| 1. |
- Mobini, Reza, 1965, et al.
(författare)
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Metabolic effects of Lactobacillus reuteri DSM 17938 in people with type 2 diabetes: A randomized controlled trial
- 2017
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 19:4, s. 579-589
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the metabolic effects of 12-week oral supplementation with Lactobacillus reuteri DSM 17938 in patients with type 2 diabetes on insulin therapy. Materials and methods: In a double-blind trial, we randomized 46 people with type 2 diabetes to placebo or a low (10(8) CFU/d) or high dose (10(10) CFU/d) of L. reuteri DSM 17938 for 12 weeks. The primary endpoint was the effect of supplementation on glycated haemoglobin (HbA1c). Secondary endpoints were insulin sensitivity (assessed by glucose clamp), liver fat content, body composition, body fat distribution, faecal microbiota composition and serum bile acids. Results: Supplementation with L. reuteri DSM 17938 for 12 weeks did not affect HbA1c, liver steatosis, adiposity or microbiota composition. Participants who received the highest dose of L. reuteri exhibited increases in insulin sensitivity index (ISI) and serum levels of the secondary bile acid deoxycholic acid (DCA) compared with baseline, but these differences were not significant in the between-group analyses. Post hoc analysis showed that participants who responded with increased ISI after L. reuteri supplementation had higher microbial diversity at baseline, and increased serum levels of DCA after supplementation. In addition, increases in DCA levels correlated with improvement in insulin sensitivity in the probiotic recipients. Conclusions: Intake of L. reuteri DSM 17938 for 12 weeks did not affect HbA1c in people with type 2 diabetes on insulin therapy; however, L. reuteri improved insulin sensitivity in a subset of participants and we propose that high diversity of the gut microbiota at baseline may be important.
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| 2. |
- Persson, Sofie, et al.
(författare)
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Days absent from work as a result of complications associated with type 2 diabetes : Evidence from 20 years of linked national registry data in Sweden
- 2020
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 22:9, s. 1586-1597
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To analyse days absent from work related to individual microvascular, macrovascular and other complications of type 2 diabetes (T2D) and to identify key drivers of absence. Materials and methods: National health and socio-economic individual-level data were analysed for the years 1997 to 2016 for people with T2D, and age-, sex- and residential region-matched controls (5:1) using linkage to Swedish national administrative registers, based on personal identity numbers. Regression analyses accounting for individual-level clustering and education were estimated to obtain days absent by individual complications. Alternative analyses, for example, workforce indicator and age subgroups, were explored for robustness and comparison purposes. Results: A total of 413 000 people with T2D aged <66 years, comprising 4.9 million person-years, was included. The crude proportion with any absence was higher among those with T2D compared to controls (47% vs. 26%) in the index year, and the median (IQR) number of days was higher (223 [77;359] vs. 196 [59;352]) if any absence. Regression analyses showed that complications per se were a key driver of days absent: stroke (+102 days); end-stage renal disease (+70 days); severe vision loss (+56 days); and angina pectoris, heart failure, and osteoarthritis (+53 days each). The alternative analyses showed similar levels of days absent and age subgroups differed in expected directions. Conclusions: This study provides evidence of the persisting impact on productivity from complications that supports continued efforts to reduce risk factors in T2D. Future studies on burden of disease and economic evaluations of new therapies and disease management may use this new set of complication-specific estimates to improve understanding of the value of reducing complications.
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| 3. |
- 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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| 4. |
- Ekström, Nils, et al.
(författare)
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Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register
- 2016
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 18:10, s. 990-998
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. Research design and methods: Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score. Results: Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was similar to 60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF. Conclusions: This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality.
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| 5. |
- Lindblad, Ulf, 1950, et al.
(författare)
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Can sulphonylurea addition to lifestyle changes help to delay diabetes development in subjects with impaired fasting glucose? The Nepi ANtidiabetes StudY (NANSY)
- 2011
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Ingår i: Diabetes, Obesity and Metabolism. - Malden,USA : Wiley. - 1462-8902 .- 1463-1326. ; 13:2, s. 185-188
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Tidskriftsartikel (refereegranskat)abstract
- The Nepi ANtidiabetes StudY (NANSY) is a 5-year randomized, double-blind, placebo-controlled trial in Swedish primary care, examining whether the development of type 2 diabetes (T2D) and retinopathy (separately reported) would be delayed in 40- to 70-year-old subjects with impaired fasting glucose (IFG) who, in addition to lifestyle changes, were treated with either placebo or low-dosage sulphonylurea (SU) (1-mg glimepiride; Amaryl (R)). Of 274 subjects (163 men, 111 women), 138 were allocated to placebo (46.0% men, 56.8% women) and 136 to glimepiride (54.0% men, 43.2% women). The primary endpoint was conversion to diabetes. Average follow-up time was 3.71 years; 96 subjects converted to diabetes, 55 allocated to placebo and 41 to glimepiride (absolute difference 9.8%; p = 0.072). In conclusion, the study failed to support the notion that low-dose SU added to lifestyle changes in IFG subjects would help to delay the conversion to diabetes.
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| 6. |
- Östgren, Carl Johan, et al.
(författare)
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Atrial fibrillation and its association with type 2 diabetes and hypertension in a Swedish community.
