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AIM: To assess the long-term clinical benefits of early combination treatment with vildagliptin-metformin vs. standard-of-care, metformin monotherapy in the ongoing VERIFY study. METHODS: We randomized 2001 participants with multi-ethnic background, aged 18-70 years, having HbA1c levels 48-58 mmol/mol (6.5-7.5%) and BMI 22-40 kg/m2 . Baseline data included HbA1c , fasting plasma glucose and homeostasis model ß-cell and insulin sensitivity. Standardized meal-tests, insulin secretion rate relative to glucose, and oral glucose insulin sensitivity were assessed in a subpopulation. RESULTS: Out of 4524 screened, data were collected from the 2001 eligible participants (53% women) across Europe (52.4%), Latin America (26.8%), Asia (17.2%), South Africa (3.1%) and Australia (0.5%). The median (interquartile range) disease duration was 3.4 (0.9, 10.2) months; mean (±SD) age 54.3±9.4 years; weight 85.5±17.5 kg and BMI 31.1±4.7 kg/m2 . Baseline HbA1c was 52±3 mmol/mol (6.9±0.3%), fasting plasma glucose 7.5±1.5 mmol/l and the median (interquartile range) of fasting insulin was 109 (75-160) mU/l. Homeostasis model ß-cell and insulin sensitivity values were 84% (60, 116) and 46% (31, 68), respectively. In those undertaking meal-tests, insulin secretion rate relative to glucose was 28±12 pmol/min/m2 /mmol/l and oral glucose insulin sensitivity was 353±57 ml/min/m2 . CONCLUSIONS: Our current, multi-ethnic, newly diagnosed VERIFY population reflects a characteristic presence of early insulin resistance in participants with increased demand for insulin associated with obesity. The VERIFY study will provide unique evidence in characterizing therapeutic intervention in a diverse population with hyperglycaemia, focusing on durability of early glycaemic control.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/administración & dosificación , Vildagliptina/administración & dosificación , Adolescente , Adulto , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Humanos , Resistencia a la Insulina/fisiología , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/fisiología , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Factores de Tiempo , Vildagliptina/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Fasting plasma glucose (FPG) is the most commonly used screening tool for diabetes in Sri Lanka. Cut-off values from American Diabetes Association recommendations are adopted in the absence of local data. We aimed to establish FPG cut offs for Sri Lankans to screen for diabetes and pre-diabetes. METHODS: Data on FPG and diabetes/pre-diabetes status were obtained from Sri Lanka Diabetes and Cardiovascular Study (SLDCS), a community based island wide observational study conducted in 2005-6. Sensitivity specificity and area under the ROC curve were calculated for different FPG values. RESULTS: Study included 4014 community dwelling people after excluding people already on treatment for diabetes or pre-diabetes. Mean age was 45.3 (± 15) years and 60.4% were females. FPG cut off of 5.3 mmol/L showed better sensitivity and specificity than 5.6 mmol/L in detecting diabetes (87.8% and 84.4% Vs 80.8% and 92.1%) and pre-diabetes (54.7% and 87.0% Vs 43.8% and 94.2%). CONCLUSIONS: A lower FPG cut off of 5.3 mmol/L has a better sensitivity and acceptable specificity in screening for diabetes and pre-diabetes in Sri Lankan adults.
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Biomarcadores/sangre , Glucemia/análisis , Diabetes Mellitus/diagnóstico , Ayuno , Prueba de Tolerancia a la Glucosa/métodos , Tamizaje Masivo , Estado Prediabético/diagnóstico , Estudios Transversales , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Femenino , Estudios de Seguimiento , Intolerancia a la Glucosa , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estado Prediabético/sangre , Estado Prediabético/epidemiología , Pronóstico , Curva ROC , Factores de Riesgo , Sri Lanka/epidemiologíaRESUMEN
AIMS: To formulate a combined cardiovascular risk score in diabetes that could be useful both to physicians and healthcare funders. METHODS: Data were derived from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation Observational (ADVANCE-ON) study, a randomized controlled trial (mean duration 5 years) with a post-randomization follow-up (mean 4.9 years), that included 11 140 high-risk patients with diabetes. The outcome analysed was the occurrence of either fatal or non-fatal macrovascular or renal disease. A Cox regression model was used to determine weightings in the risk score. The resultant score was recalibrated to each of three major global regions, as covered by the ADVANCE-ON study. RESULTS: Over a median of 9.9 years, 1145 patients experienced at least one component of the combined outcome event. The resultant score, the AD-ON risk score, incorporated 13 demographic or clinical variables. Its discrimination was modest [c-statistic = 0.668 (95% confidence interval 0.651, 0.685)] but its calibration was excellent (predicted and observed risks coincided well, within disparate global regions). In terms of the integrated discrimination improvement index, its performance was marginally superior, over a 10-year risk horizon, to existing risk scores in clinical use, from a restricted version of the same data, for macrovascular and renal disease separately. CONCLUSIONS: The AD-ON risk score has advantages over the existing vascular risk scores in diabetes that used data from the original ADVANCE trial, which treat macrovascular and renal diseases separately. These advantages include its simplicity of use and global application.
