RESUMO
Some studies indicate potential beneficial effects of metformin on body composition and bone. This trial compared metformin + insulin vs placebo + insulin. Metformin treatment had a small but positive effect on bone quality in the peripheral skeleton, reduced weight gain, and resulted in a more beneficial body composition compared with placebo in insulin-treated patients with type 2 diabetes. INTRODUCTION: Glucose-lowering medications affect body composition. We assessed the long-term effects of metformin compared with placebo on whole body bone and body composition measures in patients with type 2 diabetes mellitus. METHODS: This was a sub-study of the Copenhagen Insulin and Metformin Therapy trial, which was a double-blinded randomized placebo-controlled trial assessing 18-month treatment with metformin compared with placebo, in combination with different insulin regimens in patients with type 2 diabetes mellitus (T2DM). The sub-study evaluates the effects on bone mineral content (BMC), density (BMD), and body composition from whole body dual-energy X-ray absorptiometry (DXA) scans which were assessed at baseline and after 18 months. RESULTS: Metformin had a small, but positive, (p < 0.05) effect on subtotal, appendicular, and legs BMC and BMD compared with placebo. After adjustment for sex, age, vitamin D, smoking, BMI, T2DM duration, HbA1c, and insulin dose, the effects on appendicular BMC and BMD persisted (p < 0.05 for both). The changes in appendicular BMC and BMD corresponded approximately to a 0.7% and 0.5% increase in the metformin group and 0.4% and 0.4% decrease in the placebo group, respectively. These effects were mostly driven by an increase in BMC and BMD in the legs and a loss of BMC and BMD in the arms. During 18 months, all participants increased in weight, fat mass (FM), FM%, and lean mass (LM), but decreased in LM%. The metformin group increased less in weight (subtotal weight (weight-head) - 2.4 [- 3.5, - 1.4] kg, p value < 0.001) and FM (- 1.5 [- 2.3, - 0.8] kg, p value < 0.001) and decreased less in LM% (0.6 [0.2, 1.1] %, p value < 0.001) compared with the placebo group. CONCLUSION: Metformin treatment had a small positive effect on BMC and BMD in the peripheral skeleton and reduced weight gain compared with placebo in insulin-treated patients with T2DM.
Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Composição Corporal , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Insulina , Metformina/uso terapêutico , SobrepesoRESUMO
Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS) in patients with type 2 diabetes. Metformin had no significant effect on BMD in the spine and hip or TBS compared with a placebo. INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures despite a high bone mass. Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS). METHODS: This was a sub-study of a multicenter, randomized, 18-month placebo-controlled, double-blinded trial with metformin vs. placebo in combination with different insulin regimens (the Copenhagen Insulin and Metformin Therapy trial) in patients with T2DM. BMD in the spine and hip and TBS in the spine were assessed by dual-energy X-ray absorptiometry at baseline and after 18 months follow-up. RESULTS: Four hundred seven patients were included in this sub-study. There were no between-group differences in BMD or TBS. From baseline to 18 months, TBS decreased significantly in both groups (metformin group, - 0.041 [- 0.055, - 0.027]; placebo group - 0.046 [- 0.058, - 0.034]; both p < 0.001). BMD in the spine and total hip did not change significantly from baseline to 18 months. After adjustments for gender, age, vitamin D, smoking, BMI, duration of T2DM, HbA1c, and insulin dose, the TBS between-group differences increased but remained non-significant. HbA1c was negatively associated with TBS (p = 0.009) as was longer duration of diabetes, with the femoral neck BMD (p = 0.003). Body mass index had a positive effect on the hip and femoral neck BMD (p < 0.001, p = 0.045, respectively). CONCLUSIONS: Eighteen months of treatment with metformin had no significant effect on BMD in the spine and hip or TBS in patients with T2DM compared with a placebo. TBS decreased significantly in both groups. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00657943).
