| 21. |
- Edlund, Jenny, et al.
(författare)
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The roles of NADPH-oxidase and nNOS for the increased oxidative stress and the oxygen consumption in the diabetic kidney
- 2010
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 26:5, s. 349-356
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Tidskriftsartikel (refereegranskat)abstract
- Background Sustained hyperglycaemia induces increased renal oxygen consumption resulting in reduced oxygen availability in the diabetic kidney. We investigated the roles of the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and the neuronal nitric oxide synthase (nNOS) for the increased oxygen consumption in streptozotocin-diabetic rats.MethodsOxygen consumption was measured in isolated proximal tubular cells (PTC) from streptozotocin-induced diabetic rats (n = 7-9 per group) with and without chronic treatment with apocynin, a NADPH-oxidase inhibitor, or S-methyl-L-thiocitrulline (SMTC), a selective nNOS inhibitor, or a combination of the two and the results were compared to normoglycaemic controls (n = 10). Oxidative stress was estimated from thiobarbituric acid reactive substances and protein expression measured by Western blot.ResultsProximal tubular cells from untreated diabetic rats had increased oxygen consumption compared to controls (40.6 +/- 7.9 versus 10.9 +/- 2.0 nmol/mg protein/min). All treatments reduced the diabetes-induced increase in oxygen consumption (apocynin 10.5 +/- 1.7, SMTC 19.7 +/- 3.0 and apocynin +/- SMTC 21.6 +/- 3.6 nmol/mg protein/min). Neither apocynin nor SMTC had any effect on the oxygen consumption in cells pre-incubated with ouabain, an inhibitor of active electrolyte transport. Oxidative stress was elevated in the diabetic kidney and inhibited by all treatments. The increased oxygen consumption by diabetic proximal tubular cells correlated with increased protein expressions of p47phox and nNOS and the treatments prevented these increases.ConclusionsDiabetes induces oxidative stress, which increases oxygen consumption in proximal tubular cells. Inhibition of either NADPH-oxidase or nNOS prevented the increased oxygen consumption. The effect of blocking both these enzymes was less than additive suggesting overlapping pathways which warrant further studies.
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| 22. |
- Edstorp, Jessica, et al.
(författare)
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Does a prior diagnosis of infectious disease confer an increased risk of latent autoimmune diabetes in adults?
- 2024
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Ingår i: Diabetes/Metabolism Research and Reviews. - 1520-7552. ; 40:3, s. e3758-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Infections are proposed risk factors for type 1 diabetes in children. We examined whether a diagnosis of infectious disease also confers an increased risk of latent autoimmune diabetes in adults (LADA). Materials and methods: We used data from a population-based Swedish case-control study with incident cases of LADA (n = 597) and matched controls (n = 2386). The history of infectious disease was ascertained through national and regional patient registers. We estimated adjusted odds ratios (OR) with 95% confidence intervals for ≥1 respiratory (any/upper/lower), gastrointestinal, herpetic, other or any infectious disease episode, or separately, for 1 and ≥2 infectious disease episodes, within 0–1, 1–3, 3–5 and 5–10 years before LADA diagnosis/matching. Stratified analyses were performed on the basis of HLA risk genotypes and Glutamic acid decarboxylase antibodies (GADA) levels. Results: Individuals who developed LADA did not have a higher prevalence of infectious disease 1–10 years before diabetes diagnosis. For example, OR was estimated at 0.87 (0.66, 1.14) for any versus no respiratory infectious disease within 1–3 years. Similar results were seen for LADA with high-risk HLA genotypes (OR 0.95 [0.64, 1.42]) or high GADA levels (OR 1.10 [0.79, 1.55]), ≥2 episodes (OR 0.89 [0.56, 1.40]), and in infections treated using antibiotics (OR 1.03 [0.73, 1.45]). The only significant association was observed with lower respiratory disease the year preceding LADA diagnosis (OR 1.67 [1.06, 2.64]). Conclusions: Our findings do not support the idea that exposure to infections increases the risk of LADA. A higher prevalence of respiratory infection in the year before LADA diagnosis could reflect increased susceptibility to infections due to hyperglycemia.
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| 23. |
- Eltayeb-Elsheikh, Nezar, et al.
