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Vascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of the extracellular matrix, can contribute to the onset and progression of diabetic vascular complications. The aim of our study was to assess whether there is a major difference in single nucleotide polymorphisms in the MMP-2 (at position -1306CËT) and MMP-9 (at position -1562CËT) gene in type 2 diabetic patients and healthy controls and to determine whether there is an association of these gene variants with the presence of microvascular complications in diabetic patients. Our study included 102 type 2 diabetes patients and a control group which was comprised of 56 healthy controls. All diabetic patients were screened for microvascular diabetes complications. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies were determined. The MMP-2 variant -1306C>T showed a negative correlation with type 2 diabetes (p=0.028). It was also shown that the presence of the -1306C allele increases the probability of developing type 2 diabetes. This was a 2.2 fold increase and that the -1306 T allele has a protective role in regards to type 2 diabetes. The MMP-2 variant -1306T showed a negative correlation with diabetic polyneuropathy (p=0.017), meaning that allele-1306T has a protective role in regards to diabetic polyneuropathy while the presence of allele -1306C increases the probability of developing diabetic polyneuropathy by 3.4 fold. Our study showed that the MMP-2 gene variant (-1306C) doubles the risk of developing type 2 diabetes, and for the first time an association of this gene variant and the presence of diabetic polyneuropathy was shown.
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AIMS: To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries. METHODS: People with diabetes aged 18-65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale. Demographic and medical record data were collected. RESULTS: A total of 2783 people with Type 2 diabetes (45.3% men, mean duration of diabetes 8.8 years) participated. Overall, 10.6% were diagnosed with current major depressive disorder and 17.0% reported moderate to severe levels of depressive symptomatology (Patient Health Questionnaire scores >9). Multivariable analyses showed that, after controlling for country, current major depressive disorder was significantly associated with gender (women) (P<0.0001), a lower level of education (P<0.05), doing less exercise (P<0.01), higher levels of diabetes distress (P<0.0001) and a previous diagnosis of major depressive disorder (P<0.0001). The proportion of those with either current major depressive disorder or moderate to severe levels of depressive symptomatology who had a diagnosis or any treatment for their depression recorded in their medical records was extremely low and non-existent in many countries (0-29.6%). CONCLUSIONS: Our international study, the largest of this type ever undertaken, shows that people with diabetes frequently have depressive disorders and also significant levels of depressive symptoms. Our findings indicate that the identification and appropriate care for psychological and psychiatric problems is not the norm and suggest a lack of the comprehensive approach to diabetes management that is needed to improve clinical outcomes.
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Trastorno Depresivo Mayor/epidemiología , Diabetes Mellitus Tipo 2/psicología , Adolescente , Adulto , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Salud Global , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Prevalencia , Adulto JovenRESUMEN
AIM: People with diabetes are at an increased risk of developing depression and other psychological disorders. However, little is known about the prevalence, correlates or care pathways in countries other than the UK and the USA. A new study, the International Prevalence and Treatment of Diabetes and Depression Study (INTERPRET-DD) aims to address this dearth of knowledge and identify optimal pathways to care across the globe. METHOD: INTERPRET-DD is a 2-year longitudinal study, taking place in 16 countries' diabetes outpatients' facilities, investigating the recognition and management of depressive disorders in people with Type 2 diabetes. Clinical interviews are used to diagnose depression, with clinical and other data obtained from medical records and through patient interviews. Pathways to care and the impact of treatment for previously unrecognized (undocumented) depression on clinical outcomes and emotional well-being are being investigated. RESULTS: Initial evidence indicates that a range of pathways to care exist, with few of them based on available recommendations for treatment. Pilot data indicates that the instruments we are using to measure both the symptoms and clinical diagnosis of depression are acceptable in our study population and easy to use. CONCLUSIONS: Our study will increase the understanding of the impact of comorbid diabetes and depression and identify the most appropriate (country-specific) pathways via which patients receive their care. It addresses an important public health problem and leads to recommendations for best practice relevant to the different participating centres with regard to the identification and treatment of people with comorbid diabetes and depression.