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Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/etiología , Indicadores de Salud , Anciano , Antihipertensivos/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Gliclazida/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéutico , Indapamida/uso terapéutico , Masculino , Persona de Mediana Edad , Perindopril/uso terapéutico , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
AIMS: To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist]. METHODS: CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. RESULTS: Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [-0.56% (95% confidence interval [CI]: -0.77, -0.35), and -0.75% (95% CI: -0.95, -0.54), respectively] and GLP-1 receptor agonists [-1.00% (95% CI: -1.35, -0.65), and -1.06% (95% CI: -1.43, -0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis-related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues. CONCLUSIONS: In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.
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Canagliflozina/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Incretinas/administración & dosificación , Anciano , Biomimética , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Método Doble Ciego , Quimioterapia Combinada , Femenino , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hipoglucemia/inducido químicamente , Masculino , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Enfermedades Urológicas/inducido químicamente , Enfermedades Urológicas/microbiología , Pérdida de Peso/efectos de los fármacosRESUMEN
BACKGROUND: Screening for undiagnosed diabetes is not widely undertaken due to the high costs and invasiveness of blood sampling. Simple non-invasive tools to identify high risk individuals can facilitate screening. The main objectives of this study are to develop and validate a risk score for screening undiagnosed diabetes among Sri Lankan adults and to compare its performance with the Cambridge Risk Score (CRS), the Indian Diabetes Risk Score (IDRS) and three other Asian risk scores. METHODS: Data were available from a representative sample of 4276 adults without diagnosed diabetes. In a jack-knife approach two thirds of the sample was used for the development of the risk score and the remainder for the validation. Age, waist circumference, BMI, hypertension, balanitis or vulvitis, family history of diabetes, gestational diabetes, physical activity and osmotic symptoms were significantly associated with undiagnosed diabetes (age most to osmotic symptoms least). Individual scores were generated for these factors using the beta coefficient values obtained in multiple logistic regression. A cut-off value of sum = 31 was determined by ROC curve analysis. RESULTS: The area under the ROC curve of the risk score for prevalent diabetes was 0.78 (CI 0.73-0.82). In the sample 36.3 % were above the cut-off of 31. A risk score above 31 gave a sensitivity, specificity, positive predictive value and negative predictive value of 77.9, 65.6, 9.4 and 98.3 % respectively. For Sri Lankans the AUC for the CRS and IDRS were 0.72 and 0.66 repectively. CONCLUSIONS: This simple non-invasive screening tool can identify 80 % of undiagnosed diabetes by selecting 40 % of Sri Lankan adults for confirmatory blood investigations.
