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1.
Diabet Med ; 37(9): 1509-1518, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32530523

RESUMO

AIMS: To present the longer-term impact of multifactorial treatment of type 2 diabetes on self-reported health status, diabetes-specific quality of life, and diabetes treatment satisfaction at 10-year follow up of the ADDITION-Europe trial. METHODS: The ADDITION-Europe trial enrolled 3057 individuals with screen-detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care . The trial ended in 2009 and a 10-year follow-up was performed at the end of 2014. We measured self-reported health status (36-item Short-Form Health Survey and EQ-5D), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed-effects model was applied to estimate the effect of intensive treatment (intention-to-treat analyses) on patient-reported outcome measures for each centre. Centre-specific estimates were pooled using a fixed effects meta-analysis. RESULTS: There was no difference in patient-reported outcome measures between the routine care and intensive treatment arms in this 10-year follow-up study [EQ-5D: -0.01 (95% CI -0.03, 0.01); Physical Composite Score (36-item Short-Form Health Survey): -0.27 (95% CI -1.11, 0.57), Audit of Diabetes-Dependent Quality of Life questionnaire: -0.01 (95% CI -0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: -0.20 (95% CI -0.70, 0.29)]. CONCLUSIONS: Intensive, multifactorial treatment of individuals with screen-detected type 2 diabetes did not affect self-reported health status, diabetes-specific quality of life, or diabetes treatment satisfaction at 10-year follow-up compared to routine care.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Hipoglicemiantes/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Qualidade de Vida , Idoso , Pressão Sanguínea , Colesterol/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Nível de Saúde , Humanos , Masculino , Programas de Rastreamento , Saúde Mental , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente
2.
Diabet Med ; 36(1): 105-109, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30175888

RESUMO

AIMS: To examine whether the development of obesity with age was different for individuals with and without a spouse with diabetes. METHODS: We analysed data from the English Longitudinal Study of Ageing [n= 7123, median (interquartile range) age 59 (53-67) years, 51% men], which included four clinical examination waves between 1998 and 2012. The main exposure was having a spouse with diabetes. Outcomes of interest were BMI and waist circumference. We fitted quadratic age-related trajectories using mixed-effect models stratified by sex and adjusted for education, smoking and the corresponding interaction terms between age and spousal diabetes status. RESULTS: The baseline spousal diabetes prevalence was 4.4%. Men with a wife with diabetes experienced a steeper increase in BMI (1.6 kg/m2 ) between ages 50 to 65 years than men with a wife without diabetes (0.9 kg/m2 ). Women with a husband with diabetes had a similarly shaped BMI trajectory to women with a husband without diabetes, but their average BMI levels were higher between ages 55 and 65 years. Waist circumference trajectories showed a similar shape by spousal diabetes status for men and women, although individuals with a spouse with diabetes had higher waist circumference values throughout follow-up. CONCLUSIONS: We found a positive association between spousal diabetes status and obesity development, which differed by sex among middle-aged individuals. Evidence from couple-based interventions is needed to test whether the latter could improve the current individual-focused public health strategies for obesity prevention.


Assuntos
Envelhecimento , Diabetes Mellitus Tipo 2/epidemiologia , Promoção da Saúde , Obesidade/epidemiologia , Cônjuges/estatística & dados numéricos , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Inglaterra/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/fisiopatologia , Prevalência , Fatores de Risco , Circunferência da Cintura
3.
Diabet Med ; 36(10): 1256-1260, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30897241

