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- Christensen, Michael, et al.
(author)
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Metformin attenuates renal medullary hypoxia in diabetic nephropathy through inhibition uncoupling protein-2
- 2019
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In: Diabetes/Metabolism Research Reviews. - : WILEY. - 1520-7552 .- 1520-7560. ; 35:2
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Journal article (peer-reviewed)abstract
- Background: The purpose of the study is to examine the effect of metformin on oxygen metabolism and mitochondrial function in the kidney of an animal model of insulinopenic diabetes in order to isolate any renoprotective effect from any concomitant effect on blood glucose homeostasis.Methods: Sprague-Dawley rats were injected with streptozotocin (STZ) (50 mg kg(-1)) and when stable started on metformin treatment (250 mg kg(-1)) in the drinking water. Rats were prepared for in vivo measurements 25 to 30 days after STZ injection, where renal function, including glomerular filtration rate and sodium transport, was estimated in anesthetized rats. Intrarenal oxygen tension was measured using oxygen sensors. Furthermore, mitochondrial function was assessed in mitochondria isolated from kidney cortex and medulla analysed by high-resolution respirometry, and superoxide production was evaluated using electron paramagnetic resonance.Results: Insulinopenic rats chronically treated with metformin for 4 weeks displayed improved medullary tissue oxygen tension despite of no effect of metformin on blood glucose homeostasis. Metformin reduced UCP2-dependent LEAK and differentially affected medullary mitochondrial superoxide radical production in control and diabetic rats.Conclusions: Metformin attenuates diabetes-induced renal medullary tissue hypoxia in an animal model of insulinopenic type 1 diabetes. The results suggest that the mechanistic pathway to attenuate the diabetes-induced medullary hypoxia is independent of blood glucose homeostasis and includes reduced UCP2-mediated mitochondrial proton LEAK.
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- Jendle, Johan, 1963-, et al.
(author)
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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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In: Diabetes/Metabolism Research Reviews. - : Wiley-Blackwell. - 1520-7552 .- 1520-7560. ; 32:8, s. 776-790
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Research review (peer-reviewed)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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- Julin, Bettina, et al.
(author)
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Association between sociodemographic determinants and health outcomes in individuals with type 2 diabetes in Sweden
- 2018
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In: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 34:4, s. -9
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Journal article (peer-reviewed)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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- Lehtisalo, Jenni, et al.
(author)
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Diabetes, glycaemia, and cognitiona secondary analysis of the Finnish Diabetes Prevention Study
- 2016
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In: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 32:1, s. 102-110
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Journal article (peer-reviewed)abstract
- Background: Type 2 diabetes is linked with cognitive dysfunction and dementia in epidemiological studies, but these observations are limited by lack of data on the exact timing of diabetes onset. We investigated diabetes, dysglycaemia, and cognition in the Finnish Diabetes Prevention Study, in which the timing and duration of diabetes are well documented.Methods: The Finnish Diabetes Prevention Study comprised middle-aged, overweight participants with impaired glucose tolerance but no diabetes at baseline (n=522), randomized to lifestyle intervention or a control group. After an intervention period (mean duration 4years) and follow-up (additional 9years), cognitive assessment with the CERAD test battery and Trail Making Test A (TMT) was executed twice within a 2-year interval. Of the 364 (70%) participants with cognitive assessments, 171 (47%) had developed diabetes.Results: Cognitive function did not differ between those who developed diabetes and those who did not. Lower mean 2-h glucose at an oral glucose tolerance test (OGTT) and HbA(1C) during the intervention period predicted better performance in the TMT (p=0.012 and 0.024, respectively). Those without diabetes or with short duration of diabetes improved in CERAD total score between the two assessments (p=0.001) whereas those with long duration of diabetes did not (p=0.844).Conclusions: Better glycemic control among persons with baseline impaired glucose tolerance predicted better cognitive performance 9years later in this secondary analysis of the Finnish Diabetes Prevention Study population. In addition, learning effects in cognitive testing were not evident in people with long diabetes duration.
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- Otten, Julia, 1973-, et al.
(author)
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Benefits of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control : a randomized controlled trial in individuals with type 2 diabetes
- 2017
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In: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 33:1
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Journal article (peer-reviewed)abstract
- BackgroundMeans to reduce future risk for cardiovascular disease in subjects with type 2 diabetes are urgently needed.MethodsThirty-two patients with type 2 diabetes (age 59 ± 8 years) followed a Paleolithic diet for 12 weeks. Participants were randomized to either standard care exercise recommendations (PD) or 1-h supervised exercise sessions (aerobic exercise and resistance training) three times per week (PD-EX).ResultsFor the within group analyses, fat mass decreased by 5.7 kg (IQR: −6.6, −4.1; p < 0.001) in the PD group and by 6.7 kg (−8.2, −5.3; p < 0.001) in the PD-EX group. Insulin sensitivity (HOMA-IR) improved by 45% in the PD (p < 0.001) and PD-EX (p < 0.001) groups. HbA1c decreased by 0.9% (−1.2, −0.6; p < 0.001) in the PD group and 1.1% (−1.7, −0.7; p < 0.01) in the PD-EX group. Leptin decreased by 62% (p < 0.001) in the PD group and 42% (p < 0.001) in the PD-EX group. Maximum oxygen uptake increased by 0.2 L/min (0.0, 0.3) in the PD-EX group, and remained unchanged in the PD group (p < 0.01 for the difference between intervention groups). Male participants decreased lean mass by 2.6 kg (−3.6, −1.3) in the PD group and by 1.2 kg (−1.3, 1.0) in the PD-EX group (p < 0.05 for the difference between intervention groups).ConclusionsA Paleolithic diet improves fat mass and metabolic balance including insulin sensitivity, glycemic control, and leptin in subjects with type 2 diabetes. Supervised exercise training may not enhance the effects on these outcomes, but preserves lean mass in men and increases cardiovascular fitness.
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- Papadopoulou-Marketou, Nektaria, 1974-, et al.
(author)
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Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis
- 2017
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In: Diabetes/Metabolism Research Reviews. - : WILEY. - 1520-7552 .- 1520-7560. ; 33:2
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Research review (peer-reviewed)abstract
- Diabetic nephropathy constitutes a devastating complication in patients with type 1 diabetes mellitus, and its diagnosis is traditionally based on microalbuminuria. The aim of this review is to update through the medical literature the suggested early natural course of diabetic nephropathy, the theories behind the pathways of its pathogenesis, and its diagnosis. Poor glycemic control, dyslipidemia, smoking, advanced glycation end products, and environmental and genetic clues play an important role in the development of diabetic nephropathy. Microalbuminuria has been traditionally considered as a primary early marker of microvascular complication unraveling the risk for progress to the advanced stages of chronic kidney disease, but because of our inability to make an early diagnosis of diabetic nephropathy in young patients as well as nonalbuminuric diabetic nephropathy, recently, other additional markers of renal injury like serum and urinary neutrophil gelatinase-associated lipocalin, chitinase-3-like protein 1, cystatin C, and plasma growth differentiation factor 15 have been proposed to unmask early renal dysfunction, even before microalbuminuria supervenes. Copyright (C) 2016 John Wiley amp; Sons, Ltd.
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