Could pre-diabetes be considered a clinical condition? opinions from an endocrinologist and a cardiologist

The prevalence of pre-diabetes is increasing worldwide and may start 7 to 10 years before the clinical diagnosis of diabetes. In this stage the presence and accumulation of risk factors is common and already implies an increase in cardiovascular risk. Likewise, the onset of cardiovascular diseases (CVD), mainly coronary artery disease (CAD), peripheral vascular disease and cerebrovascular disease can also take place, all of which account for high rates of morbidity and mortality worldwide. Considering pre-diabetes as a clinical entity, non-pharmacological and pharmacological treatments are indicated with drugs which have shown clinical benefits related to reduction in morbidity and mortality. However, there is still need for new long-term studies to assess the real benefits of several new therapeutical approaches, as well as its cost-effectiveness

Baixos níveis de glicemia e outras complicações durante suplementação de hormônio do crescimento na sepse

O perfil glicêmico esperado em pacientes pós-operatórios sépticos recebendo nutrição enteral de elevado teor calórico é de valores sanguíneos no limite superior do normal ou mesmo hiperglicemia moderada.A adição de hormônio do crescimento (GH) como agente anabólico deveria reforçar ainda mais esta tendência.Num paciente com câncer submetido a gastrectomia parcial e linfadenectomia, que se complicou no pós operatório com abscesso subfrênico e sepse prolongada, administrou-se conjuntamente dieta de sonda (38,3 kcal/kg/dia) e GH (0,17 UI/kg/dia).Antes da introdução de GH as taxas glicêmicas situavam-se nos limites inferiores do normal, e esta tendência persistiu durante a maior parte do período terapêutico.Duas complicações adicionais, nominalmente parada cardíaca e edema periférico, foram documentadas nesta mesma etapa.Conclui-se que a sepse é o mais provável mecanismo de redução da glicemia neste caso, e que o emprego de dieta enteral e de GH não conseguiu prevenir tal efeito.É questionável se a parada cardíaca foi devida ao suplemento hormonal, mas o edema periférico é um secundarismo bem conhecido deste agente em estudos clínicos.Blood glucose levels in the high normal range or even moderate hyperglycemia is the expected profile in septic postoperative patients receiving high-calorie enteral alimentation. The addition of growth hormone as an anabolic agent should additionally reinforce this tendency. In a cancer patient undergoing partial gastrectomy with lymphadenectomy and suffering from postoperative subphrenic abscess and prolonged sepsis, tube feeding (38.3 kcal/kg/day) and growth hormone (0.17 IU/kg/day) were simultaneously administered for 25 days. Blood glucose levels were in the lower limits of the normal range before growth hormone introduction, and continued with a similar tendency during most of the therapeutic period. Two additional complications, namely heart arrest and peripheral edema, were documented during the same period. It is concluded that sepsis was the most likely mechanism for low glucose values, and that high-calorie enteral diet and growth hormone supplementation did not prevent that result. It is uncertain whether heart arrest was due to the drug, but its association with peripheral edema is well documented in clinical series

Effects of descending positive end-expiratory pressure on lung mechanics and aeration in healthy anaesthetized piglets

INTRODUCTION: Atelectasis and distal airway closure are common clinical entities of general anaesthesia. These two phenomena are expected to reduce the ventilation of dependent lung regions and represent major causes of arterial oxygenation impairment in anaesthetic conditions. The behaviour of the elastance of the respiratory system (E(rs)), as well as the lung aeration assessed by computed tomography (CT) scan, was evaluated during a descendent positive end-expiratory pressure (PEEP) titration. This work sought to evaluate the potential usefulness of E(rs )monitoring to set the PEEP in order to prevent tidal recruitment and hyperinflation of healthy lungs under general anaesthesia. METHODS: PEEP titration (from 16 to 0 cmH(2)O, tidal volume of 8 ml/kg) was performed, and at each PEEP, CT scans were obtained during end-expiratory and end-inspiratory pauses in six healthy, anaesthetized and paralyzed piglets. The distribution of lung aeration was determined and the tidal re-aeration was calculated as the difference between end-expiratory and end-inspiratory poorly aerated and normally aerated areas. Similarly, tidal hyperinflation was obtained as the difference between end-inspiratory and end-expiratory hyperinflated areas. E(rs )was estimated from the equation of motion of the respiratory system during all PEEP titration with the least-squares method. RESULTS: Hyperinflated areas decreased from PEEP 16 to 0 cmH(2)O (ranges decreased from 24–62% to 1–7% at end-expiratory pauses and from 44–73% to 4–17% at end-inspiratory pauses) whereas normally aerated areas increased (from 30–66% to 72–83% at end-expiratory pauses and from 19–48% to 73–77% at end-inspiratory pauses). From 16 to 8 cmH(2)O, E(rs )decreased with a corresponding reduction in tidal hyperinflation. A flat minimum of E(rs )was observed from 8 to 4 cmH(2)O. For PEEP below 4 cmH(2)O, E(rs )increased in association with a rise in tidal re-aeration and a flat maximum of the normally aerated areas. CONCLUSION: In healthy piglets under a descending PEEP protocol, the PEEP at minimum E(rs )presented a compromise between maximizing normally aerated areas and minimizing tidal re-aeration and hyperinflation. High levels of PEEP, greater than 8 cmH(2)O, reduced tidal re-aeration but increased hyperinflation with a concomitant decrease in normally aerated areas

