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1.
Ars pharm ; 62(1): 52-65, ene.-mar. 2021. tab, graf
Artigo em Inglês | IBECS-Express | IBECS | ID: ibc-ET6-1768

RESUMO

INTRODUCTION: The prevalence of diabetes type 2 is increasing worldwide, thus the search of novel alternative ther¬apies is needed. According to their traditional use, we selected five Bolivian plants Chenopodium quinoa (CQ) Ama¬ranthus caudatus (AC), Chenopodium pallidicaule (CP), Lupinus mutabilis (LM) and Smallanthus sonchifolius (SS) that are traditionally used to control glycemia. METHODS: The effect of a single oral administration of Ethanolic (EtOH), hydro-ethanolic (EtOH70) and aqueous (Aq) extracts from all plant species were tested for their effect on blood glucose in non-fasted mice and during the oral glucose tolerance test (OGTT). The effect on insulin secretion was evaluated in mice pancreatic islets. RESULTS: EtOH70 extracts of all the plants showed glucose-reducing effect at the highest dose evaluated (2000 mg/ kg b.w.). EtOH70 extracts improved the glucose tolerance evaluated by the OGTT in mice fasted for 12 hours. The extracts have different effects on glucose homeostasis since just extracts of AC, LM and CQ but not CP and SS in¬creased insulin secretion as shown on mice pancreatic islets. The phytochemical qualitative characterization of EtOH70 extracts detected phenolic acids and flavonoids in AC, CP and CQ; alkaloids in LM and anthocyanidins in SS. None of EtOH70 extracts tested showed in vitro or in vivo acute toxicity at concentrations where they exhibit glucose lowering effects. CONCLUSIONS: We report here that extracts from AC, CQ, CP, LM and SS exhibit glucose lowering effect while just AC, CQ and LM stimulate directly the insulin secretion


INTRODUCCIÓN: La prevalencia de diabetes tipo 2 está aumentando en todo el mundo, por lo que se necesita la búsqueda de nuevas terapias alternativas. Según su uso tradicional, seleccionamos cinco plantas bolivianas Chenopodium quinoa (CQ) Amaranthus caudatus (AC), Chenopodium pallidicaule (CP), Lupinus mutabilis (LM) y Smallanthus sonchifolius (SS) que se usan tradicionalmente para controlar la glucemia. MÉTODOS: Se evaluó el efecto de la administración oral única de extractos etanólicos (EtOH), hidroetanólicos (EtOH70) y acuosos (Aq) de las plantas mencionadas para determinar su efecto sobre la glucosa en sangre en ratones en o sin ayunas y durante la prueba de tolerancia a la glucosa oral (PTGO). El efecto sobre la secreción de insulina se evaluó en islotes pancreáticos de ratones. RESULTADOS: Los extractos de EtOH70 de todas las plantas disminuyeron la glucemia a la dosis más alta evaluada (2000 mg / kg b.w.). Los extractos de EtOH70 mejoraron la tolerancia a la glucosa evaluada mediante la PTGO en ratones con ayuno de 12 horas. Los extractos tienen diferentes efectos sobre la homeostasis de la glucosa, ya que solo los extractos de AC, LM y CQ pero no CP y SS aumentaron la secreción de insulina como se muestra en los islotes pancreáticos de los ratones. La caracterización cualitativa fitoquímica de extractos de EtOH70 detectó ácidos fenólicos y flavonoides en AC, CP y CQ, alcaloides en LM y antocianidinas en SS. Ninguno de los extractos de EtOH70 probados mostró toxicidad aguda in vitro o in vivo a concentraciones en las que exhiben efectos reductores de glucosa. CONCLUSIÓN: Los extractos de AC, CQ, CP, LM y SS exhiben un efecto reductor de la glucosa, mientras que solo AC, CQ y LM estimulan directamente la secreción de insulina

2.
Prim Care Diabetes ; 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33339766

RESUMO

BACKGROUND: A painful burning sensation in the feet is a common problem. The most common cause is small fibre neuropathy, a type of peripheral neuropathy that is often a consequence of diabetes and prediabetes. AIM: To examine the association between a self-reported burning sensation in the feet and HbA1c levels in primary healthcare patients. METHODS: This study used data from patients in the 4D diabetes project in Swedish primary healthcare. The study population included 824 patients. Logistic regression was performed to study the association between the outcome and explanatory variables. RESULTS: A total of 24% of patients reported a burning sensation in the feet. This sensation was not associated with HbA1c levels. However, the probability of reporting a burning sensation was two times higher in non-Swedish-born than Swedish-born patients (OR, 2.31; 95% CI, 1.55-3.44) and higher in smokers than those who had never smoked, regardless of region of birth (OR, 1.69; 95% CI, 1.07-2.65). CONCLUSIONS: Our results do not support the hypothesis that a self-reported burning sensation in the feet is associated with HbA1c levels. Rather, they indicate a strong relationship between a burning sensation and region of birth, as well as between a burning sensation and smoking.