(författare)
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Association of HLA-DR-DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis
- 2020
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Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 36:8
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Type 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis.Methods: A total of 222 children with T1D and 342 controls were genotyped for HLA-DRB1, -DQA1, and -DQB1 using reverse sequence-specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package.Results: DRB1*03:01-DQA1*05:01-DQB1*02:01 (32.4%; OR = 3.68; P-c < .0001), DRB1*04:05-DQA1*03:02-DQB1*03:02 (6.6%; OR = 6.76; P-c < .0001), DRB1*04:02-DQA1*03:01-DQB1*03:02 (6.0%; OR = 3.10; P-c = .0194), DRB1*04:01-DQA1*03:01-DQB1*03:02 (3.7%; OR = 4.22; P-c = .0335), and DRB1*04:05-DQA1*03:02-DQB1*02:02 (2.7%; OR = 6.31; P-c = .0326) haplotypes were significantly increased in cases compared to controls, whereas DRB1*07:01-DQA1*02:01-DQB1*02:02 (OR = 0.41; P-c = .0001), DRB1*13:01-DQA1*01:03-DQB1*06:03 (OR = 0.05; P-c < .0001), DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.03; P-c < .0001), and DRB1*11:01-DQA1*05:05-DQB1*03:01 (OR = 0.07; P-c = .0291) were significantly decreased. Homozygous DRB1*03:01-DQA1*05:01-DQB1*02:01 genotypes and combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*04:05-DQA1*03:02-DQB1*03:02, DRB1*04:02-DQA1*03:01-DQB1*03:02, and DRB1*04:01-DQA1*03:01-DQB1*03:02 were significantly increased in cases than controls. Combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*07:01-DQA1*02:01-DQB1*02:02 and DRB1*13:02-DQA1*01:02-DQB1*06:04 showed low OR values but did not remain significantly decreased after Bonferroni correction.Conclusions: HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and diplotypes in Saudis with T1D are not markedly different from those observed in Western and Middle-Eastern populations but are quite different than those of East Asians.
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| 24. |
- Eneroth, Magnus, et al.
(författare)
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The value of debridement and Vacuum-Assisted Closure (V.A.C.) Therapy in diabetic foot ulcers.
- 2008
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Ingår i: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 24:S1, s. 76-80
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment of diabetic foot ulcers includes a number of different regimes such as glycaemic control, re-vascularization, surgical, local wound treatment, offloading and other non-surgical treatments. Although considered the standard of care, the scientific evidence behind the various debridements used is scarce. This presentation will focus on debridement and V.A.C. Therapy, two treatments widely used in patients with diabetes and foot ulcers. METHODS: A review of existing literature on these treatments in diabetic foot ulcers, with focus on description of the various types of debridements used, the principles behind negative pressure wound therapy (NPWT) using the V.A.C. Therapy system and level of evidence. RESULTS: Five randomized controlled trials (RCT) of debridement were identified; three assessed the effectiveness of a hydrogel as a debridement method, one evaluated surgical debridement and one evaluated larval therapy. Pooling the three hydrogel RCTs suggested that hydrogels are significantly more effective than gauze or standard care in healing diabetic foot ulcers. Surgical debridement and larval therapy showed no significant benefit. Other debridement methods such as enzyme preparations or polysaccharide beads have not been evaluated in RCTs of people with diabetes. More than 300 articles have been published on negative pressure wound therapy, including several small RCTs and a larger multi-centre RCT of diabetic foot ulcers. Negative pressure wound therapy seems to be a safe and effective treatment for complex diabetic foot wounds, and could lead to a higher proportion of healed wounds, faster healing rates, and potentially fewer re-amputations than standard care. CONCLUSIONS: Although debridement of the ulcer is considered a prerequisite for healing of diabetic foot ulcers, the grade of evidence is quite low. This may be due to a lack of studies rather than lack of effect. Negative pressure wound therapy seems to be safe and effective in the treatment of some diabetic foot ulcers, although there is still only one well-performed trial that evaluates the effect. Copyright (c) 2008 John Wiley & Sons, Ltd.
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| 25. |
- Fritz, T., et al.