- 2004
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 6:5, s. 367-374
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To explore the prevalence of atrial fibrillation in patients with hypertension and type 2 diabetes and to identify possible mechanisms for the development of atrial fibrillation. Methods: A community-based, cross-sectional observational study was conducted in the primary health care in Skara, Sweden, and 1739 subjects (798 men, 941 women) were surveyed. Patients were categorized as those with hypertension only (n = 597); those with both hypertension and type 2 diabetes (n = 171), and those with type 2 diabetes only (n = 147). In the reference population, 824 normotensive subjects without diabetes were identified and used as controls. Participants were examined for cardiovascular risk factors including fasting blood glucose, serum insulin, blood pressure, lipids and anthropometric measures. Resting electrocardiogram (ECG) was recorded and Minnesota-coded. Insulin resistance was measured by the homeostasis model assessment (HOMA). Results: Age-adjusted prevalence of atrial fibrillation was 2% in patients with hypertension only, 6% in patients with both hypertension and type 2 diabetes, 4% in patients with type 2 diabetes only and 2% in controls, respectively. Age and sex adjusted odds ratios (OR) (95% CI) were; hypertension 0.7 (0.30-1.5), combined hypertension and type 2 diabetes 3.3 (1.6-6.7), and type 2 diabetes 2.0 (0.9-4.7). The association with combined hypertension and type 2 diabetes remained significant when adjusted for cardiovascular disease (CVD) risk factors and body mass index (BMI), was attenuated with adjustment for ischemic ECG; 2.4 (1.1-5.0) and lost significance with adjustment for insulin resistance; 1.3 (0.5-3.1). Conclusions: Atrial fibrillation is associated with the combined occurrence of type 2 diabetes and hypertension. Insulin resistance may be a common underlying mechanism.
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| 9. |
- Frías, Juan P., et al.
(författare)
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Long-term effects of dapagliflozin plus saxagliptin versus glimepiride on a background of metformin in patients with type 2 diabetes: Results of a 104-week extension to a 52-week randomized, phase 3 study and liver fat MRI substudy
- 2022
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 24:1, s. 61-71
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To report the results of a 104-week extension to a 52-week study in which dapagliflozin plus saxagliptin (DAPA+SAXA) improved glycaemic control, liver fat and metabolic variables compared with glimepiride (GLIM) in participants with type 2 diabetes (T2D) receiving background metformin. Materials and methods: This extension to a 52-week global, multicentre, parallel-group, active-controlled, double-blind study (NCT02419612) continued randomized participants (1:1) on DAPA+SAXA (10/5 mg) plus placebo, or GLIM (1-6 mg) plus placebo, once daily. Eligible participants were aged ≥18 years, had T2D (glycated haemoglobin [HbA1c] 58.5-91.3 mmol/mol [7.5%-10.5%]), and a body mass index of 20.0 to 45.0 kg/m2, and were receiving metformin (MET; ≥1500 mg/d). Key outcomes were: requirement for treatment intensification, based on HbA1c ≥53 mmol/mol (7%); achieving therapeutic glycaemic response; and changes in adipose tissue and liver fat on magnetic resonance imaging in a substudy. Results: Overall, 382 participants entered and 338 completed the 104-week extension period (MRI substudy, n = 82). The need for treatment intensification during the 156-week period was lower for DAPA+SAXA+MET (37.0%) than GLIM+MET (55.6%; hazard ratio 0.52, 95% confidence interval [CI] 0.39-0.68; P < 0.001). At week 156, 21.4% of DAPA+SAXA+MET versus 11.7% of GLIM+MET participants achieved therapeutic glycaemic response (HbA1c <53 mmol/mol; odds ratio 2.1, 95% CI 1.23-3.42; P = 0.006). DAPA+SAXA+MET led to greater adjusted mean reductions from baseline in liver fat and visceral and subcutaneous adipose tissue volumes versus GLIM+MET at week 122 (least-squares mean difference from GLIM+MET −4.89%, −0.41 L and −0.44 L, respectively; nominal P values ≤ 0.008). Safety was consistent with that of the monocomponents. Conclusions: Overall, glycaemic control, metabolic benefits and efficacy were better maintained with DAPA+SAXA+MET than with GLIM+MET in T2D.
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| 10. |
- Leohr, Jennifer, et al.
(författare)
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A Semi-physiological Model of Postprandial Triglyceride Response in Lean, Obese and Very obese Subjects Following a high-fat meal
- 2018
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Ingår i: Diabetes, obesity and metabolism. - : John Wiley & Sons. - 1462-8902 .- 1463-1326. ; 20:3, s. 660-666
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To quantify the postprandial triglyceride (TG) response of chylomicrons and very-low-density lipoprotein-V6 (VLDL-V6) after a high-fat meal in lean, obese and very obese healthy individuals, using a mechanistic population lipokinetic modelling approach.METHODS:. Healthy subjects from three BMI population categories: lean (18.5-24.9), obese (30-33), and very obese (34-40) were enrolled in a clinical study to assess the triglyceride response after a high-fat meal, containing 60% fat. Nonlinear mixed-effect modeling was used to analyze the triglyceride concentrations of chylomicrons and large VLDL-V6 particlesRESULTS: The triglycerides in chylomicrons and VLDL-V6 particles had a prominent postprandial peak and represented the majority of the postprandial response; only the VLDL-V6 showed a difference across the populations. A turn-over model successfully described the TG concentration-time profiles of both chylomicrons and large VLDL-V6 particles after the high-fat meal. This model consisted of four compartments: two transit compartments for the lag between meal consumption and appearance of TGs in the blood, and one compartment each for the chylomicrons and large VLDL-V6 particles. The rate constants for the production of chylomicrons and elimination of large VLDL-V6 particles, along with the conversion rate of chylomicrons to large VLDL-V6 particles were well defined.CONCLUSIONS: This is the first lipokinetic model to describe the absorption of triglycerides from dietary fats into the blood stream and compares the dynamics of triglycerides in chylomicrons and large VLDL-V6 particles among lean, obese and very obese people. Such a model can be used to identify where pharmacological therapies act, thereby improving the determination of efficacy, and identifying complementary mechanisms for combinational drug therapies.
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