3.
Glob Health Action ; 13(1): 1795439, 2020 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-32746747

RESUMO

BACKGROUND: Type 2 diabetes and its high-risk stage, prediabetes, are often undiagnosed. Early detection of these conditions is of importance to avoid organ complications due to the metabolic disturbances associated with diabetes. Diabetes screening can detect persons unaware of diabetes risk and the elevated glucose levels can potentially be reversed through lifestyle modification and medication. There are mainly two approaches to diabetes screening: opportunistic facility-based screening at health facilities and community screening. OBJECTIVE: To determine the difference in population reach and participant characteristics between community- and facility-based screening for detection of type 2 diabetes and persons at high risk of developing diabetes. METHODS: Finnish diabetes risk score (FINDRISC) is a risk assessment tool used by two diabetes projects to conduct community- and facility-based screenings in disadvantaged suburbs of Stockholm. In this study, descriptive and limited inferential statistics were carried out analyzing data from 2,564 FINDRISC forms from four study areas. Community- and facility-based screening was compared in terms of participant characteristics and with population data from the respective areas to determine their reach. RESULTS: Our study found that persons born in Africa and Asia were reached through community screening to a higher extent than with facility-based screening, while persons born in Sweden and other European countries were reached more often by facility-based screening. Also, younger persons were reached more frequently through community screening compared with facility-based screening. Both types of screening reached more women than men. CONCLUSION: Community-based screening and facility-based screening were complementary methods in reaching different population groups at high risk of developing type 2 diabetes. Community screening in particular reached more hard-to-reach groups with unfavorable risk profiles, making it a critical strategy for T2D prevention. More men should be recruited to intervention studies and screening initiatives to achieve a gender balance.

4.
Diabetologia ; 63(8): 1603-1615, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32472192

RESUMO

AIMS/HYPOTHESIS: Chronic stimulation of ß2-adrenoceptors, opposite to acute treatment, was reported to reduce blood glucose levels, as well as to improve glucose and insulin tolerance in rodent models of diabetes by essentially unknown mechanisms. We recently described a novel pathway that mediates glucose uptake in skeletal muscle cells via stimulation of ß2-adrenoceptors. In the current study we further explored the potential therapeutic relevance of ß2-adrenoceptor stimulation to improve glucose homeostasis and the mechanisms responsible for the effect. METHODS: C57Bl/6N mice with diet-induced obesity were treated both acutely and for up to 42 days with a wide range of clenbuterol dosages and treatment durations. Glucose homeostasis was assessed by glucose tolerance test. We also measured in vivo glucose uptake in skeletal muscle, insulin sensitivity by insulin tolerance test, plasma insulin levels, hepatic lipids and glycogen. RESULTS: Consistent with previous findings, acute clenbuterol administration increased blood glucose and insulin levels. However, already after 4 days of treatment, beneficial effects of clenbuterol were manifested in glucose homeostasis (32% improvement of glucose tolerance after 4 days of treatment, p < 0.01) and these effects persisted up to 42 days of treatment. These favourable metabolic effects could be achieved with doses as low as 0.025 mg kg-1 day-1 (40 times lower than previously studied). Mechanistically, these effects were not due to increased insulin levels, but clenbuterol enhanced glucose uptake in skeletal muscle in vivo both acutely in lean mice (by 64%, p < 0.001) as well as during chronic treatment in diet-induced obese mice (by 74%, p < 0.001). Notably, prolonged treatment with low-dose clenbuterol improved whole-body insulin sensitivity (glucose disposal rate after insulin injection increased up to 1.38 ± 0.31%/min in comparison with 0.15 ± 0.36%/min in control mice, p < 0.05) and drastically reduced hepatic steatosis (by 40%, p < 0.01) and glycogen (by 23%, p < 0.05). CONCLUSIONS/INTERPRETATION: Clenbuterol improved glucose tolerance after 4 days of treatment and these effects were maintained for up to 42 days. Effects were achieved with doses in a clinically relevant microgram range. Mechanistically, prolonged treatment with a low dose of clenbuterol improved glucose homeostasis in insulin resistant mice, most likely by stimulating glucose uptake in skeletal muscle and improving whole-body insulin sensitivity as well as by reducing hepatic lipids and glycogen. We conclude that selective ß2-adrenergic agonists might be an attractive potential treatment for type 2 diabetes. This remains to be confirmed in humans. Graphical abstract.