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Depresión/epidemiología , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo/epidemiología , Diabetes Mellitus Tipo 2/psicología , Salud Global , Estrés Psicológico/epidemiología , Adulto , Instituciones de Atención Ambulatoria , Comorbilidad , Depresión/diagnóstico , Depresión/terapia , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/terapia , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/terapia , Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Proyectos Piloto , Guías de Práctica Clínica como Asunto , Prevalencia , Escalas de Valoración Psiquiátrica , Derivación y Consulta , Estrés Psicológico/diagnóstico , Estrés Psicológico/terapiaRESUMEN
The transferrin (Tf) family of iron binding proteins includes important endogenous modulators of the immune function that may modulate autoimmune diseases. To define more clearly the role of apotransferrin (apoTf) in type 1 diabetes we determined the impact of this protein on type 1 diabetes as investigated in islet cells, animal models and patient sera. First, we demonstrated that recombinant apoTf counteracts the cytokine-induced death of murine pancreatic islet cells. Secondly, human apoTf administration favourably influences the course of type 1 diabetes in animal models, resulting in protection against disease development that was associated with reduction of insulitis and reduced levels of proinflammatory cytokines. Finally, we confirmed that patients with newly diagnosed type 1 diabetes manifest significantly lower apoTf serum levels compared to healthy controls and patients with long-lasting disease. In conclusion, our data suggest the apoTf pivotal role in the perpetuation of type 1 diabetes pathology.
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Apoproteínas/inmunología , Diabetes Mellitus Tipo 1/inmunología , Transferrina/inmunología , Adulto , Animales , Apoproteínas/sangre , Apoproteínas/química , Línea Celular Tumoral/efectos de los fármacos , Citocinas/metabolismo , Citocinas/farmacología , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 1/prevención & control , Progresión de la Enfermedad , Femenino , Humanos , Insulinoma/patología , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/inmunología , Islotes Pancreáticos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Pancreatitis/inmunología , Pancreatitis/prevención & control , Ratas , Ratas Endogámicas BB , Proteínas Recombinantes/farmacología , Subgrupos de Linfocitos T/inmunología , Transferrina/química , Adulto JovenRESUMEN
BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.
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Diabetes Mellitus Tipo 2/prevención & control , Medicina Basada en la Evidencia , Directrices para la Planificación en Salud , Adulto , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/economía , Diabetes Mellitus Tipo 2/epidemiología , Europa (Continente)/epidemiología , Medicina Basada en la Evidencia/economía , Humanos , Estilo de Vida , Tamizaje Masivo , Factores de RiesgoRESUMEN
AIMS: To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries. METHODS: People with type 2 diabetes treated in out-patient settings aged 18-65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of 'upset') between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables. RESULTS: In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS. CONCLUSION: This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.
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Trastorno Depresivo Mayor/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Tamizaje Masivo/métodos , Calidad de Vida , Estrés Psicológico/etiología , Adulto , Anciano , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/psicología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuestionario de Salud del Paciente , Estudios Prospectivos , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Distrés Psicológico , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Previous studies suggest that multiple transplantations might be equally efficient to a single regimen for human adult islets. The aim of this study was to compare metabolic parameters after each of the two regimens of human fetal islet (HFI) transplantation in type 1 diabetics. In group A (single transplant, n = 9), 180 +/- 20 x 1000 HFI equivalents (IEQs) were implanted by a single IM injection; in group B (multiple transplants, n = 8) islets were implanted as three consecutive injections (60 +/- 10 x 1000 IEQs) at 7-day intervals. We analyzed the metabolic parameters on days -1, 30, 60, 90, 120, 150, and 180 after the procedure. Among the metabolic parameters, we evaluated insulin secretion capacity-ISC (C peptide, RIA), metabolic control (HbA1c, chromatography), and insulin daily dose IDD. We found that C peptide levels increased, peaking on day 90 (A: 0.38 +/- 0.15; B: 0.34 +/- 0.19 nmol/L, P = NS) and then rapidly decreasing without differences, the HbA1c levels and IDD decreased in the same manner without differences between the groups. Our results demonstrate that multiple and single islet transplant regimens are equally efficient to temporarily restore a significant ISC with improvement of metabolic and clinical parameters. The results imply that the two regimens have an equal clinical value.