RESUMO

AIMS: We examined whether late evening food consumption was prospectively associated with the risk of developing prediabetes or diabetes in a large observational study of individuals with normoglycaemia. METHODS: Participants were 2642 men and women with normoglycaemia (HbA1c < 39 mmol/mol; < 5.7%) from the Whitehall II study. Time of last eating episode (TLEE) before the examination day was assessed at baseline. We studied the associations of TLEE with 5-year changes in HbA1c and risk of developing prediabetes or diabetes (HbA1c ≥ 39 mmol/mol; ≥ 5.7%). Potential heterogeneity in the association between TLEE and prediabetes or diabetes was examined using recursive partitioning modelling for time-to-event outcomes. RESULTS: There was a tendency of an overall association of TLEE with change in HbA1c but with little effect size [ß per 1-h increase in TLEE = 0.2 mmol/mol, 95% CI -0.0 to 0.3 (0.01%, -0.00 to 0.03); P = 0.055] and no association with the risk of developing prediabetes/diabetes (risk ratio per 1-h increase in TLEE = 1.03, 95% CI 0.94 to 1.13; P = 0.511). According to the recursive partitioning modelling, women with HbA1c ≤ 36 mmol/mol and TLEE after 21:00 had a 1.51 times (95% CI 1.16 to 1.93) higher 5-year risk of developing prediabetes or diabetes than those having their TLEE between 16:00 and 21:00 (35.4% vs. 23.5%; P = 0.003). CONCLUSIONS: There was no overall association of TLEE with the development of prediabetes or diabetes in the Whitehall II population. However, explorative analyses suggested that eating late in the evening was associated with increased risk of developing prediabetes/diabetes among women with good glycaemic control. Whether restricting late evening food consumption is effective and feasible for the prevention of Type 2 diabetes needs testing in randomized controlled trials.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Comportamento Alimentar , Estado Pré-Diabético/epidemiologia , Idoso , Glicemia/análise , Índice de Massa Corporal , Estudos de Coortes , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Reino Unido/epidemiologia
4.
Lupus ; 26(11): 1205-1211, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28478696

RESUMO

The gold standard for the classification of lupus nephritis is renal histology but reporting variation exists. The aim of this study was to assess the inter-observer variability of the 2003 International Society of Nephrology/Royal Pathology Society (ISN/RPS) lupus nephritis histological classification criteria in children. Histopathologists from a reference centre and three tertiary paediatric centres independently reviewed digitalized renal histology slides from 55 children with lupus nephritis. Histological ISN/RPS Class was assigned and features scored; lupus nephritis-activity [scored 0-24], lupus nephritis-chronicity [0-12] and tubulointerstitial activity [0-21]. In the cohort (73% females), the age at the time of biopsy was 15.5 ± 0.39 (mean ± standard error) years. Based on the reference centre, 42% (23/55) had ISN/RPS Class IV with lupus nephritis-activity score 4.23 ± 0.50, lupus nephritis-chronicity 1.81 ± 0.18 and tubulointerstitial activity 4.45 ± 0.35. There were 4-54 (mean 16.7) glomeruli per biopsy. Pathologists had fair agreement for ISN/RPS assignment (kappa; 0.26 ± 0.12), lupus nephritis-chronicity (intra-class correlation 0.36 ± 0.09) and tubulointerstitial activity (0.22 ± 0.09) scores. There was good agreement for lupus nephritis-activity scores (intra-class correlation 0.69 ± 0.06). When categorized into proliferative and non-proliferative disease, poor agreement among sites remained (kappa 0.24 ± 0.11). Despite unified criteria for the interpretation of histological features of lupus nephritis, marked reporting variation remains in clinical practice. As proliferative lupus nephritis is managed more intensively, this may influence renal outcomes.


Assuntos
Glomérulos Renais/patologia , Nefrite Lúpica/patologia , Patologistas , Adolescente , Biópsia , Feminino , Humanos , Nefrite Lúpica/classificação , Masculino , Variações Dependentes do Observador , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Reino Unido , Estados Unidos
5.
Diabet Med ; 33(12): 1625-1631, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27504739

RESUMO

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


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Aldeído Pirúvico/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , Albuminúria/fisiopatologia , Creatinina/urina , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade
6.
Diabet Med ; 32(6): 778-85, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25761542

RESUMO

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


Assuntos
Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Neuropatias Diabéticas/sangue , Aldeído Pirúvico/sangue , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/epidemiologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
7.
Diabet Med ; 31(8): 1001-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24724616

RESUMO

AIMS: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic ß-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to type 2 diabetes in humans. METHODS: Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for type 2 diabetes susceptibility in up to 25 000 people (8148 with type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. RESULTS: rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*104) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (P = 5.5*104) but again not in men (P = 0.34). CONCLUSION: The present data identify DRD2/ANKK1 as a potential sex-specific type 2 diabetes susceptibility gene.


Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D2/genética , Alelos , Estudos de Casos e Controles , Estudos de Coortes , Dinamarca , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Frequência do Gene , Estudos de Associação Genética , Loci Gênicos , Humanos , Hiperglicemia/sangue , Hiperglicemia/genética , Hiperglicemia/metabolismo , Insulina/sangue , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Países Baixos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Dopamina D2/metabolismo , Caracteres Sexuais
8.
Plant Dis ; 98(6): 843, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30708687

RESUMO

Anthracnose of alfalfa (Medicago sativa), caused by Colletotrichum trifolii, is widespread in the United States. In addition to loss of forage due to death of stems, the pathogen causes crown rot, reducing stand life and winter survival (2), making it one of the most serious diseases of alfalfa. Three physiological races have been described (2). Race 1 is reported to be the dominant race that is present wherever alfalfa is grown, while race 2 was reported in a limited area in the Mid-Atlantic states, and race 4 was found in Ohio (1). Conspicuous, straw-colored dead stems with a "shepherd's crook" wilt and large, sunken, diamond-shaped lesions with a dark border were observed in experimental plots and breeding nurseries of experimental lines in Clinton and West Salem, WI, in August 2011 and in West Salem, WI, in mid-August 2012. Acervuli with black setae and orange spore masses were observed in lesions placed in moist chambers for 2 days at room temperature with ambient room lighting. Conidia were germinated on 1% water agar and then single hyphae were transferred to potato dextrose agar (PDA) plates. DNA was extracted from pure cultures of strains DA-1 (Clinton, WI) and FGI-3 (West Salem, WI), the rDNA ITS1-5.8S-ITS2 region was amplified with primers ITS1 (5'-TCCGTAGGTGAACCTGCGG-3') and ITS4 (5'-TCCTCCGCTTATTGATATGC-3'), the products sequenced directly, and the sequences compared to the ITS region of known race 1 and race 2 strains of C. trifolii. The sequences from DA-1 and FGI-3 were identical to the ITS sequence of C. trifolii 2sp2 (race 1; KF444778) and C. trifolii SB-2 (race 2; KF444779), but distinct from the ITS sequence of C. destructivum (JQ005764) and C. dematium (JX567507), which can cause anthracnose on alfalfa (1). Conidia from DA-1 and FGI-3 were harvested from 7-day-old cultures grown on PDA plates, diluted to 2 × 106 conidia/ml, and sprayed to runoff on 10-day-old growth chamber grown plants of three differential cultivars: Saranac (susceptible to races 1 and 2), Arc (resistant to race 1, susceptible to race 2), and Saranac AR (resistant to races 1 and 2). Plants were maintained at 100% relative humidity for 48 h and then grown in a growth chamber at 24°C with a 16-h photoperiod. Symptoms were rated at 14 days after inoculation. In the three repetitions of the experiment using 75 plants of each cultivar in each experiment, less than 10% of the Saranac and Arc plants survived, while survival of Saranac AR was 31 to 44%. The approximate expected survival of differential cultivars inoculated with race 1 is 1% for Saranac, 65 to 70% for Arc, and 45% for Saranac AR (2). Aggressiveness of race 2 strains on Saranac AR is variable, ranging from 12 to 68% plant survival (3). The susceptibility of Arc when inoculated with DA-1 and FGI-3 is consistent with the reaction to race 2 strains, indicating that both strains are race 2. The isolation of race 2 strains in major alfalfa growing regions in Wisconsin indicates that this physiological race is currently more widespread than previously observed. Although most modern alfalfa cultivars have resistance to race 1, few cultivars with resistance to race 2 are available. The occurrence of C. trifolii race 2 in the Midwest United States should be considered in alfalfa breeding programs when developing multi-pest resistant alfalfa cultivars. References: (1) J. J. Ariss and L. H. Rhodes. Plant Dis. 91:1362, 2007. (2) N. R. O'Neill. Plant Dis. 80:450, 1996. (3) N. R. O'Neill et al. Phytopathology 79:750, 1989.