Assuntos
Densidade Óssea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/fisiopatologia , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Metformina/farmacologia , Adulto , Idoso , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Colo do Fêmur/fisiopatologia , Articulação do Quadril/fisiopatologia , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/efeitos adversos , Insulina/uso terapêutico , Vértebras Lombares/fisiopatologia , Masculino , Metformina/efeitos adversos , Metformina/uso terapêutico , Pessoa de Meia-Idade , Fraturas por Osteoporose/induzido quimicamenteRESUMO
OBJECTIVE: The positive metabolic outcome of Roux-en-Y gastric bypass (RYGB) surgery may involve fibroblast growth factor 21 (FGF21), in both the fasting state and postprandially. We measured the fasting levels of FGF21 before and after bariatric surgery as well as the postprandial FGF21 responses after a glucose load and after a mixed meal. DESIGN: Observational intervention trial. PATIENTS AND MEASUREMENTS: Eight obese, nondiabetic patients underwent RYGB. Plasma FGF21 was measured both before and after surgery on three different days during oral glucose loads (25 g or 50 g glucose) or a mixed meal. Blood samples were taken right before the meal and at 15-min intervals until 90 min and at 150 min and 210 min relative to the start of the meal. RESULTS: Overall, fasting plasma FGF21 did not change significantly before and after surgery (262 ± 71 vs 411 ± 119 pg/ml), but for three subjects, fasting plasma FGF21 increased significantly after surgery. Furthermore, FGF21 levels increased significantly at t = 90 and t = 150 min in response to 50 g glucose, but not after a mixed meal. CONCLUSIONS: In conclusion, the observed increase in postprandial plasma FGF21 in response to glucose and the lack of FGF21 response to a mixed meal may have important implications for the physiologic role of FGF21. The increase in postprandial FGF21 in response to glucose in the early postoperative period may contribute to the metabolic improvements observed after gastric bypass.
Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Derivação Gástrica , Obesidade/sangue , Adulto , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Período Pós-PrandialRESUMO
AIMS: To test whether concomitant use of an automated bolus calculator for people with Type 1 diabetes carrying out advanced carbohydrate counting would induce further improvements in metabolic control. METHODS: We conducted a 12-month, randomized, parallel-group, open-label, single-centre, investigator-initiated clinical study. We enrolled advanced carbohydrate counting-naïve adults with Type 1 diabetes and HbA1c levels 64-100 mmol/mol (8.0-11.3%), who were receiving multiple daily insulin injection therapy. In a 1:1-ratio, participants were randomized to receive training in either advanced carbohydrate counting using mental calculations (MC group) or advanced carbohydrate counting using an automated bolus calculator (ABC group) during a 3.5-h group training course. For 12 months after training, participants attended a specialized diabetes centre quarterly. The primary outcome was change in HbA1c from baseline to 12 months. RESULTS: Between August 2012 and September 2013, 168 participants (96 men and 72 women) were recruited and randomly assigned to the MC group (n = 84) and the ABC group (n = 84). Drop-out rates were 23.8 and 21.4%, respectively (P = 0.712); 130 participants completed the study. The baseline HbA1c was 75 ± 9 mmol/mol (9.0 ± 0.8%) in the MC group and 74 ± 8 mmol/mol (8.9 ± 0.7%) in the ABC group. At 12 months, change in HbA1c was significant within both groups: MC group: -2 mmol/mol (95% CI -4 to -1) or -0.2% (95% CI -0.4 to -0.1; P = 0.017) and ABC group: -5 mmol/mol (95% CI -6 to -3) or -0.5% (95% CI -0.6 to -0.3; P < 0.0001), but HbA1c reductions were significantly greater in the ABC group (P = 0.033). No episodes of severe hypoglycaemia were reported. CONCLUSIONS: People with Type 1 diabetes initiating advanced carbohydrate counting obtained significantly greater HbA1c reductions when guided by an automated bolus calculator (NCT02084498).
Assuntos
Diabetes Mellitus Tipo 1/dietoterapia , Dieta com Restrição de Carboidratos , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/análise , Refeições , Educação de Pacientes como Assunto , Adulto , Automação , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Diabetes Mellitus Tipo 1/sangue , Ingestão de Alimentos/fisiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The cerebral serotonin (5-HT) system shows distinct differences in obesity compared with the lean state. Here, it was investigated whether serotonergic neurotransmission in obesity is a stable trait or changes in association with weight loss induced by Roux-in-Y gastric bypass (RYGB) surgery. In vivo cerebral 5-HT2A receptor and 5-HT transporter binding was determined by positron emission tomography in 21 obese [four men; body mass index (BMI), 40.1 ± 4.1 kg/m(2)] and 10 lean (three men; BMI, 24.6 ± 1.5 kg/m(2)) individuals. Fourteen obese individuals were re-examined after RYGB surgery. First, it was confirmed that obese individuals have higher cerebral 5-HT2A receptor binding than lean individuals. Importantly, we found that higher presurgical 5-HT2A receptor binding predicted greater weight loss after RYGB and that the change in 5-HT2A receptor and 5-HT transporter binding correlated with weight loss after RYGB. The changes in the 5-HT neurotransmission before and after RYGB are in accordance with a model wherein the cerebral extracellular 5-HT level modulates the regulation of body weight. Our findings support that the cerebral 5-HT system contributes both to establish the obese condition and to regulate the body weight in response to RYGB.
