Honkanen, Jarno, et al.
(författare)
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Poor in vitro induction of FOXP3 and ICOS in type 1 cytokine environment activated T-cells from children with type 1 diabetes
- 2008
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 24:8, s. 635-641
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundType 1 diabetes (T1D) is characterised by loss of tolerance to beta-cell antigens, and the insulin-producing beta-cells in the pancreatic islets are destroyed by the host's own immune system. Immunological risk factors associated with T1D are related to the defects in the polarization of T-cells and in the function of regulatory T (Treg)-cells. We set out to study whether an impaired induction of regulatory mechanisms during the generation of T-cell responses upon stimulation is associated with T1D.MethodsNaive T-cells were isolated from 18 children with recent T1D (0–14days from diagnosis; mean age 9.3 years), 11 children who had had T1D for at least 1 year (mean age 10.6) and 14 non-diabetic children (mean age 8.1). CD45RA+ T-cells were stimulated with PHA for 72 h in type 1 cytokine [interleukin (IL)-12 and anti-IL-4] or type 2 cytokine (IL-4 and anti-IL-12) environment. T-cell polarization and regulation related markers were analysed by quantitative reverse transcription polymerase chain reaction (QRT-PCR) (Th1 promoting T-bet, Th2 promoting GATA-3 and regulation related FOXP3, ICOS and NFATc2).ResultsChildren with recently diagnosed T1D showed decreased induction of FOXP3, ICOS and NFATc2 in T-cells activated in type 1 cytokine milieu (p = 0.007, p = 0.001, and p = 0.02), whereas no differences between the diabetic and healthy children were seen in the up-regulation of activation markers, T-bet and GATA-3.ConclusionsThe poor induction of factors that mediate down-modulation of T-cell responses upon stimulation in type 1 cytokine environment may contribute to the development of autoreactive type 1 responses in T1D.
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| 34. |
- Jendle, Johan, 1963-, et al.
(författare)
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Efficacy and Safety of Dulaglutide in the Treatment of Type 2 Diabetes : A Comprehensive Review of the Dulaglutide Clinical Data Focusing on the AWARD Phase 3 Clinical Trial Program
- 2016
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley-Blackwell. - 1520-7552 .- 1520-7560. ; 32:8, s. 776-790
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Forskningsöversikt (refereegranskat)abstract
- Dulaglutide (DU) is a once weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved for the treatment of type 2 diabetes mellitus (T2DM). Glycaemic efficacy and safety characteristics of DU have been assessed in six Phase 3 studies in the AWARD program. The objective of this review article is to summarise these results from the 6 completed AWARD studies. At the primary endpoint, in 5 of the 6 studies, once weekly dulaglutide 1.5 mg was superior to the active comparator (exenatide, insulin glargine [two studies], metformin, and sitagliptin), with a greater proportion of patients reaching glycated haemoglobin A1c (HbA1c) targets of <7.0% (53.0 mmol/mol) and ≤6.5% (47.5 mmol/mol). Dulaglutide 1.5 mg was non-inferior to liraglutide in AWARD-6. Once weekly dulaglutide 0.75 mg was evaluated in 5 of these trials and demonstrated superiority to the active comparator in 4 of 5 AWARD studies (exenatide, glargine, metformin, and sitagliptin), and non-inferiority to glargine in the AWARD-2 study. Similar to other GLP-1 RAs, treatment with dulaglutide was associated with weight loss or attenuation of weight gain and low rates of hypoglycaemia when used alone or with non-insulin-secretagogue therapy. The most frequently reported adverse events were gastrointestinal, including nausea, diarrhoea, and vomiting. The incidence of dulaglutide antidrug antibody formation was 1%-2.8% with rare injection site reactions. In conclusion, dulaglutide is an effective treatment for T2DM and has an acceptable tolerability and safety profile.
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| 35. |
- Julin, Bettina, et al.