Estimating cardiovascular risk in patients with type 2 diabetes: a national multicenter study in Brazil

According to Brazilian National Data Survey diabetes is the fifth cause for hospitalization and is one of the ten major causes of mortality in this country.Aimsto stratify the estimated cardiovascular risk (eCVR) in a population of type 2 diabetics (T2DM) according to the Framingham prediction equations as well as to determine the association between eCVR with metabolic and clinical control of the disease.MethodsFrom 2000 to 2001 a cross-sectional multicenter study was conducted in 13 public out-patients diabetes/endocrinology clinics from 8 Brazilian cities. the 10-year risk of developing coronary heart disease (CHD) was estimated by the prediction equations described by Wilson et al (Circulation 1998). LDL equations were preferably used; when patients missed LDL data we used total cholesterol equations instead.ResultsData from 1382 patients (59.0% female) were analyzed. Median and inter-quartile range (IQ) of age and duration of diabetes were 57.4 (51-65) and 8.8 (3-13) years, respectively without differences according to the gender. Forty-two percent of these patients were overweight and 35.4% were obese (the prevalence of higher BMI and obesity in this T2DM group was significantly higher in women than in men; p 20%) in 738 (53.4%), intermediate in 202 (14.6%) and low in 442 (32%) patients. Men [25.1(15.4-37.3)] showed a higher eCVR than women [18.8 (12.4-27.9) p < 0.001]. the most common risk factor was high LDL-cholesterol (80.8%), most frequently found in women than in men (p = 0.01). the median of risk factors present was three (2-4) without gender differences. Overall we observed that 60 (4.3%) of our patients had none, 154(11.1%) one, 310 (22.4%) two, 385 (27.9%) three, 300 (21.7%) four, 149 (10.5%) five and six, (2%) six risk factors. A higher eCVR was noted in overweight or obese patients (p = 0.01 for both groups). No association was found between eCVR with age or a specific type of diabetes treatment. A correlation was found between eCVR and duration of diabetes (p < 0.001), BMI (p < 0.001), creatinine (p < 0.001) and triglycerides levels (p < 0.001) but it was not found with HbA1c, fasting blood glucose and postprandial glucose. A higher eCVR was observed in patients with retinopathy (p < 0.001) and a tendency in patients with microalbuminuria (p = 0.06). Conclusion: our study showed that in this group of Brazilian T2DM the eCVR was correlated with the lipid profile and it was higher in patients with microvascular chronic complications. No correlation was found with glycemic control parameters. These data could explain the failure of intensive glycemic control programs aiming to reduce cardiovascular events observed in some studies.Univ Estado Rio de Janeiro, Diabet Unit, Rio de Janeiro, BrazilUniv São Paulo Scholl Med, Hosp Clin, Lab Clin & Expt Gatroenterol LIM07, São Paulo, BrazilUniv Fed Maranhao, Div Endocrinol, Sao Luis, BrazilUniv Estadual Campinas, Div Endocrinol, Campinas, BrazilCtr Estudos Diabet & Endocrinol Estado Bahia CEDE, Salvador, BA, BrazilUniv Fed Parana, Div Endocrinol, BR-80060000 Curitiba, Parana, BrazilHosp Agamenon Magalhaes, Div Endocrinol, Recife, PE, BrazilPosto Assistencia Med Jaguribe, Joao Pessoa, Paraiba, BrazilSanta Casa Porto Alegre, Div Endocrinol, Porto Alegre, RS, BrazilInst Assistencia & Previdencia Servidor Estado Ba, Div Endocrinol, Salvador, BA, BrazilSanta Casa Belo Horizonte, Diabet Unit, Belo Horizonte, MG, BrazilHosp Geral Goiania, Div Endocrinol, Goiania, Go, BrazilSecretaria Municipal Saude Brasilia, Brasilia, DF, BrazilUniversidade Federal de São Paulo, Div Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Endocrinol, São Paulo, BrazilWeb of Scienc