5.
Transplantation ; 104(10): 2048-2058, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32345869

RESUMO

BACKGROUND: During intraportal pancreatic islet transplantation (PITx), early inflammatory reactions cause an immediate loss of more than half of the transplanted graft and potentiate subsequent allograft rejection. Previous findings suggest that cibinetide, a selective innate repair receptor agonist, exerts islet protective and antiinflammatory properties and improved transplant efficacy in syngeneic mouse PITx model. In a stepwise approach toward a clinical application, we have here investigated the short- and long-term effects of cibinetide in an allogeneic mouse PITx model. METHODS: Streptozotocin-induced diabetic C57BL/6N (H-2) mice were transplanted with 320 (marginal) or 450 (standard) islets from BALB/c (H-2) mice via the portal vein. Recipients were treated perioperative and thereafter daily during 14 d with cibinetide (120 µg/kg), with or without tacrolimus injection (0.4 mg/kg/d) during days 4-14 after transplantation. Graft function was assessed using nonfasting glucose measurements. Relative gene expressions of proinflammatory cytokines and proinsulin of the graft-bearing liver were assessed by quantitative polymerase chain reaction. Cibinetide's effects on dendritic cell maturation were investigated in vitro. RESULTS: Cibinetide ameliorated the local inflammatory responses in the liver and improved glycemic control immediately after allogeneic PITx and significantly delayed the onset of allograft loss. Combination treatment with cibinetide and low-dose tacrolimus significantly improved long-term graft survival following allogeneic PITx. In vitro experiments indicated that cibinetide lowered bone-marrow-derived-immature-dendritic cell maturation and subsequently reduced allogeneic T-cell response. CONCLUSIONS: Cibinetide reduced the initial transplantation-related severe inflammation and delayed the subsequent alloreactivity. Cibinetide, in combination with low-dose tacrolimus, could significantly improve long-term graft survival in allogeneic PITx.

6.
JCI Insight ; 5(3)2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32051343

RESUMO

SNAP23 is the ubiquitous SNAP25 isoform that mediates secretion in non-neuronal cells, similar to SNAP25 in neurons. However, some secretory cells like pancreatic islet ß cells contain an abundance of both SNAP25 and SNAP23, where SNAP23 is believed to play a redundant role to SNAP25. We show that SNAP23, when depleted in mouse ß cells in vivo and human ß cells (normal and type 2 diabetes [T2D] patients) in vitro, paradoxically increased biphasic glucose-stimulated insulin secretion corresponding to increased exocytosis of predocked and newcomer insulin granules. Such effects on T2D Goto-Kakizaki rats improved glucose homeostasis that was superior to conventional treatment with sulfonylurea glybenclamide. SNAP23, although fusion competent in slower secretory cells, in the context of ß cells acts as a weak partial fusion agonist or inhibitory SNARE. Here, SNAP23 depletion promotes SNAP25 to bind calcium channels more quickly and longer where granule fusion occurs to increase exocytosis efficiency. ß Cell SNAP23 antagonism is a strategy to treat diabetes.

7.
BMJ Open ; 9(12): e028757, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843819

RESUMO

OBJECTIVE: The first aim was to determine the extent of the relationship between place of birth and self-rated health (SRH) in primary healthcare patients born outside Sweden and those born in Sweden. The second aim was to investigate whether socioeconomic and lifestyle factors explained any differences. SETTING: Two academic primary healthcare centres in Stockholm County, Sweden. PARTICIPANTS: 825 patients at high risk of developing pre-diabetes and diabetes, aged 18-74 years, attending academic healthcare centres in areas with large numbers of immigrants, 56.8% born abroad and 43.2% born in Sweden. Patients with a diagnosis of diabetes were excluded. Inclusion criteria were based on previous research showing that people born in Middle Eastern and Asian countries who live in Sweden have a high prevalence of and risk for diabetes. OUTCOME: SRH was dichotomised as optimal (very good/good) and suboptimal (fair/bad/very bad) and compared in those born outside Sweden and in Sweden. RESULTS: There was a statistically significant difference in the SRH of the two groups (p=0.008). Logistic regression analysis showed a crude OR for reduced SRH of 1.46 (95% CI 1.10 to 1.92) in patients born outside Sweden. After controlling for education, employment and marital status, the OR increased to 1.50 (95% CI 1.11 to 2.02). After controlling for physical activity and smoking, it decreased to 1.36 (95% CI 1.00 to 1.85). CONCLUSION: Socioeconomic and lifestyle factors influenced SRH. It could therefore be useful for clinicians to consider these factors when providing care for patients born outside Sweden and resettled in areas with large numbers of immigrants.