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Diabetes Mellitus/diagnóstico , Tamizaje Masivo/métodos , Adulto , Factores de Edad , Glucemia , Índice de Masa Corporal , Estudios de Cohortes , Diabetes Mellitus/epidemiología , Femenino , Humanos , Hipertensión/complicaciones , Modelos Logísticos , Masculino , Prevalencia , Curva ROC , Medición de Riesgo , Factores de Riesgo , Sri Lanka/epidemiología , Circunferencia de la CinturaRESUMEN
AIMS: To describe the influence of family history on diabetes prevalence and associated metabolic risk factors in a nationally representative sample from Sri Lanka. METHODS: A cross sectional national survey was conducted among 5000 adults in Sri Lanka. Family history was evaluated at three levels: (1) parents, (2) grandparents (paternal and maternal) and (3) siblings. A binary-logistic regression analysis controlling for confounders (age, gender, BMI and physical activity) was performed in all patients with 'presence of diabetes' as the dichotomous dependent variable and using family history in father, mother, maternal grandmother/grandfather, paternal grandmother/grandfather, siblings and children as binary independent variables. RESULTS: The sample size was 4485, mean age was 46.1 ± 15.1 years and 39.5% were males. In all adults, the prevalence of diabetes was significantly higher in patients with a family history (23.0%) than those without (8.2%) (P < 0.001). When family history was present in both parents, the prevalence of diabetes was 32.9%. Presence of a family history significantly increased the risk of diabetes [odds ratio (OR): 3.35, 95% confidence interval (CI): 2.78-4.03], obesity (OR: 2.45, 95% CI: 1.99-2.99), hypertension (OR: 1.25, 95% CI: 1.08-1.45) and metabolic syndrome (OR: 2.28, 95% CI: 1.97-2.63). In all adults, the presence of a family history of diabetes in a father (OR: 1.29, 95% CI: 1.02-1.63), mother (OR: 1.23, 95% CI: 1.11-1.36), paternal grandfather (OR: 1.27, 95% CI: 1.14-1.41), siblings (OR: 4.18, 95% CI: 3.34-5.22) and children (OR: 5.47, 95% CI: 2.93-10.19) was associated with a significantly increased risk of developing diabetes. CONCLUSIONS: Family history and diabetes had a graded association in the Sri Lankan population, because the prevalence increased with the increasing number of generations affected. Family history of diabetes was also associated with the prevalence of obesity, metabolic syndrome and hypertension. Individuals with a family history of diabetes form an easily identifiable group who may benefit from targeted interventions.
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Diabetes Mellitus/epidemiología , Salud de la Familia , Encuestas Epidemiológicas , Síndrome Metabólico/epidemiología , Linaje , Adulto , Estudios Transversales , Femenino , Humanos , Hipertensión/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Sri Lanka/epidemiologíaRESUMEN
AIM: To assess the efficacy and safety of recently approved once-weekly glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing any GLP-1 RA licensed for once-weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate. RESULTS: In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was -0.66% [six studies; 95% confidence interval (CI) -1.14 to -0.19; I(2) = 88%] with albiglutide, and -1.18% (seven studies; 95% CI -1.34 to -1.02; I(2) = 65%) with dulaglutide. Based on data from placebo-controlled trials, we did not detect statistically significant weight-sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once-weekly GLP-1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c-lowering (mean differences -0.40%; 95% CI -0.66 to -0.14; I(2) = 85%, -0.44%; 95% CI -0.58 to -0.29; I(2) = 40% and -0.28; 95% CI -0.45 to -0.10; I(2) = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions. CONCLUSIONS: Given their dosing scheme and overall efficacy and safety profile, once-weekly GLP-1 RAs are a convenient therapeutic option for use as add-on to metformin.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/administración & dosificación , Incretinas/administración & dosificación , Adulto , Diabetes Mellitus Tipo 2/sangre , Esquema de Medicación , Quimioterapia Combinada , Exenatida , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/análogos & derivados , Hemoglobina Glucada/efectos de los fármacos , Humanos , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Masculino , Metformina/administración & dosificación , Péptidos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes de Fusión/administración & dosificación , Ponzoñas/administración & dosificaciónRESUMEN
AIMS: Durability of good glycaemic control (HbA1c ) is of importance as it can be the foundation for delaying diabetic complications. It has been hypothesized that early initiation of treatment with the combination of oral anti-diabetes agents with complementary mechanisms of action can increase the durability of glycaemic control compared with metformin monotherapy followed by a stepwise addition of oral agents. Dipeptidyl peptidase-4 inhibitors are good candidates for early use as they are efficacious in combination with metformin, show weight neutrality and a low risk of hypoglycaemia. We aimed to test the hypothesis that early combined treatment of metformin and vildagliptin slows ß-cell deterioration as measured by HbA1c . METHODS: Approximately 2000 people with Type 2 diabetes mellitus who were drug-naive or who were treated with metformin for less than 1 month, and who have HbA1c of 48-58 mmol/mol (6.5-7.5%), will be randomized in a 1:1 ratio in VERIFY, a 5-year multinational, double-blind, parallel-group study designed to compare early initiation of a vildagliptin-metformin combination with standard-of-care initiation of metformin monotherapy, followed by the stepwise addition of vildagliptin when glycaemia deteriorates. Further deterioration will be treated with insulin. The primary analysis for treatment failure will be from a Cox proportional hazard regression model and the durability of glycaemic control will be evaluated by assessing treatment failure rate and the rate of loss in glycaemic control over time as co-primary endpoints. SUMMARY: VERIFY is the first study to investigate the long-term clinical benefits of early combination treatment vs. the standard-of-care metformin monotherapy with a second agent added by threshold criteria.