9.
Diabetologia ; 56(1): 101-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23064291

RESUMO

AIMS/HYPOTHESIS: There is limited evidence on how multifactorial treatment improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. Cardiac autonomic neuropathy (CAN) in people with diabetes indicates widespread damage to the autonomic nervous system, which may severely affect health and quality of life. We examined effects of early detection and subsequent intensive treatment of type 2 diabetes in primary care on the prevalence of CAN at the 6-year follow-up examination in a pragmatic cluster-randomised parallel group trial. METHODS: One hundred and ninety general practices were randomised to deliver either intensive multifactorial treatment (IT) or routine care (RC) as recommended by national guidelines to patients with type 2 diabetes, identified through a stepwise screening programme in the primary care setting. 1533 people (IT, n = 910; RC, n = 623) were identified and included. At the 6-year follow-up examination, measures of CAN were applied in an unselected subsample of 777 participants using heart rate variability analysis and standard tests of CAN. RESULTS: At the 6-year follow-up examination, the prevalence of early CAN was 15.1% in the RC group and 15.5% in the IT group, while manifest CAN was present in 7.1% and 7.3%, respectively. We found no statistically significant effect of intensive treatment on the prevalence of CAN compared with routine care. CONCLUSIONS/INTERPRETATION: In the Danish arm of the ADDITION Study, signs of CAN were highly prevalent 6 years after a screening-based diagnosis of type 2 diabetes. Intensive multifactorial treatment did not significantly affect the prevalence of CAN compared with routine care. However, at follow-up the level of medication was also high in the RC group.


Assuntos
Doenças do Sistema Nervoso Autônomo/prevenção & controle , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Cardiomiopatias Diabéticas/prevenção & controle , Neuropatias Diabéticas/prevenção & controle , Adulto , Idoso , Doenças do Sistema Nervoso Autônomo/complicações , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/epidemiologia , Estudos de Coortes , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiomiopatias Diabéticas/diagnóstico , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/fisiopatologia , Diagnóstico Precoce , Feminino , Seguimentos , Medicina Geral , Frequência Cardíaca , Humanos , Hipoglicemiantes/uso terapêutico , Incidência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Atenção Primária à Saúde , Índice de Gravidade de Doença
10.
Diabetologia ; 56(2): 294-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23143165

RESUMO

AIMS/HYPOTHESIS: We aimed to study diurnal variation in glucose regulation by examining the effects of time of day and fasting duration on fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG) and HbA(1c) levels. METHODS: We analysed data from 5,978 non-diabetic white men and women from the prospective Whitehall II Study. All studied participants fasted for at least 8 h before a clinical examination, which included an OGTT and anthropometric measurements. We fitted mixed-effects models for FPG, 2hPG and HbA(1c) as outcome variables, and time of day and/or fasting duration as explanatory variables. Models were adjusted for age, BMI and study phase. RESULTS: Time of day and fasting duration were associated inversely with FPG and positively with 2hPG. The mean difference between measures at 08:00 and 15:00 hours in men/women was -0.46 (95% CI -0.50, -0.42) mmol/l/-0.39 (95% CI -0.46, -0.31) mmol/l and 1.39 (95% CI 1.25, 1.52) mmol/l/1.19 (95% CI 0.96, 1.42) mmol/l for FPG and 2hPG, respectively. HbA(1c) levels were independent of either time. Time of day and fasting duration were independently associated with 2hPG. In contrast, the effect of fasting duration on FPG was markedly attenuated with adjustment for time of day. Ageing, but not obesity, was associated with increased diurnal variation in glucose tolerance. CONCLUSIONS/INTERPRETATION: Both time of day and fasting duration should be considered in clinical practice and epidemiological studies, since they have clinically relevant effects on FPG and 2hPG levels. As biochemically expected, HbA(1c) levels are independent of time of blood sampling and fasting duration.


