RESUMO
AIMS: There is an unmet need among healthcare providers to identify subgroups of patients with type 2 diabetes who are most likely to respond to treatment. METHODS: Data were taken from electronic medical records of participants of an observational, retrospective study in Italy. We used logistic regression models to assess the odds of achieving glycated haemoglobin (HbA1c) reduction ≥ 1.0% point after 12-month treatment with liraglutide (primary endpoint), according to various patient-related factors. RECursive Partitioning and AMalgamation (RECPAM) analysis was used to identify distinct homogeneous patient subgroups with different odds of achieving the primary endpoint. RESULTS: Data from 1325 patients were included, of which 577 (43.5%) achieved HbA1c reduction ≥ 1.0% point (10.9 mmol/mol) after 12 months. Logistic regression showed that for each additional 1% HbA1c at baseline, the odds of reaching this endpoint were increased 3.5 times (95% CI: 2.90-4.32). By use of RECPAM analysis, five distinct responder subgroups were identified, with baseline HbA1c and diabetes duration as the two splitting variables. Patients in the most poorly controlled subgroup (RECPAM Class 1, mean baseline HbA1c > 9.1% [76 mmol/mol]) had a 28-fold higher odds of reaching the endpoint versus patients in the best-controlled group (mean baseline HbA1c ≤ 7.5% [58 mmol/mol]). Mean HbA1c reduction from baseline was as large as - 2.2% (24 mol/mol) in the former versus - 0.1% (1.1 mmol/mol) in the latter. Mean weight reduction ranged from 2.5 to 4.3 kg across RECPAM subgroups. CONCLUSIONS: Glycaemic response to liraglutide is largely driven by baseline HbA1c levels and, to a lesser extent, by diabetes duration.
Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Idoso , Glicemia/análise , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Hemoglobinas Glicadas/análise , Humanos , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
BACKGROUND AND AIMS: Literature data suggest an association between Helicobacter pylori infection and glucose homeostasis. However, a causative link between them has not been demonstrated yet. The aim of this study is to investigate the effect of H. pylori eradication on glucose homeostasis in patients with type 2 diabetes. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled trial was conducted to investigate the effect of H. pylori eradication on glucose homeostasis in 154 patients with type 2 diabetes and who tested positive for H. pylori infection (mean age (SD), 63.1 (8.1) years). Subjects were assigned to H. pylori eradication treatment or placebo. Metabolic and inflammatory parameters were measured in all subjects at baseline and 4 weeks after the treatment. H. pylori eradication led to an improvement in glucose homeostasis, measured by HOMA-IR (p < 0.001) and KITT (0 = 0.041), due to the decrease in fasting insulin levels (p = 0.004). The results also showed that lower levels of inflammatory parameters were present after eradication. CONCLUSION: To our knowledge this is the first randomized, double blind, controlled study where the effect of H. pylori eradication on glucose homeostasis in subjects with type 2 diabetes has been investigated. Our findings demonstrate that H. pylori eradication improves glucose homeostasis in patients with type 2 diabetes through a decrease in pro-inflammatory factors. TRIAL REGISTRATION NUMBER: ACTRN12609000255280 (https://www.anzctr.org.au/).
