Pituitary neuroendocrine tumors and differentiated thyroid cancer: do metabolic and inflammatory risk factors play roles?

PURPOSE: It is postulated that patients with different types of pituitary neuroendocrine tumors (PitNETs) may present a higher incidence of cancer. Factors underlying individuals becoming overweight, such as insulin resistance, hyperleptinemia, and low-grade inflammation, may play a role in the risk of differentiated thyroid carcinoma (DTC) in such patients. This study aimed to investigate the frequency of and obesity-related risk factors associated with DTC in patients with PitNETs. METHODS: This cross-sectional study involved 149 patients with nonacromegalic PitNETs (AG group), 71 patients with acromegaly (ACRO group), and 156 controls (CG group). All participants underwent insulin and blood glucose measurements with the determination of the homeostatic model assessment-insulin resistance (HOMA-IR) index, leptin, and high-sensitivity C-reactive protein (hsCRP), and they also underwent thyroid ultrasound. Clinically significant nodules were biopsied for subsequent cytopathological evaluation, and participants were operated on when indicated. RESULTS: Patients in the AG group had high levels of insulin resistance and significantly higher levels of leptin and hsCRP compared with those of patients in the ACRO group. There were no cases of DTC in the AG group; two findings, one incidental, of DTC occurred in the CG group, and three cases of DTC were present in the ACRO group. Acromegaly was associated with DTC after adjusted analysis. CONCLUSIONS: Our findings in patients with nonacromegalic PitNETs do not indicate a high risk for DTC despite the presence of metabolic and inflammatory risk factors for neoplastic events. In contrast, acromegaly promotes a greater risk of DTC.

Genomic ancestry and metabolic syndrome in individuals with type 1 diabetes from an admixed population: a multicentre, cross-sectional study in Brazil.

AIMS: To evaluate the relationship between self-reported colour-race, genomic ancestry, and metabolic syndrome in an admixed Brazilian population with type 1 diabetes. METHODS: We included 1640 participants with type 1 diabetes. The proportions of European, African and Amerindian genomic ancestries were determined by 46 ancestry informative markers of insertion deletion. Two different sets of analyses were performed to determine whether self-reported colour-race and genomic ancestry were predictors of metabolic syndrome. RESULTS: Metabolic syndrome was identified in 29.8% of participants. In the first model, the factors associated with metabolic syndrome were: female gender (odds ratio 1.95, P < 0.001); diabetes duration (odds ratio 1.04, P < 0.001); family history of type 2 diabetes (odds ratio 1.36, P = 0.019); and acanthosis nigricans (odds ratio 5.93, P < 0.001). Colour-race was not a predictive factor for metabolic syndrome. In the second model, colour-race was replaced by European genomic ancestry. The associated factors were: female gender (odds ratio 1.95, P < 0.001); diabetes duration (odds ratio 1.04, P < 0.001); family history of type 2 diabetes (odds ratio 1.39, P = 0.011); and acanthosis nigricans (odds ratio 6.12, P < 0.001). Physical exercise (≥3 times a week) was a protective factor (odds ratio 0.77, P = 0.041), and European genomic ancestry was not associated with metabolic syndrome but showed an odds ratio of 1.77 (P = 0.05). CONCLUSIONS: Although a higher level of European genomic ancestry was observed among participants with metabolic syndrome in the univariate analysis, this association did not persist after multivariable adjustments. Further prospective studies in other highly admixed populations remain necessary to better evaluate whether the European ancestral component modulates the development of metabolic syndrome in type 1 diabetes.

Postpartum follow up of gestational diabetes in a Tertiary Care Center.