Assuntos
Encéfalo/patologia , Derivação Gástrica/métodos , Obesidade/cirurgia , Receptor 5-HT2A de Serotonina/metabolismo , Redução de Peso/fisiologia , Adulto , Índice de Massa Corporal , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estudos de Casos e Controles , Dinamarca , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Ketanserina/análogos & derivados , Ketanserina/farmacocinética , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico por imagem , Ligação Proteica/efeitos dos fármacos , Cintilografia , Antagonistas da Serotonina/farmacocinética , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. METHODS: Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. RESULTS: Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. CONCLUSION: These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/uso terapêutico , Sistemas de Infusão de Insulina/estatística & dados numéricos , Insulina/uso terapêutico , Sistema de Registros , Adolescente , Adulto , Áustria , Dinamarca , Diabetes Mellitus Tipo 1/metabolismo , Inglaterra , Feminino , França , Alemanha , Grécia , Fidelidade a Diretrizes , Humanos , Irlanda , Itália , Letônia , Masculino , Países Baixos , Nova Zelândia , Irlanda do Norte , Noruega , Guias de Prática Clínica como Assunto , Escócia , Suécia , Ucrânia , Estados Unidos , País de Gales , Austrália Ocidental , Adulto JovemRESUMO
AIMS: Diabetic foot disease and amputations severely reduce quality of life and have major economic consequences. The aim of this study was to estimate time trends in the incidence of lower-extremity amputations in Danish people with diabetes. METHODS: We studied major and minor lower-extremity amputations from 2000 to 2011 among 11,332 people with diabetes from the Steno Diabetes Center. Amputations were identified by linkage of the electronic medical system with the National Patient Registry. Sex-specific incidence rates of amputations by age, diabetes duration, calendar time and diabetes type were modelled by Poisson regression. RESULTS: From 2000 to 2011, 384 incident lower-extremity amputations (205 major, 179 minor) occurred during 100,495 years of patient follow-up. From 2000 to 2011, the incidence of all lower-extremity amputations decreased by 87.5% among men and 47.4% among women with type 1 diabetes and by 83.3% among men and 79.1% among women with type 2 diabetes (P < 0.001). In particular, there was a decline in major lower-extremity amputations. In 2011, the incidence rates of major lower-extremity amputations were 0.25 (95% CI 0.07-0.82) among men and 0.21 (95% CI 0.06-0.71) among women per 1000 patient-years at age 50 years and 0.56 (95% CI 0.18-1.89) among men and 0.41 (95% CI 0.16-1.09) among women per 1000 patient-years at age 70 years. No significant change in incidence of minor amputations was observed. CONCLUSION: The incidence of major lower-extremity amputations reduced significantly from 2000 to 2011 in Danish people with diabetes followed at a diabetes specialist centre.
Assuntos
Amputação Cirúrgica/tendências , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Pé Diabético/cirurgia , Extremidade Inferior/cirurgia , Adulto , Fatores Etários , Idoso , Amputação Cirúrgica/estatística & dados numéricos , Estudos de Coortes , Dinamarca/epidemiologia , Pé Diabético/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Distribuição de Poisson , Análise de Regressão , Fatores SexuaisRESUMO
AIMS: To investigate the prevalence of symptomatic obstructive sleep apnoea in unselected patients with Type 2 diabetes referred to a tertiary diabetes clinic. METHODS: In a cross-sectional design, all newly referred patients were offered a stepwise screening for obstructive sleep apnoea with: (1) The Berlin questionnaire; then, if indicative: (2) overnight home monitoring with the ApneaLink™ device. Patients with an apnoea-hypopnoea index ≥ 5/h were offered referral for diagnostic polygraphy and treatment initiation. RESULTS: A total of 200 patients participated (61% men; age 59.6 ± 10.5 years, diabetes duration 8.3 ± 6.3 years and BMI 31.7 ± 6.7 kg/m²). According to the questionnaire, 106 patients showed 'high risk' of obstructive sleep apnoea, and 72 of these were referred to polygraphy based on ApneaLink screening corresponding to a prevalence of symptomatic obstructive sleep apnoea of 39%. Patients with symptomatic obstructive sleep apnoea had significantly higher BMI, poorer glycaemic control and lower plasma HDL cholesterol levels as compared with patients unlikely to have