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1.
Ann R Coll Surg Engl ; 103(5): e141-e143, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33682434

RESUMO

At the onset of the COVID-19 crisis, a 63-year-old woman with multiple life-limiting comorbidities was referred with a necrotic infected left breast mass on a background of breast cancer treated with conservation surgery and radiotherapy 22 years previously. The clinical diagnosis was locally advanced breast cancer, but four separate biopsies were non-diagnostic. Deteriorating renal function and incipient sepsis and endocarditis resulted in urgent salvage mastectomy during the peak of the COVID19 pandemic. The final diagnosis was infected ischaemic/infarcted breast (wet gangrene) secondary to vascular insufficiency related to diabetes, cardiac revascularisation surgery and breast radiotherapy.


Assuntos
Antibacterianos/uso terapêutico , Mama/cirurgia , Angiopatias Diabéticas/terapia , Infecções por Enterobacteriaceae/terapia , Gangrena/terapia , Mastectomia/métodos , Mastite/terapia , Tratamento de Ferimentos com Pressão Negativa/métodos , Mama/irrigação sanguínea , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Ponte de Artéria Coronária , Desbridamento/métodos , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/etiologia , Diagnóstico Diferencial , Infecções por Enterobacteriaceae/diagnóstico , Feminino , Gangrena/diagnóstico , Humanos , Infarto , Artéria Torácica Interna/cirurgia , Mastectomia Segmentar , Mastite/diagnóstico , Pessoa de Meia-Idade , Morganella morganii , Recidiva Local de Neoplasia/diagnóstico , Radioterapia , Terapia de Salvação
2.
Am J Physiol Heart Circ Physiol ; 320(3): H1089-H1101, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33449847

RESUMO

The pathological involvement of anion channels in vascular dysfunction that occurs during type 2 diabetes (T2D) is unclear. Here, we tested the hypothesis that TMEM16A, a calcium-activated chloride (Cl-) channel, contributes to modifications in arterial contractility during T2D. Our data indicate that T2D increased TMEM16A mRNA in arterial smooth muscle cells and total and surface TMEM16A protein in resistance-size cerebral and hindlimb arteries of mice. To examine vascular cell types in which TMEM16A protein increased and the functional consequences of TMEM16A upregulation during T2D, we generated tamoxifen-inducible, smooth muscle cell-specific TMEM16A knockout (TMEM16A smKO) mice. T2D increased both TMEM16A protein and Cl- current density in arterial smooth muscle cells of control (TMEM16Afl/fl) mice. In contrast, T2D did not alter arterial TMEM16A protein or Cl- current density in smooth muscle cells of TMEM16A smKO mice. Intravascular pressure stimulated greater vasoconstriction (myogenic tone) in the arteries of T2D TMEM16Afl/fl mice than in the arteries of nondiabetic TMEM16Afl/fl mice. This elevation in myogenic tone in response to T2D was abolished in the arteries of T2D TMEM16A smKO mice. T2D also reduced Akt2 protein and activity in the arteries of T2D mice. siRNA-mediated knockdown of Akt2, but not Akt1, increased arterial TMEM16A protein in nondiabetic mice. In summary, data indicate that T2D is associated with an increase in TMEM16A expression and currents in arterial smooth muscle cells that produces vasoconstriction. Data also suggest that a reduction in Akt2 function drives these pathological alterations during T2D.NEW & NOTEWORTHY We investigated the involvement of TMEM16A channels in vascular dysfunction during type 2 diabetes (T2D). TMEM16A message, protein, and currents were higher in smooth muscle cells of resistance-size arteries during T2D. Pressure stimulated greater vasoconstriction in the arteries of T2D mice that was abolished in the arteries of TMEM16A smKO mice. Akt2 protein and activity were both lower in T2D arteries, and Akt2 knockdown elevated TMEM16A protein. We propose that a decrease in Akt2 function stimulates TMEM16A expression in arterial smooth muscle cells, leading to vasoconstriction during T2D.


