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1.
Eur J Cancer Prev ; 29(1): 42-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30950925

RESUMO

Preclinical studies have suggested the antitumorigenic properties of metformin on prostate cancer; results from epidemiological studies remain contradictory. We aim to investigate the evidence of metformin and the risk of prostate cancer. PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies. Meta-analyses were carried out using the most fully adjusted hazard ratios and the corresponding 95% confidence intervals. Eighteen cohort studies and six case-control studies representing 2 009 504 male patients with type 2 diabetes mellitus were identified. The pooled HR of prostate cancer for metformin therapy was 0.97 (0.84-1.12) in case-control studies and 0.94 (0.79-1.12) in cohort studies, respectively. In cohort studies, we found that there was a modest association in studies with samples from Europe, but not in studies with samples from North America, Asia, and Oceania. In addition, metformin showed a slightly protective effect compared with sulfonylurea, but not insulin and other comparators. Meta-regression analyses found that obesity and prostate-specific antigen adjustment in statistical models may be the sources of heterogeneity. However, there were no significant differences in subgroups stratified by time-related biases, analytical approaches, types of risk estimates, study quality, publication year, and whether adjusted for smoking, alcohol abuse, hemoglobin A1c, diabetes duration, and other confounding factors. Our study showed that metformin therapy was not associated with the risk of prostate cancer in patients with type 2 diabetes mellitus. However, exploratory analyses suggest that metformin use may be protective in a certain subgroup of patients.

2.
Diabetes Obes Metab ; 22(1): 6-15, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31379119

RESUMO

People with diabetes mellitus are at higher risk of ischaemic stroke and worse outcomes thereafter. However, whether it is better to prescribe intensive glucose-lowering treatment compared with conventional treatment in people with diabetes to prevent recurrent stroke is debated. It is also crucial to consider whether specific antidiabetic agents are more efficacious and safer than others for prevention of stroke. In this review, we provide an overview of the efficacy of intensive and conventional glucose-lowering treatment in post-stroke management. Our conclusion is that the overall evidence for a beneficial effect of intensive glycaemic control on risk of stroke is limited. We also discuss evidence from recent large clinical trials of thiazolidinediones and new antidiabetic medications, including dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose co-transporter-2 inhibitors. On the basis of the findings of these trials, our conclusion is that pioglitazone and the GLP-1RA class (other than short-acting lixisenatide) are likely to lessen the occurrence of cerebrovascular disease (by mechanisms not dependent on glucose-lowering per se), whereas there is no consistent evidence for other drug classes.

3.
Eur J Gastroenterol Hepatol ; 32(1): 110-115, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31567641

RESUMO

OBJECTIVE: The objective was to explore the characteristics of energy metabolism in patients with alcoholic liver cirrhosis (ALC) and diabetes mellitus (DM). METHODS: Thirty-four male patients with ALC and DM, 30 male patients with ALC without DM and 10 male healthy controls (HC) were enrolled in this study. Resting energy expenditure (REE), respiratory quotient (RQ) were measured by indirect calorimetry. Data were analyzed using the Student's t-test, Mann-Whitney U-test and χ2 tests between two groups. Logistic regression analysis was used to analyze the risk factors for hypermetabolism. RESULTS: Measured REE was significantly higher in patients with ALC and DM (1740 ± 338 kcal/d) than in patients with ALC (1400 ± 304 kcal/d, P < 0.01). Fasting blood glucose was an independent factor predicting hypermetabolism in all of the patients with ALC (P = 0.005). RQ was lower in patients with ALC and DM (0.80 ± 0.06) than in patients with ALC (0.83 ± 0.05, P = 0.027) and the HC (0.86 ± 0.03, P = 0.001). In the ALC and DM group, measured REE as percentage of predicted REE by Harris-Benedict formula was higher in patients with HbA1c ≥ 7.5% than in those with HbA1c < 7.5% (126.36 ± 15.19% vs. 109.48 ± 23.89%, P = 0.040). CONCLUSION: REE was increased and RQ was significantly decreased in patients with ALC and DM. These changes were associated with poor glucose control. HbA1c less than 7.5% may reduce the risk of hypermetabolism.