BACKGROUND: Gestational diabetes is a risk factor for future development of type 2 diabetes. The primary aim of this study was to estimate the prevalence of postpartum glucose tolerance status evaluation in pregnancies complicated by gestational diabetes 6-12 weeks after delivery. The secondary one was to identify the factors that are implicated with postpartum glucose retesting. METHODS: This was a retrospective study performed with a cohort of women with gestational diabetes, with prenatal care and delivery at a tertiary care center, from January 2013 to April 2017. The diagnosis of gestational diabetes was based on IADPSG criteria (Fasting ≥ 92 mg/dl, 1 h ≥ 180 mg/dl and/or 2 h ≥ 153 mg/dl, respectively) and the diagnosis of type 2 diabetes and prediabetes were made using the 2016 ADA's criteria (fasting and 2 h after glucose load ≥ 126 mg/dl and/or ≥ 200 and 100-125 mg/dl and/or 140 and 199 mg/dl, respectively). All women had an appointment scheduled 6-12 weeks postpartum with the results of a 75-g oral glucose tolerance test (OGTT). RESULTS: Of the 152 evaluated women, 21 (13.8%) returned with the postpartum OGTT results. Of these, 9 (45.0%) had a diagnosis of prediabetes. The use of insulin during gestation was the only factor implicated in a higher adherence rate to postpartum testing OR 6.33 (p 0.002). No significance was found for other demographic and clinical variables (age, family income, years of study, parity, gestational age at first visit, smoking, family history of type 2 diabetes, diagnosis of gestational diabetes before the third trimester, pregestational body mass index, previous history of gestational diabetes and ethnicity). CONCLUSION: The majority of patients with gestational diabetes did not return postpartum to perform OGTT and in our study the only factor implicated in a higher postpartum return was the use of insulin during pregnancy. Considering that 45.0% were diagnosed with prediabetes, diabetes care teams should initially identify non-adherent patients.

Adherence to insulin therapeutic regimens in patients with type 1 diabetes. A nationwide survey in Brazil.

AIMS: Determine the relationship between self-reported adherence to insulin therapeutic regimens in Brazilian patients with type 1 diabetes and demographic, clinical data, glycemic control and cardiovascular risk factors. METHODS: This was a cross-sectional, multicenter study conducted between August 2011 and August 2014 in 10 Brazilian cities. Data were obtained from 1698 patients, aged 30.0±11.90years (55.5% females, 53.6% Caucasians) with a diabetes duration of 15.4±1.9years. Adherence was evaluated using an adapted 4-item Morisky Medication Scale (MMAS) questionnaire. RESULTS: A total of 166 (9.8%), 717 (42.2%) and 815 (48.0%) of the patients reported maximal (group 0), moderate (group 1) and minimal (group 2) adherence to their insulin therapeutic regimen, respectively. A significant difference in HbA1c was observed in patients from group 2, 9.2±2.2% (77±25mmol/mol) compared to group 1, 8.9±2.0% (74±22mmol/mol) and group 0, 8.6±1.9% (71±21mmol/mol) (p=0.003). A multivariate logistic analysis revealed that the significant independent variables related to higher insulin therapeutic regimen adherence were older age, higher adherence to diet, lower rate of self-reported hypoglycemia in the last month, low economic status and living in the Southeast region. Insulin therapeutic regimens, number of daily insulin injections, self-monitoring of blood glucose, gender, ethnicity and cardiovascular risk factors were not related to adherence. CONCLUSIONS: Most Brazilian T1D patients did not adhere to their prescribed insulin therapeutic regimen, according to the MMAS 4-item scale. This tool should be initially used to identify non-adherent patients and help them overcome the barriers to adherence to their prescriptions.

Early age at menarche: a risk factor for overweight or obesity in patients with type 1 diabetes living in urban areas?

AIMS: Determine the relationship between age at menarche, glycemic control and cardiovascular risk factors in patients with type 1 diabetes living in urban areas. METHODS: This was a multicenter cross-sectional study conducted in 20 cities in four Brazilian geographic regions. Data were obtained from 1527 female patients, 59.3% Caucasians, aged 25.1 ± 10.6 years. Diabetes duration was 11.4 ± 8.1 years. Age at menarche was stratified in four groups: 8-11 (group 1, early menarche), 12 (group 2), 13 (group 3) and 14-18 years (group 4, late menarche). RESULTS: The mean age at menarche was 12.7 ± 1.7 years without difference among geographical regions, economic status, level of care and ethnicity. BMI had an inverse correlation with age at menarche (r=-0.14, p<0.001). No significant difference was observed among the four groups for blood pressure, lipid profile and diabetes-related chronic complications. Logistic regression analysis showed that early age at menarche, 8-11 years (odds ratio (ORs) 1.77 [1.30-2.41], p<0.001) and duration of diabetes [ORs 1.01 (1.00-1.03), p=0.02], were related to greater risk of patients' overweight or obesity; adherence to diet [ORs 0.78 (0.60-0.93), p=0.01], physical activity [ORs 0.75 (0.94-0.94), p=0.01], and lower insulin dose (U/kg) [ORs 0.54 (0.59-0.90), p=0.001] were related to lower risk for overweight or obesity. CONCLUSIONS: Early menarche occurred in 23.4% of women with type 1 diabetes living in Brazilian urban areas and was strongly associated with overweight/obesity in pubertal/adult life. Further studies are warranted to establish the relationship between early menarche, glycemic control and cardiovascular risk factors.