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Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hiperglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Nitrilos/uso terapéutico , Pirrolidinas/uso terapéutico , Proyectos de Investigación , Adamantano/uso terapéutico , Adolescente , Adulto , Anciano , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Método Doble Ciego , Quimioterapia Combinada , Hemoglobina Glucada/análisis , Humanos , Análisis de Intención de Tratar , Persona de Mediana Edad , Obesidad/complicaciones , Sobrepeso/complicaciones , Vildagliptina , Adulto JovenRESUMEN
We describe a microscopy design methodology and details of microscopes built to this 'open' design approach. These demonstrate the first implementation of time-domain fluorescence microscopy in a flexible automated platform with the ability to ease the transition of this and other advanced microscopy techniques from development to use in routine biology applications. This approach allows easy expansion and modification of the platform capabilities, as it moves away from the use of a commercial, monolithic, microscope body to small, commercial off-the-shelf and custom made modular components. Drawings and diagrams of our microscopes have been made available under an open license for noncommercial use at http://users.ox.ac.uk/~atdgroup. Several automated high-content fluorescence microscope implementations have been constructed with this design framework and optimized for specific applications with multiwell plates and tissue microarrays. In particular, three platforms incorporate time-domain FLIM via time-correlated single photon counting in an automated fashion. We also present data from experiments performed on these platforms highlighting their automated wide-field and laser scanning capabilities designed for high-content microscopy. Devices using these designs also form radiation-beam 'end-stations' at Oxford and Surrey Universities, showing the versatility and extendibility of this approach.
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Biología/métodos , Microscopía Fluorescente/instrumentación , Microscopía Fluorescente/métodos , Automatización de Laboratorios/métodosRESUMEN
AIMS: To investigate efficacy and safety of dual therapy with liraglutide and metformin in comparison to glimepiride and metformin, and metformin monotherapy over 2 years in patients with type 2 diabetes. METHODS: In the 26-week the Liraglutide Effect and Action in Diabetes (LEAD)-2 core trial, patients (n = 1091) were randomized (2 : 2 : 2 : 1: 2) to liraglutide (0.6, 1.2 or 1.8 mg once-daily), placebo or glimepiride; all with metformin. Patients were enrolled if they were 18-80 years old with HbA1c 7.0-11.0% (previous monotherapy ≥3 months), or 7.0-10.0% (previous combination therapy ≥3 months), and body mass index ≤40 kg/m(2) . Patients completing the 26-week double-blinded phase could enter an 18-month open-label extension. RESULTS: HbA1c decreased significantly with liraglutide (0.4% with 0.6 mg, 0.6% with 1.2 and 1.8 mg) versus 0.3% increase with metformin monotherapy (p < 0.0001). HbA1c decrease with liraglutide was non-inferior versus 0.5% decrease with glimepiride. Liraglutide groups experienced significant weight loss (2.1, 3.0 and 2.9 kg with 0.6, 1.2 and 1.8 mg, respectively) compared to weight gain (0.7 kg) with glimepiride (p < 0.0001). Weight loss with liraglutide 1.2 and 1.8 mg was significantly greater than with metformin monotherapy (1.8 kg; p = 0.0185 and p = 0.0378 for 1.2 and 1.8 mg, respectively). The occurrence of minor hypoglycaemia was <5.0% in all liraglutide groups, significantly less than with glimepiride (24.0%; p < 0.0001). Liraglutide was well tolerated overall: gastrointestinal events were more common than with glimepiride or metformin monotherapy, but occurrence decreased with time. CONCLUSIONS: Liraglutide provided sustained glycaemic control over 2 years comparable to that provided by glimepiride. Liraglutide was well tolerated, and was associated with weight loss and a low rate of hypoglycaemia.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Pérdida de Peso/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Quimioterapia Combinada , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/uso terapéutico , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Liraglutida , Masculino , Metformina/administración & dosificación , Persona de Mediana Edad , Compuestos de Sulfonilurea/administración & dosificaciónRESUMEN
We are currently facing a global pandemic of obesity and Type 2 diabetes. In some settings, the population prevalence of Type 2 diabetes is 50%, and half of those affected will die from diabetes-related complications. Eight centuries ago, an epidemic of bubonic plague swept across Europe, killing at least half of its victims. We here draw comparisons between these two pandemics, proposing close analogies between the 'Black Death' of the 14th century and the modern-day equivalent of Type 2 diabetes. Both diseases can be considered in terms of an aetiological agent, a reservoir, a vector and a predisposing toxic environment; populations can be considered as highly susceptible to the transmissable agents of Type 2 diabetes in the setting of calorie excess, inadequate food labelling, poorly regulated advertising and sedentary lifestyles. As for tackling a pandemic of a contagious microbial pathogen, we believe that breaking the cycle of transmission in the diabetes epidemic must be underpinned by political will and prompt, decisive legislation backed by the medical community. Far from fearing that such measures edge us towards a 'nanny state', we believe individuals should expect a responsible government to safeguard them from the toxic milieu that puts them at risk of obesity and its complications, and that communities and populations have the right to have their health protected.