4.
J Hypertens ; 38(1): 45-51, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31568056

RESUMO

OBJECTIVE: To evaluate whether the relationship between hypertension and type 2 diabetes mellitus (T2DM) is different for patients with uncontrolled hypertension, controlled hypertension or patients with apparent therapy-resistant hypertension (aTRH), compared with patients without hypertension. METHODS: Using Cox proportional hazard models we evaluated the risk of new-onset T2DM in 8756 patients, at high risk for vascular disease. Hypertensive patients were subdivided according to blood pressure (BP) and use of BP-lowering drugs. BP ≥ 140/90 mmHg was defined as uncontrolled BP. aTRH was defined as uncontrolled BP despite being treated with at least three BP-lowering drugs including a diuretic, or the use at least four BP-lowering drugs irrespective of BP levels. Further analysis evaluated the risk of new-onset T2DM for patients with uncontrolled hypertension and for patients with aTRH, compared with patients with controlled hypertension and without hypertension, respectively. RESULTS: Forty-five percent had controlled hypertension, 20% had uncontrolled hypertension, 5.7% had aTRH, and 29% were nonhypertensive. During a follow-up of 7.0 (interquartile range: 0-14) years there were 705 new cases of T2DM. Patients with hypertension had a 1.48 (95% confidence interval 1.22-1.80) times higher risk of new-onset T2DM than nonhypertensive patients. There was no significant difference in risk among different hypertension groups. CONCLUSION: Patients at high risk for cardiovascular disease with hypertension have a 1.48 times higher risk of new-onset T2DM than nonhypertensive counterparts. The risk did not differ between patients with controlled hypertension, uncontrolled hypertension, or aTRH.

5.
Eur J Gastroenterol Hepatol ; 32(1): 101-109, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31651649

RESUMO

OBJECTIVE: Assess the risk of progression to cirrhosis and hepatocellular carcinoma (HCC) due to hepatitis B virus (HBV)-infection in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). METHODS: Retrospective cohort study in the UK Clinical Practice Research Datalink with three cohorts: subjects with T2DM and HBV infection (T2DM+HBV cohort; N = 297), with T2DM without HBV-infection (T2DM cohort; N = 261 865), and with HBV-infection without T2DM (HBV cohort; N = 3630). Primary analyses were performed on the three cohorts and secondary analyses on subcohorts including patients with NAFLD diagnosis code (N = 6599). Case/outcome definitions were formulated with International Classification of Diseases/Read codes/laboratory results and classified using validated algorithms. Adjusted incidence rate ratios (IRR) were estimated with a Poisson regression model. RESULTS: When comparing the T2DM+HBV and T2DM cohorts, adjusted IRRs were 14.06 (95% confidence interval: 4.47-44.19) for cirrhosis and 2.83 (1.06-7.55) for HCC. When comparing the T2DM+HBV and HBV cohorts, adjusted IRRs were 0.68 (0.21-2.27) for cirrhosis and 1.39 (0.46-4.20) for HCC. No cirrhosis cases were identified in T2DM+NAFLD+HBV patients; IRs were 16.92/10 000 person-years (12.97-21.69) and 85.24/10 000 person-years (10.32-307.91) in the T2DM+NAFLD and NAFLD+HBV cohorts. CONCLUSION: HBV-infection increased significantly the risk for cirrhosis among T2DM patients, however, not beyond the expected incremental risk among infected non-T2DM subjects. Our approach to evaluate the role of T2DM/NAFLD and HBV-infection in liver disease progression could be applied to other settings with higher HBV prevalence.