Assuntos
Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Glicemia/metabolismo , Claritromicina/administração & dosagem , Diabetes Mellitus Tipo 2/sangue , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Idoso , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Biomarcadores/sangue , Claritromicina/efeitos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/microbiologia , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Esomeprazol/efeitos adversos , Feminino , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Homeostase , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , Insulina/sangue , Resistência à Insulina , Itália , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Diabetic women have a more adverse plasma lipid profile than men. Sex differences in dietary habits may play a role, but are little investigated. The study evaluates the quality of diet, adherence to the nutritional recommendations of the Diabetes and Nutrition Study Group and their relation with plasma lipid in men and women with diabetes. METHODS AND RESULTS: We studied 2573 people, aged 50-75, enrolled in the TOSCA.IT study (clinicaltrials.gov; NCT00700856). Plasma lipids were measured centrally. Diet was assessed with a semi-quantitative food frequency questionnaire. Women had a more adverse plasma lipid profile than men. Women consumed significantly more legumes, vegetables, fruits, eggs, milk, vegetable oils, and added sugar, whereas men consumed more starchy foods, soft drinks and alcoholic beverages. This stands for a higher proportion (%) of energy intake from saturated fat and added sugar (12.0 ± 2.4 vs 11.5 ± 2.5 and 3.4 ± 3.2 vs 2.3 ± 3.2, P < 0.04), and a higher intake of fiber (11.2 ± 2.8 vs 10.4 ± 2.6 g/1000 Kcal/day) in women. Adherence to the recommendations for saturated fat and fiber consumption was associated with significantly lower LDL-cholesterol regardless of sex. Adherence to the recommendations for added sugars was associated with significantly lower triglycerides and higher HDL-cholesterol in men and women. CONCLUSIONS: Men and women with diabetes show significant differences in adherence to nutritional recommendations, but sex differences in plasma lipid profile are unlikely to be explained by nutritional factors. Adherence to the nutritional recommendations is associated with a better plasma lipid profile regardless of sex, thus reinforcing the importance of substituting saturated for unsaturated fat sources, increasing fiber and reducing added sugar intake.
Assuntos
Comportamento de Escolha , Diabetes Mellitus Tipo 2/dietoterapia , Dieta Saudável , Comportamento Alimentar , Lipídeos/sangue , Cooperação do Paciente , Recomendações Nutricionais , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/psicologia , Feminino , Preferências Alimentares , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: The optimal macronutrient composition of the diet for the management of type 2 diabetes is debated, particularly with regard to the ideal proportion of fat and carbohydrates. The aim of the study was to explore the association of different proportions of fat and carbohydrates of the diet-within the ranges recommended by different guidelines-with metabolic risk factors. METHODS: We studied 1785 people with type 2 diabetes, aged 50-75, enrolled in the TOSCA.IT Study. Dietary habits were assessed using a validated food-frequency questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein (CRP) were measured. RESULTS: Increasing fat intake from <25 to ≥35 % is associated with a significant increase in LDL-cholesterol, triglycerides, HbA1c and CRP (p < 0.05). Increasing carbohydrates intake from <45 to ≥60 % is associated with significantly lower triglycerides, HbA1c and CRP (p < 0.05). A fiber intake ≥15 g/1000 kcal is associated with a better plasma lipids profile and lower HbA1c and CRP than lower fiber consumption. A consumption of added sugars of ≥10 % of the energy intake is associated with a more adverse plasma lipids profile and higher CRP than lower intake. CONCLUSIONS: In people with type 2 diabetes, variations in the proportion of fat and carbohydrates of the diet, within the relatively narrow ranges recommended by different nutritional guidelines, significantly impact on the metabolic profile and markers of low-grade inflammation. The data support the potential for reducing the intake of fat and added sugars, preferring complex, slowly absorbable, carbohydrates.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Inflamação/sangue , Idoso , Proteína C-Reativa/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Fibras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Triglicerídeos/sangueRESUMO
OBJECTIVE: To clarify adherence of type II diabetic patients to dietary recommendations. SUBJECTS AND METHODS: The dietary habits of a group of 540 patients, with type II diabetes (male 322/female 218, mean age 61+/-5 years, body mass index (BMI) 29.7+/-5.2 kg/m(2); mean+/-s.d.) referring to six Italian diabetes centres were evaluated by means of a 3-day diet record (2 workdays, 1 holiday). Diet records were analysed according to Italian food composition tables and compared with the dietary recommendations of the Diabetes and Nutrition Study Group of the European Association for the study of Diabetes. RESULTS: Calorie intake was 1725+/-497 kcal (1800 for men, 1610 for women). Mean intake for each nutrient was close to the recommended amount, except for fibre (12/1000 vs 20 g/1000 kcal). Calculating the percentage of patients who complied with each recommendation, the intakes of saturated fat and fibre least reflected the dietary target: in 43% of patients saturated fat was >10% of total calories, in only 6% was fibre intake > or =20 g/1000 kcal (considered ideal), and in 25% it was > or =15 g/1000 kcal (acceptable). CONCLUSIONS: These results indicate that compliance to dietary recommendations is not completely satisfactory, even in Italy. Calorie intake is a bit elevated, given the high BMI of our diabetic population. As to dietary composition, there are two crucial issues: the high intake of saturated fat and--most importantly--the low intake of fibre. All strategies aiming to a proper implementation of guidelines should take these results into due account.
Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Dieta para Diabéticos , Ingestão de Energia/fisiologia , Comportamento Alimentar , Cooperação do Paciente , Índice de Massa Corporal , Registros de Dieta , Gorduras na Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIMS: C-reactive protein (CRP) has been identified as a possible factor able to promote atherosclerosis. "In vitro" studies have demonstrated that CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2 diabetic subjects, we decided to study the relationship between CRP and PAI-1, and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in a diabetic population without complications. METHODS AND RESULTS: Two hundred and ninety-five type 2 diabetic patients (age 60.9+/-10.5 years) and 290 healthy controls (age 59.2+/-11.5 years) were enrolled. A significant correlation between PAI-1 and CRP in diabetic subjects was found (r=0.45, p<0.001), whereas no relationship was evident in the control subjects between these inflammatory markers. Multiple regression analysis highlighted that CRP is the only one significant variable of PAI-1 antigen in diabetic subjects (partial r=0.31, p<0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in 4G/4G (partial r=0.64 p<0.001) and 4G/5G (partial r=0.47, p<0.001) subjects was found, whereas no correlation in 5G/5G was present. Multiple regression analysis confirmed the presence of this correlation in 4G/4G (partial r=0.45, p<0.001) and in 4G/5G (partial r=0.34, p=0.007) diabetic patients. CONCLUSIONS: These findings demonstrate that CRP plays an important role in the complex mechanism regulating PAI-1 antigen in 4G diabetic carriers.
Assuntos
Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Inibidor 1 de Ativador de Plasminogênio , Polimorfismo Genético , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Inibidor 1 de Ativador de Plasminogênio/genética , Reação em Cadeia da Polimerase/métodos , Regiões Promotoras Genéticas/genética , Análise de RegressãoRESUMO
INTRODUCTION AND AIM: Guidelines for cardiovascular prevention in diabetes have been issued by the national and international scientific societies. No audit as ever been performed to evaluate the implementation of these documents in clinical practice in Italy. The study evaluates the prevalence, treatment, and control of major cardiovascular risk factors in type 2 diabetic patients, to assess the clinical practice of primary cardiovascular prevention in type 2 diabetes. PATIENTS AND METHODS: Two thousand four hundred and sixty-five men and women with type 2 diabetes, aged 50-75 and free of cardiovascular events were recruited on a consecutive basis at 10 hospital based outpatients diabetes clinics. Clinical variables were measured by standard protocol. Biochemical parameters were evaluated at each centre. The laboratories were monitored by an external quality control assessment in order to reach and maintain a standard of quality and traceability among the participating centres. RESULTS: A minority of patients (5%) met the recommended targets for LDL cholesterol, blood pressure, glycated haemoglobin and smoking habits, whereas the vast majority (66%) had unsatisfactory control of three or more of the above. Achievement of desirable control of risk factors differed according to gender and known diabetes duration. Lipid lowering and, to a lesser extent, antihypertensive medications were under-used and their titration insufficiently target-driven. Prophylactic use of antiplatelet agents was scarce, only one out of five patients was treated independent of absolute cardiovascular risk. CONCLUSION: In clinical practice there is poor adherence to national and international guidelines for primary cardiovascular prevention in type 2 diabetes in Italy. The study underlines the great potential for prevention, particularly in women and in high-risk patients.
Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Auditoria Médica , Guias de Prática Clínica como Assunto , Idoso , Doenças Cardiovasculares/complicações , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Interleukin-6 (IL-6), a powerful inflammatory mediator, plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Recently, the IL-6 promoter polymorphism, at position -174 (G > C), has been associated to insulin sensitivity although contrasting data have been reported. The aim of this study was to evaluate the effect of the IL-6-174 G > C polymorphism on insulin resistance. In 238 type 2 diabetic patients without diabetic complications and in 255 control subjects, age and gender-matched, we evaluated the IL-6 -174 G > C genotype, the IL-6 plasma levels and the insulin resistance by the homeostasis model assessment (HOMA). The levels of IL-6 and HOMA were not genotype-dependent and were higher in diabetic patients (p < 0.01). Control subjects, both C+ (CG + CC genotypes) and C- (GG genotype) carriers, showed IL-6 plasma levels significantly related to BMI, fasting insulin and HOMA. The same relationships were found in C+ diabetic carriers. Differently, diabetic C- carriers did not show any relationship between IL-6 levels and all the evaluated variables. Interestingly, all the correlations were dependent on BMI. These findings highlight that IL-6-174 G > C polymorphism affects insulin resistance in type 2 diabetes, where C+ carriers have an insulin resistance "IL-6-sensitive", while C- carriers do not. The identification of two categories of diabetic patients may, therefore, lead to different therapeutic strategies in the management of insulin resistance.
Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/imunologia , Resistência à Insulina/genética , Interleucina-6/sangue , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Jejum , Feminino , Genótipo , Homeostase , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Plasminogen activator inhibitor type 1 (PAI-1) is an independent cardiovascular risk factor and increases in patients with Type 2 diabetes mellitus. The 4G/5G polymorphism of PAI-1 has been reported to be involved in the incidence of cardiovascular disease by regulation of PAI-1 levels, but this relation is still under debate. The aim of the study was to test the effect of 4G/5G polymorphism on the lowering of PAI-1 levels in Type 2 diabetic patients during vitamin E supplementation. Ninety-three Type 2 diabetic subjects (age +/- SD, 62.1 +/- 6.1 yr) were enrolled and treated with vitamin E (500 IU/die) for 10 weeks. We determined the 4G/5G polymorphism and PAI-1 activity at baseline, during (5th and 10th week) and after (30th week) vitamin E supplementation. No significant differences were found in PAI-1 and its determinants among the three genotypic groups at baseline. Decrements were detected in the whole group in PAI-1 at the 5th and the 10th week from baseline followed by an increase at the 30th week (p<0.001). Patients with 4G/4G and 4G/5G genotypes showed a different trend with respect to those with 5G/5G in PAI-1. In particular, there was a decrease in 4G/4G and 4G/5G PAI-1 levels from the 10th week, while a decrease in 5G/5G PAI-1 was observed from the 5th week (p<0.01). The delayed decrease, found in patients with at least one 4G allele with respect to those with 5G/5G genotype, demonstrates that 4G/5G polymorphism mainly influences the rate of decrease of PAI-1 after supplementation with vitamin E in Type 2 diabetic subjects.
Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Tipo 2/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Polimorfismo Genético , Vitamina E/farmacologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Feminino , Genótipo , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Regiões Promotoras GenéticasRESUMO
AIMS: To analyse the association of smoking with paraoxonase (PON1) in Type 2 diabetic patients. METHODS: Type 2 diabetic patients were recruited independently in two centres (Ancona, Italy and Geneva, Switzerland) and serum PON1 mass and activities were assayed. Current smoking status was established and its association with serum PON1 analysed. RESULTS: Type 2 diabetic patients who smoked had significantly lower serum PON1 mass and activity. This was evident in both groups of patients, even though Swiss patients were composed of coronary patients. Multivariate analyses established that smoking was an independent determinant of serum PON1 status. CONCLUSIONS: Smoking is associated with reduced serum levels of the antioxidant enzyme, PON1, even against an already unfavourable background of diabetes and coronary disease. It suggests that a combination of smoking and diabetes may be particularly deleterious for PON1 and consequently for the anti-oxidant capacity of high-density lipoproteins.
Assuntos
Arildialquilfosfatase/sangue , Diabetes Mellitus Tipo 2/enzimologia , Fumar/sangue , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/enzimologia , Angiopatias Diabéticas/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Análise de Regressão , Fatores de RiscoRESUMO
Diabetic microangiopathy produces widespread small vessel impairment which particularly affects renal glomeruli functions. Microalbuminuria is the earliest marker of microangiopathic kidney disease and has also recently been recognised as a marker of macroangiopathic cardiovascular involvement. To determine correlations between daily microalbuminuria, local microangiopathic kidney damage, systemic macroangiopathic involvement and functional brain microcirculation, 70 Type 2 diabetic subjects who were diagnosed more than 5 years ago underwent carotid (to determine index of macro- and microangiopathy) and interlobar kidney artery color Doppler (to determine microangiopathic involvement), transcranial Doppler (to determine alterations in brain vasomotor reserve), and evaluation of daily albumin excretion rate. All the indices of microcirculatory involvement in the kidney, brain and small vessels downstream-from the carotid arteries were closely related (for all p<0.001) but never correlated with the macroangiopathy index. Daily microalbuminuria correlated with all the micro- (p<0.0001) and macroangiopathic (p<0.005) Doppler indices. These findings confirm that microangiopathy is the main cause of the diabetic increase in the albumin excretion rate and support the view that microalbuminuria can be considered a powerful biomarker of widespread macroangiopathy. Our results suggest microalbuminuria may also identify cerebrovascular diabetic involvement, as it predicts both macroangiopathic carotid alteration and microvascular brain impairment.
Assuntos
Albuminúria/urina , Encéfalo/irrigação sanguínea , Artérias Carótidas/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Artéria Renal/fisiopatologia , Idoso , Velocidade do Fluxo Sanguíneo , Doenças Cardiovasculares/urina , Artérias Carótidas/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Angiopatias Diabéticas/complicações , Nefropatias Diabéticas/urina , Feminino , Humanos , Masculino , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Artéria Renal/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Ultrassonografia Doppler Transcraniana , Resistência VascularRESUMO
As stated in the St. Vincent Declaration, the reduction of the number of lower extremity amputations (LEA) is one of the major targets in diabetes care. Little information on the prevalence of this complication is available in Italy at present. The aim of this study was to evaluate the impact of diabetes on LEA in a region of central Italy. The regional database of hospital discharge records was used to identify all the cases of non-traumatic LEA (Nt-LEA) that had occurred in 1997 and 1998. Diagnosis of diabetes and the type of surgical intervention were defined on the basis of the medical records. Amputations were categorised as minor or major according to the level of the surgical procedure. The duration of hospitalisation was used to analyse the impact of diabetes on the health care system. Prevalence of diabetes in people who underwent Nt-LEA was 55.9% and it was similar in patients who underwent minor or major amputation (58.7 and 55.0%, respectively). No difference between diabetic and non-diabetic patients was observed as regards sex, level of amputation and duration of hospitalisation. Age was the only predictor of diabetes in amputees. The lack of specific protocols for diabetes foot care or a non-homogeneous application of these protocols in the health care service could account for a similar prevalence of diabetes among patients who underwent minor or major amputation.
