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1.
Horm Behav ; 141: 105120, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35220091

RESUMO

It is increasingly recognized that psychological stress is linked with type 2 diabetes mellitus and its late complications. Thus, the aim of the current study was to investigate the psychophysiological response to acute psychosocial stress in patients with type 2 diabetes. In total, 53 type 2 diabetes patients with complications, 16 type 2 diabetes patients without complications, and 47 age and gender matched non-diabetic participants underwent the Trier Social Stress Test. Subjective as well as biological parameters (i.e., blood levels of cortisol, adrenocorticotropic hormone (ACTH), norepinephrine, methylglyoxal) were assessed repeatedly before and after stress induction. Data were analyzed by means of multilevel regression. Patients with type 2 diabetes showed an exaggerated cortisol response to acute stress as compared to age matched control participants (diabetes*T2 est. = 1.23, p < .001), while stress-induced alterations of ACTH and subjective parameters did not differ. Norepinephrine levels were lower among patients (diabetes est. = -4.36, p = .044) and tended to decrease earlier than in controls. The subjective reaction of type 2 diabetes patients with complications was stronger than that of patients without complications (complication*T2 est. = -1.83, p = .032), while their endocrine response to stress was similar. Stress had no effect on methylglyoxal level, and there were no group differences regarding methylglyoxal response. These results show that the cortisol reactivity of patients with type 2 diabetes to acute psychosocial stress is increased compared to a control group. Thus, alterations of the hypothalamus-pituitary-adrenal axis - especially regarding its dynamic regulation - are a plausible link between psychological stress and type 2 diabetes and its complications.


Assuntos
Diabetes Mellitus Tipo 2 , Hidrocortisona , Hormônio Adrenocorticotrópico , Diabetes Mellitus Tipo 2/complicações , Humanos , Sistema Hipotálamo-Hipofisário , Norepinefrina/farmacologia , Sistema Hipófise-Suprarrenal , Aldeído Pirúvico/farmacologia , Saliva , Estresse Psicológico
2.
Br J Surg ; 105(3): 168-181, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29405276

RESUMO

BACKGROUND: This study aimed to examine the effect of metabolic surgery on pre-existing and future microvascular complications in patients with type 2 diabetes mellitus (T2DM) in comparison with medical treatment. Although metabolic surgery is the most effective treatment for obese patients with T2DM regarding glycaemic control, it is unclear whether the incidence or severity of microvascular complications is reduced. METHODS: A systematic literature search was performed in MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) with no language restrictions, looking for RCTs, case-control trials and cohort studies that assessed the effect of metabolic surgery on the incidence of microvascular diabetic complications compared with medical treatment as control. The study was registered in the International prospective register of systematic reviews (CRD42016042994). RESULTS: The literature search yielded 1559 articles. Ten studies (3 RCTs, 7 controlled clinical trials) investigating 17 532 patients were included. Metabolic surgery reduced the incidence of microvascular complications (odds ratio 0·26, 95 per cent c.i. 0·16 to 0·42; P < 0·001) compared with medical treatment. Pre-existing diabetic nephropathy was strongly improved by metabolic surgery versus medical treatment (odds ratio 15·41, 1·28 to 185·46; P = 0·03). CONCLUSION: In patients with T2DM, metabolic surgery prevented the development of microvascular complications better than medical treatment . Metabolic surgery improved pre-existing diabetic nephropathy compared with medical treatment.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/prevenção & controle , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/terapia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/etiologia , Humanos , Incidência , Microvasos , Razão de Chances , Resultado do Tratamento
3.
Neuroscience ; 387: 28-37, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28942323

RESUMO

A 62-year-old diabetologist diagnosed himself to have diabetes type-2, with an HbA1c of 9.5. Five months after lifestyle intervention and a multi-drug approach, HbA1c was 6.3, systolic blood pressure was below 135mmHg and BMI reduced to 27. But he suffered from severe painful diabetic neuropathy. Therefore he decided to visit his friend, a famous neuroscientist at an even more famous university. He asked him several plain questions: 1. What is the natural course of painful diabetic neuropathy? 2. Why do I have, despite almost normalizing HbA1c, more problems than before? 3. Are you sure my problems are due to diabetes or should we do a nerve biopsy? 4. Are there imaging techniques helpful for the diagnosis of this diabetic complication, starting in the distal nerve endings of the foot and slowly moving ahead? 5. Can you suggest any drug, specific and effective, for relieving painful diabetic neuropathy? This review will use the experts' answers to the questions of the diabetologist, not only to give a summary of the current knowledge, but even more to highlight areas of research needed for improving the fate of patients with painful diabetic neuropathy. Based on the unknowns, which exceed the knowns in diabetic neuropathy, a quest for more public support of research is made.