6.
Clin Nucl Med ; 45(1): 7-10, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31789912

RESUMO

BACKGROUND: Patients with left bundle-branch block (LBBB) can be classified to discordant LBBB (dLBBB) and concordant LBBB (cLBBB) according to T-wave orientation in lateral leads. This classification indicates different functional left ventricular (LV) parameters with worse prognosis in dLBBB patients. However, there are no data regarding the impact of this classification on perfusion status of the left ventricle. The aim of this study is to evaluate and compare the SPECT myocardial perfusion imaging (MPI) findings of LV perfusion and function between dLBBB and cLBBB patients. METHODS: All patients who were referred for SPECT MPI during an 11 months' period were evaluated. Patients with evidence of LBBB on standard baseline 12-lead ECG were included, and their demographic, medical history, and imaging data were recorded. Quantitative perfusion and function parameters of LV included summed stress score, summed rest score, summed difference score, total perfusion deficit (TPD) at both phases with delta TPD, ejection fraction, end-diastolic volume, end-systolic volume, summed motion score, summed thickening score, phase SD, and phase histogram bandwidth. All baseline ECGs were further assessed by a cardiologist to categorize patients as the cLBBB or dLBBB group according to concordance of the T wave with QRS complex in lateral leads. RESULTS: Finally, 97 patients with 46 cLBBB and 51 dLBBB cases were included. Baseline characteristics and cardiovascular risk factors including diabetes mellitus, hypertension, hyperlipidemia, history of coronary artery disease (CAD), family history of CAD, and smoking were not significantly different between the 2 groups. However, summed stress score (12.2 vs 6.7), summed difference score (4.0 vs 2.6), stress TPD (11.0 vs 6.4), and delta TPD (4.8 vs 3.9) were significantly higher in dLBBB patients. In addition, functional parameters were also significantly worse in dLBBB patients with lower ejection fraction and higher end-diastolic volume, end-systolic volume, summed motion score, and summed thickening score in these patients. Mean phase SD and phase histogram bandwidth were also significantly higher in dLBBB patients. CONCLUSIONS: This study revealed that LBBB patients with discordant T wave in lateral leads have significantly higher ischemic scores and worse functional parameters with more dyssynchrony in gated SPECT MPI.

7.
Clin Podiatr Med Surg ; 37(1): 151-169, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31735265

RESUMO

Biomechanical changes to the lower extremity in patients with diabetes mellitus are typically greatest with peripheral neuropathy, although peripheral arterial disease also impacts limb function. Changes to anatomic structures can impact daily function. These static changes, coupled with kinetic and kinematic changes of gait, lead to increased vertical and shear ground reactive forces, resulting in ulcerations. Unsteadiness secondary to diminished postural stability and increased sway increase fall risk. These clinical challenges and exacerbation of foot position and dynamic changes associated with limb salvage procedures, amputations, and prostheses are necessary and can impact daily function, independence, quality of life, and mortality.

8.
Einstein (Sao Paulo) ; 18: eGS4913, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31531556

RESUMO

OBJECTIVE: To evaluate indications, results and strategy of retinal exams requested at Primary Care Units. METHODS: A retrospective study that analyzed the indications and results of retinal exams, in the modalities clinical dilated fundus exams and color fundus photographs. In the following situations, patients were considered eligible for color fundus photographs if visual acuity was normal and ocular symptoms were absent: diabetes mellitus and/or hypertension, in use of drugs with potential retinal toxicity, diagnosis or suspicion of glaucoma, stable and asymptomatic retinopathies, except myopia greater than -3.00 diopters. RESULTS: A total of 1,729 patients were evaluated (66% female, age 63.5±15.5 years), and 1,190 underwent clinical dilated fundus exam and 539 underwent color fundus photographs. Diabetes was present in 32.2%. The main indications were diabetes (23.7%) and glaucoma evaluation (23.5%). In 3.4% of patients there was no apparent indication. The main results were a large cup/disc ratio (30.7%) and diabetic retinopathy (13.2%). Exam was normal in 9.6%, detected peripheral changes in 7% and could not be performed in 1%. Considering patients eligible for fundus photographs (22.4%), more than half underwent clinical dilated fundus exams. CONCLUSION: Regarding exam modality, there were no important differences in the distribution of indications or diagnosis. Color fundus photograph is compatible with telemedicine and more cost-effective, and could be considered the strategy of choice in some scenarios. Since there are no clear guidelines for retinal exams indications or the modality of choice, this study may contribute to such standardization, in order to optimize public health resources.


Assuntos
Técnicas de Diagnóstico Oftalmológico , Atenção Primária à Saúde/estatística & dados numéricos , Retina , Doenças Retinianas/diagnóstico , Idoso , Retinopatia Diabética/diagnóstico , Técnicas de Diagnóstico Oftalmológico/economia , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Fotografação , Exame Físico , Estudos Retrospectivos , Telemedicina , Acuidade Visual
9.
J Affect Disord ; 260: 124-130, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31494364