Assuntos
Anoctamina-1/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/metabolismo , Membro Posterior/irrigação sanguínea , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Vasoconstrição , Animais , Anoctamina-1/deficiência , Anoctamina-1/genética , Artérias/metabolismo , Artérias/fisiopatologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/fisiopatologia , Células HEK293 , Humanos , Resistência à Insulina , Masculino , Potenciais da Membrana , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Estreptozocina , Regulação para Cima
3.
Angiology ; 71(10): 876-885, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32638622

RESUMO

Vascular complications in patients with diabetes mellitus (DM) are common. Since impaired oxygen balance in plasma plays an important role in the pathogenesis of chronic DM-associated complications, the administration of hyperbaric oxygen therapy (HBOT) has been recommended to influence development of vascular complications. Hyperbaric oxygen therapy involves inhalation of 100% oxygen under elevated pressure from 1.6 to 2.8 absolute atmospheres in hyperbaric chambers. Hyperbaric oxygen therapy increases plasma oxygen solubility, contributing to better oxygen diffusion to distant tissues and preservation of the viability of tissues reversibly damaged by atherosclerosis-induced ischemia, along with microcirculation restoration. Hyperbaric oxygen therapy exerts antiatherogenic, antioxidant, and cardioprotective effects by altering the level and composition of plasma fatty acids and also by promoting signal transduction through membranes, which are impaired by hyperglycemia and hypoxia. In addition, HBOT affects molecules involved in the regulation of nitric oxide synthesis and in that way exerts anti-inflammatory and angiogenic effects in patients with DM. In this review, we explore the recent literature related to the effects of HBOT on DM-related vascular complications.


Assuntos
Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/terapia , Oxigenação Hiperbárica , Animais , Angiopatias Diabéticas/etiologia , Modelos Animais de Doenças , Humanos
4.
Diab Vasc Dis Res ; 17(3): 1479164120928303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32538145

RESUMO

AIM: The aim of this study was to investigate the correlation between skin microvascular reactivity and clinical microangiopathy in patients with type 1 diabetes. METHODS: We included 61 patients with type 1 diabetes, that is, 31 patients with and 30 without clinical microangiopathy, and 31 healthy controls. A microangiopathy scoring system was introduced for comparison of data between patients with microangiopathy. Responses to iontophoresis of acetylcholine and sodium nitroprusside were assessed by laser Doppler imaging. RESULTS: Patients with microangiopathy had reduced acetylcholine- and sodium nitroprusside-mediated flux in forearm skin microcirculation compared to healthy controls (p = 0.03 and p < 0.001, respectively, repeated measures analysis of variance), whereas no significant differences were found between patients without microangiopathy and controls. Skin reactivity was reduced in patients with microangiopathy compared to patients without microangiopathy: 1.43 ± 0.38 versus 1.59 ± 0.39 arbitrary units for acetylcholine-mediated peak flux and 1.44 ± 0.46 versus 1.74 ± 0.34 arbitrary units for sodium nitroprusside-mediated peak flux (p < 0.05 for both). A tendency of gradual decrease in acetylcholine and sodium nitroprusside responses was found in patients with increasing microangiopathy scores. CONCLUSION: We conclude that skin microvascular reactivity is associated with clinical microangiopathy in patients with type 1 diabetes. Impaired skin microvascular function in type 1 diabetes seems to be multifactorial and involves both endothelial-dependent and endothelial-independent pathways. We introduce a novel microangiopathy score that could easily be used in a clinical setting for comparison of patients with various degrees of microangiopathy.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Microcirculação , Pele/irrigação sanguínea , Vasodilatação , Administração Cutânea , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/fisiopatologia , Feminino , Antebraço , Humanos , Iontoforese , Fluxometria por Laser-Doppler , Masculino , Microcirculação/efeitos dos fármacos , Angioscopia Microscópica , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Fatores de Risco , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem
5.
Microvasc Res ; 131: 104013, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32428521

RESUMO

Diabetes is frequently associated with structural and functional impairment of the microcirculation. Blood perfusion is an important indicator of both physiological and pathological conditions of the microcirculation. Given that temperature is closely related to blood perfusion and is more easily measured, blood perfusion can be estimated from variations in skin temperature using an inverse method. The aim of this paper was to develop a thermal analysis method for estimation of blood perfusion and apply it in the assessment of skin blood perfusion in diabetic rats. First, diabetes was induced in the rat models of the experimental group. Skin temperature from the rats left hind paws was measured during a 10-min local heating period followed by a 15-min cooling period. A simple one-dimensional heat transfer model, including an arteriolar vessel node, was used to describe the skin heat transfer process. The blood perfusion of the arteriole was estimated by correlating the calculated skin temperature with known experimental temperatures using a genetic algorithm. The results indicated that the average blood perfusion in the control group was higher during local heating and decreased faster during the cooling period, showing dynamic responses to the thermal stimuli. In contrast, the blood perfusion of diabetic rats was reduced compared with that of the control rats during the heating phase and the rate of decrease in perfusion during the cooling stage was similarly reduced, implying a slower response to thermal stimulation in these rats. It is interesting to note that diabetic rats fed a normal diet showed a similar blood perfusion pattern to that in the control rats, implying that diet may be important in the treatment of diabetes-associated microvascular dysfunction.


