Insulin resistance contributes to the development of type 2 diabetes (T2D) and is also a cardiovascular risk factor. The aim of this study was to investigate the potential association between insulin ...resistance measured by estimated glucose disposal rate (eGDR) and risk of stroke and mortality thereof in people with T2D.
Nationwide population based observational cohort study that included all T2D patients from the Swedish national diabetes registry between 2004 and 2016 with full data on eGDR and categorised as following: < 4, 4-6, 6-8, and ≥ 8 mg/kg/min. We calculated crude incidence rates and 95% confidence intervals (CIs) and used multiple Cox regression to estimate hazard ratios (HRs) to assess the association between the risk of stroke and death, according to the eGDR categories in which the lowest category < 4 (i.e., highest grade of insulin resistance), served as a reference. The relative importance attributed of each factor in the eGDR formula was measured by the R
(± SE) values calculating the explainable log-likelihoods in the Cox regression.
A total of 104 697 T2D individuals, 44.5% women, mean age of 63 years, were included. During a median follow up-time of 5.6 years, 4201 strokes occurred (4.0%). After multivariate adjustment the HRs (95% CI) for stroke in patients with eGDR categories between 4-6, 6-8 and > 8 were: 0.77 (0.69-0.87), 0.68 (0.58-0.80) and 0.60 (0.48-0.76), compared to the reference < 4. Corresponding numbers for the risk of death were: 0.82 (0.70-0.94), 0.75 (0.64-0.88) and 0.68 (0.53-0.89). The attributed relative risk R
(± SE) for each variable in the eGDR formula and stroke was for: hypertension (0.045 ± 0.0024), HbA1c (0.013 ± 0.0014), and waist (0.006 ± 0.0009), respectively.
A low eGDR (a measure of insulin resistance) is associated with an increased risk of stroke and death in individuals with T2D. The relative attributed risk was most important for hypertension.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Type 2 diabetes (T2D) impairs post-stroke recovery, and the underlying mechanisms are unknown. Insulin resistance (IR), a T2D hallmark that is also closely linked to aging, has been associated with ...impaired post-stroke recovery. However, whether IR worsens stroke recovery is unknown. We addressed this question in mouse models where early IR, with or without hyperglycemia, was induced by chronic high-fat diet feeding or sucrose supplementation in the drinking water, respectively. Furthermore, we used 10-month-old mice, spontaneously developing IR but not hyperglycemia, where IR was normalized pharmacologically pre-stroke with Rosiglitazone. Stroke was induced by transient middle cerebral artery occlusion and recovery was assessed by sensorimotor tests. Neuronal survival, neuroinflammation and the density of striatal cholinergic interneurons were also assessed by immunohistochemistry/quantitative microscopy. Pre-stroke induction and normalization of IR, respectively, worsened and improved post-stroke neurological recovery. Moreover, our data indicate a potential association of this impaired recovery with exacerbated neuroinflammation and a decreased density of striatal cholinergic interneurons. The global diabetes epidemic and population aging are dramatically increasing the percentage of people in need of post-stroke treatment/care. Our results suggest that future clinical studies should target pre-stroke IR to reduce stroke sequelae in both diabetics and elderly people with prediabetes.
Post-stroke functional recovery is severely impaired by type 2 diabetes (T2D). This is an important clinical problem since T2D is one of the most common diseases. Because weight loss-based strategies ...have been shown to decrease stroke risk in people with T2D, we aimed to investigate whether diet-induced weight loss can also improve post-stroke functional recovery and identify some of the underlying mechanisms.
T2D/obesity was induced by 6 months of high-fat diet (HFD). Weight loss was achieved by a short- or long-term dietary change, replacing HFD with standard diet for 2 or 4 months, respectively. Stroke was induced by middle cerebral artery occlusion and post-stroke recovery was assessed by sensorimotor tests. Mechanisms involved in neurovascular damage in the post-stroke recovery phase, i.e. neuroinflammation, impaired angiogenesis and cellular atrophy of GABAergic parvalbumin (PV)+ interneurons were assessed by immunohistochemistry/quantitative microscopy.
Both short- and long-term dietary change led to similar weight loss. However, only the latter enhanced functional recovery after stroke. This effect was associated with pre-stroke normalization of fasting glucose and insulin resistance, and with the reduction of T2D-induced cellular atrophy of PV+ interneurons. Moreover, stroke recovery was associated with decreased T2D-induced neuroinflammation and reduced astrocyte reactivity in the contralateral striatum.
The global diabetes epidemic will dramatically increase the number of people in need of post-stroke treatment and care. Our results suggest that diet-induced weight loss leading to pre-stroke normalization of glucose metabolism has great potential to reduce the sequelae of stroke in the diabetic population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate early and long-term outcomes after treatment of carotid artery stenosis in patients with type 2 diabetes (T2D) compared to patients without T2D.