RESUMO

BACKGROUND: Depression is a known risk factor for noncompliance to medical treatment. However, it remains unclear whether comorbidities alter the relationship between depression and treatment compliance. We explored whether depression is associated with disease-specific treatment service utilization. METHODS: This cross-sectional study utilized data from 499,492 individuals who had at least one comorbidity in the Korean Community Health Survey, 2009-2013. Self-reported lifetime depression diagnosis by a physician, current depressive symptoms, and utilization of medical services were queried. The association between depression status and the use of overall treatment services was investigated using multiple logistic regression models and further stratified by use of specific medical treatment under conditions predefined with the Charlson Comorbidity Index (CCI). RESULTS: Compared with non-depressed people, individuals with a "lifetime history of depression with current depressive symptom" showed higher odds of using overall medical treatment services in both men (OR=1.21, 95%CI: 1.00-1.47) and women (OR=1.13, 95% CI: 1.02-1.25). However, depressed individuals with CCI comorbidities (e.g., diabetes mellitus or angina) exhibited less utilization of treatment services than non-depressed individuals. LIMITATIONS: The nature of the cross-sectional study limits the ability to infer a temporal causal relationship. CONCLUSION: Overall, depressed individuals with a lifetime history of depression used treatment services more frequently than non-depressed individuals; however, depressed individuals with major illnesses tended to seek treatment for their medical conditions less. The mental health of patients who seek for medical services should be carefully considered in primary care for the proper health service utilization.

10.
Food Chem ; 306: 125630, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31593892

RESUMO

The Myrtaceae family is one of the world's leading commercial fruit tree families. Among the 121 genera belonging to this family, the Syzygium, Eugenia and Campomanesia genera are constituted by a wide variety of fruit species with great potential to be explored economically, besides presenting excellent nutritional value and being considered sources of phytochemicals such as phenolic compounds, carotenoids and volatile compounds. Many of these phytochemicals have been linked to the prevention and management of several chronic and degenerative diseases including cancer, cardiovascular diseases, type 2 diabetes mellitus, obesity, amnesia among other disorders. In this context, this review discusses about the importance of four fruits species representative of Myrtaceae family such as Syzygium cumini, Syzygium malaccense, Eugenia pyriformis and Campomanesia xanthocarpa, focusing on the nutrients and phytochemical constituents as well as demonstrating their biological effects in order to stimulate the cultivation and consumption of these fruits.

11.
J Ethnopharmacol ; 247: 112273, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31586692

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Luohanguo (LHG), a traditional Chinese medicine, could clear heat, moisten the lung, soothe the throat, restore the voice, and lubricate intestine and open the bowels. LHG has been utilized for the treatment of sore throats and hyperglycemia in folk medicine as a homology of medicine and food. The hypoglycemic pharmacology of LHG has attracted considerable attention, and mogrosides have been considered to be active ingredients against diabetes mellitus. We have found that these mogrosides could be metabolized into their secondary glycosides containing 1-3 glucose residues in type 2 diabetes mellitus (T2DM) rats in previous studies. These metabolites may be the antidiabetic components of LHG in vivo. Thus far, no reports have been found on reducing blood glucose of mogrosides containing 1-3 glucose residues. AIMS OF THE STUDY: The aim of this study was to confirm that mogrosides containing 1-3 glucose residues were the active components of LHG for antidiabetic effects and to understand their potential mechanisms of action. MATERIALS AND METHODS: First, the special fraction of mogrosides containing 1-3 glucose residues was separated from a 50% ethanol extract of LHG, and the chemical components were identified by ultra-performance liquid chromatography (UPLC) and named low-polar Siraitia grosvenorii glycosides (L-SGgly). Second, the antidiabetic effects of L-SGgly were evaluated by HFD/STZ-induced (high-fat diet and streptozocin) obese T2DM rats by indexing fasting blood glucose (FBG), fasting insulin (FINS), and insulin resistance, and then compared with other fractions in the separation process. The changes in serum lipid levels were also detected. Finally, possible mechanisms of antidiabetic activity of L-SGgly were identified as increasing GLP-1 levels and activating liver AMPK in T2DM rats. RESULTS: The chemical analysis of L-SGgly showed that they contain 11-oxomogroside V, mogroside V, mogroside III, mogroside IIE, mogroside IIIA1, mogroside IIA1, and mogroside IA1, respectively. The total content of the mogrosides in L-SGgly was 54.4%, including 15.7% mogroside IIA1 and 12.6% mogroside IA1. L-SGgly showed excellent effects on obese T2DM rats compared with the other fractions of LHG extract, including significantly reducing the levels of FBG (p < 0.001) and modifying insulin resistance (p < 0.05). Meanwhile, they could significantly decrease the content of triglyceride (p < 0.01), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.01) and free fatty acid (p < 0.001) and increase the content of high-density lipoprotein cholesterol (p < 0.001) in serum of T2DM rats. Moreover, L-SGgly can significantly increase (p < 0.01) GLP-1 levels and decrease (p < 0.01) IL-6 levels in T2DM rat serum. AMPK-activating activity in T2DM rats was also upregulated by L-SGgly, but no statistical significance was shown. CONCLUSION: L-SGgly, fractions separated from LHG extract, were verified to have obvious anti-hyperglycemic and anti-hyperlipidemic effects on T2DM rats. Furthermore, L-SGgly regulated insulin secretion in T2DM rats by increasing GLP-1 levels. These findings provide an explanation for the antidiabetic role of LHG.

