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1.
Diabet Med ; 37(8): 1291-1298, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-30701607

RESUMO

AIM: Comparing people with Type 2 diabetes mellitus with and without heart failure in terms of metabolic control, therapeutic regimen and comorbidities. METHODS: The Prospective Diabetes Registry (DPV) is a longitudinal documentation system for demographics, medical care and outcome in people with diabetes mellitus. It consists of follow-up data from people with diabetes mellitus who have agreed to be recorded in the registry. Clinical data are submitted by general practitioners, specialists and clinics throughout Germany and Austria. Some 289 954 people with Type 2 diabetes mellitus (years 2000 to 2015) were analysed using demographic statistics and adjustment for confounders based on linear and logistic regression analysis. RESULTS: People with Type 2 diabetes mellitus (ICD code: E11) and heart failure (ICD code: I50) (N = 14 723) were older, more often women and presented with longer diabetes duration compared with those without heart failure. After adjustment for age, gender and diabetes duration, people with heart failure showed lower HbA1c , higher BMI and more intense insulin therapy. Analysis revealed that people with heart failure were more often treated with insulin, and more frequently received anti-hypertensives and lipid-lowering medication. They presented with lower systolic and diastolic BP. People with heart failure more frequently showed a history of comorbidities. CONCLUSION: Heart failure is common in diabetes mellitus, but the prevalence in the DPV is lower frequent than expected. The reason for improved metabolic control in heart failure may be intensified therapy with insulin, lipid-lowering medication and anti-hypertensives in this cohort.


Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Insuficiência Cardíaca/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Comorbidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hemoglobinas Glicadas/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Sistema de Registros , Resultado do Tratamento
2.
Forensic Sci Int ; 286: 106-112, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29574345

RESUMO

Due to a lack of reference values for blood concentration of metformin in the literature, the forensic evaluation of metformin findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested metformin amounts are often vague. Furthermore, post mortem evaluation of death due to lactic acidosis because of metformin is difficult since renal performance or lactate concentrations can not always reliably be determined after death. To describe a concentration range in clinical samples after chronic use of metformin, metformin serum concentrations were determined in serum samples of 95 diabetic patients receiving daily doses of 500mg-3000mg of metformin. The analyses of metformin was carried out using a validated high performance liquid chromatograph coupled to triple quadrupole mass spectrometry (LC-QQQ-MS). On average, metformin concentrations were 1846ng/mL (

Assuntos
Acidose Láctica/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/sangue , Metformina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida , Nefropatias Diabéticas/patologia , Feminino , Taxa de Filtração Glomerular , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Espectrometria de Massas , Metformina/uso terapêutico , Pessoa de Meia-Idade , Nefrite Intersticial/patologia
3.
Horm Metab Res ; 48(10): 630-637, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27589345

RESUMO

Implantation of a duodenal-jejunal endoluminal bypass liner (DJBL) has shown to induce weight loss and to improve metabolic parameters. DJBL is a reversible endoduodenal sleeve mimicking duodenal bypass while lacking risks and limitations of bariatric surgery.Effects on metabolic control, body mass parameters, appetite regulation, glucose tolerance, organ health, and lipid profile were determined in 16 morbidly overweight patients with type 2 diabetes mellitus. In addition, relevant hormones (leptin, ghrelin, gastric inhibitory peptide, glucagon-like peptide, and insulin) were measured by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA) at 0, 1, 32, and 52 weeks post-implant following a mixed meal tolerance test. Lipoprotein subclasses were analysed by proton nuclear magnetic resonance (1H NMR) spectrometry. DJBL provoked weight loss, a decrease in fat mass, and an improvement in insulin resistance and hepatic function in most but not all of the patients, but in the long term did not increase gut hormone fasting levels pointing to a combined effect of more than gut parameters alone. Lipidome analysis was done in 10 patients, allowing classification to responders and non-responders by reduction of sLDL-p subfraction; and to further analyse the atherogenic profile. Responders showed an overall more pronounced effect regarding improvement of HbA1c, BMI, and HOMA index.Implantation of a DJBL in obese type 2 diabetes patients does not per se lead to an improvement of the metabolic situation. Further analyses including larger cohorts have to be performed to identify responding patients, to better treat non-responders and to analyse the key effectors.