Should thyroid-stimulating hormone goals be reviewed in patients with type 1 diabetes mellitus? Results from the Brazilian Type 1 Diabetes Study Group.

AIMS: To investigate if thyroid-stimulating hormone (TSH) levels are associated with any differences in glycaemic control or diabetes-related complications in individuals with Type 1 diabetes. METHODS: This observational, cross-sectional and multicentre study included patients with Type 1 diabetes for ≥ 5 years, with a recent TSH measurement and without a known previous thyroid disease. Patients were divided into three groups according to TSH levels: 0.4-2.5 mU/l; 2.5-4.4 mU/l; and ≥ 4.5 mU/l. RESULTS: We included 1205 individuals with a mean ± sd age of 23.8 ± 11.3 years. Seven patients had TSH levels <0.4 mU/l and were excluded from the comparison between groups. HbA1c levels, systolic and diastolic blood pressure, LDL cholesterol and disease duration were similar in all groups (P = 0.893, P = 0.548, P = 0.461, P = 0.575 and P = 0.764, respectively). The rates of diabetic retinopathy and GFR < 60/mL/min/1.73 m(2) differed between groups (P = 0.006 and P < 0.001, respectively) and were lower in those with lower TSH levels. Multivariate analysis confirmed these associations. The frequencies of retinopathy and GFR < 60 mL/min/1.73 m(2) were higher not only in patients with TSH ≥ 4.5 mU/l (odds ratio 1.878 and 2.271, respectively) but also in those with TSH levels of 2.5-4.4 mU/l (odds ratio 1.493 and 2.286, respectively), when compared with patients with TSH levels of 0.4-2.5 mU/l. CONCLUSIONS: TSH levels of 0.4-2.5 mU/l are associated with a lower risk of diabetic retinopathy and renal failure in individuals with Type 1 diabetes, independently of glycaemic control and duration of the disease.

Post-operative endothelial dysfunction assessment using laser Doppler perfusion measurement in cardiac surgery patients.

BACKGROUND: Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) is associated with systemic inflammatory response and endothelial dysfunction. Our hypothesis is that CPB-induced post-operative endothelial dysfunction may be detected using laser Doppler perfusion monitoring (LDPM) in the skin microcirculation. METHODS: We used LDPM to investigate the subacute effects of the CPB on systemic microvascular reactivity among patients undergoing CABG surgery with CPB. Thirty patients were submitted to the study of skin microcirculation and blood sample collection at baseline (pre-surgery) and at 7 days post-surgical procedure. The skin microcirculation was evaluated by acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis, and thermal hyperemia (TH). Plasma levels of nitrite/nitrate were also analyzed, and cytokine profiles were determined using a multiplex system. RESULTS: On-pump CABG surgery induced a significant reduction of the increased microvascular dermal flux observed after cumulative doses of ACh iontophoresis and after TH. On-pump CABG surgery did not induce any significant changes in the microvascular flux after cumulative doses of SNP. Patients still presented high levels of interleukin (IL)-6, IL-8, and C-reactive protein, and low bioavailability of nitric oxide 7 days after the CABG surgery with CPB. CONCLUSION: We observed a significant impairment of systemic microvascular endothelial function and well-preserved endothelium-independent vasodilatation in the skin microcirculation of patients 1 week after CABG surgery with CPB. Our results suggest that LDPM is a useful tool for the assessment of on-pump CABG-induced subacute post-operative endothelial dysfunctions.

Determinants of self-monitoring of blood glucose in patients with Type 1 diabetes: a multi-centre study in Brazil.