Assuntos
Pesquisa Biomédica , Neuropatias Diabéticas/complicações , Dor/complicações , Animais , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/tratamento farmacológico , Progressão da Doença , Humanos
4.
Sci Rep ; 7(1): 2261, 2017 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-28536464

RESUMO

Renal sinus fat (RSF) is a perivascular fat compartment located around renal arteries. In this in vitro and in vivo study we hypothesized that the hepatokine fetuin-A may impair renal function in non alcoholic fatty liver disease (NAFLD) by altering inflammatory signalling in RSF. To study effects of the crosstalk between fetuin-A, RSF and kidney, human renal sinus fat cells (RSFC) were isolated and cocultured with human endothelial cells (EC) or podocytes (PO). RSFC caused downregulation of proinflammatory and upregulation of regenerative factors in cocultured EC and PO, indicating a protective influence of RFSC. However, fetuin-A inverted these benign effects of RSFC from an anti- to a proinflammatory status. RSF was quantified by magnetic resonance imaging and liver fat content by 1H-MR spectroscopy in 449 individuals at risk for type 2 diabetes. Impaired renal function was determined via urinary albumin/creatinine-ratio (uACR). RSF did not correlate with uACR in subjects without NAFLD (n = 212, p = 0.94), but correlated positively in subjects with NAFLD (n = 105, p = 0.0005). Estimated glomerular filtration rate (eGRF) was inversely correlated with RSF, suggesting lower eGFR for subjects with higher RSF (r = 0.24, p < 0.0001). In conclusion, our data suggest that in the presence of NAFLD elevated fetuin-A levels may impair renal function by RSF-induced proinflammatory signalling in glomerular cells.


Assuntos
Gordura Intra-Abdominal/fisiologia , Glomérulos Renais/citologia , Glomérulos Renais/metabolismo , Rim/anatomia & histologia , Rim/fisiologia , Artéria Renal/anatomia & histologia , alfa-2-Glicoproteína-HS/metabolismo , Adipócitos/metabolismo , Adulto , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Gordura Intra-Abdominal/diagnóstico por imagem , Rim/diagnóstico por imagem , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Artéria Renal/diagnóstico por imagem
5.
J Thromb Haemost ; 14(11): 2212-2226, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27590316

RESUMO

Essentials The role of protein C (PC) activation in experimental autoimmune encephalitis (EAE) is unknown. PC activation is required for mitochondrial function in the central nervous system. Impaired PC activation aggravates EAE, which can be compensated for by soluble thrombomodulin. Protection of myelin by activated PC or solulin is partially independent of immune-modulation. SUMMARY: Background Studies with human samples and in rodents established a function of coagulation proteases in neuro-inflammatory demyelinating diseases (e.g. in multiple sclerosis [MS] and experimental autoimmune encephalitis [EAE]). Surprisingly, approaches to increase activated protein C (aPC) plasma levels as well as antibody-mediated inhibition of PC/aPC ameliorated EAE in mice. Hence, the role of aPC generation in demyelinating diseases and potential mechanisms involved remain controversial. Furthermore, it is not known whether loss of aPC has pathological consequences at baseline (e.g. in the absence of disease). Objective To explore the role of thrombomodulin (TM)-dependent aPC generation at baseline and in immunological and non-immunological demyelinating disease models. Methods Myelination and reactive oxygen species (ROS) generation were evaluated in mice with genetically reduced TM-mediated protein C activation (TMPro/Pro ) and in wild-type (WT) mice under control conditions or following induction of EAE. Non-immunological demyelination was analyzed in the cuprizone-diet model. Results Impaired TM-dependent aPC generation already disturbs myelination and mitochondrial function at baseline. This basal phenotype is linked with increased mitochondrial ROS and aggravates EAE. Reducing mitochondrial ROS (p66Shc deficiency), restoring aPC plasma levels or injecting soluble TM (solulin) ameliorates EAE in TMPro/Pro mice. Soluble TM additionally conveyed protection in WT-EAE mice. Furthermore, soluble TM dampened demyelination in the cuprizone-diet model, demonstrating that its myelin-protective effect is partially independent of an immune-driven process. Conclusion These results uncover a novel physiological function of TM-dependent aPC generation within the CNS. Loss of TM-dependent aPC generation causes a neurological defect in healthy mice and aggravates EAE, which can be therapeutically corrected.