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Diabetes Mellitus Tipo 2/epidemiología , Obesidad/epidemiología , Peste/epidemiología , Historia del Siglo XV , Historia del Siglo XXI , Humanos , Pandemias , Peste/historia , Peste/transmisión , Reino Unido/epidemiología , Estados Unidos/epidemiologíaAsunto(s)
Glucemia/efectos de los fármacos , Canagliflozina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina , Células Secretoras de Insulina/efectos de los fármacos , Glucemia/metabolismo , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Método Doble Ciego , Hemoglobina Glucada/metabolismo , Humanos , Células Secretoras de Insulina/fisiología , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Resultado del TratamientoRESUMEN
Obesity is associated with increased cardiovascular risk. Anthropometric cut-off values derived for Caucasians may not be applicable to other populations. The main objective of the present study was to derive population-specific anthropometric cut-off values to define high CVD risk for Sri Lankan adults. A nationally representative sample of 4474 non-institutionalised adults aged ≥ 18 years was analysed. Cut-off values to provide optimum sensitivity and specificity were derived using receiver-operating characteristic curve analysis. BMI, waist circumference (WC), waist-to-hip ratio (WHR), blood pressure and overnight fasting venous blood samples were collected to measure glucose, HDL-cholesterol and TAG. An oral glucose tolerance test was also performed. The results suggested that the age-adjusted BMI, WC and WHR were significantly associated with all cardiovascular risk factors (P < 0·001). Cut-off values for BMI, WC and WHR for males were 20·7 kg/m2, 76·5 cm and 0·89, respectively. The respective values for females were 22·0 kg/m2, 76·3 cm and 0·85. The common cut-off value for BMI for males and females was 21·5 kg/m2. Similarly, WC and WHR cut-off values for both males and females were 76·3 cm and 0·87, respectively. The Asian and Caucasian anthropometric cut-off levels showed lower sensitivity and higher false negative percentage compared with newly derived cut-off levels. In conclusion, BMI, WC and WHR were all associated with increased CVD risk. We propose the following anthropometric cut-off points to determine high CVD risk level for Sri Lankan adults: BMI ≥ 21·5 kg/m2, WC ≥ 76 cm and WHR ≥ 0·85 (women) and 0·90 (men).
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Pueblo Asiatico , Índice de Masa Corporal , Enfermedades Cardiovasculares/etnología , Obesidad/etnología , Circunferencia de la Cintura/etnología , Relación Cintura-Cadera , Adulto , Antropometría , Enfermedades Cardiovasculares/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Curva ROC , Valores de Referencia , Factores de Riesgo , Factores Sexuales , Sri Lanka , Población BlancaRESUMEN
We present recent data on dynamic imaging of Rac1 activity in live T-cells. Förster resonance energy transfer between enhanced green and monomeric red fluorescent protein pairs which form part of a biosensor molecule provides a metric of this activity. Microscopy is performed using a multi-functional high-content screening instrument using fluorescence anisotropy to provide a means of monitoring protein-protein activity with high temporal resolution. Specifically, the response of T-cells upon interaction of a cell surface receptor with an antibody coated multi-well chamber was measured. We observed dynamic changes in the activity of the biosensor molecules with a time resolution that is difficult to achieve with traditional methodologies for observing Förster resonance energy transfer (fluorescence lifetime imaging using single photon counting or frequency domain techniques) and without spectral corrections that are normally required for intensity based methodologies.