AIM: The aim of this study was to determine the relationship between the daily frequency of self-monitoring of blood glucose and glycaemic control, demographic and socio-economic status in patients with Type 1 diabetes under routine clinical care in Brazil. METHODS: This was a cross-sectional, multi-centre study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The data were obtained from 3176 patients, aged 22 ± 11.8 years, of whom 56.3% were female and 57.4% were Caucasian. The mean time since diabetes diagnosis was 11.7 ± 8.1 years. RESULTS: The prevalence of self-monitoring of blood glucose was 88.5%. There was a significant increase in self-monitoring frequency associated with female gender, lower ages, more intensive diabetes management and higher socio-economic status. A correlation between HbA(1c) levels and the daily frequency of self-monitoring was observed (r(s) = -0.13; P = 0.001). The mean HbA1c levels were related to the daily frequency of self-monitoring (P < 0.001) without additional benefit to patients who performed self-monitoring more than four times daily (9.2, 11.2, 10.2,15.2 and 15% for one, two, three, four, five or more self-monitoring tests daily, respectively; P < 0.0001). CONCLUSIONS: The majority of our patients (88.5%) performed three or more self-monitoring tests daily, with more frequent testing reported by females, younger patients, those on intensive insulin regimens and of higher socio-economic status. No additional benefit was found in patients who performed self-monitoring more than four times daily. The diabetes care team must improve patients' education regarding self-monitoring of blood glucose and its benefits.

Temporal changes in the diagnosis of type 1 diabetes by diabetic ketoacidosis in Brazil: a nationwide survey.

AIMS: To examine the temporal trends in the frequency of diabetic ketoacidosis at onset compared to other modalities of diagnosis of Type 1 diabetes in Brazil. METHODS: This was a retrospective, cross-sectional and multicenter study conducted between December 2008 and December 2010 in 28 public clinics at secondary and tertiary levels of care, located in 20 cities in four geographic regions of Brazil. Each clinic provided data extracted from at least 50 outpatients with Type 1 diabetes diagnosed between 1960 and 2010, using standardized chart review forms. Data were obtained from 3591 patients (56.0% females, 57.1% Caucasians). Median values (range) for age, age at diagnosis and duration of diabetes were, respectively, 19 years (1-66 years), 10 years (< 1-44 years) and 7 years (< 1-50 years). Logistic regression was performed with diabetic ketoacidosis (Yes/No) as the dependent variable and other clinical features as independent variables. RESULTS: Type 1 diabetes diagnosis was made by diabetic ketoacidosis in 1,520 (42.3%), by fasting plasma glucose in 1413 (39.4%), by random blood glucose in 516 (14.4%), by oral glucose tolerance test in 66 (1.8%) and by other methods in 76 (2.1%) cases, respectively. Diagnosis made before the year 2000 had a greater odds to occur by diabetic ketoacidosis (Odds ratio 1.26, 95% confidence intervals (CI) 1.09-1.48). Since then, a decrease has occurred. Economic status, geographic region and age were significantly related to diabetic ketoacidosis at diagnosis. CONCLUSIONS: Although high prevalence of diabetic ketoacidosis at diagnosis of Type 1 diabetes in Brazil is observed, recently, more patients have been diagnosed by other methods.

Uric acid levels are associated with microvascular endothelial dysfunction in patients with Type 1 diabetes.

AIMS: Recent data identified uric acid as an independent risk factor for cardiovascular disease. The aim of the present study was to assess the association between uric acid and endothelial dysfunction in 57 patients with Type 1 diabetes and 53 healthy control subjects. METHODS: Microvascular endothelial function was evaluated using laser Doppler perfusion monitoring coupled with pharmacological (iontophoretic administration of acetylcholine and sodium nitroprusside) and physiological (post-occlusive reactive hyperaemia and thermal hyperaemia) stimuli. RESULTS: Uric acid was higher in subjects without diabetes than in those with diabetes (P = 0.03). Microvascular vasodilator response to acetylcholine was significantly reduced in Type 1 diabetes (P = 0.002) and was correlated to disease duration (r = -0.3, P = 0.01), triglyceride (r = -0.37, P = 0.005), insulin dose (r = -0.28, P = 0.03), fasting plasma glucose levels (r = -0.3, P = 0.02), HbA(1c) (r = -0.34, P = 0.001) and uric acid (r = -0.3, P = 0.005). On stepwise multivariate analysis, age, HbA(1c) and uric acid were the most important independent variables that were associated with the endothelium-dependent response in Type 1 diabetes (P = 0.02). CONCLUSIONS: Glycaemic control and uric acid in the normal range were the most important contributing factors to the decreasing endothelium-dependent responses associated with Type 1 diabetes. Consequently, uric acid could be a new potential marker of microvascular endothelial dysfunction in these patients. Further studies are required to explore the clinical relevance of the relationship between uric acid levels, oxidative stress and endothelial dysfunction in patients with Type 1 diabetes, as well as whether treatment with uric acid-lowering drugs for slight elevations in uric acid would benefit these patients.