Assuntos
Algoritmos , Diabetes Mellitus Experimental/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico , Microcirculação , Modelos Cardiovasculares , Temperatura Cutânea , Pele/irrigação sanguínea , Termometria , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Transferência de Energia , Valor Preditivo dos Testes , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional , Fatores de Tempo
7.
World Neurosurg ; 139: e52-e60, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32200014

RESUMO

OBJECTIVE: This study aimed to investigate OIP5-AS1 effects on microangiopathy in diabetic mouse. METHODS: The expression levels of OIP5-AS1, miR-200b, and ACE2 expression were measured by RT-qPCR. Western blot was conducted to detect The ACE2 and Ang-(1-7) expression. Luciferase reporter assays were used to identify the interaction between miR-200b and OIP5-AS1 or ACE2. Morris water maze test was performed for detecting cognitive function. RESULTS: Our results indicated that diabetic mice exhibited much lower OIP5-AS1 expression in the hippocampus than normal mice. Diabetic mice of OIP5-AS1 KO group showed remarkably lower OIP5-AS1 expression in the hippocampus, longer escape latency and lower percentage of CD31+ cells in the hippocampusthan those of WT group. OIP5-AS1 knockdown directly up-regulated miR-200b expression and ACE2 was directly inhibited by miR-200b. Relative to normal mice, diabetic mice had markedly higher miR-200b expression and lower ACE2 expression in the hippocampus. Diabetic mice of OIP5-AS1 KO group were with obviously higher miR-200b expression and lower ACE2 expression in the hippocampus than those of WT group. Compared with diabetic mice of OIP5-AS1 KO group, those of WT group, OIP5-AS1 KO + miR-200b inhibitor group and OIP5-AS1 KO + ACE2 group had obviously shorter escape latency and higher percentage of CD31+ cells and more caspase-3 protein expression in the hippocampus. CONCLUSIONS: OIP5-AS1 attenuated microangiopathy in diabetic mouse by regulating miR-200b/ACE2.


Assuntos
Angiotensina I/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Angiopatias Diabéticas/genética , Hipocampo/metabolismo , MicroRNAs/genética , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/genética , RNA Longo não Codificante/genética , Animais , Caspase 3/metabolismo , Cognição , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Técnicas de Silenciamento de Genes , Aprendizagem em Labirinto , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Peptidil Dipeptidase A/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas , RNA Longo não Codificante/metabolismo
8.
Curr Opin Endocrinol Diabetes Obes ; 27(2): 115-123, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32073426

RESUMO

PURPOSE OF REVIEW: To summarize recent advancements in our understanding of the impact of dyslipidemia on microvascular complications in type 2 diabetes (T2D), with an emphasis on peripheral neuropathy and nephropathy. RECENT FINDINGS: Mounting evidence suggests that rigorous glycemic control only mitigates certain microvascular complications in T2D patients. Particularly, well regulated blood glucose levels only marginally improve peripheral neuropathy in the T2D setting. Dyslipidemia, an abnormal lipid profile, is emerging as a key factor in peripheral neuropathy. Furthermore, although glycemic control may prevent or slow nephropathy, recent developments demonstrate that dyslipidemia can also affect kidney outcomes in normoglycemic patients. Transcriptomic, epigenomic, and lipidomic investigations, as well as integrative approaches, are shedding light on potential pathomechanisms. These molecular studies are identifying possible targets for therapeutic intervention. Complementing molecular research, lifestyle interventions are on-going to assess whether dietary choices and/or exercise, weight-loss, or surgical interventions, such as bariatric surgery, can ameliorate peripheral neuropathy and nephropathy in T2D patients. SUMMARY: Dyslipidemia is an emerging mechanism in microvascular complications in T2D. Elucidating the molecular pathomechanisms may pinpoint potential lipid-centric treatments. Interventional studies of dietary changes, exercise, or weight-loss surgery may also positively impact these highly prevalent and morbid complications.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Dislipidemias/complicações , Cirurgia Bariátrica , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/prevenção & controle , Dietoterapia/métodos , Dislipidemias/sangue , Dislipidemias/terapia , Terapia por Exercício/métodos , Humanos , Fatores de Risco , Perda de Peso/fisiologia
9.
Diab Vasc Dis Res ; 17(1): 1479164120903044, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32037878