Assuntos
Adiposidade , Cirurgia Bariátrica , Diabetes Mellitus Tipo 2/cirurgia , Duodeno/cirurgia , Jejuno/cirurgia , Obesidade Mórbida/fisiopatologia , Adulto , Idoso , Glicemia/análise , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Duodeno/metabolismo , Feminino , Seguimentos , Polipeptídeo Inibidor Gástrico/metabolismo , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Insulina/metabolismo , Secreção de Insulina , Jejuno/metabolismo , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Redução de Peso
4.
Internist (Berl) ; 56(6): 653-61; quiz 662-3, 2015 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-26002020

RESUMO

Cardiovascular diseases continue to be the mainstay in morbidity and mortality in modern society with diabetes mellitus being a known risk factor for coronary artery disease, heart failure and vascular events. Most patients present with a combination of hypertension, dyslipoproteinaemia and (pre)diabetic metabolism potentiating the risk. From the perspective of organ damage two of three patients with coronary artery disease present with impaired glucose metabolism. In case of myocardial infarction 25-28% of patients do not present with impaired glucose metabolism. Women are more often affected than men and exhibit a more severe outcome, if diagnoses of vascular events and diabetes occur in parallel. Atrial fibrillation and heart failure are significantly associated with diabetes and significantly confer to the overall prognosis. Epidemiologically, the risk for vascular events is closely associated with the glucose burden of the affected patient.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/epidemiologia , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Distribuição por Idade , Comorbidade , Humanos , Incidência , Fatores de Risco
6.
Horm Metab Res ; 46(2): 77-84, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24108388

RESUMO

Methylglyoxal (MG) is a highly reactive dicarbonyl compound derived mainly from glucose degradation pathways, but also from protein and fatty acid metabolism. MG modifies structure and function of different biomolecules and thus plays an important role in the pathogenesis of diabetic complications. Hyperglycemia-associated accumulation of MG might be associated with generation of oxidative stress and subsequently insulin resistance. Therefore, the effects of MG on insulin signaling and on translocation of glucose transporter 4 (GLUT4) were investigated in the rat skeletal muscle cell line L6-GLUT4myc stably expressing myc-tagged GLUT4. Twenty four-hour MG treatment resulted in elevated GLUT4 presentation on the surface of L6 myoblasts and in an increased uptake of glucose even without insulin stimulation. Exogenously added MG neither effected IRS-1 expression nor IRS-1 phosphorylation. A decreased expression of Akt1 but not Akt2 and concomitantly increased apoptosis were detected following MG treatment. To exclude that oxidative stress caused by MG treatment leads to increased GLUT4 translocation, effects of pretreatment with 2 antioxidants were investigated. The antioxidant and MG scavenger NAC prevented the MG-induced GLUT4 translocation. In contrast, tiron, a well-known antioxidant that does not exert MG-scavenger function, had no impact on MG-induced GLUT4 translocation supporting the hypothesis of a direct effect of MG on GLUT4 trafficking. In conclusion, prolonged treatment with MG augments GLUT4 level on the surface of L6 myoblasts, at least in part through a higher translocation of GLUT4 from the intracellular compartment as well as a reduction of GLUT4 internalization, resulting in increased glucose uptake.