(författare)
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Association between sociodemographic determinants and health outcomes in individuals with type 2 diabetes in Sweden
- 2018
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 34:4, s. -9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Concurrent multifactorial treatment is needed to reduce consequent risks of diabetes, yet most studies investigating the relationship between sociodemographic factors and health outcomes have focused on only one risk factor at a time. Swedish health care is mainly tax-funded, thus providing an environment that should facilitate equal health outcomes in patients, independent of background, socioeconomic status or health profile. This study aimed at investigating the association between several sociodemographic factors and diabetes-related health outcomes represented by HbA1c , systolic blood pressure, LDL cholesterol, predicted 5-year risk of cardiovascular disease as well as statin use.METHODS: This large retrospective registry-study was based on patient-level data from individuals diagnosed with type 2 diabetes mellitus during 2010-2011 (n = 416,228) in any of seven Swedish regions (~65% of the Swedish population). Health equity in diabetes care was analyzed through multivariate regression analyses on intermediary outcomes (HbA1c , systolic blood pressure, LDL), predicted 5-year risk of cardiovascular disease and process (i.e. statin use) after one-year follow-up, adjusting for several sociodemographic factors.RESULTS: We observed differences in intermediary risk measures, predicted 5-year risk of cardiovascular disease as well as process dependent on place of birth, sex, age, education and social setting, despite Sweden's articulated vision of equal health care.CONCLUSIONS: Diabetes patients' health was associated with sociodemographic prerequisites. In addition to demographics (age, sex) and disease history; educational level, marital status and region of birth are important factors to consider when benchmarking health outcomes, e.g. average HbA1c level, between organizational units or between different administrative regions.
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| 36. |
- Karlsson Faresjö, Maria, 1971-, et al.
(författare)
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Diminished IFN-γ response to diabetes-associated autoantigens in children at diagnosis and during follow up of type 1 diabetes
- 2006
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 22:6, s. 462-470
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundImbalance of T-helper (Th)1- and Th2-like cytokines has been associated with type 1 diabetes. We therefore studied the immune deviation in antigen-specific T cells from diagnosis onwards in type 1 diabetic children.MethodsPeripheral blood mononuclear cells (PBMC) were collected from 15 children after 4 days, 3 months and 18 months of being diagnosed with type 1 diabetes, from 15 healthy children matched by age and gender to the type 1 diabetic children and from 14 children with and 35 children without HLA-risk genes. Secretion of interferon-γ (IFN-γ) and interleukin-4 (IL-4) was detected by ELISPOT after stimulation with glutamic acid decarboxylase (GAD65, protein and aa 247–279), recombinant tyrosinphosphatase (IA-2), insulin, ovalbumin and phytohaemagglutinin (PHA).ResultsSecretion of IFN-γ in PBMC stimulated with GAD65 (p < 0.05), the GAD65-peptide (p < 0.01), IA-2 (p < 0.01), and insulin (p < 0.01) was lower in diabetic children at diagnosis than in healthy children. Stimulation of PBMC with GAD65 and IA-2 decreased the secretion of IFN-γ in children with HLA-risk genotype. Spontaneous and antigen-induced IFN-γ secretion increased significantly after diagnosis of the disease, but did not exceed the levels observed in healthy children. Fasting C-peptide levels at diagnosis correlated with insulin-induced IFN-γ (R = 0.52; p = 0.05) and negatively with spontaneous IL-4 secretion (R = −0.62; p < 0.05).ConclusionA diminished IFN-γ secretion and the association of fasting C-peptide levels with cytokine response in children with type 1 diabetes suggest that factors related to β-cell function in type 1 diabetes may modify T-cell function. Thus, the T-cell responses detected at or after diagnosis may not reflect the pathogenic process leading to type 1 diabetes.
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| 37. |
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| 38. |
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| 39. |
- Lazzarini, P A, et al.