Assuntos
Sistema Nervoso Central/metabolismo , Mitocôndrias/metabolismo , Bainha de Mielina/química , Proteína C/metabolismo , Trombomodulina/sangue , Animais , Encéfalo/metabolismo , Cardiolipinas/química , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Humanos , Sistema Imunitário , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Neurônios , Estresse Oxidativo , Células PC12 , Fenótipo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Solubilidade , Trombomodulina/química
6.
Diabet Med ; 33(12): 1625-1631, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27504739

RESUMO

AIMS: The glycolysis-derived metabolite methylglyoxal has been linked to clinical microvascular complications, including diabetic nephropathy. We aimed to further investigate the hypothesis that methylglyoxal is involved in decline in renal function by assessing the associations between measures of renal function during a 6-year follow-up in 1481 people with screen-detected Type 2 diabetes, as part of the Danish arm of the ADDITION-Europe trial (ADDITION-DK). METHODS: Biobank serum samples collected at ADDITION-DK baseline (2001-2006) and follow-up (2009-2010) were used in the current analysis of methylglyoxal. We assessed cross-sectional baseline and longitudinal associations between methylglyoxal and urinary albumin-to-creatinine ratio (ACR) or estimated GFR (eGFR), and between methylglyoxal and categories of albuminuria or reduced eGFR. RESULTS: Baseline methylglyoxal was positively associated with ACR at baseline (12% higher ACR per doubling in methylglyoxal levels), and change in methylglyoxal during 6 years of follow-up was inversely associated with change in eGFR (-1.6 ml/min/1.73 m2 per doubling in methylglyoxal change), in models adjusted for age, sex, HbA1c , systolic blood pressure, anti-hypertensive treatment, LDL-cholesterol, lipid-lowering treatment, C-reactive protein and smoking. CONCLUSIONS: In a population of people with screen-detected Type 2 diabetes, we observed associations between methylglyoxal and markers of renal function: 6-year change in methylglyoxal was inversely associated with 6-year change in eGFR. Also, methylglyoxal at baseline was positively associated with ACR at baseline. Our study lends further support to a role for methylglyoxal in the pathogenesis of diabetic nephropathy.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Aldeído Pirúvico/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , Albuminúria/fisiopatologia , Creatinina/urina , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade
8.
Exp Clin Endocrinol Diabetes ; 123(8): 466-72, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26393401

RESUMO

BACKGROUND: Predicting an individual's success in a non-surgical weight loss approach is a demanding need since obesity is becoming an epidemic burden. A possible predictive marker is myostatin, a member of the transforming growth factor b superfamily, which has been shown to be an important regulator of muscle homeostasis. METHODS: In the present study, we analyzed myostatin as a marker to predict weight loss of patients that participated in a 2 phased weight reduction program, comprising a weight loss period of 12 weeks and a weight stabilization period of 40 weeks. Therefore, 62 obese individuals with a mean BMI of 40.6 kg/m(2) were included. Plasma myostatin was measured with ELISA at the beginning (T0), after weight loss (T1) and at the end of the program (T2). RESULTS: Although significant weight loss of -23.9±14.9 kg was achieved, myostatin did not change significantly during the program (T0>T1: p=0.46; T1>T2: p=0.70; T0>T2: p=0.57). Myostatin at baseline did neither negatively correlate with the achieved weight loss in the weight reduction phase (T0>T1: r=0.27, p=0.16) nor with weight loss during the whole program (T0>T2: r=0.20, p=0.29). Only a minor correlation with myostatin levels after weight loss with weight regain during maintenance period was detected. (T1>T2: r=-0.37, p=0.05). CONCLUSION: Plasma myostatin might be suitable in predicting weight regain after marked weight loss, but no association with weight loss was observed in patients undergoing a non-surgical weight loss program. Therefore, myostatin does not seem to be a predictor for success in non-surgical weight loss approaches.