Nationwide multicenter study on the prevalence of overweight and obesity in type 2 diabetes mellitus in the Brazilian population

AIM: To evaluate the prevalence of overweight and obesity in type 2 diabetic (DM2) outpatients from different regions of Brazil. PATIENTS AND METHODS: We studied 2,519 randomly selected patients, from 11 hospitals, 2 endocrine and one general public care clinics from 10 cities. Overweight was defined as body-mass index (BMI) > 25 and obesity as BMI > 30 kg/m². Glycemic control (GC) was evaluated by GC index (GCI= patient's HbA1 or HbA1c/upper limit of normal for the method x 100). RESULTS: 39% of the population studied was male, the mean age was 58.8 ± 11.6 y, the duration from clinical diagnosis of DM2 was 9.0 ± 7.3y, and BMI was 28.3 ± 5.2 kg/m². No measurements of BMI were recorded from 265 patients (10.5%). Patients from the Northeast presented lower BMI as compared with those from the Midwest, Southeast and South areas, respectively (26.4 ± 4.7 vs. 27.9 ± 4.8 vs. 29.2 ± 5.1 vs. 29.4 ± 5.4 kg/m²; p 25 e obesidade um IMC > 30 kg/m². O controle glicêmico (CG) foi avaliado pelo índice de CG [ICG= HbA1 e ou HbA1c do paciente/limite superior de normalidade do método x 100]. RESULTADOS: Os pacientes tinham idade de 58,8 ± 11,6 anos, tempo de diagnóstico clínico de DM de 9,0 ± 7,3 anos, IMC de 28,3 ± 5,2 kg/m², e 39% eram do sexo masculino. Do total da amostra, 265 pacientes (10,5%) não apresentavam avaliação do IMC. Os pacientes da região Nordeste apresentaram menor IMC em comparação com os das regiões Centro-Oeste, Sudeste e Sul, respectivamente (26,4 ± 4,7 vs. 27,9 ± 4,8 vs. 29,2 ± 5,1 vs. 29,4 ± 5,4 kg/m²; p< 0,001). Houve maior prevalência de obesidade na região Sudeste e Sul em comparação à região Nordeste (p< 0,001) e nos pacientes do sexo feminino, respectivamente (69 vs. 31%; p< 0,001). Os pacientes com peso normal apresentaram menor ICG. Aqueles em tratamento com associação de duas ou mais drogas orais e associação de insulina + droga oral apresentaram maior IMC do que aqueles em tratamento com dieta, hipoglicemiante oral e insulina; p< 0,001. O IMC não diferiu entre os pacientes assistidos ou não por especialistas. CONCLUSÕES: Da população estudada, 75% não estava na faixa de peso ideal, sendo que um terço tinha obesidade. Nossos dados indicam que o sobrepeso e a obesidade já atingem um percentual de pacientes com DM2 no Brasil semelhante ao relatado em estudos europeus, mas ainda menor do que o observado nos EUA. A prevalência de obesidade nos pacientes diabéticos foi três vezes maior do que a observada na população brasileira em geral de acordo com os dados do IBGE.UERJUSPUNIFESP-EPMUNICAMPUNIFEUniversidade Federal do MaranhãoCEDEBVA Serviço de Endocrinologia e DiabetesHospital Agamenon Magalhães Serviços de EndocrinologiaSanta Casa Serviços de EndocrinologiaIAPSEB Serviços de EndocrinologiaHospital Geral Serviços de EndocrinologiaPAM Jaguaribe Serviços de EndocrinologiaSanta Casa Serviço de DiabetesSecretaria Municipal de SaúdeUNIFESP, EPMSciEL