Assuntos
Glicemia/metabolismo , Jejum/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Estudos Prospectivos , Fatores de Tempo
11.
Diabetologia ; 56(7): 1542-6, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23613086

RESUMO

AIMS/HYPOTHESIS: Recent evidence links the soluble urokinase plasminogen activator receptor (suPAR), a stable biomarker of systemic immune activation, to several chronic diseases, including type 2 diabetes. suPAR is also associated with adiposity and smoking. We hypothesised that this biomarker would be linked to incident type 2 diabetes in individuals with impaired glucose regulation and that this association would be modified by smoking and body weight status. METHODS: The study included 1,933 participants with impaired glucose regulation, who were drawn from the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION) and for whom data on suPAR, BMI and smoking were available. Logistic regression analysis was used to estimate the odds for incident type 2 diabetes per twofold increase in suPAR levels. Interactions between both smoking and body weight status and suPAR were tested. RESULTS: During a 3-year follow-up (599 incident diabetes cases), there was a 48% overall increase in the odds of developing type 2 diabetes per twofold increase in suPAR (p = 0.006). This association was modified by body weight status in overweight, but not in obese individuals (OR 2.36, 95% CI 1.48, 3.76 in overweight group), and by smoking status (OR 2.05, 95% CI 1.20, 3.51 in non-smokers). After adjustment for other diabetes risk factors, the association between suPAR and type 2 diabetes was attenuated in the whole sample and among non-smokers, but remained robust among overweight participants. CONCLUSIONS/INTERPRETATION: suPAR may be a good novel biomarker for systemic sub-clinical inflammation and immune activation linked to incident type 2 diabetes risk in overweight individuals and non-smokers. The observed interactions with adiposity and smoking should be investigated further.


Assuntos
Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/metabolismo , Sobrepeso/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Fumar/efeitos adversos , Índice de Massa Corporal , Peso Corporal/fisiologia , Feminino , Humanos , Masculino
12.
Int J Obes (Lond) ; 37(2): 175-81, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22349573

RESUMO

CONTEXT: Uncoupling protein 2 (UCP2) is involved in regulating ATP synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in ß-cells. Polymorphisms in UCP2 may be associated with obesity and type 2 diabetes mellitus. OBJECTIVE: To determine the influence of a functional UCP2 promoter polymorphism (-866G>A, rs659366) on obesity, type 2 diabetes and intermediary metabolic traits. Furthermore, to include these and previously published data in a meta-analysis of this variant with respect to its impact on obesity and type 2 diabetes. DESIGN: We genotyped UCP2 rs659366 in a total of 17 636 Danish individuals and established case-control studies of obese and non-obese subjects and of type 2 diabetic and glucose-tolerant subjects. Meta-analyses were made in own data set and in publicly available data sets. Quantitative traits relevant for obesity and type 2 diabetes were analysed within separate study populations. RESULTS: We found no consistent associations between the UCP2 -866G-allele and obesity or type 2 diabetes. Yet, a meta-analysis of data from 12 984 subjects showed an association with obesity (GA vs GG odds ratio (OR) (95% confidence interval (CI)): 0.894(0.826-0.968) P=0.00562, and AA vs GG OR(95% CI): 0.892(0.800-0.996), P=0.0415. Moreover, a meta-analysis for type 2 diabetes of 15 107 individuals showed no association. The -866G-allele was associated with elevated fasting serum insulin levels (P=0.002) and HOMA insulin resistance index (P=0.0007). Insulin sensitivity measured during intravenous glucose tolerance test in young Caucasian subjects (n=377) was decreased in carriers of the GG genotype (P=0.05). CONCLUSIONS: The UCP2 -866G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Resistência à Insulina , Canais Iônicos/sangue , Proteínas Mitocondriais/sangue , Obesidade/sangue , Polimorfismo de Nucleotídeo Único , População Branca/genética , Alelos , Animais , Glicemia/metabolismo , Estudos de Casos e Controles , Dinamarca/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Resistência à Insulina/genética , Canais Iônicos/genética , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Obesidade/epidemiologia , Obesidade/genética , Regiões Promotoras Genéticas , Proteína Desacopladora 2
13.
Diabet Med ; 30(4): 443-51, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23331167