Assuntos
Miostatina/sangue , Obesidade/sangue , Obesidade/terapia , Redução de Peso , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Exp Clin Endocrinol Diabetes ; 123(10): 617-21, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26240957

RESUMO

Comprehensive diabetes treatment has been shown to reduce quality of life in diabetic patients. However, there is evidence to suggest that group singing can have positive effects on quality of life in various clinical settings. In this randomized controlled pilot study, the effect of singing as a therapy to reduce stress and improve quality of life was investigated in insulin-dependent diabetic patients, undergoing a lifestyle intervention program. Patients from the singing group felt less discontented following treatment. This effect, however, was lost after 3 months. No effect on serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels could be seen when comparing the singing group with the control group, although reduced levels of ACTH and cortisol 3 days after treatment could be found and were still present after 3 months within the group of patients who undertook singing as a therapy. Singing led to an increase in bodyweight, which interestingly had no effect on glucose control or methylglyoxal levels. Therefore, singing during a lifestyle intervention program for insulin-dependent diabetic patients had a short lasting and weak effect on patients' mood without affecting glucose control, but no significant effect on stress related hormones.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Canto , Estresse Psicológico/terapia , Adulto , Idoso , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia , Fatores de Tempo
10.
Diabet Med ; 32(6): 778-85, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25761542

RESUMO

AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy was assessed by vibration detection threshold (n = 319), 10 g monofilament (n = 543) and the Michigan Neuropathy Screening Instrument questionnaire (n = 966). Painful diabetic neuropathy was assessed using the Brief Pain Inventory short form (n = 882). RESULTS: No associations between methylglyoxal and cardiovascular autonomic reflex tests or any measures of diabetic peripheral neuropathy or painful diabetic neuropathy were observed. However, a positive association between methylglyoxal and several heart rate variability indices was observed, although these associations were not statistically significant when corrected for multiple testing. CONCLUSION: Serum methylglyoxal is not associated with cardiovascular autonomic neuropathy, diabetic peripheral neuropathy or painful diabetic neuropathy in this cohort of well-treated patients with short-term diabetes.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Neuropatias Diabéticas/sangue , Aldeído Pirúvico/sangue , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/epidemiologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
11.
Exp Clin Endocrinol Diabetes ; 122(6): 341-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24798861

RESUMO

Current guidelines for the treatment of type 2 diabetes focus on pharmacological treatment of glucose and cardio-vascular risk factors. The aim of this prospective randomized controlled intervention study was to examine the effects of a psychosocial intervention on clinical endpoints and risk factors in patients with type 2 diabetes and early diabetic kidney disease.110 patients were randomized to receive an 8-week mindfulness-based stress reduction (MBSR) training (n = 53) compared to standard care (n = 57). The study was carried out open-labelled and randomization was performed computer-generated in a 1:1 ratio. Primary outcome of the study was the change in urinary albumin excretion (albumin-creatinine-ratio, ACR); secondary outcomes were metabolic parameters, intima media thickness (IMT), psychosocial parameters and cardiovascular events.89 patients (42 in control group and 47 in intervention group) were analysed after 3 years of follow-up. After 1 year, the intervention group showed a reduction of ACR from 44 [16/80] to 39 [20/71] mg/g, while controls increased from 47 [16/120] to 59 [19/128] mg/g (p = 0.05). Parallel to the reduction of stress levels after 1 year, the intervention-group additionally showed reduced catecholamine levels (p < 0.05), improved 24 h-mean arterial (p < 0.05) and maximum systolic blood pressure (p < 0.01), as well as a reduction in IMT (p < 0.01). However, these effects were lost after 2 and 3 years of follow-up.This is the first study to show that a psychosocial intervention improves cardiovascular risk factors in high risk type 2 diabetes patients. Trial-Registration: NCT00263419 http://clinicaltrials.gov/ct2/show/NCT00263419 TRIAL REGISTRATION: clinicaltrials.gov-Identifier: NCT00263419.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Estresse Psicológico , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/psicologia , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/terapia , Nefropatias Diabéticas/psicologia , Nefropatias Diabéticas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estresse Psicológico/psicologia , Estresse Psicológico/terapia
12.
Exp Clin Endocrinol Diabetes ; 122(5): 316-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24710646