obstructive sleep apnoea. The groups were not different with respect to sex, age, diabetes duration, blood pressure, diabetic complications or medication use. In multiple regression analyses, age, BMI and HDL cholesterol levels were all significant, independent predictors of obstructive sleep apnoea. CONCLUSIONS: At least one third of people with Type 2 diabetes referred to a diabetes clinic in Denmark has symptomatic obstructive sleep apnoea. Our data suggest higher age, a compromised plasma lipid profile and a more obese phenotype in patients with Type 2 diabetes who have obstructive sleep apnoea, highlighting the need to focus on screening and treatment of obstructive sleep apnoea in these patients.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Apneia Obstrutiva do Sono/complicações , Fatores Etários , Idoso , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Dislipidemias/complicações , Estudos de Viabilidade , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Sobrepeso/complicações , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologia , Ronco/complicações , Centros de Atenção TerciáriaRESUMO
AIMS: The aim of this study was to investigate associations between HbA1c recall by patients with Type 2 diabetes and self-management behaviours, patient activation, perception of care and diabetes distress. METHODS: In a cross-sectional survey, 993 patients with Type 2 diabetes reported their latest HbA(1c). Validated scales measured self-management behaviours, patient activation, perception of care and diabetes distress. Self-reported HbA(1c) was compared with latest measured HbA(1c). Using logistic regressions, associations between HbA(1c) recall and the variables of interest were investigated. RESULTS: Sixty-four per cent of patients recalled their latest HbA(1c). Poor HbA(1c) recall was significantly associated with unhealthy eating behaviour, low level of exercise, low level of patient activation, poor glycaemic control, not knowing target HbA(1c) level, low educational level and being female. There were no associations between recall of HbA(1c) and diabetes distress or perceived care. CONCLUSIONS: Recall of HbA(1c) level may increase patient activation and health-promoting behaviours. However, low educational level may be a barrier for using HbA(1c) as a motivator for health-promoting behaviours. This study indicates a need for studies of causal relationships, as well as mechanisms and challenges in using patient awareness of HbA(1c) as a driver for health-promoting behaviours.
Assuntos
Diabetes Mellitus Tipo 2/psicologia , Hemoglobinas Glicadas/metabolismo , Rememoração Mental , Autocuidado/psicologia , Estresse Psicológico/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Diabetes Mellitus Tipo 2/terapia , Escolaridade , Exercício Físico , Comportamento Alimentar/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Percepção , Fatores Sexuais , Adulto JovemRESUMO
AIMS: To develop risk scores for diabetes and diabetes or impaired glycaemia for individuals living in the Middle East and North Africa region. In addition, to derive national risk scores for Algeria, Saudi Arabia and the United Arab Emirates and to compare the performance of the regional risk scores with the national risk scores. METHODS: An opportunistic sample of 6588 individuals aged 30-75 years was screened. Screening consisted of a questionnaire and a clinical examination including measurement of HbA(1c). Two regional risk scores and national risk scores for each of the three countries were derived separately by stepwise backwards multiple logistic regression with diabetes [HbA(1c) ≥ 48 mmol/mol (≥ 6.5%)] and diabetes or impaired glycaemia [HbA(1c) ≥ 42 mmol/mol (≥ 6.0%)] as outcome. The performance of the regional and national risk scores was compared in data from each country by receiver operating characteristic analysis. RESULTS: The eight risk scores all included age and BMI, while additional variables differed between the scores. The areas under the receiver operating characteristic curves were between 0.67 and 0.70, and for sensitivities approximately 75%; specificities varied between 50% and 57%. The regional and the national risk scores performed equally well in the three national samples. CONCLUSIONS: Two regional risk scores for diabetes and diabetes or impaired glycaemia applicable to the Middle East and North Africa region were identified. The regional risk scores performed as well as the national risk scores derived in the same manner.