RESUMO

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/epidemiologia
14.
Nutr Metab Cardiovasc Dis ; 23(9): 822-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22831954

RESUMO

BACKGROUND AND AIM: A high intake of dairy has been linked to lower risk of type 2 diabetes (T2D). The relationship between dairy intake and glucose metabolism is still not well understood. The aim of this study was to investigate the relation between the intake of total dairy and dairy subgroups and T2D and measures of glucose metabolism. METHODS AND RESULTS: A total of 5953 Danish men and women aged 30-60 years without baseline diabetes or cardiovascular diseases were included in this prospective analysis. The dairy intake at baseline was categorised into low-fat dairy, full-fat dairy, milk and milk products, cheese and fermented dairy. Fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), HbA1c, insulin resistance (HOMA2-IR) and beta-cell function (HOMA2-B) were considered at 5-year follow-up. In the maximally-adjusted model (demographics, lifestyle factors, dietary factors and waist), cheese intake was inversely associated with 2hPG (ß = -0.048, 95% CI -0.095; -0.001). Fermented dairy intake was inversely associated with FPG (ß = -0.028, 95% CI -0.048; -0.008) and HbA1c (ß = -0.016, 95% CI -0.030; -0.001). Total dairy intake and the dairy subgroups were not related to HOMA-IR and HOMA-B in the maximally-adjusted model. Furthermore, there was no significant association between intake of total dairy or any of the dairy subgroups and incidence of T2D. CONCLUSION: Our data suggest a modest beneficial effect of cheese and fermented dairy on glucose regulation measures; however, this did not translate into a significant association with incident T2D.


Assuntos
Laticínios , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Dieta , Adulto , Glicemia/metabolismo , Dinamarca/epidemiologia , Feminino , Seguimentos , Teste de Tolerância a Glucose , Humanos , Incidência , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , População Branca
15.
Diabetologia ; 55(4): 948-58, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22120574

RESUMO

AIMS/HYPOTHESIS: Cancer is more frequent among diabetes patients, but it is unknown how this excess varies with duration of diabetes and insulin use. The aim of this study was to analyse disease data to examine this issue further. METHODS: We linked the Danish National Diabetes Register and Cancer Registry and performed a cohort analysis of the entire Danish population by diabetes status, duration of diabetes and insulin use, comparing cancer incidence rates in diabetic patients with the non-diabetic population for the 15 year period 1995-2009, using Poisson regression with natural splines to describe the variation by duration. RESULTS: We found 20,032 cancer cases among patients not using insulin and 2,794 cancer cases among diabetic patients using insulin. The cancer incidence rate ratio among non-insulin users relative to the non-diabetic population decreased from over 2 at diagnosis to 1.15 after 2 years of diabetes duration. The cancer incidence rate ratio was higher among patients using insulin, decreasing from 5 at the start of insulin treatment to about 1.3 [corrected] after 5 years of insulin use. Among non-insulin users, cancers of the stomach, colorectum, liver, pancreas, lung, corpus uteri, kidney and brain, and lymphomas were elevated. Among insulin users the rate ratio of prostate cancer was decreasing by duration whereas we found higher risk of cancer of the stomach, lung, liver, pancreas and kidney. Breast cancer incidence rates were not affected by either diabetes or insulin use. CONCLUSIONS: The observed duration effects suggest that both increased surveillance for cancer in the first years after diagnosis of diabetes, and reverse causation, where undiagnosed cancers increase the likelihood of diabetes diagnosis, play a role. For longer durations, a combination of common causes for diabetes and cancer, as well as the effects of diabetes and insulin exposure per se, may play a role in the association between diabetes and some cancers.