RESUMO

The effect of metformin on methylglyoxal (MG) metabolism was studied in a prospective non-randomized 24 weeks trial in patients with type 2 diabetes.Metformin treatment, in addition to life style intervention, significantly reduced morning glucose and HbA1c whilst body weight and BMI were only marginally reduced during the 24 week trial. Treatment significantly reduced both plasma MG and carboxymethyl-lysine (CML), a marker of oxidative stress. The reduction in MG was paralleled by a significant increase in the activity of Glyoxalase 1 (Glo1), the major route of MG detoxification, in peripheral blood mononuclear cells and red blood cells. Multivariate analysis showed that the changes in MG were dependent upon the metformin treatment.This study supports previous findings that metformin can reduce plasma MG in type 2 diabetic patients. However, given the observed increase in Glo1 activity, this reduction is due not only to the scavenging properties of metformin, but the restoration of Glo1 activity.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/análogos & derivados , Aldeído Pirúvico/sangue , Adulto , Feminino , Humanos , Lactoilglutationa Liase/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
Exp Clin Endocrinol Diabetes ; 122(4): 201-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24623503

RESUMO

The clinical symptoms of diabetic neuropathy (DN) manifest in a time dependent manner as a positive symptoms (i. e. pain, hypersensitivity, tingling, cramps, cold feet etc.) during its early stages and by a loss of function (i. e. loss of sensory perception, delayed wound healing etc.) predominating in the later stages. Elevated blood glucose alone cannot explain the development and progression of DN and the lowering of blood glucose is insufficient in preventing and/or reversing neuropathy in patients with type 2 diabetes. Recently it has been shown that the endogenous reactive metabolite methylglyoxal (MG) can contribute to the gain of function via post-translational modification in DN of neuronal ion channels involved in chemosensing and action potential generation in nociceptive nerve endings. Dicarbonyls, such as MG, that are elevated in diabetic patients, modify DNA as well as extra- and intracellular proteins, leading to the formation of advanced glycation endproducts (AGEs). Increased formation of AGEs leads to increased cellular stress, dysfunction and ultimately cell death. The interaction of AGE-modified proteins through cell surface receptors, such as RAGE, can lead to increased cellular activation and sustained inflammatory responses, which are the molecular hallmarks of the later, degenerative, stages of DN. The direct and indirect effects of dicarbonyls on nerves or neuronal microvascular network provides a unifying mechanism for the development and progression of DN. Targeting the accumulation of MG and/or prevention of RAGE interactions may therefore provide new, more effective, therapeutic approaches for the treatment of DN.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/terapia , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Neuropatias Diabéticas/sangue , Produtos Finais de Glicação Avançada/sangue , Produtos Finais de Glicação Avançada/metabolismo , Glioxal/sangue , Glioxal/metabolismo , Humanos , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/sangue , Receptores Imunológicos/metabolismo
15.
J Endocrinol Invest ; 37(3): 229-32, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24474679

RESUMO

BACKGROUND: Prospective, placebo-controlled, double-blind, randomized studies on osteoporosis treatment with bisphosphonates in men are rare. This review focuses on a recent trial and compares the results with other studies. METHODS: This review provides a summary of recent literature on fracture risk in men following treatment with zoledronic acid. According to a recent clinical study with 1,199 men, zoledronic acid was linked to a lower risk of vertebral fractures. In this manuscript, a re-analysis of the presented statistical data will be demonstrated by performing a Bonferroni-correction to adjust for type 1 error accumulation in multiple statistical tests. RESULTS: It will be shown that the provided evidence linking zoledronic acid to a lower fracture risk in male osteoporosis is true, but less pronounced than originally assumed. CONCLUSION: Comparative clinical studies are recommended, where the benefits of different bisphosphonates are compared to each other under the same experimental conditions.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas Ósseas/prevenção & controle , Imidazóis/uso terapêutico , Osteoporose/tratamento farmacológico , Humanos , Masculino , Medição de Risco , Ácido Zoledrônico
16.
Exp Clin Endocrinol Diabetes ; 121(10): 601-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24057510