Assuntos
Transportador de Glucose Tipo 4/metabolismo , Glucose/metabolismo , Músculo Esquelético/metabolismo , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Aldeído Pirúvico/farmacologia , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/metabolismo , Animais , Apoptose , Transporte Biológico/efeitos dos fármacos , Linhagem Celular , Membrana Celular/química , Desoxiglucose/análogos & derivados , Desoxiglucose/metabolismo , Transportador de Glucose Tipo 4/análise , Transportador de Glucose Tipo 4/efeitos dos fármacos , Insulina/metabolismo , Músculo Esquelético/citologia , Mioblastos/química , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/análise , Proteínas Proto-Oncogênicas c-akt/metabolismo , Aldeído Pirúvico/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
7.
Horm Metab Res ; 46(7): 490-2, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24356795

RESUMO

Recent evidence suggests that omega-3 polyunsaturated fatty acids [n-3 PUFAs: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], improve insulin sensitivity in humans. In a double-blind, placebo-controlled, randomized, crossover study, we investigated the effects of EPA/DHA on paraoxonase-1 activity as well as fasting and postprandial levels of circulating adiponectin and leptin in 34 subjects with type 2 diabetes mellitus who received daily for 6 weeks either 2 g purified EPA/DHA or olive oil (placebo), separated by a 6 weeks washout. At the end of each treatment, measurements were performed in fasting state and 2, 4, and 6 h following a standardized high-fat meal (600 kcal). No significant differences in fasting and postprandial circulating adiponectin, leptin, and paraoxonase-1 activity were seen between n-3 PUFAs and placebo. Our data do not support an insulin sensitizing effect of n-3 PUFAs by means of influencing circulating adipocytokines in this population. Clinical Trial Register Number: NCT00328536.


Assuntos
Adiponectina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , Leptina/sangue , Adulto , Idoso , Humanos , Pessoa de Meia-Idade
8.
Metab Syndr Relat Disord ; 11(6): 392-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23869419

RESUMO

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder characterized by morbid obesity resulting from insatiable appetite. Complications like diabetes mellitus or other cardiovascular diseases typically occur during lifetime. Lifestyle advice and education as well as limited caloric intake are the major concepts in assistance of PWS patients. METHODS: A 12.9-month follow-up study, which included 8 formerly genetically diagnosed PWS patients, was conducted. Physical and laboratory examinations were done at the beginning and at the end of the follow-up. Improved medical care and lifestyle advice were given. The participants lived in an assisted living environment with a fixed daily schedule and limited caloric intake. RESULTS: The group of patients consisted of manifest diabetics (n=6) as well as nondiabetics (n=2). Therapeutic concepts were simplified in 2 patients by switching from insulin to oral antidiabetics. The reduction in body weight was moderate, but attributable to a loss of fat mass. A significant reduction in blood cholesterol and triglyceride content was achieved along the observational period as well as a significant reduction of glycosylated hemoglobin (HbA1c) in the group of diabetic PWS patients. Systolic blood pressure improved during the study. CONCLUSION: A combination of an assisted living environment following conservative treatments as well as consistent patient care improved the daily and medical situation of PWS patients. Weight loss and, as a consequence, improvements in terms of metabolic condition and blood pressure were observed. A combination of medical and daily routine management should be established in PWS patients to improve their quality of life.


Assuntos
Síndrome de Prader-Willi/terapia , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Peso Corporal , Espessura Intima-Media Carotídea , Colesterol/sangue , Complicações do Diabetes/sangue , Complicações do Diabetes/terapia , Feminino , Seguimentos , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Estilo de Vida , Masculino , Obesidade Mórbida/sangue , Obesidade Mórbida/terapia , Síndrome de Prader-Willi/sangue , Qualidade de Vida , Sístole , Triglicerídeos/sangue , Redução de Peso , Adulto Jovem
9.
Diabet Med ; 30(10): 1204-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23701274