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Diabetes Mellitus Tipo 1/cirugía , Trasplante de Tejido Fetal/métodos , Trasplante de Islotes Pancreáticos/métodos , Trasplante de Tejido Fetal/patología , Inyecciones Intramusculares , Insulina/metabolismo , Secreción de Insulina , Trasplante de Islotes Pancreáticos/patología , Factores de Tiempo , Recolección de Tejidos y Órganos/métodosRESUMEN
OBJECTIVES: The purpose of this study is to compare cases with type 2 diabetes and their controls for the frequency of stressful life events and social support before the occurrence of the disease. METHODS: The study of cases and their controls was undertaken in Belgrade. A case group comprised 179 subjects in whom type 2 diabetes was for the first time diagnosed in the 'Savski Venac' Medical Center during the period 2005-2007 year. The diagnosis was made by a specialist of internal medicine according to criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. For each case two controls were chosen among patients with trauma (fracture, reposition, internal/external fixation) who were treated at the 'Banjica' Institute for Orthopedic-Surgical Diseases during the same period. Cases and controls were matched by sex, age (±2 years) and place of residence (Belgrade). Data were collected on demographic characteristics, habits, personal history, stressful life events, social support and family medical history. RESULTS: According to multivariate analysis low social support in personal history, such as relatives/friends help and financial assistance in solving problems, and bad management of monthly income were significantly positively related to type 2 diabetes. However, significantly more controls than cases had no financial insurance in case of urgent need CONCLUSION: Examine psychosocial factors play a role in the development of type 2 diabetes.
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Diabetes Mellitus Tipo 2/psicología , Acontecimientos que Cambian la Vida , Apoyo Social , Estrés Psicológico/epidemiología , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , SerbiaAsunto(s)
Desarrollo Embrionario y Fetal , Insulina/metabolismo , Islotes Pancreáticos/citología , Islotes Pancreáticos/metabolismo , Aborto Inducido , Aborto Espontáneo , Femenino , Feto , Edad Gestacional , Glucosa/farmacología , Humanos , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Embarazo , ProstaglandinasAsunto(s)
Glucosa/toxicidad , Hormona de Crecimiento Humana/farmacología , Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Células Cultivadas , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Sinergismo Farmacológico , Feto , Humanos , Secreción de Insulina , Islotes Pancreáticos/citología , Islotes Pancreáticos/efectos de los fármacos , Factores de TiempoAsunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/cirugía , Trasplante de Tejido Fetal , Sistemas de Infusión de Insulina , Insulina/sangre , Trasplante de Islotes Pancreáticos , Diabetes Mellitus Tipo 1/sangre , Humanos , Insulina/metabolismo , Secreción de Insulina , Proinsulina/sangre , Factores de TiempoAsunto(s)
Diabetes Mellitus Tipo 1/cirugía , Trasplante de Tejido Fetal , Trasplante de Islotes Pancreáticos , Biomarcadores , Péptido C/sangre , Relación CD4-CD8 , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/fisiopatología , Trasplante de Tejido Fetal/efectos adversos , Trasplante de Tejido Fetal/inmunología , Trasplante de Tejido Fetal/fisiología , Glucagón/administración & dosificación , Hemoglobina Glucada/metabolismo , Rechazo de Injerto/etiología , Humanos , Insulina/administración & dosificación , Insulina/metabolismo , Secreción de Insulina , Interleucina-2/sangre , Trasplante de Islotes Pancreáticos/efectos adversos , Trasplante de Islotes Pancreáticos/inmunología , Trasplante de Islotes Pancreáticos/fisiología , Factores de TiempoRESUMEN