(författare)
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Effectiveness of offloading interventions for people with diabetes-related foot ulcers : A systematic review and meta-analysis
- 2023
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Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 40:3
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Offloading treatment is crucial to heal diabetes-related foot ulcers (DFU). This systematic review aimed to assess the effectiveness of offloading interventions for people with DFU.METHODS: We searched PubMed, EMBASE, Cochrane databases, and trials registries for all studies relating to offloading interventions in people with DFU to address 14 clinical question comparisons. Outcomes included ulcers healed, plantar pressure, weight-bearing activity, adherence, new lesions, falls, infections, amputations, quality of life, costs, cost-effectiveness, balance, and sustained healing. Included controlled studies were independently assessed for risk of bias and had key data extracted. Meta-analyses were performed when outcome data from studies could be pooled. Evidence statements were developed using the GRADE approach when outcome data existed.RESULTS: From 19,923 studies screened, 194 eligible studies were identified (47 controlled, 147 non-controlled), 35 meta-analyses performed, and 128 evidence statements developed. We found non-removable offloading devices likely increase ulcers healed compared to removable offloading devices (risk ratio [RR] 1.24, 95% CI 1.09-1.41; N = 14, n = 1083), and may increase adherence, cost-effectiveness and decrease infections, but may increase new lesions. Removable knee-high offloading devices may make little difference to ulcers healed compared to removable ankle-high offloading devices (RR 1.00, 0.86-1.16; N = 6, n = 439), but may decrease plantar pressure and adherence. Any offloading device may increase ulcers healed (RR 1.39, 0.89-2.18; N = 5, n = 235) and cost-effectiveness compared to therapeutic footwear and may decrease plantar pressure and infections. Digital flexor tenotomies with offloading devices likely increase ulcers healed (RR 2.43, 1.05-5.59; N = 1, n = 16) and sustained healing compared to devices alone, and may decrease plantar pressure and infections, but may increase new transfer lesions. Achilles tendon lengthening with offloading devices likely increase ulcers healed (RR 1.10, 0.97-1.27; N = 1, n = 64) and sustained healing compared to devices alone, but likely increase new heel ulcers.CONCLUSIONS: Non-removable offloading devices are likely superior to all other offloading interventions to heal most plantar DFU. Digital flexor tenotomies and Achilles tendon lengthening in combination with offloading devices are likely superior for some specific plantar DFU locations. Otherwise, any offloading device is probably superior to therapeutic footwear and other non-surgical offloading interventions to heal most plantar DFU. However, all these interventions have low-to-moderate certainty of evidence supporting their outcomes and more high-quality trials are needed to improve our certainty for the effectiveness of most offloading interventions.
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| 40. |
- Lazzarini, Peter A., et al.
(författare)
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Effectiveness of offloading interventions to heal foot ulcers in persons with diabetes : a systematic review
- 2020
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Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 36:Suppl. 1
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Offloading interventions are commonly used in clinical practice to heal foot ulcers. The aim of this updated systematic review is to investigate the effectiveness of offloading interventions to heal diabetic foot ulcers.METHODS: We updated our previous systematic review search of PubMed, EMBASE, and Cochrane databases to also include original studies published between July 29, 2014 and August 13, 2018 relating to four offloading intervention categories in populations with diabetic foot ulcers: (a) offloading devices, (b) footwear, (c) other offloading techniques, and (d) surgical offloading techniques. Outcomes included ulcer healing, plantar pressure, ambulatory activity, adherence, adverse events, patient-reported measures, and cost-effectiveness. Included controlled studies were assessed for methodological quality and had key data extracted into evidence and risk of bias tables. Included non-controlled studies were summarised on a narrative basis.RESULTS: We identified 41 studies from our updated search for a total of 165 included studies. Six included studies were meta-analyses, 26 randomised controlled trials (RCTs), 13 other controlled studies, and 120 non-controlled studies. Five meta-analyses and 12 RCTs provided high-quality evidence for non-removable knee-high offloading devices being more effective than removable offloading devices and therapeutic footwear for healing plantar forefoot and midfoot ulcers. Total contact casts (TCCs) and non-removable knee-high walkers were shown to be equally effective. Moderate-quality evidence exists for removable knee-high and ankle-high offloading devices being equally effective in healing, but knee-high devices have a larger effect on reducing plantar pressure and ambulatory activity. Low-quality evidence exists for the use of felted foam and surgical offloading to promote healing of plantar forefoot and midfoot ulcers. Very limited evidence exists for the efficacy of any offloading intervention for healing plantar heel ulcers, non-plantar ulcers, and neuropathic ulcers with infection or ischemia.CONCLUSION: Strong evidence supports the use of non-removable knee-high offloading devices (either TCC or non-removable walker) as the first-choice offloading intervention for healing plantar neuropathic forefoot and midfoot ulcers. Removable offloading devices, either knee-high or ankle-high, are preferred as second choice over other offloading interventions. The evidence bases to support any other offloading intervention is still weak and more high-quality controlled studies are needed in these areas.
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