Assuntos
Diabetes Mellitus/epidemiologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Neoplasias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Dinamarca/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Incidência , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Sistema de Registros , Risco , Fatores de Risco , Taxa de Sobrevida
16.
Diabetologia ; 55(6): 1607-18, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22476947

RESUMO

Substantial evidence suggests that people with type 2 diabetes have an increased risk of developing several types of cancers. These associations may be due to a number of direct and indirect mechanisms. Observational studies of these associations, including the potential role for glucose-lowering therapy, are being increasingly reported, but face a number of methodological challenges. This paper is the first of two review papers addressing methodological aspects underpinning the interpretations of links between diabetes and cancer, and suggests potential approaches to study designs to be considered in observational studies. This paper reviews factors related to cancer incidence in the diabetic population; the second paper relates to studies of cancer mortality.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias/epidemiologia , Neoplasias/etiologia , Humanos , Neoplasias/mortalidade , Fatores de Risco
17.
Diabetologia ; 55(1): 105-13, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21953277

RESUMO

AIMS/HYPOTHESIS: Genome-wide association studies have identified novel WHR and BMI susceptibility loci. The aim of this study was to elucidate if any of these loci had an effect on quantitative measures of glucose homeostasis, including estimates of insulin release and insulin sensitivity in an epidemiological setting. METHODS: By applying an additive genetic model, 14 WHR-associated gene variants and 18 BMI-associated variants were investigated for their relationships with glucose-related metabolic traits in treatment-naive individuals from the population-based Inter99 study sample (n = 6,039). RESULTS: Of the variants associated with BMI, the QPCTL rs2287019 C allele was associated with an increased insulinogenic index of 7.4% per risk allele (p = 4.0 × 10⁻7) and increased disposition index of 5.6% (p = 6.4 × 10⁻5). The LRP1B rs2890652 C allele was associated with insulin resistance, showing a 3.3% increase (p = 0.0011) using the HOMA-insulin resistance (HOMA-IR) index and a 2.2% reduction (p = 0.0014) with the Matsuda index. Of the variants associated with WHR, LYPLAL1/SLC30A10 rs4846567 G allele carriers showed a 5.2% lower HOMA-IR (p = 0.00086) in women, indicating improved insulin sensitivity. Female carriers of the VEGFA rs6905288 A allele were insulin resistant, with a 3.7% increase in HOMA-IR (p = 0.00036) and 4.0% decrease in Matsuda index (p = 2 × 10⁻4). CONCLUSIONS: Our correlative findings from analysing single-locus data suggest that some variation in validated BMI and WHR loci are associated with either increased or decreased insulin sensitivity and thereby potentially with metabolically healthy or metabolically unhealthy subsets of obesity. The results call for testing in larger study samples and for further physiological exploration of the possible metabolic implications of these loci.


Assuntos
Aminoaciltransferases/genética , Lisofosfolipase/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Receptores de LDL/genética , Fator A de Crescimento do Endotélio Vascular/genética , Índice de Massa Corporal , Portador Sadio , Estudos Transversais , Dinamarca , Feminino , Estudos de Associação Genética , Humanos , Hiperinsulinismo/complicações , Hiperinsulinismo/genética , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Obesidade/complicações , Caracteres Sexuais , Relação Cintura-Quadril
18.
Diabet Med ; 29(6): 755-60, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22132939