This observational nationwide ...population-based retrospective cohort study investigated all T2D patients treated for carotid stenosis registered in the National Swedish Vascular Surgery and the National Diabetes Registries. Data was collected prospectively for all patients after carotid intervention, during 2009-2015. We estimated crude early (within 30-days) hazard ratios (HRs) risk of stroke and death, and long-term HRs risk, adjusted for confounders with 95% confidence intervals (CIs), for stroke and death and major adverse cardiovascular events (MACE) by using inverse probability of treatment weighting matching.
A total of 1341 patients with T2D and 4162 patients without T2D were included; 89% treated for symptomatic carotid stenosis, 96% with carotid endarterectomy. There was an increased early risk, HRs (95% CI), for stroke in T2D patients 1.65 (1.17-2.32), whereas risk for early death 1.00 (0.49-2.04) was similar in both groups. During a median follow-up of 4.3 (T2D) and 4.6 (without T2D), with a maximum of 8.0 years; after propensity score matching there was an increased HRs (95% CI) of stroke 1.27 (1.05-1.54) and death 1.27 (1.10-1.47) in T2D patients compared to patients without T2D. Corresponding numbers for MACE were 1.21 (1.08-1.35).
Patients with T2D run an increased risk for stroke, death, and MACE after carotid intervention. They also have an increased perioperative risk for stroke, but not for death.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:People with type 2 diabetes (T2D) have an increased risk of cardiovascular disease. In this thesis the focus is on stroke with different aspects of aims, e.g. the risk of stroke in people ...with T2D, the role of glycemic control and insulin resistance (IR) in stroke, the potential intervention to minimize stroke damage, and the role of early-, and long-term outcome after carotid surgery in people with T2D.Method:We used data from different Swedish national quality registries in conjunction with Swedish national health registries. With the use of Cox regression analysis, utilizing inverse probability of treatment weighting, we focused on the outcome of stroke and death in relation to T2D, glycemic control (HbA1c), estimated glucose disposal rate (eGDR), i.e. a proxy for IR, and after carotid intervention. In addition, we used a mouse model to evaluate the effect of IR on stroke recovery.Results:There was a 50% relative increased risk of stroke and death in people with T2D compared to a matched general population. Glycemic control was independently associated with an increased risk of stroke and death (Study I). In people with T2D a low eGDR, i.e. high grade of IR, was associated with an increased stroke risk and death (Study II). Long-term dietary change led to weight loss with enhanced functional recovery after stroke. This effect was associated with pre-stroke normalization of fasting glucose and IR, and reduction of neuroinflammation together with enhancing neuroplasticity (Study III). After carotid surgery there was an increased early risk of stroke, but not for death, and in the long run there was an increased risk of stroke and death in people with T2D compared to people without diabetes (Study IV). Poor glycemic control (high HbA1c levels) in people with T2D have an increased long-term risk of stroke, and death after carotid surgery (Study V).Conclusions:The thesis expands the knowledge on stroke risk in T2D. Its relationship to glycemic control, and IR supporting the evidence for adequate management of glycemic control and the need for assessing IR. It also demonstrates that intervention with reversal of IR improve stroke recovery in rodents, a further research aim in people. There is an increased early-, and long-term risk after carotid intervention in people with T2D supporting further studies to reduce that risk.
Background and Purpose
Glucagon‐like peptide‐1 (GLP‐1) receptor activation decreases stroke risk in people with Type 2 diabetes (T2D), while animal studies have shown the efficacy of this strategy to ...counteract stroke‐induced acute brain damage. However, whether GLP‐1 receptor activation also improves recovery in the chronic phase after stroke is unknown. We investigated whether post‐acute, chronic administration of the GLP‐1 receptor agonist, exendin‐4, improves post‐stroke recovery and examined possible underlying mechanisms in T2D and non‐T2D mice.
Experimental Approach
We induced stroke via transient middle cerebral artery occlusion (tMCAO) in T2D/obese mice (8 months of high‐fat diet) and age‐matched controls. Exendin‐4 was administered for 8 weeks from Day 3 post‐tMCAO. We assessed functional recovery by weekly upper‐limb grip strength tests. Insulin sensitivity and glycaemia were evaluated at 4 and 8 weeks post‐tMCAO. Neuronal survival, stroke‐induced neurogenesis, neuroinflammation, atrophy of GABAergic parvalbumin+ interneurons, post‐stroke vascular remodelling and fibrotic scar formation were investigated by immunohistochemistry.