RESUMO

AIMS: In a pilot study we suggested that benfotiamine, a thiamine prodrug, prevents postprandial endothelial dysfunction in people with Type 2 diabetes mellitus. The aim of this study was to test these effects in a larger population. METHODS: In a double-blind, placebo-controlled, randomized, crossover study, 31 people with Type 2 diabetes received 900 mg/day benfotiamine or a placebo for 6 weeks (with a washout period of 6 weeks between). At the end of each treatment period, macrovascular and microvascular function were assessed, together with variables of autonomic nervous function in a fasting state, as well as 2, 4 and 6 h following a heated, mixed test meal. RESULTS: Participants had an impaired baseline flow-mediated dilatation (2.63 ± 2.49%). Compared with the fasting state, neither variable changed postprandially following the placebo treatment. The 6 weeks' treatment with high doses of benfotiamine did not alter this pattern, either in the fasting state or postprandially. Among a subgroup of patients with the highest flow-mediated dilatation, following placebo treatment there was a significant postprandial flow-mediated dilatation decrease, while this effect was attenuated by benfotiamine pretreatment. CONCLUSIONS: In people with Type 2 diabetes and markedly impaired fasting flow-mediated dilatation, a mixed test meal does not further deteriorate flow-mediated dilatation or variables of microvascular or autonomic nervous function. Because no significant deterioration of postprandial flow-mediated dilatation, microvascular or autonomic nervous function tests occurred after placebo treatment, a prevention of the postprandial deterioration of these variables with benfotiamine was not feasible.


Assuntos
Antioxidantes/uso terapêutico , Vias Autônomas/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Período Pós-Prandial , Tiamina/análogos & derivados , Adulto , Idoso , Vias Autônomas/fisiopatologia , Biomarcadores/sangue , Glicemia/metabolismo , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/fisiopatologia , Método Duplo-Cego , Endotélio Vascular/fisiopatologia , Jejum , Feminino , Humanos , Fluxometria por Laser-Doppler , Masculino , Microcirculação/efeitos dos fármacos , Pessoa de Meia-Idade , Projetos Piloto , Período Pós-Prandial/efeitos dos fármacos , Tiamina/uso terapêutico
11.
Dtsch Med Wochenschr ; 137(9): 437-41, 2012 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-22354800

RESUMO

Patients with type 2 diabetes have an increased risk for developing symptoms of heart failure. These can be accompanied by a reduction of left ventricular ejection fraction (HFREF, systolic heart failure) or by a preserved function (HFPEF, diastolic heart failure). The pathophysiology of both entities is distinct and involves impairment of myocardial metabolism and coronary circulation alike. Although diabetes and heart failure often coincide, the management of these patients particularly with respect to the specific benefits or possible hazards of antidiabetic treatment is vague. Therefore, from a pathophysiological as well as clinical viewpoint, 1) diabetic patients with symptoms of heart failure have to be differentiated regarding systolic as well as diastolic left ventricular function by echocardiography and tissue doppler imaging. 2) Heart failure in diabetic patients needs similar attention due to a prognosis and interactions. 3) Optimized blood glucose lowering in combination with improvement of other cardiovascular risk factors is evident for HFREF and is assumed to be beneficial for HFPEF. 4) Antidiabetic medication has to be specifically adapted for both entities. As prospective, controlled studies are scarce, future interventional studies should specifically focus on clinical outcome in diabetic patients with different entities of heart failure.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Insuficiência Cardíaca Diastólica/etiologia , Insuficiência Cardíaca/etiologia , Disfunção Ventricular Esquerda/etiologia , Terapia Combinada , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Cardiomiopatias Diabéticas/diagnóstico , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/terapia , Ecocardiografia , Ecocardiografia Doppler , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca Diastólica/fisiopatologia , Insuficiência Cardíaca Diastólica/terapia , Hemodinâmica/fisiologia , Humanos , Hipoglicemiantes/uso terapêutico , Prognóstico , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia
12.
Int J Clin Pract ; 66(4): 384-93, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22284892