Association of genetic variants in the promoter region of genes encoding p22phox (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease in patients with type 1 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Oxidative stress is recognized as a major pathogenic factor of cellular damage caused by hyperglycemia. NOX/NADPH oxidases generate reactive oxygen species and NOX1, NOX2 and NOX4 isoforms are expressed in kidney and require association with subunit p22phox (encoded by the <it>CYBA </it>gene). Increased expression of p22phox was described in animal models of diabetic nephropathy. In the opposite direction, glutathione is one of the main endogenous antioxidants whose plasmatic concentrations were reported to be reduced in diabetes patients. The aim of the present investigation was to test whether functional single nucleotide polymorphisms (SNPs) in genes involved in the generation of NADPH-dependent O₂^•-(-675 T → A in <it>CYBA</it>, unregistered) and in glutathione metabolism (-129 C → T in <it>GCLC </it>[rs17883901] and -65 T → C in <it>GPX3 </it>[rs8177412]) confer susceptibility to renal disease in type 1 diabetes patients.</p> <p>Methods</p> <p>401 patients were sorted into two groups according to the presence (n = 104) or absence (n = 196) of overt diabetic nephropathy or according to glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease (MDRD) equation: ≥ 60 mL (n = 265) or < 60 mL/min/1.73 m²(n = 136) and were genotyped.</p> <p>Results</p> <p>No differences were found in the frequency of genotypes between diabetic and non-diabetic subjects. The frequency of GFR < 60 mL/min was significantly lower in the group of patients carrying <it>CYBA </it>genotypes T/A+A/A (18.7%) than in the group carrying the T/T genotype (35.3%) (P = 0.0143) and the frequency of GFR < 60 mL/min was significantly higher in the group of patients carrying <it>GCLC </it>genotypes C/T+T/T (47.1%) than in the group carrying the C/C genotype (31.1%) (<it>p </it>= 0.0082). Logistic regression analysis identified the presence of at least one A allele of the <it>CYBA </it>SNP as an independent protection factor against decreased GFR (OR = 0.38, CI95% 0.14-0.88, <it>p </it>= 0.0354) and the presence of at least one T allele of the <it>GCLC </it>rs17883901 SNP as an independent risk factor for decreased GFR (OR = 2.40, CI95% 1.27-4.56, <it>p </it>= 0.0068).</p> <p>Conclusions</p> <p>The functional SNPs <it>CYBA </it>-675 T → A and <it>GCLC </it>rs17883901, probably associated with cellular redox imbalances, modulate the risk for renal disease in the studied population of type 1 diabetes patients and require validation in additional cohorts.</p

Estimating cardiovascular risk in patients with type 2 diabetes: a national multicenter study in Brazil

<p>Abstract</p> <p>According to Brazilian National Data Survey diabetes is the fifth cause for hospitalization and is one of the ten major causes of mortality in this country.</p> <p>Aims</p> <p>to stratify the estimated cardiovascular risk (eCVR) in a population of type 2 diabetics (T2DM) according to the Framingham prediction equations as well as to determine the association between eCVR with metabolic and clinical control of the disease.</p> <p>Methods</p> <p>From 2000 to 2001 a cross-sectional multicenter study was conducted in 13 public out-patients diabetes/endocrinology clinics from 8 Brazilian cities. The 10-year risk of developing coronary heart disease (CHD) was estimated by the prediction equations described by Wilson et al (Circulation 1998). LDL equations were preferably used; when patients missed LDL data we used total cholesterol equations instead.</p> <p>Results</p> <p>Data from 1382 patients (59.0% female) were analyzed. Median and inter-quartile range (IQ) of age and duration of diabetes were 57.4 (51-65) and 8.8 (3-13) years, respectively without differences according to the gender. Forty-two percent of these patients were overweight and 35.4% were obese (the prevalence of higher BMI and obesity in this T2DM group was significantly higher in women than in men; p < 0.001). The overall estimated eCVR in T2DM patients was 21.4 (13.5-31.3). The eCVR was high (> 20%) in 738 (53.4%), intermediate in 202 (14.6%) and low in 442 (32%) patients. Men [25.1(15.4-37.3)] showed a higher eCVR than women [18.8 (12.4-27.9) p < 0.001]. The most common risk factor was high LDL-cholesterol (80.8%), most frequently found in women than in men (p = 0.01). The median of risk factors present was three (2-4) without gender differences. Overall we observed that 60 (4.3%) of our patients had none, 154(11.1%) one, 310 (22.4%) two, 385 (27.9%) three, 300 (21.7%) four, 149 (10.5%) five and six, (2%) six risk factors. A higher eCVR was noted in overweight or obese patients (p = 0.01 for both groups). No association was found between eCVR with age or a specific type of diabetes treatment. A correlation was found between eCVR and duration of diabetes (p < 0.001), BMI (p < 0.001), creatinine (p < 0.001) and triglycerides levels (p < 0.001) but it was not found with HbA1c, fasting blood glucose and post-prandial glucose. A higher eCVR was observed in patients with retinopathy (p < 0.001) and a tendency in patients with microalbuminuria (p = 0.06). Conclusion: our study showed that in this group of Brazilian T2DM the eCVR was correlated with the lipid profile and it was higher in patients with microvascular chronic complications. No correlation was found with glycemic control parameters. These data could explain the failure of intensive glycemic control programs aiming to reduce cardiovascular events observed in some studies.</p