Assuntos
Diabetes Mellitus/epidemiologia , Intolerância à Glucose/epidemiologia , Adulto , Idoso , Argélia/epidemiologia , Métodos Epidemiológicos , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Arábia Saudita/epidemiologia , Emirados Árabes Unidos/epidemiologiaRESUMO
AIMS: To investigate the relationship between structural and functional social support and patient activation, diabetes-related emotional distress, perceived diabetes care, self-management behaviour and HbA(1c) levels among patients with Type 2 diabetes. METHODS: Self-administered questionnaires were collected from 2572 patients with Type 2 diabetes. After adjusting for gender, age and education, Tobit and logistic regression models were used to examine associations between social network and patient activation, psychosocial problems, self-management behaviours and HbA(1c) levels. RESULTS: Frequent contact with friends was associated with more positive scores for activation, fewer psychosocial problems, more positive assessment of care and health-promoting self-management behaviours such as frequent exercising and frequent foot examinations. Frequent contact with family was associated with more positive assessments of care. Living with a partner was associated with lower prevalence of smoking, a higher frequency of foot examinations and higher HbA(1c) levels. A poor functional social network, measured as perceived lack of help in the event of severe illness, was associated with low patient activation, greater emotional distress, negative assessment of care, less health-promoting eating habits and less frequent foot examinations. CONCLUSIONS: Good social support is significantly associated with health-promoting behaviours and well-being among patients with Type 2 diabetes. However, HbA(1c) levels are higher for cohabitant persons, indicating barriers for social support. Intervention research is needed to investigate the causal relationship between social networks and health-promoting behaviours. This knowledge should be used in clinical practice when targeting and designing education, support and care for patients with Type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/psicologia , Autocuidado/psicologia , Estresse Psicológico/etiologia , Estudos Transversais , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Feminino , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Apoio Social , Estresse Psicológico/epidemiologia , Inquéritos e QuestionáriosRESUMO
AIM: As both impaired fasting glucose and silent myocardial ischaemia are risk factors for cardiovascular disease and death, we hypothesized that these risk factors in combination would identify those subjects at the highest risk of adverse events. METHODS: Healthy individuals without diabetes (n=596, 55-75 years) were examined for silent myocardial infarction (≥ 1 mm ST-interval during ≥ 1 min) by ambulant 48-h continuous electrocardiogram monitoring and impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/l). RESULTS: After 6.3 years, 77 subjects met the endpoint of myocardial infarction and/or death. The prevalence of silent myocardial ischaemia at inclusion was 12.3% in subjects with impaired fasting glucose and 11.7% in subjects with normal fasting glucose, P=0.69. Subjects with impaired fasting glucose/silent myocardial ischaemia more often met the endpoint (36%) than subjects with impaired fasting glucose/no silent myocardial ischaemia (15%), subjects with normal fasting glucose/silent myocardial ischaemia (12%), and subjects with normal fasting glucose/no silent myocardial ischaemia (10%), respectively, (P<0.001). In a Cox model including these four study groups of interest, gender, age, smoking habits, blood pressure and total cholesterol, only subjects with impaired fasting glucose/silent myocardial ischaemia exhibited an increased risk of death or myocardial infarction (hazard ratio 2.5, P=0.016). CONCLUSION: The combination of impaired fasting glucose and silent myocardial ischaemia was associated with the poorest prognosis in middle-aged and older subjects without previously known glucose metabolic aberration and heart disease.
Assuntos
Glicemia/metabolismo , Angiopatias Diabéticas/mortalidade , Jejum/sangue , Intolerância à Glucose/mortalidade , Isquemia Miocárdica/mortalidade , Idoso , Angiopatias Diabéticas/sangue , Feminino , Intolerância à Glucose/sangue , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Isquemia Miocárdica/sangue , Estado Pré-Diabético/sangue , Estado Pré-Diabético/mortalidade , PrognósticoRESUMO
AIMS: To investigate the association between glycaemic control and patient socio-demographics, activation level, diabetes-related distress, assessment of care, knowledge of target HbA(1c), and self-management behaviours, and to determine to what extent these factors explain the variance in HbA(1c) in a large Danish population of patients with Type 2 diabetes. METHODS: Cross-sectional survey and record review of 2045 patients from a specialist diabetes clinic. Validated scales measured patient activation, self-management behaviours, diabetes-related emotional distress, and perceived care. The electronic patient record provided information about HbA(1c), medication, body mass index, and duration of diabetes. Data were analysed using multiple linear regression models with stepwise addition of covariates. RESULTS: The response rate was 54% (n = 1081). Good glycaemic control was significantly associated with older age, higher education, higher patient activation, lower diabetes-related emotional distress, better diet and exercise behaviours, lower body mass index, shorter duration of disease and knowledge of HbA(1c) targets (P < 0.05 for all). Patient socio-demographics, behaviour; perceptions of care and diabetes distress accounted for 14% of the total variance in HbA(1c) levels (P = 0.0134), but the variance explained was higher for respondents treated with medications other than insulin. CONCLUSIONS: Our study emphasizes the complex relationships between patient activation, distress and behaviour, specific treatment modalities and glycaemic control. Knowledge of treatment goals, achieving patient activation in coping with diabetes, and lowering disease-related emotional stress are important patient education goals. However, the large unexplained component of HbA(1c) variance highlights the need for more research to understand the mechanisms of glycaemic control.
Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobinas Glicadas/metabolismo , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Autocuidado , Adulto JovemRESUMO
AIM: Skeletal muscle insulin resistance has been linked to mitochondrial dysfunction. We examined how improvements in muscular insulin sensitivity following rosiglitazone (ROSI) or pioglitazone (PIO) treatment would affect muscle mitochondrial function in patients with type 2 diabetes mellitus (T2DM). METHODS: Muscle biopsies were obtained from 21 patients with T2DM before and after 12 weeks on either ROSI (4 mg once daily) [n = 12; age, 59.2 +/- 2.2 years; body mass index (BMI), 29.6 +/- 0.7 kg/m(2)] or PIO (30 mg once daily) (n = 9; age, 56.3 +/- 2.4 years; BMI, 29.5 +/- 1.5 kg/m(2)). An age- and BMI-matched control group was also included (n = 8; age, 61.8 +/- 2.3 years; BMI, 28.4 +/- 0.6 kg/m(2)). Insulin sensitivity, citrate synthase- and beta-hydroxyacyl-CoA-dehydrogenase (HAD) activity, intramuscular triglyceride (IMTG) and protein content of complexes I-IV were measured, while mitochondrial respiration per milligram muscle was measured in saponin-treated skinned muscle fibres using high-resolution respirometry. RESULTS: Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls at baseline and decreased during ROSI treatment but increased during PIO treatment. Citrate synthase activity and average protein content of complexes I-IV were unchanged in the ROSI group, but protein content of complexes II and III increased during PIO treatment. Insulin sensitivity improved in all patients, but IMTG levels were unchanged. CONCLUSIONS: We show opposite effects of ROSI and PIO on mitochondrial respiration, and also show that insulin sensitivity can be improved independently of changes in mitochondrial respiration. We confirm that mitochondrial respiration is reduced in T2DM compared to age- and BMI-matched control subjects.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Mitocôndrias Musculares/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Índice de Massa Corporal , Respiração Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Imuno-Histoquímica , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Pioglitazona , RosiglitazonaRESUMO
AIM: Several mechanisms have been targeted as culprits of weight gain during antihyperglycaemic treatment in type 2 diabetes (T2DM). These include reductions in glucosuria, increased food intake from fear of hypoglycaemia, the anabolic effect of insulin, decreased metabolic rate and increased efficiency in fuel usage. The purpose of the study was to test the hypothesis that mitochondrial efficiency increases as a result of insulin treatment in patients with type 2 diabetes. METHODS: We included ten patients with T2DM (eight males) on oral antidiabetic treatment, median age: 51.5 years (range: 39-67) and body mass index (BMI): 30.1 +/- 1.2 kg/m2 (mean +/- s.e.). Muscle biopsies from m. vastus lateralis and m. deltoideus were obtained before and after seven weeks of intensive insulin treatment, and mitochondrial respiration was measured using high-resolution respirometry. State 3 respiration was measured with the substrates malate, pyruvate, glutamate, succinate and ADP. State 4o was measured with addition of oligomycine. An age, sex and BMI-matched control group was also included. RESULTS: HbA1c improved significantly and the patients gained on average 3.4 +/- 0.9 kg. Before treatment, respiratory control ratios (RCRs) of the T2DM were lower than the obese controls [2.6 vs. 3.2 (p < 0.05)], but RCR returned to the levels of the control subjects during treatment. Average state 4o of arm and leg declined by 14% (p < 0.05) during insulin treatment. CONCLUSIONS: Tight glycaemic control leads to reductions in inner mitochondrial membrane leak and increased efficiency of mitochondria. This change in mitochondrial physiology could contribute to the weight gain seen with antihyperglycaemic treatment.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Mitocôndrias Musculares/metabolismo , Membranas Mitocondriais/metabolismo , Adulto , Idoso , Respiração Celular/efeitos dos fármacos , Respiração Celular/fisiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/fisiologia , Membranas Mitocondriais/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismoRESUMO
BACKGROUND: Patients with type 2 diabetes (T2DM) have an increased mortality rate primarily because of macrovascular disease. Where T2DM patients cannot be managed sufficiently through diet, exercise and peroral antidiabetic drugs, that is when haemoglobin A1c (HbA1c) is above 7.0%, it is yet unknown whether a combination of metformin and insulin analogues is superior to insulin analogues alone. Nor is it known which insulin analogue regimen is the optimal. OBJECTIVE: The primary objective of this trial is to evaluate the effect of an 18-month treatment with metformin vs. placebo in combination with one of three insulin analogue regimens, the primary outcome measure being carotid intima-media thickness (CIMT) in T2DM patients. DESIGN: A randomized, stratified, multicentre trial having a 2 x 3 factorial design. The metformin part is double masked and placebo controlled. The insulin treatment is open. The intervention period is 18 months. PATIENT POPULATION: Nine hundred and fifty patients with T2DM and HbA1c > or = 7.5% on treatment with oral hypoglycaemic agents or on insulin treatment and deemed able, by the investigator, to manage once-daily insulin therapy with a long-acting insulin analogue. RANDOMIZATION: Central randomization stratified for age (above 65 years), previous insulin treatment and treatment centre. INTERVENTIONS: Metformin 1 g x two times daily vs. placebo (approximately 475 patients vs. 475 patients) in combination with insulin detemir before bedtime (approximately 315 patients) or biphasic insulin aspart 30 before dinner with the possibility to increase to two or three injections daily (approximately 315 patients) or insulin aspart before the main meals (three times daily) and insulin detemir before bedtime (approximately 315 patients). Intervention follows a treat-to-target principle in all six arms aiming for an HbA1c < or = 7.0%. OUTCOME MEASURES: Primary outcome measure is the change in CIMT from baseline to 18 months. Secondary outcome measures comprises the composite outcome of death, acute myocardial infarction, stroke or amputation assessed by an adjudication committee blinded to intervention, other cardiovascular clinical outcomes, average postprandial glucose increment from 0 to 18 months, hypoglycaemia and any inadvertent medical episodes. In addition, change in plaque formation in the carotids, HbA1c, cardiovascular biomarkers, body composition, progression of microvascular complications and quality of life will be assessed as tertiary outcome measures. TIME SCHEDULE: Patient enrolment started May 2008. Follow-up is expected to finish in March 2011. CONCLUSION: CIMT is designed to provide evidence as to whether metformin is advantageous even during insulin treatment and to provide evidence regarding which insulin analogue regimen is most advantageous with regard to cardiovascular disease.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Metformina/uso terapêutico , Adulto , Idoso , Insulinas Bifásicas , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Quimioterapia Combinada , Métodos Epidemiológicos , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insulina/uso terapêutico , Insulina Aspart , Insulina Detemir , Insulina Isófana , Insulina de Ação Prolongada , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Projetos de Pesquisa , Resultado do Tratamento , Túnica Íntima/patologia , Túnica Média/patologia , Adulto JovemRESUMO
The data in this article describe the use of dietary supplements in Danish patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). The data were collected from a web-based dietary survey on dietary habits in 774 patients with T1D (nâ¯=â¯426) and T2D (nâ¯=â¯348). The data demonstrate that 99% of the patients with diabetes use dietary supplements with no gender differences. In comparison, only 64% in the general population use dietary supplements [2]. A higher proportion of people in the general population use multivitamin/mineral supplementation as compared to patients with diabetes (48% vs. 34-37%) and a higher proportion of women than men with diabetes use multivitamin/mineral supplementation (T1D: 43% women vs. 26% men and T2D: 45% women vs. 34% men). More patients with diabetes than the general population use supplements such as calcium together with vitamin D, vitamin D, vitamin B, vitamin C, vitamin E, magnesium, calcium, Q10, ginger, garlic, and other herbal supplements.