RESUMO

Diabetes is a proinflammatory and prothrombotic condition that increases the risk of vascular complications. The aim of this study was to develop a diabetic microvascular flow model that allows to study the complex interactions between endothelial cells, blood cells and plasma proteins and their effects on clot formation. Primary human cardiac microvascular endothelial cells from donors without diabetes or donors with diabetes (type 1 or type 2) were grown in a microfluidic chip, perfused with non-diabetic or diabetic whole blood, and clot formation was assessed by measuring fibrin deposition in real time by confocal microscopy. Clot formation in non-diabetic whole blood was significantly increased in the presence of endothelial cells from donors with type 2 diabetes compared with cells from donors without diabetes. There was no significant difference in clot formation between non-diabetic and diabetic whole blood. We present for the first time a diabetic microvascular flow model as a new tool to study clot formation as a result of the complex interactions between endothelial cells, blood cells and plasma proteins in a diabetes setting. We show that endothelial cells affect clot formation in whole blood, attributing an important role to the endothelium in the development of atherothrombotic complications.


Assuntos
Coagulação Sanguínea , Vasos Coronários/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/etiologia , Células Endoteliais/metabolismo , Fibrina/metabolismo , Microcirculação , Trombose/etiologia , Adulto , Estudos de Casos e Controles , Células Cultivadas , Vasos Coronários/fisiopatologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fluxo Sanguíneo Regional , Trombose/sangue , Trombose/fisiopatologia , Fatores de Tempo
10.
Lancet Diabetes Endocrinol ; 8(3): 206-215, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32032540

RESUMO

BACKGROUND: Latent autoimmune diabetes of adulthood (LADA) differs in clinical features from type 2 diabetes. Whether this difference translates into different risks of complications remains controversial. We examined the long-term risk of microvascular complications in people enrolled in the UK Prospective Diabetes Study (UKPDS), according to their diabetes autoimmunity status. METHODS: We did a post-hoc analysis of 30-year follow-up data from UKPDS (UKPDS 86). UKPDS participants with diabetes autoantibody measurements available and without previous microvascular events were included. Participants with at least one detectable autoantibody were identified as having latent autoimmune diabetes, and those who tested negative for all autoantibodies were identified as having type 2 diabetes. The incidence of the primary composite microvascular outcome (first occurrence of renal failure, renal death, blindness, vitreous haemorrhage, or retinal photocoagulation) was compared between adults with latent autoimmune diabetes and those with type 2 diabetes. The follow-up ended on Sept 30, 2007. Baseline and updated 9-year mean values of potential confounders were tested in Cox models to adjust hazard ratios (HRs). UKPDS is registered at the ISRCTN registry, 75451837. FINDINGS: Among the 5028 participants included, 564 had latent autoimmune diabetes and 4464 had type 2 diabetes. After median 17·3 years (IQR 12·6-20·7) of follow-up, the composite microvascular outcome occurred in 1041 (21%) participants. The incidence for the composite microvascular outcome was 15·8 (95% CI 13·4-18·7) per 1000 person-years in latent autoimmune diabetes and 14·2 (13·3-15·2) per 1000 person-years in type 2 diabetes. Adults with latent autoimmune diabetes had a lower risk of the composite outcome during the first 9 years of follow-up than those with type 2 diabetes (adjusted HR 0·45 [95% CI 0·30-0·68], p<0·0001), whereas in subsequent years their risk was higher than for those with type 2 diabetes (1·25 [1·01-1·54], p=0·047). Correcting for the higher updated 9-year mean HbA1c seen in adults with latent autoimmune diabetes than in those with type 2 diabetes explained entirely their subsequent increased risk for the composite microvascular outcome (adjusted HR 0·99 [95% CI 0·80-1·23], p=0·93). INTERPRETATION: At diabetes onset, adults with latent autoimmune diabetes have a lower risk of microvascular complications followed by a later higher risk of complications than do adults with type 2 diabetes, secondary to worse glycaemic control. Implementing strict glycaemic control from the time of diagnosis could reduce the later risk of microvascular complications in adults with latent autoimmune diabetes. FUNDING: European Foundation for the Study of Diabetes Mentorship Programme (AstraZeneca).