Assuntos
Amputação Cirúrgica , Diabetes Mellitus/cirurgia , Extremidade Inferior/cirurgia , Idoso , Idoso de 80 Anos ou mais , Amputação Traumática , Pé Diabético/cirurgia , Feminino , Humanos , Incidência , Itália/epidemiologia , Tempo de Internação , Modelos Logísticos , Masculino , Fatores Sexuais , Perfil de Impacto da Doença , Resultado do TratamentoRESUMO
AIMS: To determine if apolipoprotein E polymorphism is associated with cardiovascular or all-cause mortality in Italian Type 2 diabetic patients. METHODS: A prospective study of mortality in Type 2 diabetic patients (n = 433) as a function of apolipoprotein E phenotype, which was assessed at entry into the study. During follow up (10 years), 110 (25.4%) patients died of which 66 (15.2%) were the result of cardiovascular causes. Cause of death was established from death certificates and clinical records. The clinical status of the survivors was determined at the end of the study. RESULTS: Apolipoprotein E polymorphisms were not associated with excess cardiovascular or all-cause mortality in the Italian Type 2 diabetic patients either in univariate or multivariate analyses. Age, duration of diabetes and glycated haemoglobin levels at entry were the primary determinants of premature mortality in the diabetic population. CONCLUSIONS: Apolipoprotein E polymorphisms are not markers for premature mortality in Italian Type 2 diabetic patients. The impact of apolipoprotein E mutations may be attenuated by environmental factors, notably a healthier diet, in Italian patients.
Assuntos
Apolipoproteínas E/genética , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/genética , Diabetes Mellitus Tipo 2/mortalidade , Angiopatias Diabéticas/mortalidade , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Estudos Prospectivos , Análise de Sobrevida , Taxa de SobrevidaRESUMO
A large body of evidence suggests that diabetes increases the risk of coronary heart disease (CHD), but whether fasting hyperglycemia is associated with a major risk for CHD is still under debate. The aim of the present study was to investigate the role played by fasting hyperglycemia in the development of cardiovascular disease (CVD) in an elderly population when associated with common risk factors for CVD (i.e., hypertension, hypercholesterolemia, smoking, etc). We analyzed a sample of 455 subjects aged > or = 60 years. The risk factors taken into account were systolic and diastolic blood pressure levels, use of antihypertensive drugs, total serum cholesterol, serum triglycerides, and smoking habit. Glycemia was measured at entry on a fasting sample. During the follow-up period (mean 6 years), the occurrence of CVD was monitored (criteria for the occurrence of CVD included total cardiovascular mortality, fatal or nonfatal myocardial infarction, symptomatic coronary heart disease [stable and unstable angina], the need for percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal or nonfatal stroke, and transient ischemic attack). A total of 427 subjects completed the follow-up. During this period, 73 subjects (17.10%) developed CVD according to the above criteria. A Cox proportional hazard model was designed to evaluate the contribution of variables in predicting CVD. Relative risks and 95% confidence intervals for CVD were calculated from the regression coefficients to study the association between the risk of developing CVD and predicting variables. We found a relation between occurrence of CVD and fasting hyperglycemia: subjects with fasting glycemia, > 126 mg/dl at enrollment, but without previous clinical diagnosis of diabetes, showed a 2.01 times higher risk than those with fasting glycemia < 126 mg/dl. Hence, random fasting hyperglycemia can predict the occurrence of CVD in elderly subjects.