12.
J Ethnopharmacol ; 247: 112264, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31600561

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The global problem of diabetes, together with the limited access of large numbers of patients to conventional antidiabetic medicines, continues to drive the search for new agents. Ancient Asian systems such as traditional Chinese medicine, Japanese Kampo medicine, and Indian Ayurvedic medicine, as well as African traditional medicine and many others have identified numerous plants reported anecdotally to treat diabetes; there are probably more than 800 such plants for which there is scientific evidence for their activity, mostly from studies using various models of diabetes in experimental animals. AIM OF THE REVIEW: Rather than a comprehensive coverage of the literature, this article aims to identify discrepancies between findings in animal and human studies, and to highlight some of the problems in developing plant extract-based medicines that lower blood glucose in patients with diabetes, as well as to suggest potential ways forward. METHODS: In addition to searching the 2018 PubMed literature using the terms 'extract AND blood glucose, a search of the whole literature was conducted using the terms 'plant extracts' AND 'blood glucose' AND 'diabetes' AND 'double blind' with 'clinical trials' as a filter. A third search using PubMed and Medline was undertaken for systematic reviews and meta-analyses investigating the effects of plant extracts on blood glucose/glycosylated haemoglobin in patients with relevant metabolic pathologies. FINDINGS: Despite numerous animal studies demonstrating the effects of plant extracts on blood glucose, few randomised, double-blind, placebo-controlled trials have been conducted to confirm efficacy in treating humans with diabetes; there have been only a small number of systematic reviews with meta-analyses of clinical studies. Qualitative and quantitative discrepancies between animal and human clinical studies in some cases were marked; the factors contributing to this included variations in the products among different studies, the doses used, differences between animal models and the human disease, and the impact of concomitant therapy in patients, as well as differences in the duration of treatment, and the fact that treatment in animals may begin before or very soon after the induction of diabetes. CONCLUSION: The potential afforded by natural products has not yet been realised in the context of treating diabetes mellitus. A systematic, coordinated, international effort is required to achieve the goal of providing anti-diabetic treatments derived from medicinal plants.

13.
Adv Exp Med Biol ; 1131: 943-963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646540

RESUMO

Insulin secretion in humans is usually induced by mixed meals, which upon ingestion, increase the plasma concentration of glucose, fatty acids, amino acids, and incretins like glucagon-like peptide 1. Beta-cells can stay in the off-mode, ready-mode or on-mode; the mode-switching being determined by the open state probability of the ATP-sensitive potassium channels, and the activity of enzymes like glucokinase, and glutamate dehydrogenase. Mitochondrial metabolism is critical for insulin secretion. A sound understanding of the intermediary metabolism, electrophysiology, and cell signaling is essential for comprehension of the entire spectrum of the stimulus-secretion coupling. Depolarization brought about by inhibition of the ATP sensitive potassium channel, together with the inward depolarizing currents through the transient receptor potential (TRP) channels, leads to electrical activities, opening of the voltage-gated calcium channels, and exocytosis of insulin. Calcium- and cAMP-signaling elicited by depolarization, and activation of G-protein-coupled receptors, including the free fatty acid receptors, are intricately connected in the form of networks at different levels. Activation of the glucagon-like peptide 1 receptor augments insulin secretion by amplifying calcium signals by calcium induced calcium release (CICR). In the treatment of type 2 diabetes, use of the sulfonylureas that act on the ATP sensitive potassium channel, damages the beta cells, which eventually fail; these drugs do not improve the cardiovascular outcomes. In contrast, drugs acting through the glucagon-like peptide-1 receptor protect the beta-cells, and improve cardiovascular outcomes. The use of the glucagon-like peptide 1 receptor agonists is increasing and that of sulfonylurea is decreasing. A better understanding of the stimulus-secretion coupling may lead to the discovery of other molecular targets for development of drugs for the prevention and treatment of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Cálcio/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Glucose , Humanos , Insulina , Células Secretoras de Insulina/enzimologia , Células Secretoras de Insulina/patologia
14.
Mol Cell Endocrinol ; 499: 110613, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605742