RESUMO

BACKGROUND AND AIM: Most studies show that diabetes increases with migration and urbanization. Previous studies from Greenland have shown inconsistent associations between cardiovascular risk and urbanization. Thus, the aim was to study the association between diabetes and urbanization among Greenland Inuit. METHODS: A total of 3089 adult Inuit aged 18 years and older participated in a geographically representative, population-based study 'Inuit Health in Transition Study'. The examination included a 75 g oral glucose tolerance test and anthropometric measurements. Information on socio-demographic characteristic and health behaviour was obtained by interview or questionnaire. The participants were categorized according to degree of urbanization into three groups based on current place of residence: (1) participants living in towns (> 2000 inhabitants), (2) participants living in small towns (< 2000 inhabitants) and (3) participants living in villages (< 500 inhabitants). RESULTS: The total prevalence of diabetes was 9% of which 79% were previously unknown. Nine per cent had impaired glucose tolerance and 19% had impaired fasting glycaemia (IFG). Compared with towns, odds rations (ORs) for diabetes and impaired fasting glycaemia were higher in small towns [OR(diabetes) = 1.5 (1.0-2.3), OR(IFG) = 1.9 (1.2-2.3)] and villages [OR(diabetes) = 1.2 (0.8-1.9), OR(IFG) = 1.3 (0.9-2.0)], whereas no association was seen for impaired glucose tolerance. The inverse association between urbanization and diabetes and impaired fasting glycaemia persisted after adjustment for relevant confounders. CONCLUSION: Diabetes and impaired fasting glycaemia decreased with urbanization contrary to the results of most studies. It appears that Greenland Inuit follow the pattern usually observed in industrialized countries with the highest risk of diabetes in the lower socio-economic groups.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Intolerância à Glucose/epidemiologia , Inuíte , Urbanização , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Feminino , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Groenlândia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Distribuição por Sexo , Inquéritos e Questionários , Urbanização/tendências , Adulto Jovem
19.
Diabet Med ; 29(9): e354-60, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22587629

RESUMO

AIMS: Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. METHODS: The study comprised 771 participants from the Danish, population-based cross-sectional 'Health2008' study. Sleep duration and sleep quality were measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA(1c), two measures of insulin sensitivity (the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity), the homeostasis model assessment of ß-cell function and glucose tolerance status. Associations of sleep duration and sleep quality with markers of glucose homeostasis and tolerance were analysed by multiple linear and logistic regression. RESULTS: A 1-h increment in sleep duration was associated with a 0.3 mmol/mol (0.3%) decrement in HbA(1c) and a 25% reduction in the risk of having impaired glucose regulation. Further, a 1-point increment in sleep quality was associated with a 2% increase in both the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity, as well as a 1% decrease in homeostasis model assessment of ß-cell function. CONCLUSIONS: In the present study, shorter sleep duration was mainly associated with later alterations in glucose homeostasis, whereas poorer sleep quality was mainly associated with earlier alterations in glucose homeostasis. Thus, adopting healthy sleep habits may benefit glucose metabolism in healthy populations.


Assuntos
Glucose/metabolismo , Homeostase/fisiologia , Sono/fisiologia , Adulto , Estudos Transversais , Dinamarca , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Tempo
20.
Diabetes Metab ; 48(1): 101263, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34023494

RESUMO

AIM: To analyze the association of objective and subjective sleep measures with HbA1c and insulin sensitivity in the general population. METHODS: Using a cross-sectional design, data from 1028 participants in the ORISCAV-LUX-2 study from the general population in Luxembourg were analyzed. Objective sleep measures were assessed using accelerometers whereas subjective measures were assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Sleep measures were defined as predictors, while HbA1c and quantitative insulin sensitivity check index (QUICKI) scores were considered outcomes. Linear and spline regression models were fitted by progressively adjusting for demographic and lifestyle variables in the total sample population as well as by stratified analyses using gender, obesity status, depressive symptoms and diabetes status. RESULTS: In fully adjusted models, total and deep sleep durations were associated with lower HbA1c (mmol/mol) levels, whereas sleep coefficients of variation (%) and poor sleep efficiency, as measured by PSQI scores (units), were associated with higher HbA1c levels. In stratified models, such associations were observed mainly in men, and in subjects who had depressive symptoms, were overweight and no diabetes. In addition, total sleep, deep sleep, coefficients of variation and poor sleep efficiency as measured by PSQI revealed non-linear associations. Similarly, greater insulin sensitivity was associated with longer total sleep time and with PSQI-6 (use of sleep medication). CONCLUSION: Associations were more frequently observed between sleep characteristics and glycaemic control with the use of objective sleep measures. Also, such associations varied within subgroups of the population. Our results highlight the relevance of measuring sleep patterns as key factors in the prevention of diabetes.


Assuntos
Resistência à Insulina , Transtornos do Sono-Vigília , Estudos Transversais , Hemoglobinas Glicadas , Humanos , Luxemburgo , Masculino , Sono , Transtornos do Sono-Vigília/complicações , Inquéritos e Questionários
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