Temporal trends in incidence of Type 1 diabetes between 1986 and 2006 in Brazil.

BACKGROUND: Scarce information is available about the variation in the incidence of Type 1 diabetes in the Brazilian population in the last decades. AIM: The objective of this study was to assess the long-term trends (1986-2006) in the incidence of Type 1 diabetes in Bauru, São Paulo State, Brazil. SUBJECTS AND METHODS: The annual incidence of Type 1 diabetes (per 100,000 per yr) from 1986 to 2006 was determined in children or=20/100,000 per yr) in 71.43% of the study-years. Incidence was slightly higher among females, Caucasians, children in the 5-9 yr of age range and belonging to lower socio-economic classes. Most diagnoses were established during the colder months and/or with higher pluviometric indexes. CONCLUSIONS: The incidence of Type 1 diabetes in children is increasing in Bauru, São Paulo State, Brazil, and the global pattern of incidence was classified as high or very high, mainly in the last 10 yr. All Brazilian regions should be involved in the study.

Congenital toxoplasmosis: evaluation of serological methods for the detection of anti-Toxoplasma gondii IgM and IgA antibodies.

A study was carried out to evaluate the presence of serological markers for the immunodiagnosis of the vertical transmission of toxoplasmosis. We tested the sensitivity, specificity and predictive values (positive and negative) of different serological methods for the early diagnosis of congenital toxoplasmosis. In a prospective longitudinal study, 50 infants with suspected congenital toxoplasmosis were followed up in the ambulatory care centre of Congenital Infections at University Hospital in Goiânia, Goiás, Brazil, from 1 January 2004-30 September 2005. Microparticle Enzyme Immunoassay (MEIA), Enzyme-Linked Fluorescent Assay (ELFA) and Immune-Fluorescent Antibody Technique (IFAT) were used to detect specific IgM anti-Toxoplasma gondii antibodies and a capture ELISA was used to detect specific IgA antibodies. The results showed that 28/50 infants were infected. During the neonatal period, IgM was detected in 39.3% (11/28) of those infected infants and IgA was detected in 21.4% (6/28). The sensitivity, specificity and predictive values (positive and negative) of each assay were, respectively: MEIA and ELFA: 60.9%, 100%, 100%, 55.0%; IFAT: 59.6%, 91.7%, 93.3%, 53.7%; IgA capture ELISA: 57.1%, 100%, 100%, 51.2%. The presence of specific IgM and IgA antibodies during the neonatal period was not frequent, although it was correlated with the most severe cases of congenital transmission. The results indicate that the absence of congenital disease markers (IgM and IgA) in newborns, even after confirming the absence with several techniques, does not constitute an exclusion criterion for toxoplasmosis.

Congenital toxoplasmosis: evaluation of serological methods for the detection of anti-Toxoplasma gondii IgM and IgA antibodies

A study was carried out to evaluate the presence of serological markers for the immunodiagnosis of the vertical transmission of toxoplasmosis. We tested the sensitivity, specificity and predictive values (positive and negative) of different serological methods for the early diagnosis of congenital toxoplasmosis. In a prospective longitudinal study, 50 infants with suspected congenital toxoplasmosis were followed up in the ambulatory care centre of Congenital Infections at University Hospital in Goiânia, Goiás, Brazil, from 1 January 2004-30 September 2005. Microparticle Enzyme Immunoassay (MEIA), Enzyme-Linked Fluorescent Assay (ELFA) and Immune-Fluorescent Antibody Technique (IFAT) were used to detect specific IgM anti-Toxoplasma gondii antibodies and a capture ELISA was used to detect specific IgA antibodies. The results showed that 28/50 infants were infected. During the neonatal period, IgM was detected in 39.3 percent (11/28) of those infected infants and IgA was detected in 21.4 percent (6/28). The sensitivity, specificity and predictive values (positive and negative) of each assay were, respectively: MEIA and ELFA: 60.9 percent, 100 percent, 100 percent, 55.0 percent; IFAT: 59.6 percent, 91.7 percent, 93.3 percent, 53.7 percent; IgA capture ELISA: 57.1 percent, 100 percent, 100 percent, 51.2 percent. The presence of specific IgM and IgA antibodies during the neonatal period was not frequent, although it was correlated with the most severe cases of congenital transmission. The results indicate that the absence of congenital disease markers (IgM and IgA) in newborns, even after confirming the absence with several techniques, does not constitute an exclusion criterion for toxoplasmosis.