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Polarización de Fluorescencia/métodos , Transferencia Resonante de Energía de Fluorescencia/métodos , Técnicas Biosensibles , Línea Celular , Polarización de Fluorescencia/instrumentación , Transferencia Resonante de Energía de Fluorescencia/instrumentación , Proteínas Fluorescentes Verdes/química , Humanos , Proteínas Luminiscentes/química , Microscopía Fluorescente , Conformación Proteica , Mapeo de Interacción de Proteínas/instrumentación , Mapeo de Interacción de Proteínas/métodos , Sensibilidad y Especificidad , Linfocitos T/química , Factores de Tiempo , Proteína de Unión al GTP cdc42/química , Proteína de Unión al GTP rac1/química , Proteína Fluorescente RojaRESUMEN
AIM: To show that vildagliptin added to metformin is non-inferior to glimepiride in reducing HbA1c levels from baseline over 2 years. METHODS: A randomized, double-blind, active-comparator study of patients with type 2 diabetes mellitus inadequately controlled (HbA1c 6.5-8.5%) by metformin monotherapy. Patients received vildagliptin (50 mg twice daily) or glimepiride (up to 6 mg/day) added to metformin. RESULTS: In all, 3118 patients were randomized (vildagliptin, n = 1562; glimepiride, n = 1556). From similar baseline values (7.3%), after 2 years adjusted mean (s.e.) change in HbA1c was comparable between vildagliptin and glimepiride treatment: -0.1% (0.0%) and -0.1% (0.0%), respectively. The primary objective of non-inferiority was met. A similar proportion of patients reached HbA1c <7% (36.9 and 38.3%, respectively), but with vildagliptin more patients reached this target without hypoglycaemia (36.0% vs. 28.8%; p = 0.004). The initial response (IR) was sustained for a mean (s.d.) of 309 (244) days with vildagliptin versus 270 (223) days for glimepiride (p < 0.001) (IR = nadir HbA1c where change from baseline > or =0.5% or HbA1c < or =6.5% within the first six months of treatment. After IR was detected, sustained response = time between nadir and an increase of >0.3% above IR). Independent of disease duration, age was a predictor of effect sustainability. Fewer patients experienced hypoglycaemia with vildagliptin (2.3% vs. 18.2% with glimepiride) with a 14-fold difference in the number of hypoglycaemic events (59 vs. 838). Vildagliptin had a beneficial effect on body weight [mean (s.e.) change from baseline -0.3 (0.1) kg; between-group difference -1.5 kg; p < 0.001]. Overall, both treatments were well tolerated and displayed similar safety profiles. CONCLUSIONS: Vildagliptin add-on has similar efficacy to glimepiride after 2 years' treatment, with markedly reduced hypoglycaemia risk and no weight gain.
Asunto(s)
Adamantano/análogos & derivados , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Nitrilos/administración & dosificación , Pirrolidinas/administración & dosificación , Compuestos de Sulfonilurea/administración & dosificación , Adamantano/administración & dosificación , Adolescente , Adulto , Anciano , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Quimioterapia Combinada/métodos , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vildagliptina , Aumento de Peso , Adulto JovenRESUMEN
BACKGROUND: Education plays a key role in the development of self-management skills for people with type 2 diabetes, although there is limited evidence for the use of video education. AIMS: To develop a video-based lifestyle education programme for people newly diagnosed with type 2 diabetes and to evaluate changes in knowledge, biomedical indices and quality of life. METHODS: Forty-two newly diagnosed type 2 diabetic subjects were recruited and randomly allocated to either a video education or control group. Data were collected at baseline and 6 months after the intervention. Subjects (43% male) had a mean (SD) age of 60.8 (9.6) years, weight 89.5 (15.5) kg, BMI 31.3 (5.1) kg m(2), glycated haemoglobin (A1c) 7.4 (1.7)%, total cholesterol 4.7 (1.2) mmol L(-1), high-density lipoprotein cholesterol 1.15 (0.34) mmol L(-1), triglycerides 1.8 (1.0) mmol L(-1), low-density lipoprotein cholesterol 2.8 (1.0) mmol L(-1), pedometer reading 5721 (3446) steps per day. There were 63.7% correct answers given to the ADKnowl questionnaire and the WHO-5 Well-Being score was 65.8%. RESULTS: At 6 months, the intervention group showed increased knowledge compared to controls (74.3% versus 56.4% correct answers, P < or = 0.0001). Although there were no significant differences in changes over 6 months between the two groups, the intervention group showed improvements in A1c (-0.7%, P = 0.024), total cholesterol (-0.5 mmol L(-1), P = 0.017), low-density lipoprotein cholesterol (-0.5, P = 0.018) and increased physical activity measured by pedometer (1266 steps per day, P = 0.043) from baseline, with no significant changes in the control group. CONCLUSIONS: A brief video intervention increased diabetes knowledge amongst those newly diagnosed with type 2 diabetes and may comprise an effective way of directing education to such individuals.