OBJECTIVE: This study examined the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) monotherapy in insulin-naive patients with Type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: In this 12-week, open-labelled, uncontrolled, clinical-experience study involving 71 patients with secondary oral antidiabetic agent failure, patients received BIAsp 30 after discontinuing oral antidiabetic drugs (OADs). Glucose and lipid concentrations, hypoglycaemic episodes and adverse events were assessed before and after treatment. Patient data were categorised according to previous OADs into the biguanides (BI) plus sulfonylureas/meglitinides (SU/MEG) and SU-only groups. RESULTS: After treatment, glucose and lipid control was significantly improved in both groups, with a greater improvement in the SU-only group. Mean glycated haemoglobin, fasting blood glucose and postprandial blood glucose excursion improved by 2.15 +/- 1.24%, 3.70 +/- 3.18 mmol/l and 1.26 +/- 2.65 mmol/l in the BI plus SU/MEG group, and by 3.09 +/- 1.62%, 6.11 +/- 5.02 mmol/l and 2.06 +/- 2.33 mmol/l in the SU-only group, respectively. Mean high-density lipoprotein cholesterol and triglycerides improved by 0.09 +/- 0.18 mmol/l and 0.94 +/- 1.17 mmol/l in the BI plus SU/MEG group and by 0.09 +/- 0.18 mmol/l and 1.04 +/- 2.72 mmol/l in the SU-only group, respectively. No major hypoglycaemic episodes or serious treatment-related adverse events were reported. CONCLUSIONS: Our study showed that BIAsp 30 treatment safely improved glucose and lipid control in insulin-naive patients with Type 2 diabetes poorly controlled on BI plus SU/MEG and SU-only. Key limitations were the lack of a comparator group and the short study duration.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Anciano , HDL-Colesterol/sangre , Preparaciones de Acción Retardada , Diabetes Mellitus Tipo 2/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Inyecciones Subcutáneas , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina/análogos & derivados , Masculino , Persona de Mediana Edad , Montenegro , Proyectos de Investigación , Factores de Tiempo , Resultado del Tratamiento , Triglicéridos/sangre , YugoslaviaRESUMEN
The factors determining the outcome of human fetal islet transplantation in patients with insulin-dependent diabetes mellitus (IDDM) remain unclarified. In this study we analysed the ratio between immunoregulatory lymphocyte subpopulations in order to search for a possible marker of the immune destruction of transplanted islets. Human fetal islets were isolated by collagenase digestion, cultured for 14 days at 37 degrees C, 5% CO2, and implanted under fascia of m. rectus abdominis in 7 IDDM patients (5 pancreata per patient). After transplantation we evaluated simultaneously the level of metabolic control through HbA1c values determined by chromatography, the capacity of insulin secretion through the C-peptide levels (determined by radioimmunoassay) before and 6 minutes after 1 mg glucagon i.v. stimulation, and the ratio between CD4+ and CD8+ lymphocytes determined by immunofluorescence using monoclonal antibodies. We found that metabolic control after transplantation was improved together with the decrease of the insulin daily dose, and the improvement was simultaneous to the increase of both basal and glucagon-stimulated C-peptide levels. Four months after transplantation we detected a remarkable decrease in the secretion capacity, accompanied by the necessity for an increase in daily insulin dose to maintain optimal metabolic control. However, the loss of islet function was preceded by the increase in CD4+/CD8+ ratio, thus reflecting the presumable accumulation of CD4+ inducer T-lymphocytes. When the islet secretion capacity was destroyed, we found a decrease in CD4+/CD8+ ratio, reflecting the recruitment of CD8+ effector cells.(ABSTRACT TRUNCATED AT 250 WORDS)