Assuntos
Autoanticorpos/sangue , Biomarcadores/análise , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Microvasos/patologia , Adolescente , Adulto , Idoso , Autoanticorpos/imunologia , Glicemia/análise , Estudos de Casos e Controles , Criança , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/epidemiologia , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Incidência , Masculino , Microvasos/imunologia , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Tempo , Reino Unido/epidemiologia , Adulto Jovem
11.
Nitric Oxide ; 96: 54-63, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972252

RESUMO

The metabolic disorders in diabetes, which are usually accompanied by oxidative stress and impaired nitric oxide (NO) bioavailability, increase the risk of detrimental cardiovascular complications. Herein, we investigated the therapeutic potential of dietary nitrate, which is found in high content in green leafy vegetables, on vascular oxidative stress and endothelial dysfunction in diabetic mice induced by high-fat diet and streptozotocin injection. Dietary nitrate in drinking water fuelled a nitrate-nitrite-NO pathway, which inhibited vascular oxidative stress, endothelial dysfunction and many features of metabolic syndrome in diabetic mice. These beneficial effects of nitrate on diabetic mice were abolished by PTIO (NO scavenger) treatment and significantly prevented by febuxostat (xanthine oxidoreductase inhibitor), demonstrating the central importance of NO in bioactivation of nitrate. The favorable effects of nitrate were not further influenced by apocynin (NADPH oxidase inhibitor), suggesting NADPH oxidase as a possible target. In high glucose-incubated vascular endothelial cells, NO donor attenuated oxidative stress and endothelial dysfunction via the inhibition of NADPH oxidase, where a heme oxygenase-1 (HO-1)-dependent mechanism was demonstrated for the antioxidant abilities of NO. Altogether, boosting this nitrate-nitrite-NO signaling pathway resulted in the decreases of NADPH oxidase-derived oxidative stress, endothelial dysfunction and metabolic disorders in diabetic vasculature. These findings may have novel implications for the preventive strategy against diabetes-induced vascular dysfunction and associated complications.


Assuntos
Diabetes Mellitus Experimental/complicações , Angiopatias Diabéticas/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , NADPH Oxidases/antagonistas & inibidores , Nitratos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Animais , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Angiopatias Diabéticas/etiologia , Heme Oxigenase-1/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Síndrome Metabólica/prevenção & controle , Camundongos , Nitratos/administração & dosagem , Óxido Nítrico/metabolismo
13.
Diabetes Care ; 43(2): 382-388, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31776141

RESUMO

OBJECTIVE: Diabetes in older age is heterogeneous, and the treatment approach varies by patient characteristics. We characterized the short-term all-cause and cardiovascular mortality risk associated with hyperglycemia in older age. RESEARCH DESIGN AND METHODS: We included 5,791 older adults in the Atherosclerosis Risk in Communities Study who attended visit 5 (2011-2013; ages 66-90 years). We compared prediabetes (HbA1c 5.7% to <6.5%), newly diagnosed diabetes (HbA1c ≥6.5%, prior diagnosis <1 year, or taking antihyperglycemic medications <1 year), short-duration diabetes (duration ≥1 year but <10 years [median]), and long-standing diabetes (duration ≥10 years). Outcomes were all-cause and cardiovascular mortality (median follow-up of 5.6 years). RESULTS: Participants were 58% female, and 24% had prevalent cardiovascular disease. All-cause mortality rates, per 1,000 person-years, were 21.2 (95% CI 18.7, 24.1) among those without diabetes, 23.7 (95% CI 20.8, 27.1) for those with prediabetes, 33.8 (95% CI 25.2, 45.5) among those with recently diagnosed diabetes, 29.6 (95% CI 25.0, 35.1) for those with diabetes of short duration, and 48.6 (95% CI 42.4, 55.7) for those with long-standing diabetes. Cardiovascular mortality rates, per 1,000 person-years, were 5.8 (95% CI 4.6, 7.4) among those without diabetes, 6.6 (95% CI 5.2, 8.5) for those with prediabetes, 11.5 (95% CI 7.0, 19.1) among those with recently diagnosed diabetes, 8.2 (95% CI 5.9, 11.3) for those with diabetes of short duration, and 17.3 (95% CI 13.8, 21.7) for those with long-standing diabetes. After adjustment for other cardiovascular risk factors, prediabetes and newly diagnosed diabetes were not significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.03 [95% CI 0.85, 1.23] and HR 1.31 [95% CI 0.94, 1.82], respectively) or cardiovascular mortality (HR 1.00 [95% CI 0.70, 1.43] and HR 1.35 [95% CI 0.74, 2.49], respectively). Excess mortality risk was primarily concentrated among those with long-standing diabetes (all-cause: HR 1.71 [95% CI 1.40, 2.10]; cardiovascular: HR 1.72 [95% CI 1.18, 2.51]). CONCLUSIONS: In older adults, long-standing diabetes has a substantial and independent effect on short-term mortality. Older individuals with prediabetes remained at low mortality risk over a median 5.6 years of follow-up.