RESUMO

BACKGROUND AND AIM: Despite improvements in surgical revascularisation, limitations like anatomical factors or atherosclerosis limit the success of revascularisation in diabetic patients with critical limb ischaemia. Stem cells were shown to improve microcirculation in published studies. The aim of this study was to evaluate safety, feasibility and efficacy of transplantation of bone marrow derived cellular products regarding improvement in microcirculation and lowering of amputation rate. METHODS: Bone marrow mononuclear cells (BMCs) in comparison with expanded bone marrow cells enriched in CD90+ cells ('tissue repair cells', TRCs) were used in the treatment of diabetic ulcers to induce revascularisation. Diabetic foot patients with critical limb ischaemia without option for surgical or interventional revascularisation were eligible. Parameters examined were ABI, TcPO(2) , reactive hyperaemia and angiographic imaging before and after therapy. RESULTS: Of 30 patients included in this trial, 24 were randomised to receive either BMCs or TRCs. The high number of drop-outs in the control group (4 of 6) led to exclusion from evaluation. A total of 22 patients entered treatment; one patient in the TRC group and two in the BMC group did not show wound healing during follow up, one patient in each treatment group died before reaching the end of the study; one after having achieved wound healing (BMC group), the other one without having achieved wound healing (TRC group). Thus, 18 patients showed wound healing after 45 weeks. The total number of applicated cells was 3.8 times lower in the TRC group, but TRC patients received significantly higher amounts of CD90+ cells. Improvement in microvascularisation was detected in some, but not all patients by angiography, TcPO(2) improved significantly compared with baseline in both therapy groups. CONCLUSION: The transplantation of BMCs as well as TRCs proved to be safe and feasible. Improvements of microcirculation and complete wound healing were observed in the transplant groups.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Pé Diabético/terapia , Isquemia/complicações , Perna (Membro)/irrigação sanguínea , Monócitos/transplante , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Transplante de Medula Óssea/métodos , Doença Crônica , Estudos de Viabilidade , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante de Células-Tronco/métodos , Transplante Autólogo , Resultado do Tratamento , Cicatrização/fisiologia , Adulto Jovem
13.
Diabetologia ; 54(11): 2923-30, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21773683

RESUMO

AIMS/HYPOTHESIS: The primary aim of this study was to compare the results of HbA(1c) measurements with those of an OGTT for early diagnosis of 'silent diabetes' in patients with coronary artery disease (CAD) undergoing angiography without prediagnosed diabetes. A secondary aim was to investigate the correlation between the extent of CAD and the glycaemic status of the patient. METHODS: Data from 1,015 patients admitted for acute (n = 149) or elective (n = 866) coronary angiography were analysed. Patients with known diabetes were excluded from the study. Using the OGTT results, patients were classified as having normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes. According to the results of the HbA(1c) measurements, patients were classified into three groups: normal (HbA(1c) <5.7% [<39 mmol/mol]), borderline (HbA(1c) 5.7-6.4% [39-47 mmol/mol]) and diabetes (HbA(1c) ≥6.5% [≥48 mmol/mol]). RESULTS: Based on the OGTT, 513 patients (51%) were classified with NGT, 10 (1%) with IFG, 349 (34%) with IGT and 149 (14%) were diagnosed with diabetes. According to HbA(1c) measurements, 588 patients (58%) were classified as normal, 385 (38%) as borderline and 42 (4%) were diagnosed with diabetes. The proportion of patients with IGT and diabetes increased with the extent of CAD (IGT ρ = 0.14, p < 0.001, diabetes ρ = 0.09, p = 0.01). No differences in HbA(1c) were seen among the groups with different extents of CAD (p = 0.652). CONCLUSIONS/INTERPRETATION: An OGTT should be performed routinely for diagnosis of diabetes in patients with CAD undergoing coronary angiography, since HbA(1c) measurement alone appears to miss a substantial proportion of patients with silent diabetes. A limitation of the study is that the OGTT was not performed before the angiography.


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Diabetes Mellitus/diagnóstico , Angiopatias Diabéticas/diagnóstico por imagem , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Programas de Rastreamento/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Doença da Artéria Coronariana/complicações , Estudos Transversais , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Feminino , Alemanha/epidemiologia , Intolerância à Glucose/sangue , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Prevalência , Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença
14.
Horm Metab Res ; 41(8): 594-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19384818