RESUMO

Most peptide hormones originate from secretory protein precursors synthesized within the endoplasmic reticulum (ER). In this specialized organelle, the newly-made prohormones must fold to their native state. Completion of prohormone folding usually occurs prior to migration through the secretory pathway, as unfolded/misfolded prohormones are retained by mechanisms collectively known as ER quality control. Not only do most monomeric prohormones need to fold properly, but many also dimerize or oligomerize within the ER. If oligomerization occurs before completion of monomer folding then when a poorly folded peptide prohormone is retained by quality control mechanisms, it may confer ER retention upon its oligomerization partners. Conversely, oligomerization between well-folded and improperly folded partners might help to override ER quality control, resulting in rescue of misfolded forms. Both scenarios appear to be possible in different animal models of endocrine disorders caused by genetic defects of protein folding in the secretory pathway. In this paper, we briefly review three such conditions, including familial neurohypophyseal diabetes insipidus, insulin-deficient diabetes mellitus, and hypothyroidism with defective thyroglobulin.

15.
Diabetologia ; 63(1): 34-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31650239

RESUMO

AIMS/HYPOTHESIS: Individuals with diabetes are at increased risk of developing and dying from cancer. Evidence-based guidelines recommend universal screening for breast, cervical and colorectal cancer; however, evidence on the uptake of these tests in individuals with diabetes is mixed. We conducted a meta-analysis to quantify the association between diabetes and participation in breast, cervical and colorectal cancer screening. METHODS: MEDLINE, EMBASE and CINAHL were searched systematically for publications between 1 January 1997 and 18 July 2018. The search was supplemented by handsearching of reference lists of the included studies and known literature reviews. Abstracts and full texts were assessed in duplicate according to the following eligibility criteria: study conducted in the general population; diabetes included as a predictor vs a comparison group without diabetes; and breast (mammography), cervical (Papanicolaou smear) or colorectal (faecal and endoscopic tests) cancer screening uptake included as an outcome. Random-effects meta-analyses were performed using the most-adjusted estimates for each cancer site. RESULTS: Thirty-seven studies (25 cross-sectional, 12 cohorts) were included, with 27 studies on breast, 19 on cervical and 18 on colorectal cancer screening. Having diabetes was associated with significantly lower likelihood of breast (adjusted OR 0.83 [95% CI 0.77, 0.90]) and cervical (OR 0.76 [95% CI 0.71, 0.81]) cancer screening, relative to not having diabetes. Colorectal cancer screening was comparable across groups with and without diabetes (OR 0.95 [95% CI 0.86, 1.06]); however, women with diabetes were less likely to receive a colorectal cancer screening test than women without diabetes (OR 0.86 [95% CI 0.77, 0.97]). CONCLUSIONS/INTERPRETATION: Our findings suggest that women with diabetes have suboptimal breast, cervical and colorectal cancer screening rates, compared with women without diabetes, although the absolute differences might be modest. Given the increased risk of cancer in this population, higher quality prospective evidence is necessary to evaluate the contribution of diabetes to cancer screening disparities in relation to other patient-, provider- and system-level factors. REGISTRATION: PROSPERO registration ID CRD42017073107.

16.
Biomed Pharmacother ; 121: 109564, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31683180

RESUMO

In traditional Chinese medicine (TCM), type 2 diabetes mellitus (T2DM) is regarded as Xiao Ke disease. Liuwei Dihuang pills (LWP), a classical TCM formula, with the function of nourishing kidney yin, has been used for treating Xiao Ke disease in clinic. In this review, we systematically highlighted recent evidence on LWP and T2DM data from clinical and animal studies, summarized the clinical application, pharmacological mechanism and the active compounds of LWP for the treatment of T2DM. This systematic review will provide an insightful understanding of TCM formulas, pharmacological mechanisms, medicinal-disease interactions, and will lay a foundation for the development of new drug therapy for T2DM.