Key Results
Exendin‐4 normalised T2D‐induced impairment of forepaw grip strength recovery in correlation with normalised glycaemia and insulin sensitivity. Moreover, exendin‐4 counteracted T2D‐induced atrophy of parvalbumin+ interneurons and decreased microglia activation. Finally, exendin‐4 normalised density and pericyte coverage of micro‐vessels and restored fibrotic scar formation in T2D mice. In non‐T2D mice, the exendin‐4‐mediated recovery was minor.
Conclusion and Implications
Chronic GLP‐1 receptor activation mediates post‐stroke functional recovery in T2D mice by normalising glucose metabolism and improving neuroplasticity and vascular remodelling in the recovery phase. The results warrant clinical trial of GLP‐1 receptor agonists for rehabilitation after stroke in T2D.
LINKED ARTICLES
This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc
Aims
To compare stroke incidence in people with type 2 diabetes (T2D) with that in a matched control group, and to investigate whether glucose exposure in people with T2D can predict a first‐time ...stroke event and mortality.
Material and methods
In a nationwide observational cohort study, individuals with T2D were linked in the Swedish National Diabetes Register and matched with five individual population‐based control subjects. We calculated crude incidence rates and 95% confidence intervals (CIs), and used Cox regression and multivariable hazard ratios (HRs), to estimate the risk of stroke and mortality in relation to glycated haemoglobin (HbA1c) levels.
Results
A total of 406 271 people with T2D (age 64.1 ± 12.4 years, 45.7% women) and 2086 440 control subjects (age 64.0 ± 12.4 years, 45.7% women) were included. During a median follow‐up of 7.3 years, 26 380 people with T2D (6.5%) versus 92 375 control subjects (4.4%) were diagnosed with a stroke. The incidence rate was 10.12 events per 1000 person‐years versus 7.26 events per 1000 person‐years (HR 1.54, 95% CI 1.52‐1.56). In the T2D group after multivariable adjustments, the HRs for stroke stratified by HbA1c level were: 54‐64 mmol/mol: 1.27 (95% CI 1.22‐1.32); 65‐75 mmol/mol: 1.68 (95% CI 1.60‐1.76); 76‐86 mmol/mol: 1.89 (95% CI, 1.75‐2.05); and > 87 mmol/mol: 2.14 (95% CI 1.90‐2.42), respectively, compared with the reference category of HbA1c ≤53 mmol/mol. There was a stepwise increased risk of death after stroke, for every 10‐mmol/mol categorical increment of HbA1c (HR 1.71; 95% CI 1.47‐2.00) for the highest HbA1c category.
Conclusions
An increased risk of stroke and death was associated with poor glycaemic control in people with T2D.
Aims: To investigate the association between glycemic control and outcome in people with type 2 diabetes (T2D) after carotid intervention due to carotid stenosis. Methods: Observational nationwide ...population-based cohort study using inverse probability treatment weighting (IPTW) and Cox regressions with covariates, that is, 4 stepwise models, investigating the relationship between terciles of glycated hemoglobin (HbA1c) levels and stroke or death. Results: 1115 subjects with T2D undergoing carotid intervention were included during Jan 1st 2009 to Dec 31st 2015. Divided into terciles, with a mean HbA1c level of 44 (tercile 1), 53 (tercile 2), and 72 (tercile 3) mmol/mol. By using IPTW and Cox regression, each model was stepwise introduced for the investigating of relative risks, that is, hazard ratios (HRs) with associated 95% confidence intervals (CI). There was a significant increased risk for stroke or death, in every model observed for tercile 3, compared to tercile 1: HR for model 4: 1.35 (95% CI 1.02-1.78). No difference for stroke or death within 30 days was observed between the groups. Conclusion: Poor glycemic control in people with T2D after carotid intervention is associated with an increased long-term risk for stroke or death.
This work is intended to establish the prevalence of reverse smokers at the villages of Hato Nuevo, San Francisco and Cayo de Palma, Department of Sucre, Colombia, characterizing their socio-culture ...conditions, clinical and histological changes in the oral mucosa.
A descriptive study was done through a home to home inquiry to select the people with inclusion criteria for a posterior clinical test and a biopsy of the affected oral mucosa.
Reverse smokers's prevalence was from the 15%, mainly women (p<0.001) with an age average of 59.3 years. The lesions were classified clinically in mild, moderate and severe changes. Tongue moderate lesions presented the higher frequency (80%), followed by severe lesions on palate (74%). Oral cancer prevalence was 10.8% in the San Francisco village and 18.2% in Cayo de Palma village, no new cases were reported in Hato Nuevo village. This was the highest prevalence reported in comparison with other studies with similar population. The clinical and histological findings agree with the reported in literature, no relation was found between the degree of clinical severity and the dysplasia itself. Cases of oral submucous fibrosis-like lesions were found, which had never been reported in Latin America. Further studies are required in order to decrease the morbidity for this habit and to identify other related risk factors.
PDF