Assuntos
Diabetes Mellitus/mortalidade , Hiperglicemia/mortalidade , Estado Pré-Diabético/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Aterosclerose/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Causas de Morte , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/mortalidade , Feminino , Humanos , Hiperglicemia/complicações , Hiperglicemia/epidemiologia , Masculino , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Prevalência , Prognóstico , Fatores de Risco , Fatores de Tempo
14.
Endocr Res ; 45(2): 119-130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31724439

RESUMO

Background: The association of vascular remodeling in the kidney and the brain with a particular microRNAs (miRNA) profile is not well studied.Methods: Seventy-six patients with Type 2 diabetes and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio (UACR), biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. MiRNA were quantified in blood and urine by a real-time PCR System. Cerebrovascular ultrasound measurements were performed in the carotid and middle cerebral arteries.Results: MiRNA21 and miRNA124 correlated positively with nephrin, podocalyxin, synaptopodin, urinary N-acetyl-D-glucosaminidase (NAG), urinary kidney-injury molecule-1 (KIM-1), UACR, and negatively with eGFR; miRNA125a, 126, 146a, 192 correlated negatively with nephrin, podocalyxin, synaptopodin, urinary NAG, urinary KIM-1, UACR, and directly with eGFR. Plasma miRNA-21 and miRNA192 correlated directly with cerebral hemodynamics parameters of atherosclerosis and arteriosclerosis. MiRNA-124, 125a, 126, 146a showed negative correlations with the same parameters.Conclusions: In Type 2 diabetes patients there is an association of vascular remodeling in the brain and the kidney with a specific miRNAs pattern. Cerebrovascular changes occur even in normoalbuminuric patients, with 'high-to-normal' levels of podocyte injury and PT dysfunction biomarkers. These phenomena may be explained by the variability of miRNA expression within the two organs in early DKD.


Assuntos
Transtornos Cerebrovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/metabolismo , Nefropatias Diabéticas/metabolismo , MicroRNAs/metabolismo , Remodelação Vascular/fisiologia , Adulto , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/urina , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/urina , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/urina , Feminino , Humanos , Túbulos Renais/fisiopatologia , Masculino , MicroRNAs/sangue , MicroRNAs/urina , Pessoa de Meia-Idade , Podócitos/patologia
15.
Curr Vasc Pharmacol ; 18(1): 50-56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30156161

RESUMO

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) and distal symmetrical sensorimotor polyneuropathy (DSPN) are serious microvascular complications of diabetes mellitus (DM). Their simultaneous development remains disputable. The aim of the present study was to examine the correlation between CAN and the presence/severity of DSPN in DM. METHODS: Subjects with type 1 (group A: n=51; mean age 40.4 years) and type 2 DM (group B: n=153; mean age 64.6 years) were studied. Evaluation of DSPN was based on neuropathy disability score. Assessment of CAN was based on the battery of 4 standardized cardiovascular autonomic function tests. RESULTS: In group A, patients with moderate/severe DSPN exhibited a 12-fold higher likelihood of CAN in univariate analysis (p=0.035). However, significance was lost after adjustment for gender, age, DM duration, and haemoglobin A1c. In group A, likelihood for CAN did not correlate with the presence of mild DSPN in univariate and multivariate analysis. In group B, likelihood of CAN was similar in patients with mild and in those with moderate/severe DSPN compared with patients without DSPN in univariate and multivariate analysis. In between group comparison CAN was similarly distributed in the 2 groups (p for interaction=0.367), in patients with no, mild and moderate/severe DSPN. CONCLUSION: CAN does not always co-exist with degrees of DSPN, ranging from mild to moderate/ severe and is similarly distributed in T1DM and T2DM patients with mild and moderate/severe DSPN and in patients without DSPN.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Sistema Cardiovascular/inervação , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Córtex Sensório-Motor/fisiopatologia , Adulto , Idoso , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
16.
Curr Diabetes Rev ; 16(3): 230-237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30332971