Asunto(s)
Diabetes Mellitus Tipo 2/terapia , Promoción de la Salud/métodos , Estilo de Vida , Educación del Paciente como Asunto/métodos , Evaluación de Programas y Proyectos de Salud/métodos , Grabación de Cinta de Video , Diabetes Mellitus Tipo 2/sangre , Ejercicio Físico , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Conocimientos, Actitudes y Práctica en Salud , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios , CaminataRESUMEN
AIM: To ascertain if those with diabetes (and their carers) ascribe a similar level of risk to blood glucose control as healthcare professionals. METHODS: We used a structured questionnaire to ask fifty healthcare professionals how 'dangerous' a given blood glucose value was. Their answers were modelled to produce an algorithm of assessed risk. To examine if patients (and their carers) would apportion a similar level of risk to that of healthcare professionals, the same questionnaire was issued to fifty children and adolescents with Type 1 diabetes. For patients under 8 years old the carers completed the questionnaires (n = 23). Both patient and carers together completed the questionnaire for those aged 8-11 years (n = 15) and patients over the age of 11 years completed the questionnaire themselves (n = 12). The median results and interquartile range of the assessed level of risk, as determined by the two groups, were compared using a generalized linear model. RESULTS: A significant difference (P < 0.0001) was identified between the median risk assessments of the two groups. The zero level of assessed risk was upward shifted in the patient group by 0.8 mmol/l and indicated the patients' view of risk increased. CONCLUSIONS: Patients with Type 1 diabetes (and their carers) evaluate the risk from blood glucose values differently from healthcare professionals. The euglycaemic state (zero ascribed risk) that patients chose was 0.8 mmol/l greater than that of healthcare professionals, indicating, perhaps, hypoglycaemia avoidance, a more pragmatic approach or less exposure to current trends in glycaemic control.
Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Adolescente , Glucemia/metabolismo , Niño , Femenino , Humanos , Masculino , Medición de RiesgoRESUMEN
AIM: The effect on body composition of liraglutide, a once-daily human glucagon-like peptide-1 analogue, as monotherapy or added to metformin was examined in patients with type 2 diabetes (T2D). METHODS: These were randomized, double-blind, parallel-group trials of 26 [Liraglutide Effect and Action in Diabetes-2 (LEAD-2)] and 52 weeks (LEAD-3). Patients with T2D, aged 18-80 years, body mass index (BMI) < or =40 kg/m(2) (LEAD-2), < or =45 kg/m(2) (LEAD-3) and HbA1c 7.0-11.0% were included. Patients were randomized to liraglutide 1.8, 1.2 or 0.6 mg/day, placebo or glimepiride 4 mg/day, all combined with metformin 1.5-2 g/day in LEAD-2 and to liraglutide 1.8, 1.2 or glimepiride 8 mg/day in LEAD-3. LEAD-2/3: total lean body tissue, fat tissue and fat percentage were measured. LEAD-2: adipose tissue area and hepatic steatosis were assessed. RESULTS: LEAD-2: fat percentage with liraglutide 1.2 and 1.8 mg/metformin was significantly reduced vs. glimepiride/metformin (p < 0.05) but not vs. placebo. Visceral and subcutaneous adipose tissue areas were reduced from baseline in all liraglutide/metformin arms. Except with liraglutide 0.6 mg/metformin, reductions were significantly different vs. changes seen with glimepiride (p < 0.05) but not with placebo. Liver-to-spleen attenuation ratio increased with liraglutide 1.8 mg/metformin possibly indicating reduced hepatic steatosis. LEAD-3: reductions in fat mass and fat percentage with liraglutide monotherapy were significantly different vs. increases with glimepiride (p < 0.01). CONCLUSION: Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hemoglobina Glucada/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Compuestos de Sulfonilurea/administración & dosificación , Pérdida de Peso/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Composición Corporal , Peso Corporal/efectos de los fármacos , Preparaciones de Acción Retardada , Diabetes Mellitus Tipo 2/metabolismo , Método Doble Ciego , Femenino , Péptido 1 Similar al Glucagón/uso terapéutico , Hemoglobina Glucada/metabolismo , Humanos , Liraglutida , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