Assuntos
Doença das Coronárias/etiologia , Jejum/efeitos adversos , Hiperglicemia/complicações , Fatores Etários , Idoso , Glicemia/metabolismo , Doença das Coronárias/metabolismo , Jejum/metabolismo , Feminino , Humanos , Hiperglicemia/metabolismo , Estudos Longitudinais , Masculino , Fatores de RiscoRESUMO
Paraoxonase is a serum enzyme with an anti-oxidant function, protecting low density lipoproteins (LDL) from oxidative modifications. Diabetic patients are suggested to be at greater risk of oxidative stress, which may contribute to the significantly higher incidence of vascular disease in this population. Less efficient protection mechanisms may be one feature of the greater susceptibility to oxidation in diabetes. In this context, the present study examined the hypothesis that serum paraoxonase is reduced in type 1 (insulin-dependent) diabetic patients and that the reduction can affect the anti-oxidant capacity of HDL. Serum paraoxonase concentrations and activities were compared in type 1 patients and first degree, non-diabetic relatives with particular attention paid to the confounding effects of paraoxonase gene polymorphisms. In addition, the ability of HDL-paraoxonase to protect low density lipoproteins from oxidation was analysed in an in vitro system. Serum concentrations and enzyme activities of paraoxonase were significantly lower in type 1 patients compared to non-diabetic, first degree relatives. The differences were independent of promoter and coding region polymorphisms, which influence serum concentrations and activities of the enzyme. Overall, paraoxonase concentrations were a mean 13.3+/-4.5% lower (P<0.02) in type 1 patients. Specific activities did not differ between diabetic and non-diabetic groups. The concentration ratios of LDL cholesterol:paraoxonase (1.37+/-0.51 vs. 1.18+/-0.37, P=0.003) and apolipoprotein B:paraoxonase (0.84+/-0.33 vs. 0.71+/-0.40; P=0.012) were significantly higher in diabetic patients, consistent with a reduced capacity to protect LDL from oxidation. In vitro oxidation studies showed that a significantly higher level of lipid hydroperoxides was generated in LDL in the presence of HDL, containing paraoxonase levels equivalent to those of type 1 patients, compared to HDL containing paraoxonase levels equivalent to those of control subjects (mean difference 8.1%, P<0.05). The study demonstrates that serum concentrations of the antioxidant enzyme paraoxonase are significantly lower in type 1 (insulin-dependent) diabetic patients compared to non-diabetic, first-degree relatives, independently of known gene polymorphisms. Concentrations are reduced to an extent that can affect its anti-oxidant capacity. The results are consistent with the contention that modifications to serum paraoxonase in type 1 patients can increase risk of lipoprotein oxidation and, consequently, risk of vascular disease.
Assuntos
Antioxidantes/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Esterases/sangue , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Adulto , Alelos , Apolipoproteínas B/sangue , Arildialquilfosfatase , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 1/genética , Esterases/genética , Esterases/fisiologia , Feminino , Genótipo , Humanos , Masculino , Oxirredução , Polimorfismo Genético , Regiões Promotoras Genéticas/genéticaRESUMO
Obesity is often associated with type 2 (non insulin-dependent) diabetes. A growing body of evidence support the hypothesis that these two diseases share a common pathogenesis. Nevertheless, experience derived from clinical observation on type 2 diabetic patients indicates that reduction of body weight is not always accompanied by an improvement in metabolic control and that a good metabolic control is often obtained without influencing body composition. Aim of the present study was to evaluate the relationship between body mass and glycemic control in a type 2 diabetic population by a 3 years observational study. A cohort of 562 subjects was studied. At entry more than 80% of patients were overweight or obese according to the body mass index (BMI) scale and this proportion was not significantly reduced at the end of the follow-up. At entry all patients had a glycosylated hemoglobin (HbA1c) value above 8.1% whereas at the end of follow-up more than 2/3 of patients were in good metabolic control. No relationship was observed between modification of body mass and metabolic control. These data confirm the high frequency of obesity among type 2 diabetic individuals but they suggest that impaired glucose metabolism and alteration of body weight have different pathogenesis.