RESUMO

Chronic conditions like diabetes mellitus (DM) leading to altered metabolism might cause cardiac dysfunction. Hyperglycemia plays an important role in the pathogenesis of diabetic complications including accumulation of methylglyoxal (MG), a highly reactive alpha-dicarbonyl metabolite of glucose degradation pathways and increased generation of advanced glycation endproducts (AGEs). The aim of this investigation was to study the extent of the MG-modification argpyrimidine in human diabetic heart and in rat cardiomyoblasts grown under hyperglycemic conditions. Left ventricular myocardial samples from explanted hearts of patients with cardiomyopathy with (n=8) or without DM (n=8) as well as nonfailing donor organs (n=6), and rat cardiac myoblasts H9c2 treated with glucose were screened for the MG-modification argpyrimidine. The small heat shock protein 27 (Hsp27) revealed to be the major argpyrimidine containing protein in cardiac tissue. Additionally, the modification of arginine leading to argpyrimidine and the phosphorylation of Hsp27 are increased in the myocardium of patients with DM. In H9c2 cells hyperglycemia leads to a decrease of the Hsp27-expression and an increase in argpyrimidine content and phosphorylation of Hsp27, which was accompanied by the induction of oxidative stress and apoptosis. This study shows an association between diabetes and increased argpyrimidine-modification of myocardial Hsp27, a protein which is involved in apoptosis, oxidative stress, and cytoskeleton stabilization.


Assuntos
Cardiomiopatias/fisiopatologia , Complicações do Diabetes/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Coração/fisiopatologia , Adulto , Idoso , Animais , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Linhagem Celular , Complicações do Diabetes/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Ornitina/análogos & derivados , Ornitina/metabolismo , Fosforilação , Pirimidinas/metabolismo , Aldeído Pirúvico/metabolismo , Ratos
15.
Exp Clin Endocrinol Diabetes ; 116 Suppl 1: S40-5, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18777453

RESUMO

With the rapidly increasing prevalence of type 2 diabetes mellitus the risk for cardiovascular events is increasing. Almost 2 of 3 patients who present with symptomatic CHD have abnormal glucose homeostasis. Patients with diabetes mellitus and cardiovascular disease have an unfavourable prognosis. The most important result of diabetes metabolism is the switch from carbohydrates and fatty acids as a source of energy to an excessive use of fatty acids. The adverse influence of diabetes mellitus extends to all components of the cardiovascular system, including microvasculature, the epicardial coronary arteries, the large conduit arteries and the heart, as well as the kidneys. Focus of this review is the myocardial metabolism in heart failure and diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/metabolismo , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/etiologia , Metabolismo Energético/fisiologia , Ácidos Graxos/metabolismo , Humanos , Resistência à Insulina/fisiologia
16.
Horm Metab Res ; 40(12): 896-900, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18792885

RESUMO

Leptin modulates satiety and increases in obesity and type 2 diabetes mellitus in parallel with leptin resistance. Postprandial leptin regulation has been previously postulated to depend on meal composition, but data are controversial. The hypothesis of our study was that in people with type 2 diabetes mellitus, a postprandial leptin regulation exists that can be regulated not only by meal composition but also by the cooking method. In 20 inpatients with type 2 diabetes (mean age: 55.9 years), the acute effects of 2 meals, a high-heat-processed meal HHPM or a low-heat-processed meal LHPM, on leptin levels were studied on 2 different days in a randomized, crossover design. Both test meals had similar ingredients and differed only in the cooking method used. Parameters were measured after an overnight fast and at 2, 4, and 6 h postprandially. The HHPM induced a marked decrease in leptin levels, from 8 717+/-2 079 pg/ml at baseline to 6 788+/-1 598 pg/ml at 2 h postprandially (-1 929 pg/ml, -22%*), an effect significantly reduced by the LHPM, where values were 8 563+/-1 900 pg/ml at baseline and 7 425+/-1 591 pg/ml at 2 h postprandially (-1 138 pg/ml, -13%* (double dagger)) (*p<0.05 vs. baseline, (double dagger)p<0.05 vs. HHPM). Parameters of oxidative stress and blood AGEs increased only following the HHPM, while postprandial glucose, triglycerides, and insulin excursions were similar between meals. Postprandial leptin decreases following a HHPM meal in people with T2DM, an effect reduced by the cooking method.