RESUMO

Prevalence of diabetes mellitus has increased drastically over time, especially in more populous countries such as the United States, India, and China. Patients with diabetes have an increased risk of major cardiovascular events such as acute myocardial infarction, cerebrovascular disease, and peripheral vascular disease. Arterial stiffness is a process related to aging and vascular, metabolic, cellular and physiological deterioration. In recent years, it has been described as an independent predictor of cardiovascular mortality and coronary artery disease. Additionally, it plays an important role in the measurement of chronic disease progression. Recent studies have suggested a strong relationship between diabetes mellitus and arterial stiffness since they share a similar pathophysiology involving endothelial dysfunction. The literature has shown that microvascular and macrovascular complications in diabetic patients could be screened and measured with arterial stiffness. Additionally, new evidence proposes that there is a relationship between blood glucose levels, microalbuminuria, and arterial stiffness. Moreover, arterial stiffness predicts cardiovascular risk and is independently associated with mortality in diabetic patients. Abnormal arterial stiffness values in diabetic patients should alert the clinician to the presence of vascular disease, which merits early study and treatment. We await more studies to determine if arterial stiffness could be considered a routine useful non-invasive tool in the evaluation of diabetic patients. There is enough evidence to conclude that arterial stiffness is related to the progression of diabetes mellitus.


Assuntos
Diabetes Mellitus/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Endotélio Vascular/fisiopatologia , Rigidez Vascular/fisiologia , Angiopatias Diabéticas/etiologia , Progressão da Doença , Humanos , Fatores de Risco
17.
Curr Vasc Pharmacol ; 18(2): 110-116, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30961498

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) has emerged as a pandemic. It has different complications, both microvascular and macrovascular. OBJECTIVE: The purpose of this review is to summarize the different types of macrovascular complications associated with T2DM. METHODS: A comprehensive review of the literature was performed to identify clinical studies, which determine the macrovascular complications associated with T2DM. RESULTS: Macrovascular complications of T2DM include coronary heart disease, cardiomyopathy, arrhythmias and sudden death, cerebrovascular disease and peripheral artery disease. Cardiovascular disease is the primary cause of death in diabetic patients. Many clinical studies have shown a connection between T2DM and vascular disease, but almost always other risk factors are present in diabetic patients, such as hypertension, obesity and dyslipidaemia. CONCLUSION: T2DM causes a variety of macrovascular complications through different pathogenetic pathways that include hyperglycaemia and insulin resistance. The association between T2DM and cardiovascular disease is clear, but we need more clinical studies in order to identify the pure effect of T2DM.


Assuntos
Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Cardiopatias/etiologia , Doença Arterial Periférica/etiologia , Animais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/mortalidade , Angiopatias Diabéticas/fisiopatologia , Cardiopatias/diagnóstico , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Humanos , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Prognóstico , Medição de Risco , Fatores de Risco
18.
J Vasc Surg ; 71(3): 937-945, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31471230

