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- Knudsen, Søren Tang, et al.
(författare)
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Risk factor management of type 2 diabetic patients in primary care in the Scandinavian countries between 2003 and 2015
- 2021
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Ingår i: Primary Care Diabetes. - : Elsevier BV. - 1751-9918 .- 1878-0210. ; 15:2, s. 262-268
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To observe and report population demography, comorbidities, risk factor levels and risk factor treatment in a sample of individuals treated for type 2 diabetes in primary care in Norway, Sweden and Denmark. Methods: Retrospective observational cohort using extraction of data from electronic medical records linked with national health care registries. Results: Sixty primary care clinics participated with annual cross-sectional data (2003 to 2015). In 2015 the sample consisted of 31,632 individuals. Mean age (64.5–66.8 years) and proportion of women (43–45%) were similar. The prevalence of cardiovascular disease in 2015 was 40.7%, 41.6% and 38.0% for Norway, Sweden and Denmark, respectively and 84% to 89% of patients were receiving a pharmacological anti-diabetic treatment. More Danish patients reached targets for HbA1c and LDL cholesterol, while more patients in Sweden and Denmark met the blood pressure target of <130/80 mmHg as compared to Norway. Conclusions: In three comparable public primary health care systems we found a high prevalence of cardiovascular disease and differences in risk factor treatment and attainment of risk factor goals. With recent guideline changes there is potential for further prevention of diabetes complications in primary care in the future.
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- Kullenberg, Helena
(författare)
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Insulin-degrading enzyme : A link between insulin resistance and Alzheimer's disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Prior research has demonstrated an elevated risk of Alzheimer's disease (AD) among individuals diagnosed with type 2 diabetes mellitus (T2DM). Insulin resistance is a potential common link between these conditions, and it is associated with AD due to the insulin-degrading enzyme (IDE), which also degrades amyloid-β (Aβ) in the brain. It has been suggested that high insulin levels may hinder IDE's effective degradation of Aβ, contributing to plaque formation. IDE is measurable in blood and is a promising biomarker for AD risk assessment and diagnosis. IDE has been demonstrated to decrease in blood from patients with cognitive impairment, but the overall knowledge about IDE in human blood is sparse. The aim of the thesis was to increase knowledge of the relationship between insulin resistance and AD, focusing on IDE as a biomarker for risk assessment and diagnosis of AD.Study participants: In study I, we included patients with type 2 diabetes (n=46) and compared them with patients without metabolic diseases (n=18). Serum samples were obtained from the Sophiahemmet biobank. In study II, we used post-mortem plasma samples from patients with Alzheimer's disease (n=18) and compared them with non-demented controls (n=6). These samples were obtained from the Netherlands Brain Bank. In study III, where we had three groups, we recruited patients with Alzheimer's disease (n=9) from a dementia care facility and healthy volunteers from Sophiahemmet University and Sophiahemmet Health Center (n=64). The serum samples from these individuals were then compared with serum samples from patients diagnosed with type 2 diabetes from Study I.In Study IV, we utilized data from the Swedish BPSD (Behavioral and Psychological Symptoms of Dementia) registry. This registry is used by healthcare units that work with patients with neurocognitive disorders and contains information about the patient's diagnosis, drug treatment, and behavioral and psychological symptoms. We selected a group of AD patients prescribed some form of antidiabetic drug treatment and analyzed whether the type of treatment impacted the registered behavioral and psychological symptoms.Methods: In study I-III, ELISA was used to analyze blood samples for levels of IDE and other metabolic markers. In study II, Luminex multiplex was used to measure inflammatory markers. These biomarkers and clinical data were analyzed statistically to investigate differences between groups and correlations between variables. In study IV, the association between BPSD and antidiabetic drug treatment was investigated using a bivariate logistic regression model, adjusted for age, sex, specific diagnosis, and drug treatment.Results: The results showed that patients with T2DM had higher serum IDE levels than patients without metabolic diseases, patients diagnosed with AD, and healthy volunteers. The results also indicated that higher IDE levels were associated with older age, higher weight, and elevated blood glucose. In the samples from the brain bank, we found that higher IDE levels were correlated to increased levels of inflammatory markers and total tau.In the analysis of registry data, we found that the prescription of metformin, one of the most common drugs for type 2 diabetes, was associated with lower odds for symptoms of depression and anxiety. This association was not observed for any other antidiabetic drug.Conclusion: The results suggest that IDE may be an essential factor in metabolic function but may also be associated with significant risk factors for neurocognitive disorders, such as inflammation. Although based on smaller studies, these findings contribute to the limited knowledge of IDE in human blood. Reduced IDE levels have been linked to an increased risk of AD. If patients diagnosed with T2DM have elevated IDE levels, a decrease in IDE levels possibly would indicate that the patient is at higher risk of or even in an early stage of AD. As interest in blood-based biomarkers grows, IDE emerges as a stable and reliable candidate in this thesis. Additionally, the research raises attractive possibilities for enhancing treatment strategies for AD patients experiencing affective symptoms. Metformin is believed to increase IDE levels and has previously been suggested to treat affective disorders and AD. Further investigation is needed to explore this promising avenue.