(författare)
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Effects of Nordic walking on cardiovascular risk factors in overweight individuals with type 2 diabetes, impaired or normal glucose tolerance
- 2013
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 29:1, s. 25-32
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Tidskriftsartikel (refereegranskat)abstract
- Background Physical activity remains a valuable prevention for metabolic disease. The effects of Nordic walking on cardiovascular risk factors were determined in overweight individuals with normal or disturbed glucose regulation. Methods We included 213 individuals, aged 60 +/- 5.3 years and with body mass index (BMI) of 30.2 +/- 3.8 kg/m(2); of these, 128 had normal glucose tolerance (NGT), 35 had impaired glucose tolerance (IGT) and 50 had type 2 diabetes mellitus (T2DM). Participants were randomized to unaltered physical activity or to 5 h per week of Nordic walking with poles, for a 4-month period. Dietary habits were unaltered. BMI, waist circumference, blood pressure, glucose tolerance, clinical chemistry, maximal oxygen uptake (peak VO2) and self-reported physical activity (questionnaire) were assessed at the time of inclusion and after 4 months. The participants in the exercise-intervention group kept a walking diary. Results In the NGT exercise group, self-reported physical activity increased markedly, and body weight (-2.0 +/- 3.8 kg), BMI (-0.8 +/- 1.4 kg/m(2)) and waist circumference (- 4.9 +/- 4.4 cm) (mean +/- SD) decreased. Exercise power output (12.9 +/- 9.9 W) and peak VO2 (2.7 +/- 2.8 mL/kg/min) increased in the IGT exercise group. More cardiovascular risk factors were improved after exercise intervention in people with NGT compared with those with IGT or T2DM. Exercise capacity improved significantly in all three groups of participants who reported at least 80% compliance with the scheduled exercise. Conclusions Nordic walking improved anthropometric measurements and exercise capacity. However, unsupervised Nordic walking may not provide a sufficient increase in exercise intensity to achieve ultimate health-promoting benefits on the cardiovascular parameters assessed in this study, particularly for those with disturbed glucose regulation. Copyright (C) 2012 John Wiley & Sons, Ltd.
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| 26. |
- Fritz, Tomas, et al.
(författare)
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Low-intensity exercise increases skeletal muscle protein expression of PPARdelta and UCP3 in type 2 diabetic patients
- 2006
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 22:6, s. 492-498
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Physical exercise provides health benefits for people with type 2 diabetes mellitus, partly by enhancing skeletal muscle insulin action. We tested the hypothesis that changes in expression of key genes in skeletal muscles relate to exercise-induced improvements in type 2 diabetic patients. METHODS: We determined mRNA expression of 20 selected genes following a self-supervised program of walking (> 150 min per week) over a 4-month period. RESULTS: This level of physical activity improved clinical parameters in approximately half the participants, as determined by reduced hypertension and enhanced insulin sensitivity (defined by reduced plasma-insulin levels and improved homeostasis model assessment (HOMA)). Skeletal muscle mRNA expression of Cbl-associated protein (CAP), diacylglycerol kinase (DGK)delta, uncoupling protein (UCP) 3, nuclear respiratory factor (NRF)-1, and peroxisome proliferator-activated receptor (PPAR)delta tended to increase in type 2 diabetic patients with an improved clinical profile. Skeletal muscle protein expression of PPARdelta and UCP3 was increased significantly after physical exercise in patients with an improved clinical profile, but were unchanged in patients who did not show exercise-mediated improvements in clinical parameters. CONCLUSIONS: This study provides clinical evidence that improvements in insulin sensitivity can be achieved in type 2 diabetic patients after individually executed low-intensity exercise training. Moreover, the positive clinical response to exercise is correlated with changes in skeletal muscle proteins involved in the regulation of mitochondrial biogenesis and metabolism. These changes in skeletal muscle gene expression offer a possible molecular explanation for the improvements in clinical outcomes.
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| 27. |
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| 28. |
- Gigante, Isabella, et al.
(författare)
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Offloading of diabetes-related neuropathic foot ulcers at Swedish prosthetic and orthotic clinics
- 2023
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Ingår i: Diabetes-Metabolism Research and Reviews. - : Wiley. - 1520-7552 .- 1520-7560.