Assuntos
Diabetes Mellitus/epidemiologia , Emigrantes e Imigrantes/estatística & dados numéricos , Nível de Saúde , Estado Pré-Diabético/epidemiologia , Adolescente , Adulto , Idoso , Ásia/etnologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Oriente Médio/etnologia , Fatores de Risco , Autorrelato , Fatores Socioeconômicos , Suécia/epidemiologia , Adulto Jovem
8.
Nutrients ; 11(11)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690003

RESUMO

Diabetes risk can be controlled and even reversed by making dietary changes. The aim of this study was to improve the understanding of how older persons with a high risk of developing Type 2 diabetes manage and relate to information about diabetes risk over a ten-year period. Fifteen qualitative interviews were conducted among participants from the Stockholm Diabetes Prevention Program (SDPP). The participants were asked to recall the health examinations conducted by the SDPP related to their prediabetes and to describe their experiences and potential changes related to diet and physical activity. Data were analyzed using qualitative content analysis. The main theme found was that T2D (type 2 diabetes) risk is not perceived as concrete enough to motivate lifestyle modifications, such as changing dietary patterns, without other external triggers. Diagnosis was recognized as a reason to modify diet, and social interactions were found to be important for managing behavior change. Diagnosis was also a contributing factor to lifestyle modification, while prognosis of risk was not associated with efforts to change habits. The results from this study suggest that the potential of reversing prediabetes needs to be highlighted and more clearly defined for older persons to serve as motivators for lifestyle modification.


Assuntos
Diabetes Mellitus/prevenção & controle , Dieta , Estado Pré-Diabético/dietoterapia , Idoso , Glicemia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologia , Fatores de Risco , Suécia/epidemiologia
9.
Lakartidningen ; 1162019 May 15.
Artigo em Sueco | MEDLINE | ID: mdl-31192438

RESUMO

Since 2012, the National Diabetes Council at Swedish Association of Local Authorities and Regions (SALAR) has been active to improve health care for persons with diabetes. The Council has produced a number of national care programmes, e.g. how to address patients who do not meet treatment targets, on insulin pumps and continuous glucose meters, on preventive foot care, and web-based information on diabetes to non-medical staff in nursing homes. Moreover, seven factors behind successful diabetes care have been characterized. Triangle revision is a newly introduced method applied for quality assurance of diabetes care with the aim to improve care and, if needed, to remedy potential deficiencies.


Assuntos
Diabetes Mellitus/terapia , Garantia da Qualidade dos Cuidados de Saúde/métodos , Humanos , Suécia
10.
Elife ; 82019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30958262

RESUMO

Here, we present a method for in-depth human plasma proteome analysis based on high-resolution isoelectric focusing HiRIEF LC-MS/MS, demonstrating high proteome coverage, reproducibility and the potential for liquid biopsy protein profiling. By integrating genomic sequence information to the MS-based plasma proteome analysis, we enable detection of single amino acid variants and for the first time demonstrate transfer of multiple protein variants between mother and fetus across the placenta. We further show that our method has the ability to detect both low abundance tissue-annotated proteins and phosphorylated proteins in plasma, as well as quantitate differences in plasma proteomes between the mother and the newborn as well as changes related to pregnancy.