RESUMO
AIM: Diabetic foot ulcer (DFU) is a serious complication to diabetes. The aim was to study the incidence of first DFU among patients with type 1 (T1DM) and type 2 diabetes (T2DM), stratified according to etiology: neuropathic, neuro-ischemic or ischemic, over a period of 14years (2001-2014). METHODS: DFU incidence rates were calculated from electronic patient record data from patients with T1DM and complicated T2DM from a large specialized diabetes hospital with a multidisciplinary foot clinic in Denmark. Poisson regression was used to model incidence of first DFU according to calendar year, diabetes type and etiology. RESULTS: Among 5640 patients with T1DM 255 developed a DFU, corresponding to an incidence of 5.8 (95% confidence interval (95%CI) 5.1-6.5) per 1000 patient years; this incidence dropped from 8.1 (95%CI 5.4-11.9) per 1000 patient years in 2002 to 2.6 (95%CI 1.3-5.3) in 2014 (p=0.0059). Among 6953 patients with T2DM 310 developed a DFU, corresponding to an incidence of 11.3 (95%CI 10.1-12.6) per 1000 patient years; this incidence dropped from 17.0 (95%CI 12.2-23.8) per 1000 patient years in 2002 to 8.7 (95%CI 5.3-14.1) per 1000 patient year (p=0.0260) in 2014. CONCLUSION: The incidence of DFU has decreased substantially in T1DM as well as in T2DM. This change was driven by a decrease in incidence of neuropathic ulcers.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Pé Diabético/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
To study the effect of glucagon neutralization on urea synthesis in diabetic rats, animals with newly induced (75 mg/kg streptozocin) experimental diabetes mellitus were divided into two groups. One group was given one weekly injection of nonimmune rabbit serum (n = 6), and the other group was given one weekly injection of a specific high-titer antibody against pancreatic glucagon (n = 6). Four weeks later, serum-treated diabetic rats had fasting glucagon concentrations 2-3 times higher than nondiabetic controls given one weekly injection of saline (control). Plasma glucagon binding capacity of diabetic rats given glucagon antibodies was 10-15 times higher than the glucagon concentration. A second group of nondiabetic controls were given nonimmune serum. Blood glucose concentration and urinary glucose output were identical in both groups of diabetic animals. Food intake doubled in both groups of diabetic rats. In control rats, the accumulated nitrogen balance, determined weekly for 4 wk, was positive at 81 +/- 3.1 mmol/96 h; in serum-treated diabetic rats, the accumulated nitrogen balance was negative, -8.3 +/- 2.4 mmol/96 h throughout the 4 wk, whereas it was higher at 4.7 +/- 2.3 mmol/96 h in the glucagon antibody-treated diabetic rats (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Glucagon/fisiologia , Ureia/metabolismo , Alanina/metabolismo , Alanina/farmacologia , Animais , Anticorpos/administração & dosagem , Glicemia/metabolismo , Feminino , Glucagon/sangue , Glucagon/imunologia , Nitrogênio/metabolismo , Especificidade de Órgãos , Coelhos/imunologia , Ratos , Ratos Endogâmicos , Valores de Referência , Análise de RegressãoRESUMO
OBJECTIVE: To investigate the predictive value of microalbuminuria and the annual increase of albumin excretion as risk factors for diabetic nephropathy. RESEARCH DESIGN AND METHODS: A 5-year follow-up of patients with microalbuminuria (urinary albumin excretion [UAE] = 30-299 mg/24 h) and matched patients with normoalbuminuria (UAE < 30 mg/24 h). The initial classification was based on one single 24-h urine collection. The annual increase in UAE was calculated by linear regression analysis of log-transformed UAE on time. This study was conducted at the outpatient clinic of the Steno Diabetes Center. The study subjects included 118 insulin-dependent diabetes mellitus (IDDM) patients between 18 and 50 years of age with microalbuminuria and 112 matched control patients with normal UAE with an age at diabetes onset of < 31 years. The main outcome measures were UAE, annual change in UAE rate (percentage per year), and the prevalence of retinopathy. RESULTS: After 5 years, 39 (33%, 24-42 CI [95% confidence interval]) patients with microalbuminuria had normoalbuminuria, 57 (48%, 38-57 CI) still had microalbuminuria, and 22 (19%, 12-27 CI) had developed diabetic nephropathy. Among the 112 patients with normoalbuminuria in 1985, 9 (8%, 4-15 CI) had developed microalbuminuria, and 2 (2%, 0-6 CI) had developed diabetic nephropathy. Of the 79 patients with persistent albuminuria, only 36 (46%, 34-57 CI) were progressors with a rate of progression of > 5%/year. Progressors had significantly higher HbAlc, higher mean blood pressure, and a higher incidence of proliferative retinopathy compared with nonprogressors. Multiple regression analysis only identified mean HbAlc as an independent predictor of the rate of progression. Smoking was significantly more prevalent in patients with persistent albuminuria. CONCLUSIONS: Microalbuminuria is a predictor of progression to diabetic nephropathy; however, not as strong as suggested previously. Calculation of the annual increase in UAE seems to be a more specific method of identifying patients who will develop diabetic nephropathy.