RESUMO

The established marker for tubular damage, urinary n-acetyl-beta-d-glucosaminidase is significantly increased in type 1 and 2 diabetes patients and is related to albuminuria and other diabetic complications. In this cross sectional study of type 2 diabetes patients with a history of albuminuria, we studied the relationship between excretion of n-acetyl-beta-d-glucosaminidase in urine and diabetic neuropathy.160 type 2 diabetes patients were screened for diabetic peripheral neuropathy and cardiovascular autonomic neuropathy. N-acetyl-beta-d-glucosaminidase excretion was detected in 24 h urine samples.Urinary excretion of n-acetyl-beta-d-glucosaminidase correlated significantly with -glucose control (fasting glucose r=0.18; p=0.04; HbA1c r=0.20; p=0.02) and urine albumin excretion (r=0.22; p=0.01). Binary regression analyses showed that increased urinary n-acetyl-beta-d-glucosaminidase concentration is an independent predictor for presence of clinical symptoms of peripheral neuropathy (OR 1.8 [95%CI 1.2-2.74] and vibration deficiency [OR 1.7; 95% CI 1.2-2.66]. There was also a significant negative association between urinary n-acetyl-beta-d-glucosaminidase and E/I-Ratio (r=-0.21, p<0.02) as well as the 30:15-Ratio (r=-0.24; p<0.01) of heart rate variability. Furthermore, increased n-acetyl-beta-d-glucosaminidase excretion independently predicted cardiovascular autonomic diabetic neuropathy with an OR for decreased E/I-Ratio of 1.7 [95%CI 1.1-2.75]; (p<0.02) and 30:15-Ratio:OR 2.4 [95% CI 1.26-4.45]; (p<0.01).Urinary n-acetyl-beta-d-glucosami-nidase excretion is an independent marker for diabetic peripheral and cardiovascular autonomic neuropathy in type 2 diabetic patients.


Assuntos
Acetilglucosaminidase/urina , Diabetes Mellitus Tipo 2/urina , Neuropatias Diabéticas/urina , Idoso , Albuminúria/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Exp Clin Endocrinol Diabetes ; 121(7): 436-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23775136

RESUMO

AIMS/INTRODUCTION: Glyoxalase 1 catalyses the detoxification of methylglyoxal, a major precursor of advanced glycation end products associated with aging, neurodegenerative diseases, and microvascular complications of diabetes. Here, we examine a possible association of a single nucleotide polymorphism of glyoxalase 1 gene (Glo1 A332C, rs4746 or rs2736654) with the prevalence of microvascular diabetic complications in patients with type 1 and type 2 diabetes. MATERIALS AND METHODS: Genotyping was performed in 209 patients with type 1 and 524 patients with type 2 diabetes using polymerase chain reaction and subsequent cleavage by restriction endonuclease Bsa I. RESULTS: Frequencies of the glyoxalase 1 genotypes were different with respect to diabetes type with a significantly higher prevalence of A332A-genotype in type 1 diabetes (35.9% vs. 27.3%; p=0.03). In type 1 diabetes, there was no correlation of any genotype with diabetic retinopathy, nephropathy or neuropathy. In contrast, type 2 diabetic patients homozygous for the C332C allele showed a significantly increased prevalence of diabetic neuropathy (p=0.03; OR=1.49 [95%-CI: 1.04; 2.11]), while no association with diabetic nephropathy or retinopathy was found. However, the significance of this association was lost after correction for multiple testing. CONCLUSIONS: Our data suggest a possible association of C332C-genotype of the glyoxalase 1 gene with diabetic neuropathy in type 2 diabetes, supporting the hypothesis that methylglyoxal might be an important mediator of diabetic neuropathy in type 2 diabetes.


Assuntos
Complicações do Diabetes/genética , Diabetes Mellitus Tipo 2/genética , Genótipo , Lactoilglutationa Liase/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos Transversais , Complicações do Diabetes/enzimologia , Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/enzimologia , Feminino , Humanos , Lactoilglutationa Liase/metabolismo , Masculino , Pessoa de Meia-Idade
18.
Ophthalmologe ; 110(2): 154-9, 2013 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-22903147

RESUMO

Ocular fundus photography allows detection of both ocular and systemic diseases. This study investigated the efficacy of a broad screening in a department of internal medicine using nonmydriatic digital fundus photography. For 8 weeks a medical technician was trained in using the camera as well as interpreting the photographs. The medical technician and an ophthalmologist evaluated the fundus photographs separately by using a self-developed questionnaire. The fundus camera was user-friendly and after several weeks of adjustment and practical application the medical technician was able to detect the majority of pathological fundus photographs. Out of 218 patients examined 148 (68%) were identified as pathological by the medical technician and 163 (75%) by the ophthalmologist (p = 0.0003). The medical technician missed 15 (7%) patients. Furthermore the diagnoses made by the medical technician were faulty. In summary an ophthalmological screening by a medical technician is feasible but the diagnosis still remains the responsibility of ophthalmologists. Such a compromise could facilitate the examination of a large number of patients and disclose previously unrecognized diseases.