Assuntos
Proteínas Sanguíneas/análise , Troca Materno-Fetal , Plasma/química , Proteoma/análise , Cromatografia Líquida , Feminino , Voluntários Saudáveis , Humanos , Focalização Isoelétrica , Masculino , Gravidez , Transporte Proteico , Espectrometria de Massas em Tandem
11.
BMC Public Health ; 19(1): 273, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845949

RESUMO

BACKGROUND: Mobile health, mHealth is recognized as a strategy to improve lifestyle behaviors. Research targeting specific lifestyle behaviors has shown that interventions using smartphones can be effective. However, few studies have evaluated solutions with multicomponent interventions, tailoring the intervention to the specific needs of the participant using a combination of mHealth and conventional treatment. To accomplish this, we developed Health Integrator, an mHealth platform with services and offers in the areas of diet, physical activity, sleeping habits, stress, alcohol and tobacco use. In the system, the user selects an area of intervention together with a health coach and set weekly goals. This study protocol presents the design and methodology of the Health Integrator Study, a randomized controlled trial to promote improved lifestyle behaviors. METHODS: A three-arm parallel randomized controlled trial (1:1:1) is conducted in the Stockholm County, Sweden. In total, 209 employees at a four different companies representing both white and blue collar workers, have been recruited. Participants are randomized to either a control group or to one of two intervention groups receiving a 3-month lifestyle behavior change program including either 1) use of Health Integrator and monthly health coaching sessions or 2) only Health Integrator. At baseline and follow-up after 3- and 6-months, all participants answer questionnaires assessing lifestyle behaviors and quality of life. At baseline and the 3-month follow-up (end of intervention period), weight, height, waist circumference and blood pressure are measured, and all participants wear an Actigraph accelerometer for 7 days to assess physical activity. Blood lipid profile and HbA1c are measured among all participants at baseline. If baseline measures fall outside the normal range, a second measurement is done after 3 months. DISCUSSION: The Health Integrator Intervention Study will evaluate if a personalized intervention combining mHealth and conventional programs for lifestyle change, with or without additional health coach sessions, can improve lifestyle behaviors and quality of life. Based on the results from this trial, Health Integrator can easily be implemented within a broad public. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03579342 . Retrospectively registered, first submitted May 8, 2018.


Assuntos
Comportamentos Relacionados com a Saúde , Promoção da Saúde/métodos , Estilo de Vida Saudável , Aplicativos Móveis , Ocupações , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Peso Corporal , Dieta , Exercício Físico , Feminino , Humanos , Masculino , Saúde do Trabalhador , Qualidade de Vida , Estudos Retrospectivos , Método Simples-Cego , Sono/fisiologia , Estresse Psicológico/prevenção & controle , Suécia/epidemiologia , Telemedicina , Uso de Tabaco/epidemiologia , Local de Trabalho
12.
PLoS One ; 14(3): e0213530, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30889215

RESUMO

The burden of type 2 diabetes is increasing rapidly, not least in Sub-Saharan Africa, and disadvantaged populations are disproportionally affected. Self-management is a key strategy for people at risk of or with type 2 diabetes, but implementation is a challenge. The objective of this study is to assess the determinants of self-management from an implementation perspective in three settings: two rural districts in Uganda, an urban township in South Africa, and socio-economically disadvantaged suburbs in Sweden. Data collection followed an exploratory multiple-case study design, integrating data from interviews, focus group discussions, and observations. Data collection and analysis were guided by a contextualized version of a transdisciplinary framework for self-management. Findings indicate that people at risk of or with type 2 diabetes are aware of major self-management strategies, but fail to integrate these into their daily lives. Depending on the setting, opportunities to facilitate implementation of self-management include: improving patient-provider interaction, improving health service delivery, and encouraging community initiatives supporting self-management. Modification of the physical environment (e.g. accessibility to healthy food) and the socio-cultural environment (i.e. norms, values, attitudes, and social support) may have an important influence on people's lifestyle. Regarding the study methodology, we learned that this innovative approach can lead to a comprehensive analysis of self-management determinants across different settings. An important barrier was the difficult contextualization of concepts like perceived autonomy and self-efficacy. Intervention studies are needed to confirm whether the pathways suggested by this study are valid and to test the proposed opportunities for change.


Assuntos
Diabetes Mellitus Tipo 2 , Relações Médico-Paciente , Autogestão , Estudos Transversais , Feminino , Humanos , Masculino , Fatores Socioeconômicos , Suécia , Uganda
13.
Occup Environ Med ; 76(4): 201-207, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30804165