AIMS: The maternally inherited mt3243A > G mutation is associated with a variable clinical phenotype including diabetes and deafness (MIDD). We aimed to determine the prevalence and clinical characteristics of MIDD in a large South Asian cohort of young adult-onset diabetic patients from Sri Lanka. METHODS: DNA was available from 994 subjects (age of diagnosis 16-40 years, age at recruitment < or = 45 years). Mutation screening was performed using a QRT-PCR method on an ABI 7900HT system using sequence-specific probes. Samples with heteroplasm > or = 5.0% were considered positive. RESULTS: Nine (four males) mutation-positive subjects were identified (prevalence 0.9%). They were diagnosed at a younger age (25.9 +/- 4.8 years vs. 31.9 +/- 5.6 years, P = 0.002) and were lean (body mass index [BMI] 18.7 +/- 2.7 kg/m(2) vs. 24.7 +/- 4.0 kg/m(2), P < 0.001) compared to NMCs. One mutation-positive subject (11.1%) had metabolic syndrome, compared to 633 (64.3%) of NMCs. Insulin therapy within 6 months of diagnosis was used in four (44.0%) carriers compared to 6.9% of NMCs (P = 0.002). Combined screening criteria of any two of maternal history of diabetes, personal history of hearing impairment and family history of hearing impairment only identified five (55%) of the carriers, with a positive predictive value of 7.4%. CONCLUSIONS: The prevalence of mt3243A > G mutation among young adult-onset diabetic subjects from Sri Lanka was 0.9%. Our study demonstrates that a maternal family history of diabetes and either a personal and/or family history of deafness only distinguish half of patients with MIDD from Sri Lankan subjects with young-onset diabetes.
Asunto(s)
ADN Mitocondrial/genética , Sordera/genética , Diabetes Mellitus/genética , Mutación/genética , Adolescente , Adulto , Sordera/complicaciones , Femenino , Humanos , Masculino , Linaje , Embarazo , Sri LankaRESUMEN
AIMS: To determine the prevalence of diabetes mellitus and pre-diabetes (impaired fasting glucose and impaired glucose tolerance) in adults in Sri Lanka. Projections for the year 2030 and factors associated with diabetes and pre-diabetes are also presented. METHODS: This cross-sectional study was conducted between 2005 and 2006. A nationally representative sample of 5000 adults aged >or= 18 years was selected by a multi-stage random cluster sampling technique. Fasting plasma glucose was tested in all participants and a 75-g oral glucose tolerance test was performed in non-diabetic subjects. Prevalence was estimated for those > 20 years of age. RESULTS: Response rate was 91% (n = 4532), males 40%, age 46.1 +/- 15.1 years (mean +/- standard deviation). The age-sex standardized prevalence (95% confidence interval) of diabetes for Sri Lankans aged >or= 20 years was 10.3% (9.4-11.2%) [males 9.8% (8.4-11.2%), females 10.9% (9.7-12.1%), P = 0.129). Thirty-six per cent (31.9-40.1%) of all diabetic subjects were previously undiagnosed. Diabetes prevalence was higher in the urban population compared with rural [16.4% (13.8-19.0%) vs. 8.7% (7.8-9.6%); P < 0.001]. The prevalence of overall, urban and rural pre-diabetes was 11.5% (10.5-12.5%), 13.6% (11.2-16.0%) and 11.0% (10.0-12.0%), respectively. Overall, 21.8% (20.5-23.1%) had some form of dysglycaemia. The projected diabetes prevalence for the year 2030 is 13.9%. Those with diabetes and pre-diabetes compared with normal glucose tolerance were older, physically inactive, frequently lived in urban areas and had a family history of diabetes. They had higher body mass index, waist circumference, waist-hip ratio, systolic/diastolic blood pressure, low-density lipoprotein cholesterol and triglycerides. Insulin was prescribed to 4.4% (2.7-6.1%) of all diabetic subjects. CONCLUSIONS: One in five adults in Sri Lanka has either diabetes or pre-diabetes and one-third of those with diabetes are undiagnosed.