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study aimed to assess (1) the use of different offloading interventions in Sweden for the healing of diabetes-related plantar neuropathic forefoot ulcers, (2) factors influencing the offloading intervention choice, and (3) the awareness of current gold standard offloading devices.Methods: An online questionnaire was distributed via SurveyMonkey to 51 prosthetic and orthotic clinics in Sweden.Results: Thirty-five (69%) practitioners responded to the questionnaire. Eighty-six percent of the practitioners provided modified off-the-shelf footwear combined with insoles to treat diabetes-related plantar neuropathic forefoot ulcers. A total contact cast (TCC) was provided by 20% of the practitioners, and a nonremovable knee-high walker was provided by 0%. Multiple practitioner-, patient-, intervention-, and wound-related factors were considered when practitioners provided offloading interventions to patients with this type of ulcer. The majority of the practitioners did not or were unsure whether they considered TCC or a non-removable knee-high walker to be the gold standard treatment.Conclusions: Practitioners mainly provided the offloading intervention that the International Working Group on the Diabetic Foot strongly recommends not be provided, namely, modified off-the-shelf footwear with insoles. In contrast, TCC and nonremovable knee-high walkers, as the gold standards, were vastly underutilised. Therefore, the pattern of providing offloading interventions was almost exactly opposite to the recommendations of evidence-based guidelines. Different factors were considered when providing offloading interventions to patients with diabetes-related plantar neuropathic forefoot ulcers. The practitioners' lack of awareness regarding gold standard devices may have contributed to the underutilisation of TCC and nonremovable knee-high walkers.
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| 29. |
- Hellebö Johanson, Else, 1969, et al.
(författare)
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No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes
- 2005
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Ingår i: Diabetes Metab Res Rev. - : Wiley. - 1520-7552. ; 21:4, s. 376-81
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To study the acute effect of nateglinide, an insulinotropic agent, on the postprandial triglyceride and lipoprotein responses in subjects at risk for type 2 diabetes. METHODS: Six women and 10 men, with at least one first-degree relative with type 2 diabetes were included (Age: 48 +/- 7 years, BMI: 27.5 +/- 2.8 kg m(-2), P-triglycerides: 1.3 +/- 0.4 mmol L(-1), P-cholesterol: 5.4 +/- 0.6 mmol L(-1), B-glucose: 4.6 +/- 0.3 mmol L(-1)). They each had two 8-h meal tolerance tests with either nateglinide or placebo given 10 min prior to the meals in randomized order. Lipoprotein fractions were separated by density gradient ultracentrifugation. First-phase insulin secretion was assessed by an intravenous glucose tolerance test (300 mg kg(-1) body weight) and insulin sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m(-2) min(-1)). RESULTS: The 1-h insulin levels during the meal tolerance test were significantly higher with nateglinide (577 +/- 81 vs 376 +/- 58 pmol L(-1), p < 0.001), as well as the response during the first two hours (IAUC: 41 243 +/- 5844 vs 29 956 +/- 4662 pmol L(-1) min, p < 0.01). Accordingly, nateglinide lowered the 8-h postprandial glucose response by around 60% compared to placebo (p < 0.001). In contrast, no significant lowering was seen in the excursion of postprandial triglycerides in total plasma or lipoprotein fractions. Consistently, the concentration of exogenous (apoB-48) and endogenous (apoB-100) lipoproteins was not reduced by nateglinide. CONCLUSIONS: Acute administration of nateglinide reduces, as expected, the postprandial glucose concentration, but no reduction in triglyceride or lipoprotein responses are seen in subjects at risk for type 2 diabetes.
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| 30. |
- Hinchliffe, R J, et al.
(författare)
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A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes
- 2008
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Ingår i: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 24:S1, s. 119-144
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Forskningsöversikt (refereegranskat)abstract
- The outcome of management of diabetic foot ulcers is poor and there is uncertainty concerning optimal approaches to management. We have undertaken a systematic review to identify interventions for which there is evidence of effectiveness. A search was made for reports of the effectiveness of interventions assessed in terms of healing, ulcer area or amputation in controlled clinical studies published prior to December 2006. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network (SIGN) criteria. Selected studies fell into the following categories: sharp debridement and larvae; antiseptics and dressings; chronic wound resection hyperbaric oxygen (HBO); reduction of tissue oedema; skin grafts; electrical and magnetic stimulation and ultrasound. Heterogeneity of studies prevented pooled analysis of results. Of the 2251 papers identified, 60 were selected for grading following full text review. Some evidence was found to support hydrogels as desloughing agents and to suggest that a systemic (HBO) therapy may be effective. Topical negative pressure (TNP) may promote healing of post-operative wounds, and resection of neuropathic plantar ulcers may be beneficial. More information was needed to confirm the effectiveness and cost-effectiveness of these and other interventions. No data were found to justify the use of any other topically applied product or dressing, including those with antiseptic properties. Further evidence to substantiate the effect of interventions designed to enhance the healing of chronic ulcers is urgently needed. Until such evidence is available from robust trials, there is limited justification for the use of more expensive treatments and dressings.
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