RESUMO

BACKGROUND: There is limited evidence from longitudinal studies on transportation noise from different sources and development of ischaemic heart disease (IHD) and stroke. OBJECTIVES: This cohort study assessed associations between exposure to noise from road traffic, railway or aircraft and incidence of IHD and stroke. METHODS: In a cohort of 20 012 individuals from Stockholm County, we estimated long-term residential exposure to road traffic, railway and aircraft noise. National Patient and Cause-of-Death Registers were used to identify IHD and stroke events. Information on risk factors was obtained from questionnaires and registers. Adjusted HR for cardiovascular outcomes related to source-specific noise exposure were computed using Cox proportional hazards regression. RESULTS: No clear or consistent associations were observed between transportation noise and incidence of IHD or stroke. However, noise exposure from road traffic and aircraft was related to IHD incidence in women, with HR of 1.11 (95% CI 1.00 to 1.22) and 1.25 (95% CI 1.09 to 1.44) per 10 dB Lden, respectively. For both sexes taken together, we observed a particularly high risk of IHD in those exposed to all three transportation noise sources at≥45 dB Lden, with a HR of 1.57 (95% CI 1.06 to 2.32), and a similar tendency for stroke (HR 1.42; 95% CI 0.87 to 2.32). CONCLUSION: No overall associations were observed between transportation noise exposure and incidence of IHD or stroke. However, there appeared to be an increased risk of IHD in women exposed to road traffic or aircraft noise as well as in those exposed to multiple sources of transportation noise.


Assuntos
Incidência , Isquemia Miocárdica/epidemiologia , Ruído dos Transportes/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Ruído/efeitos adversos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Suécia/epidemiologia
14.
Sci Rep ; 9(1): 627, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679754

RESUMO

The global prevalence of type 2 diabetes is increasing rapidly; consequently there is great need for new and novel therapeutic options. Gynostemma pentaphyllum (GP) is a traditional medicinal plant, mainly present in Southeast Asian countries, that has been reported to exert antidiabetic effects, by stimulating insulin secretion. The specific compound responsible for this effect is however as yet unidentified. Screening for discovery and identification of bioactive compounds of an herbal GP extract, was performed in isolated pancreatic islets from spontaneously diabetic Goto-Kakizaki (GK) rats, a model of type 2 diabetes, and from non-diabetic control Wistar rats. From this herbal extract 27 dammarane-type saponins, including two novel compounds, were isolated and their structure was elucidated by mass spectrometry and NMR spectroscopy. One of the dammarane-type triterpenoid showed a glucose-dependent insulin secretion activity. This compound, gylongiposide I, displays unique abilities to stimulate insulin release at high glucose levels (16.7 mM), but limited effects at a low glucose concentration (3.3 mM). Further studies on this compound, also in vivo, are warranted with the aim of developing a novel anti-diabetic therapeutic with glucose-dependent insulinogenic effect.


Assuntos
Glucose/farmacologia , Gynostemma/química , Insulina/metabolismo , Saponinas/química , Saponinas/farmacologia , Triterpenos/química , Animais , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Técnicas In Vitro , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , Ratos
15.
Platelets ; 30(3): 348-355, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29547014

RESUMO

Diabetes mellitus (DM) is associated with prothrombotic alterations, and postprandial hyperglycemia is an independent risk factor for cardiovascular complications. We therefore investigated whether a standardized mixed meal alters circulating microparticles (MPs) and their procoagulant activity in DM patients. Patients with DM type 1 (T1DM, n = 11) and type 2 (T2DM; n = 9) were studied before and 90 min after a standardized meal (without premeal insulin). MPs in plasma derived from platelets (PMPs), endothelial cells (EMPs), or monocytes (MMPs) were measured by flow cytometry. MP-induced thrombin generation in plasma was assessed by a calibrated automated thrombogram. In the fasting state, MPs did not differ significantly between T1DM and T2DM. Meal intake increased the following microparticles: PMPs expressing phosphatidylserine (by 55%, on average), P-selectin (by 86%), and tissue factor (TF; by 112%); EMPs expressing E-selectin (by 96%) and MMPs expressing TF (by 164%), with no significant group differences between T1DM and T2DM. There were no increments in EMPs expressing phosphatidylserine or TF. Meal intake increased MP-induced thrombin generation similarly in T1DM and T2DM with increased endogenous thrombin potential (p = 0.02) and peak thrombin (p = 0.03) and shortened time to peak (p = 0.02). Phosphatidylserine inhibition by lactadherin completely abolished MP-induced thrombin generation, while an anti-TF antibody had no effect. In conclusion, meal intake increased several types of circulating MPs in patients with diabetes mellitus. These MPs have a procoagulant potential, which is related to phosphatidylserine expression and negatively charged MP surfaces rather than to TF.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Refeições/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
J Ultrasound Med ; 38(7): 1723-1731, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30426541