RESUMO

BACKGROUND: The ankle-brachial index (ABI) may underestimate the severity of peripheral arterial disease (PAD) in patients with noncompressible vessels. This study analyzed limitations of the ABI and toe-brachial index (TBI), if done alone, in patients with symptomatic PAD, diagnosed by duplex ultrasound (DUS) examination, particularly in patients with diabetes and chronic kidney disease (CKD). METHODS: This is a retrospective review of prospectively collected data. All patients underwent resting ABIs, TBI, and/or DUS. An ABIs of 0.90 or less in either leg was considered abnormal, and the term inconclusive ABIs (noncompressibility) was used if the ABI was 1.3 or greater. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy (OA) of ABIs in detecting 50% or greater stenosis of any arterial segment based on DUS were determined. A TBI of less than 0.7 was considered abnormal. RESULTS: We included 2226 ABIs and 1383 DUS examinations: 46% of patients had diabetes, 16% had CKD, and 39% had coronary artery disease. Fifty-three percent of the ABIs were normal, 34% were abnormal, and 13% were inconclusive. For patients with limb-threatening ischemia, 40% had normal ABIs, 40% abnormal ABIs, and 20% were inconclusive. The sensitivity and OA for ABIs in detecting 50% or greater stenosis in the whole series were 57% (95% confidence interval [CI], 53.7-61.2) and 74% (95% CI, 71.9-76.6); for diabetics 51% (95% CI, 46.1-56.3) and 66% (95% CI, 62.3-69.8); nondiabetics 66% (95% CI, 59.9-70.9) and 81% (95% CI, 78.2-83.9). For patients with CKD, the sensitivity and OA for ABIs in detecting 50% or greater stenosis was 43% (95% CI, 34.3-52.7) and 67% (95% CI, 60.2-73.0) versus patients with no CKD 60% (95% CI, 56.3-64.6) and 76% (95% CI, 73.1-78.1). If patients with inconclusive ABIs were excluded, these values were 69% (95% CI, 65.2-72.9) and 80% (95% CI, 77.2-81.9) in the whole series; 67% (95% CI, 61.6-72.7) and 75% (95% CI, 70.5-78.4) for diabetics; and 63% (95% CI, 51.3-73.0) and 78% (95% CI, 70.6-83.9) for patients with CKD. Thirty-three percent of TBIs were normal and 67% were abnormal. The sensitivity and OA for abnormal TBI in detecting 50% or greater stenosis were 85% (95% CI, 78.9-90.0) and 75% (95% CI, 70.1-80.2) in the whole series; 84% (95% CI, 76.0-90.3) and 74% (95% CI, 67.1-80.2) for diabetics; and 77% (95% CI, 61.4-88.2) and 72% (95% CI, 59.9-82.3) for patients with CKD. For those with inconclusive ABIs, these values for TBI were 75% and 69%. CONCLUSIONS: Of symptomatic patients with PAD with 50% or greater stenosis on DUS examination, 43% had normal/inconclusive resting ABIs (49% in diabetics and 57% in CKD). TBI may help in patients with inconclusive ABIs. These patients should undergo further imaging to determine proper treatment.


Assuntos
Índice Tornozelo-Braço , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/etiologia , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/etiologia , Insuficiência Renal Crônica/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiopatias Diabéticas/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Valor Preditivo dos Testes , Descanso , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia Doppler Dupla
19.
Curr Diabetes Rev ; 16(3): 270-277, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31146664

RESUMO

BACKGROUND: This cross sectional study investigated the clinical use of the ankle-brachial index (ABI) and toe brachial index (TBI) in 91 type 2 diabetic foot ulcer patients who visited the diabetic foot clinic, Prince Sultan Military Medical City, Saudi Arabia during July 2017 and January 2018. MATERIALS AND METHODS: The ABI and TBI facilitated the detection of peripheral arterial disease (PAD) and the patients' medical records were used to collect the clinical and demographic variables. The variables of duration (p = 0.047) and treatment (p = 0.046) of the ABI showed significant differences. Age (p = 0.034) and duration (p = 0.001) were the factors related to the diagnosis of TBI by the "χ2" test. RESULTS: From the TBI, 26.4% of the patients were found to have PAD, while the ABI showed that 21.8% of patients had the condition. However, no statistical significance was noted. From the regression analysis, the variable duration of diabetes (≥ 20 years of age) was recognized as an independent risk factor for TBI. CONCLUSION: In conclusion, it is recommended both the ABI and TBI to be used as screening tests for PAD in diabetic foot ulcer patients.


Assuntos
Índice Tornozelo-Braço , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Pé Diabético/fisiopatologia , Doença Arterial Periférica/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Pé Diabético/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/fisiopatologia , Arábia Saudita
20.
Crit Rev Eukaryot Gene Expr ; 30(6): 499-508, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33463917

RESUMO

In December of 2019, a novel coronavirus, which is SARS-CoV-2, broke out in the world and caused tremendous human and financial losses. According to a descriptive study by the relative hospital about the epidemiological and clinical features of 52 critically ill patients, the expert panel found that people with cardiovascular disease and diabetes comprise a large proportion of the patients with chronic disease. In this review, we discuss the structural biology of the SARS-CoV-2 in combination with the characteristics of its binding protein, ACE2, which is an important receptor in the cardiovascular system and may have potential relationships with various diabetic diseases. We hope we can provide useful recommendations for patients with diabetes after becoming infected by the virus or provide directions to doctors on treatment options.


Assuntos
/metabolismo , Angiopatias Diabéticas/etiologia , /patogenicidade , /fisiologia , Sistema Cardiovascular/metabolismo , Estado Terminal , Retinopatia Diabética/etiologia , Interações Hospedeiro-Patógeno , Humanos , Rim/fisiopatologia , /genética
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