Assuntos
Angiofluoresceinografia/estatística & dados numéricos , Assistentes de Oftalmologia/estatística & dados numéricos , Médicos/estatística & dados numéricos , Competência Profissional , Doenças Retinianas/diagnóstico , Doenças Retinianas/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Prevalência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Skeletal Radiol ; 42(2): 225-30, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22588596

RESUMO

PURPOSE: The purpose of this study was to evaluate changes in regional bone perfusion in Paget's disease (PD) following bisphosphonate therapy. We used dynamic contrast-enhanced MRI (DCE-MRI) for assessment of bone perfusion and compared MRI findings with alkaline phosphatase (AP) as a serum marker of bone turnover. MATERIALS AND METHODS: We examined 20 patients (8 women, 12 men, 66 ± 11 years) with symptomatic PD of the axial skeleton. Patients were selected for infusion therapy with the bisphosphonate pamidronate. The most affected bone of lumbar spine or pelvis was examined by DCE-MRI prior to therapy and after a 6-month follow-up. The contrast uptake was evaluated using a two-compartment model with the parameters amplitude A and exchange rate constant K(ep). Color-coded parametric images were generated to visualize bone vascularization. RESULTS: After a 6-month follow-up there was a significant decrease in alkaline phosphatase and in DCE-MRI parameters A and K(ep) (p < 0.0001). Patients without previous bisphosphonate treatment showed a significantly greater decrease in alkaline phosphatase and K(ep) (p < 0.001). CONCLUSION: DCE-MRI shows a significant reduction in regional bone perfusion in PD following parenteral bisphosphonate treatment. Reduction in bone perfusion is greater in bisphosphonate-naïve patients than in those who had been previously treated.


Assuntos
Difosfonatos/administração & dosagem , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos , Osteíte Deformante/diagnóstico , Osteíte Deformante/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/administração & dosagem , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
20.
Int J Obes (Lond) ; 37(1): 135-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22310469

RESUMO

OBJECTIVE: The A-allele of the fat mass and obesity-associated (FTO) gene variant rs9939609 has been associated with increased body weight, whereas no effect on weight loss during weight reduction programs has been observed. We questioned whether the AA-genotype interferes with weight stabilization after weight loss. DESIGN: We conducted a monocentric, longitudinal study involving obese individuals. The FTO gene variant rs9939609 was genotyped in participants attending a weight reduction program that was divided into two phases: a weight reduction period with formula diet (12 weeks) and a weight maintenance phase (40 weeks). Body weight, body mass index (BMI), blood pressure and concentrations of blood glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides were determined in week 0 (T(0)), after 12 weeks (T(1)) and at the end in week 52 (T(2)). SUBJECTS: A total of 193 obese subjects aged between 18 and 72 years (129 female, 64 male; initial body weight: 122.4±22.3 kg, initial BMI: 41.8±6.7 kg m(-2)) were included. RESULTS: Genotyping revealed 32.1% TT-, 39.4% AT- and 28.5% AA-genotype carriers. At T (0), carriers of the AA-genotype had significantly higher body weight (P=0.04) and BMI (P=0.005) than carriers of the TT-genotype. Of the 193 participants, 68 discontinued and 125 completed the program. Dropout rate was not influenced by genotype (P=0.33). Completers with AA-genotype showed significantly lower additional weight loss during the weight maintenance phase than TT-genotype carriers (P=0.02). Furthermore, among participants facing weight regain during weight maintenance (n=52), more subjects were carrying the AA-genotype (P=0.006). No influence of genotype on weight reduction under formula diet was observed (P=0.32). CONCLUSION: In this program, the AA-genotype of rs9939609 was associated with a higher initial body weight and did influence success of weight stabilization. Thus, emphasizing the maintenance phase during a weight reduction program might result in better success for AA-genotype carriers.


Assuntos
Peso Corporal/genética , Obesidade/genética , Proteínas/genética , Aumento de Peso/genética , Redução de Peso/genética , Adolescente , Adulto , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Glicemia/metabolismo , Índice de Massa Corporal , Estudos Transversais , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Alemanha/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/epidemiologia , Projetos Piloto , Triglicerídeos/sangue
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