17.
Diabetologia ; 63(1): 116-123, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31690987

RESUMO

AIMS/HYPOTHESIS: Epidemiological data on the associations of circulating fatty acid levels with type 2 diabetes are inconsistent. We conducted a two-sample Mendelian randomisation study to explore the causal associations of plasma levels of ten fatty acids with type 2 diabetes and glycaemic traits. METHODS: Thirteen SNPs associated with circulating levels of ten individual fatty acids at the genome-wide significance level (p < 5 × 10-8) were selected as instrumental variables for the exposures. For the outcomes, summary-level data were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium for type 2 diabetes (898,130 individuals) and from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) for the glycaemic traits (up to 46,186 non-diabetic individuals). The inverse-variance weighted method was used for analyses. RESULTS: Genetic predisposition to higher plasma levels of eight of the ten fatty acids were statistically significantly associated with lower or higher odds of type 2 diabetes. The OR per one SD increment of each fatty acid was 0.93 (95% CI 0.90, 0.96; p = 2.21 × 10-5) for α-linolenic acid, 0.96 (95% CI 0.94, 0.98; p = 1.85 × 10-4) for linoleic acid, 0.86 (95% CI 0.81, 0.91; p = 6.68 × 10-7) for palmitoleic acid, 0.87 (95% CI 0.81, 0.93; p = 2.21 × 10-5) for oleic acid, 1.08 (95% CI 1.03, 1.12; p = 0.002) for eicosapentaenoic acid, 1.04 (95% CI 1.02, 1.07; p = 0.001) for docosapentaenoic acid, 1.03 (95% CI 1.02, 1.05; p = 2.51 × 10-5) for arachidonic acid and 1.09 (95% CI 1.03, 1.15; p = 0.003) for stearic acid. The same eight fatty acids were also associated with fasting glucose levels and HOMA-B. The associations, except that for palmitoleic acid, were driven by variants in FADS1/2. CONCLUSIONS/INTERPRETATION: Genetic predisposition to higher circulating levels of eight out of ten fatty acids was associated with type 2 diabetes, fasting glucose and islet beta cell function. However, the associations, except that for palmitoleic acid, were driven by variants in FADS1/2, which encode enzymes with a key role in fatty acid metabolism.

18.
Diabetologia ; 63(1): 65-74, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31690988

RESUMO

AIMS/HYPOTHESIS: The aim of this work was to assess the effect of liraglutide on ectopic fat accumulation in individuals with type 2 diabetes mellitus. METHODS: This study is a pre-specified subanalysis of the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction In type 2 diAbetes mellitus (MAGNA VICTORIA) study, with primary endpoints being the effects of liraglutide on left ventricular diastolic and systolic function. The MAGNA VICTORIA study was a single-centre, parallel-group trial in 50 individuals with type 2 diabetes mellitus (BMI >25 kg/m2) who were randomly assigned (1:1, stratified for sex and insulin use) to receive liraglutide 1.8 mg once daily or placebo for 26 weeks, added to standard care. Participants, study personnel and outcome assessors were blinded to treatment allocation. The secondary endpoints of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT) and epicardial fat were measured with MRI. Hepatic triacylglycerol content (HTGC) and myocardial triacylglycerol content (MTGC) were quantified with proton MR spectroscopy. Between-group differences (change from baseline) were tested for significance using ANCOVA. Mean differences with 95% CIs were reported. RESULTS: The trial was completed in 2016. Twenty-four participants were randomised to receive liraglutide and 26 to receive placebo. One patient in the liraglutide group withdrew consent before having received the study drug and was not included in the intention-to-treat analysis. Liraglutide (n = 23) vs placebo (n = 26) significantly reduced body weight (liraglutide 98.4 ± 13.8 kg to 94.3 ± 14.9 kg; placebo 94.5 ± 13.1 kg to 93.9 ± 13.2 kg; estimated treatment effect -4.5 [95% CI -6.4, -2.6] kg). HbA1c declined in both groups without a significant treatment effect of liraglutide vs placebo (liraglutide 66.7 ± 11.5 mmol/mol to 55.0 ± 13.2 mmol/mol [8.4 ± 1.1% to 7.3 ± 1.2%]; placebo 64.7 ± 10.2 mmol/mol to 56.9 ± 6.9 mmol/mol [8.2 ± 1.0% to 7.5 ± 0.7%]; estimated treatment effect -2.9 [95% CI -8.1, 2.3] mmol/mol or -0.3 [95% CI -0.8, 0.2]%). VAT did not change significantly between groups (liraglutide 207 ± 87 cm2 to 203 ± 88 cm2; placebo 204 ± 63 cm2 to 200 ± 55 cm2; estimated treatment effect -7 [95% CI -24, 10] cm2), while SAT was reduced by a significantly greater extent with liraglutide than with placebo (liraglutide 361 ± 142 cm2 to 339 ± 131 cm2; placebo 329 ± 107 cm2 to 333 ± 125 cm2; estimated treatment effect -29 [95% CI -51, -8] cm2). Epicardial fat did not change significantly between groups (liraglutide 8.9 ± 4.3 cm2 to 9.1 ± 4.7 cm2; placebo 9.6 ± 4.1 cm2 to 9.6 ± 4.6 cm2; estimated treatment effect 0.2 [95% CI -1.5, 1.8] cm2). Change in HTGC was not different between groups (liraglutide 18.1 ± 11.2% to 12.0 ± 7.7%; placebo 18.4 ± 9.4% to 14.7 ± 10.0%; estimated treatment effect -2.1 [95% CI -5.3, 1.0]%). MTGC was not different after treatment with liraglutide (1.5 ± 0.6% to 1.2 ± 0.6%) vs placebo (1.3 ± 0.5% to 1.2 ± 0.6%), with an estimated treatment effect of -0.1 (95% CI -0.4, 0.2)%. There were no adjudicated serious adverse events. CONCLUSIONS/INTERPRETATION: Compared with placebo, liraglutide-treated participants lost significantly more body weight. Liraglutide primarily reduced subcutaneous fat but not visceral, hepatic, myocardial or epicardial fat. Future larger studies are needed to confirm the results of this secondary endpoint study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01761318. FUNDING: This study was funded by Novo Nordisk A/S (Bagsvaerd, Denmark).