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- Lundkvist, Per, 1979-
(författare)
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Metabolic and endocrine effects of SGLT2 inhibition
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity and type 2 diabetes (T2D) are two growing global health problems with similar comorbidity profiles. SGLT2 inhibitors (SGLT2i) improve blood glucose control and can relieve both T2D and obesity, as well as their associated health problems such as hypertension, kidney failure, and cardiovascular disease.In paper I, 50 obese patients without diabetes were treated for 24 weeks with SGLT2i dapagliflozin + GLP-1 receptor agonist (GLP-1RA) exenatide or placebo. They were examined regarding body weight loss and body composition. The placebo-adjusted weight loss was 4.13 kg, mostly attributable to adipose tissue loss.In paper II, 43 completers of the study in paper I entered a 28-week extension phase in which all participants received active treatment. We found major reductions in body weight, adipose tissue volume, blood pressure and prediabetes that were sustained at 52 weeks. In paper III, 84 patients with T2D and non-alcoholic fatty liver disease underwent a 12-week treatment with dapagliflozin, omega-3 (n-3) carboxylic acids (OM-3CA), the combination of both or placebo to assess effects on liver fat content. MRI showed significant reductions of liver fat versus baseline and, for the combination, versus placebo.In paper IV: 15 metformin-treated patients with T2D were assessed for changes in plasma glucagon levels following a single dose of dapagliflozin during experiments with stable versus falling plasma glucose. Changes in glucagon levels could largely be explained by changes in glucose levels.In conclusion, SGLT2 inhibition can lower body weight and cardiovascular risk factors in obese patients without diabetes when combined with GLP-1RA, and it can reduce liver fat in T2D patients, in particular when given together with OM-3CA. SGLT2i effects on glucagon secretion can largely be explained by lower glucose levels rather than direct α-cell effects.
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- Secnik, Juraj, et al.
(författare)
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Cholinesterase inhibitors in patients with diabetes mellitus and dementia : an open-cohort study of similar to 23 000 patients from the Swedish Dementia Registry
- 2020
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Ingår i: BMJ Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Cholinesterase inhibitors (ChEIs) and memantine are the only approved pharmacological treatments for Alzheimer's disease (AD). Recent literature suggests reductions in cardiovascular burden and risk of stroke in ChEI users. However, the clinical effectiveness of these drugs in patients with diabetes mellitus (DM) and dementia has not been evaluated.Research design and methods We conducted a registry-based open-cohort study of 22 660 patients diagnosed with AD and mixed-pathology dementia registered in the Swedish Dementia Registry until December 2015. Information on drug use, comorbidity and mortality was extracted using the linkage with the National Patient Registry, the Prescribed Drug Registry and the Cause of Death Registry. In total, 3176 (14%) patients with DM and 19 484 patients without DM were identified. Propensity-score matching, Cox-regression and competing-risk regression models were applied to produce HRs with 95% CIs for differences in all-cause, cardiovascular and diabetes-related mortality rates in ChEI users and non-users.Results After matching the ChEI use in patients with DM was associated with 24% all-cause mortality reduction (HR 0.76 (95% CI 0.67 to 0.86)), compared with 20% reduction (0.80 (0.75 to 0.84)) in non-DM users. Donepezil and galantamine use were associated with a reduced mortality in both patients with DM (0.84 (0.74 to 0.96); 0.80 (0.66 to 0.97)) and patients without DM (0.85 (0.80 to 0.90); 0.93 (0.86 to 0.99)). Donepezil was further associated with reduction in cardiovascular mortality, however only in patients without DM (0.84 (0.75 to 0.94)). Rivastigmine lowered mortality only in the whole-cohort analysis and in patients without DM (0.82 (0.75 to 0.89)). Moreover, ChEI use was associated with 48% reduction in diabetes-related mortality (HR 0.52 (0.32 to 0.87)) in the whole-cohort analysis. Last, low and high doses were associated with similar benefit.Conclusions We found reductions in mortality in patients with DM and AD or mixed-pathology dementia treated with ChEIs, specifically donepezil and galantamine were associated with largest benefit. Future studies should evaluate whether ChEIs help maintain self-management of diabetes in patients with dementia.
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