Assuntos
Culinária , Diabetes Mellitus Tipo 2/sangue , Leptina/sangue , Período Pós-Prandial/fisiologia , Glicemia/metabolismo , Estudos Cross-Over , Dieta , Dieta para Diabéticos , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Aldeído Pirúvico/sangue
17.
Diabetes Res Clin Pract ; 82(2): 179-84, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18778866

RESUMO

Adiponectin (APN) is present in human plasma as a low molecular weight (LMW), a middle molecular weight (MMW) and a high molecular weight form (HMW). As a support to determine properties such as anti-atherogenic or atherogenic effects, recent clinical studies suppose to determine the ratio of each APN multimer to total APN but not the absolute plasma concentration of APN. In the present study, the correlation of APN and its multimers with myeloperoxidase (MPO), an enzyme with pro-inflammatory properties, was examined in patients with type 2 diabetes mellitus. MPO and APN serum levels were assessed in 49 patients with type 2 diabetes mellitus at the beginning and at the end of an anti-diabetic treatment. After treatment a significant increase in the ratio of HMW to total APN (from 0.43+/-0.16 to 0.59+/-0.14, p<0.05) was found. Before treatment, HMW-APN was correlated positively with MPO (r=0.314, p<0.05). Moreover, a positive correlation was observed between the increased HMW ratio and MPO during treatment (r=0.304, p<0.05). HMW-APN correlates positively with MPO in patients with type 2 diabetes. Therefore, HMW-APN may exert possible pro-inflammatory effects in type 2 diabetes.


Assuntos
Adiponectina/sangue , Diabetes Mellitus Tipo 2/metabolismo , Peroxidase/metabolismo , Adiponectina/química , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peso Molecular
18.
Internist (Berl) ; 49(4): 436-40, 2008 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-18301873

RESUMO

Diabetic cardiomyopathy is a myocardial disease caused by diabetes mellitus unrelated to vascular and valvular pathology or systemic arterial hypertension. Clinical and experimental studies have shown that diabetes mellitus causes myocardial hypertrophy, apoptosis and necrosis, and increases interstitial tissue. The pathophysiology of diabetic cardiomyopathy is incompletely understood and several mechanistical approaches are under debate. Metabolic impairments like hyperglycemia, hyperlipidemia, hyperinsulinemia, and alterations in the cardiac metabolism lead to structural and functional changes which show cellular effects leading to increased oxidative stress, interstitial fibrosis, myocyte death, and disturbances in ion transport and homeostasis. Diastolic dysfunction which consecutively results in systolic dysfunction with increased left ventricular volume and reduced ejection fraction is an early diagnostic parameter. Treatment of diabetic cardiomyopathy does not differ from myocardiopathies of other etiologies and therefore has to follow the appropriate guidelines. Early intervention to reverse metabolic toxicity is the most effective method of prevention.


Assuntos
Doença da Artéria Coronariana/etiologia , Complicações do Diabetes/etiologia , Insuficiência Cardíaca Diastólica/etiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/fisiopatologia , Metabolismo Energético/fisiologia , Ácidos Graxos não Esterificados/sangue , Insuficiência Cardíaca Diastólica/diagnóstico , Insuficiência Cardíaca Diastólica/fisiopatologia , Humanos , Resistência à Insulina/fisiologia , Miocárdio/metabolismo , Miocárdio/patologia , Fatores de Risco
19.
Int J Clin Pract ; 61(4): 690-2, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17394441

RESUMO

Previous studies suggest that autologous transplantation of bone marrow mononuclear cells is safe and effective in inducing therapeutic angiogenesis in patients with peripheral arterial occlusive disease (PAOD). Here we discuss a multidisciplinary approach to treating PAOD with a focus on the use of angiological diagnostic tools. We conclude that our autologous stem cell therapy is working in this patient and it is a potential new therapeutic option for diabetic patients with chronic foot ulcers induced by critical limb ischaemia.


Assuntos
Pé Diabético/terapia , Isquemia/complicações , Perna (Membro)/irrigação sanguínea , Transplante de Células-Tronco/métodos , Diabetes Mellitus Tipo 2/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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