19.
Diabetologia ; 63(1): 137-148, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31701200

RESUMO

AIMS/HYPOTHESIS: Rapid and adequate islet revascularisation and restoration of the islet-extracellular matrix (ECM) interaction are significant factors influencing islet survival and function of the transplanted islets in individuals with type 1 diabetes. Because the ECM encapsulating the islets is degraded during islet isolation, understanding the process of revascularisation and engraftment after transplantation is essential and needs further investigation. METHODS: Here we apply a longitudinal and high-resolution imaging approach to investigate the dynamics of the pancreatic islet engraftment process up to 11 months after transplantation. Human and mouse islet grafts were inserted into the anterior chamber of the mouse eye, using a NOD.ROSA-tomato.Rag2-/- or B6.ROSA-tomato host allowing the investigation of the expansion of host vs donor cells and the contribution of host cells to aspects such as promoting the encapsulation and vascularisation of the graft. RESULTS: A fibroblast-like stromal cell population of host origin rapidly migrates to ensheath the transplanted islet and aid in the formation of a basement membrane-like structure. Moreover, we show that the vessel network, while reconstituted by host endothelial cells, still retains the overall architecture of the donor islets. CONCLUSIONS/INTERPRETATION: In this transplantation situation the fibroblast-like stromal cells appear to take over as main producers of ECM or act as a scaffold for other ECM-producing cells to reconstitute a peri-islet-like basement membrane. This may have implications for our understanding of long-term graft rejection and for the design of novel strategies to interfere with this process.

20.
Biomed Pharmacother ; 121: 109565, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704615

RESUMO

With the improvement of people's living standard and the changes of environment, the incidence of diabetes mellitus (DM) is on the rise day by day, while clinical treatment mainly aims at lowering blood glucose, instead of fundamental prevention and treatment. What's worse, the measures of prevention and treatment of DM complications remain inadequate. Both Chinese and modern medicine have advantages and disadvantages in treating DM, therefore, it would be a worthy attempt to break through the bottleneck of DM treatment by combining the advantages of both, and explore the new measures to prevent and deal with DM from the perspective of the combination of Traditional Chinese Medicine (TCM) syndrome and modern medicine. In this paper, modern research methods and possible indicators of TCM syndromes of DM were expounded from clinical and basic research aspects, aiming to find specific biomarkers of TCM syndromes, and providing experimental supports for the diagnosis and treatment of DM and the verification of TCM theory.

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