RESUMO

OBJECTIVES: Ultrasound biomicroscopy (UBM), or ultra high-frequency ultrasound, is a technique used to assess the anatomy of small research animals. In this study, UBM was used to assess differences in intimal hyperplasia thickness as a surrogate measurement of the re-endothelialization process after carotid artery balloon injury in rats. METHODS: Ultrasound biomicroscopic data from 3 different experiments and rat strains (Sprague Dawley, Wistar, and diabetic Goto-Kakizaki) were analyzed. All animals were subjected to carotid artery balloon injury and examined with UBM (30-70 MHz) 2 and 4 weeks after injury. Re-endothelialization on UBM was defined as the length from the carotid bifurcation to the most distal visible edge of the intimal hyperplasia. En face staining with Evans blue dye was performed at euthanasia 4 weeks after injury, followed by tissue harvesting for histochemical and immunohistochemical evaluations. RESULTS: A significant correlation (Spearman r = 0.63; P < .0001) was identified when comparing all measurements of re-endothelialization obtained from UBM and en face staining. The findings revealed a similar pattern for all rat strains: Sprague Dawley (Spearman r = 0.70; P < .0001), Wistar (Spearman r = 0.36; P < .081), and Goto-Kakizaki (Spearman r = 0.70; P < .05). A Bland-Altman test showed agreement between en face staining and UBM. Immunohistochemical staining confirmed the presence of the endothelium in the areas detected as re-endothelialized by the UBM assessment. CONCLUSIONS: Ultrasound biomicroscopy can be used for repeated in vivo assessment of re-endothelialization after carotid artery balloon injury in rats.


Assuntos
Lesões das Artérias Carótidas/diagnóstico por imagem , Endotélio Vascular/lesões , Microscopia Acústica , Túnica Íntima/lesões , Animais , Cateterismo/efeitos adversos , Exenatida/farmacologia , Linagliptina/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ratos Wistar
17.
Scand J Public Health ; 47(4): 408-416, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29734853

RESUMO

AIMS: We investigate (a) alcohol consumption in association with type 2 diabetes, taking heavy episodic drinking (HED), socioeconomic, health and lifestyle, and psychosocial factors into account, and (b) whether a seemingly protective effect of moderate alcohol consumption on type 2 diabetes persists when stratified by occupational position. METHODS: This population-based longitudinal cohort study comprises 16,223 Swedes aged 18-84 years who answered questionnaires about lifestyle, including alcohol consumption in 2002, and who were followed-up for self-reported or register-based diabetes in 2003-2011. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated in a multivariable-adjusted logistic regression model for all participants and stratified by high and low occupational position. We adjusted for HED, socioeconomic (occupational position, cohabiting status and unemployment), health and lifestyle (body mass index (BMI), blood pressure, smoking, physical inactivity, poor general health, anxiety/depression and psychosocial (low job control and poor social support) characteristics one by one, and the sets of these factors. RESULTS: Moderate consumption was inversely associated with type 2 diabetes after controlling for health and lifestyle (OR=0.47; 95% CI: 0.29-0.79) and psychosocial factors (OR=0.40; 95% CI: 0.22-0.79) when compared to non-drinkers. When adjusting for socioeconomic factors, there was still an inverse but non-significant association (OR=0.59; 95% CI: 0.35-1.00). In those with high occupational position, there was no significant association between moderate consumption and type 2 diabetes after adjusting for socioeconomic (OR=0.67; 95% CI: 0.3-1.52), health and lifestyle (OR=0.70; 95% CI: 0.32-1.5), and psychosocial factors (OR=0.75; 95% CI: 0.23-2.46). On the contrary, in those with low occupational position, ORs decreased from 0.55 (95% CI: 0.28-1.1) to 0.35 (95% CI: 0.15-0.82) when adjusting for psychosocial factors, a decrease that was solely due to low job control. HED did not influence any of these associations. CONCLUSIONS: Moderate alcohol consumption is associated with a lower risk of type 2 diabetes, after adjusting for HED, health and lifestyle, and psychosocial characteristics. The association was inverse but non-significant after adjusting for socioeconomic factors. When stratified by occupational position, there was an inverse association only in those with low occupational position and after adjusting for low job control.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/psicologia , Feminino , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários , Suécia/epidemiologia , Adulto Jovem
18.
BMJ Glob Health ; 3(6): e001068, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555727