RESUMO
A standard intravenous glucose tolerance test (IVGTT) was performed in 10 nondiabetic patients with essential hypertension (H group) and 9 normotensive control subjects (N group). A 2-compartment minimal model (2CMM) of glucose kinetics was applied to estimate indexes of glucose effectiveness, S2G and insulin sensitivity, S2I, by means of a maximum a posteriori (MAP) bayesian estimation technique. These estimates were contrasted to the S1G and S1I indexes provided by the classic minimal model (1CMM). In both the N group and the H group, the 2CMM underestimated the glucose effectiveness and overestimated the insulin sensitivity. In the H group, S2G was, on average, 63% of S1G (P > .05) and S2I was 137% of S1I (P > .05). In the N group S2G was 67% of S1G (P > .05) and S2I was 134% of S1I (P > .05). The 2CMM detected a reduction of approximately 40% (P > .05) and approximately 48% (P > .05) in S2G and S2I estimates, respectively, from the N group to the H group. Despite its reduced complexity, the 1CMM also detected a reduction of approximately 35% (P < .05) and approximately 49% (P < .05) in the S1G and in S1I indexes, respectively. Thus, the 1CMM and 2CMM showed a substantial equivalence in detecting a severe reduction in insulin sensitivity and impaired glucose effectiveness in hypertensive patients compared with normal.
Assuntos
Glucose/metabolismo , Hipertensão/metabolismo , Modelos Biológicos , Adulto , Feminino , Glucose/fisiologia , Humanos , Recém-Nascido , Resistência à Insulina/fisiologia , Cinética , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
OBJECTIVE: This study examined the hypothesis that kidney function is an independent determinant of lipoprotein(a) [Lp(a)] concentrations in people with diabetes. RESEARCH DESIGN AND METHODS: Lp(a) concentrations were measured in plasma samples from 273 type 2 and 223 type 1 diabetic patients recruited from a diabetes clinic. Kidney function was categorized as normal or pathological according to plasma creatinine levels and creatinine clearance rates. RESULTS: Macroalbuminuria was uniformly associated with significantly raised plasma concentrations of Lp(a) regardless of the marker used to identify kidney dysfunction. In contrast, in patients with microalbuminuria, significantly raised plasma Lp(a) levels were observed only when creatinine clearance rates or plasma creatinine levels indicated pathological kidney function. These conclusions were independent of diabetes type. CONCLUSIONS: In microalbuminuria and apparently in normoalbuminuria, altered kidney function determined by creatinine clearance rates or creatinine levels appears to be a major determinant of raised Lp(a) levels in both type 1 and type 2 diabetic patients. In contrast, Lp(a) concentrations were uniformly raised in patients with macroalbuminuria.
Assuntos
Nefropatias Diabéticas/sangue , Nefropatias/sangue , Lipoproteína(a)/sangue , Albuminúria/sangue , Albuminúria/etiologia , Creatinina/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Humanos , Triglicerídeos/sangueRESUMO
The risk for all the manifestations of atherosclerotic disease is increased in patients affected by type 2 diabetes mellitus. The aim of the present work was to evaluate the prevalence of coronary heart disease (CHD) in a well-characterized middle-aged and elderly Italian diabetic population. The population studied included 3862 subjects, i.e. all the patients affected by type 2 diabetes of age >or=50 years attending the outpatient diabetes care unit of INRCA in Ancona (Italy) from 1 August 1997 to 31 July 1998. We collected and analysed both clinical and laboratory data by means of a computerized data base for the outpatient clinic management. The prevalence rate of CHD was 20.25% in this population. The groups with CHD and without CHD did not differ significantly with respect to age at onset of diabetes, body mass index and HbA1c levels, while patients with CHD were significantly older than patients without CHD and had a longer duration of diabetes. The prevalence of patients with hypertension (52.9 vs 63.0%, P<0.001), hypercholesterolemia (11.6 vs 14.1%, P<0.05) and hyperlipidemia (17.8 vs 23.3%, P<0.001) was significantly higher in the group of diabetic subjects affected by CHD than in patients not affected by heart ischemic disease. It might be hypothesized that the improvement of metabolic profile and the currently feasible control of non-diabetic risk factors could reduce cardiovascular disease rates in type 2 diabetic patients.