RESUMO

This paper reports on the use of reciprocal learning for identifying, adopting and adapting a type 2 diabetes self-management support intervention in a multisite implementation trial conducted in a rural setting in a low-income country (Uganda), a periurban township in a middle-income country (South Africa) and socioeconomically disadvantaged suburbs in a high-income country (Sweden). The learning process was guided by a framework for knowledge translation and structured into three learning cycles, allowing for a balance between evidence, stakeholder interaction and contextual adaptation. Key factors included commitment, common goals, leadership and partnerships. Synergistic outcomes were the cocreation of knowledge, interventions and implementation methods, including reverse innovations such as adaption of community-linked models of care. Contextualisation was achieved by cross-site exchanges and local stakeholder interaction to balance intervention fidelity with local adaptation. Interdisciplinary and cross-site collaboration resulted in the establishment of learning networks. Limitations of reciprocal learning relate to the complexity of the process with unpredictable outcomes and the limited generalisability of results.

19.
Int J Mol Sci ; 19(12)2018 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-30544633

RESUMO

Purinergic signaling may be altered in diabetes accounting for endothelial dysfunction. Uridine adenosine tetraphosphate (Up4A), a novel dinucleotide substance, regulates vascular function via both purinergic P1 and P2 receptors (PR). Up4A enhances vascular contraction in isolated arteries of diabetic rats likely through P2R. However, the precise involvement of PRs in endothelial dysfunction and the vasoconstrictor response to Up4A in diabetes has not been fully elucidated. We tested whether inhibition of PRs improved endothelial function and attenuated Up4A-mediated vascular contraction using both aortas and mesenteric arteries of type 2 diabetic (T2D) Goto Kakizaki (GK) rats vs. control Wistar (WT) rats. Endothelium-dependent (EDR) but not endothelium-independent relaxation was significantly impaired in both aortas and mesenteric arteries from GK vs. WT rats. Non-selective inhibition of P1R or P2R significantly improved EDR in aortas but not mesenteric arteries from GK rats. Inhibition of A1R, P2X7R, or P2Y6R significantly improved EDR in aortas. Vasoconstrictor response to Up4A was enhanced in aortas but not mesenteric arteries of GK vs. WT rats via involvement of A1R and P2X7R but not P2Y6R. Depletion of major endothelial component nitric oxide enhanced Up4A-induced aortic contraction to a similar extent between WT and GK rats. No significant differences in protein levels of A1R, P2X7R, and P2Y6R in aortas from GK and WT rats were observed. These data suggest that altered PR sensitivity accounts for endothelial dysfunction in aortas in diabetes. Modulating PRs may represent a potential therapy for improving endothelial function.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Animais , Diabetes Mellitus Experimental , Fosfatos de Dinucleosídeos/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Masculino , Ratos , Ratos Wistar , Receptores Purinérgicos/metabolismo , Vasoconstrição/efeitos dos fármacos
20.
Int J Hyg Environ Health ; 221(8): 1133-1141, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30078646

RESUMO

BACKGROUND: The evidence on exposure to transportation noise and development of hypertension is inconclusive, mostly because of a lack of high quality studies of longitudinal design. OBJECTIVES: This cohort study aimed at investigating the association between exposure to road traffic, railway or aircraft noise and incidence of hypertension. We also assessed effects of varying lengths of exposure as well as of multiple sources of exposure. METHODS: Based on the residential histories of a cohort of 4854 men and women from Stockholm County, we estimated the residential exposure to road traffic, railway and aircraft noise in 1, 5 and 10 year time-periods. Hypertension was assessed by blood pressure measurements, information from questionnaires and hospital diagnoses. Extensive information on potential confounders was available from repeated questionnaires and registers. Hazard Ratios (HR) and 95% confidence intervals (CI) of hypertension related to noise exposure was computed from Cox regression models. RESULTS: We observed a positive association between aircraft noise exposure and incidence of hypertension with a HR of 1.16 (95% CI 1.08-1.24) per 10 dB Lden 5 years preceding the event. No clear differences in risk were indicated between the three exposure time windows. Road traffic and railway noise were not associated with incidence of hypertension during any of the exposure periods. There appeared to be a particularly high risk of hypertension among persons exposed to both aircraft and road traffic noise ≥45 dB Lden with an HR of 1.39 (95% CI 1.14-1.70). CONCLUSIONS: Exposure to aircraft noise may result in increased risk of hypertension.


Assuntos
Aeronaves , Exposição Ambiental/efeitos adversos , Hipertensão/epidemiologia , Ruído dos Transportes/efeitos adversos , Adulto , Automóveis , Exposição Ambiental/análise , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ferrovias , Suécia/epidemiologia
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