Endothelial function in patients with type 1 diabetes evaluated by skin capillary recruitment.

The aim of the present study was to evaluate skin capillary density and recruitment of the upper and lower extremities of patients with type 1 diabetes under chronic treatment without clinical manifestations of diabetes-related complications. This cross-sectional observational study included 59 (27.1+/-10.6 years) consecutive outpatients with type 1 diabetes [duration 10 (1; 45) years] and 41 age- and sex-matched healthy controls. We used intravital video-microscopy to measure basal and maximal (during venous congestion) skin capillary densities as well as capillary recruitment using post-occlusive reactive hyperemia (PORH) in the dorsum of the fingers and toes. Mean capillary density (MCD) of the fingers at baseline was not different between controls and patients (123.02+/-22.6 and 132.3+/-28.9 capillaries/mm(2), respectively; P=0.08). In contrast, baseline MCD of the toes was lower in controls, when compared to patients (84.6+/-19.8 and 96.2+/-23.4 capillaries/mm(2), respectively; P=0.01). Capillary recruitment during PORH (% increase of the number of capillaries/mm(2)) was significantly higher in controls compared to patients both in fingers [7 (-8; 33) and -1.0 (-35, 13), respectively; P=0.000] and toes [6 (-20; 46) and 0 (-24; 20), respectively; P=0.000]. During venous occlusion, capillary density increase (% increase of the number of capillaries/mm(2)) was also higher in controls compared to patients both in fingers [3 (-14; 23) and 0.0 (-30; 29.2), respectively; P=0.02] and toes [9.3 (-18; 51) and -7 (-34; 22), respectively; P=0.000]. Our results showed that patients with type 1 diabetes, although not presenting skin capillary rarefaction, display skin microvascular functional alterations in both extremities characterized by an absence of capillary reserve.

Metformin prevents the impairment of endothelium-dependent vascular relaxation induced by high glucose challenge in rabbit isolated perfused kidneys.

High glucose concentrations are involved in the development of diabetic-associated vascular complications. We have previously reported that acute high glucose challenge, corresponding to post-prandial glycemia levels observed in patients with type 2 diabetes, blunts ACh-induced endothelium-dependent relaxation of the renal circulation of non-diabetic rabbits. Isolated perfused kidneys from non-diabetic rabbits were acutely exposed (3 h) to normal (5.5 mM--control group) or high (15 mM) D-glucose concentrations in the presence or absence of a continuous infusion of metformin (20 or 100 microM). Renal vascular reactivity was evaluated with endothelium-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) vasodilating agents. ACh-induced maximal renal vasodilation was reduced by high glucose infusion (15 mM) in comparison to the control group (25+/-3% and 41+/-3% respectively; P<0.01), being restored to 41+/-4% and 43+/-2% by a simultaneous 3-h infusion of 20 or 100 microM of metformin respectively (P>0.05). Perfusion of the kidneys with the angiotensin II-converting enzyme inhibitor captopril (10 microM) also significantly prevented the deleterious effects of high glucose challenge in the renal circulation. The use of a continuous infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) did not affect the protective effect of metformin in the renal circulation (39+/-4%; P>0.05), while tetraethylammonium (TEA, 10 mM) partially blunted this effect (33+/-4, P<0.01). Renal vasodilation induced by SNP was not modified by simultaneous infusion of high glucose and/or metformin. It is concluded that the impairment of ACh-induced endothelium-dependent renal vasodilation observed after acute exposure to high glucose concentrations is abolished by metformin administration. These alterations of renal vascular reactivity can be accounted for, at least in part, by the activation of the renal renin-angiotensin system during hyperglycemia. The protective effects of metformin present some EDHF-dependent component and are not related to metabolic pathways dependent on nitric oxide.

Acute-phase proteins among patients with type 1 diabetes.

OBJECTIVE: To determine whether young type 1 diabetic patients without clinical microvascular or macrovascular complications have altered levels of acute-phase proteins (AFP), alpha(1)-acid glycoprotein (AGP), C-reactive protein (CRP) and fibrinogen and whether their AFP levels are related to glycemic control. RESEARCH DESIGN AND METHODS: We studied cross-sectionally 48 type 1 diabetic outpatients (25 males) aged 19.9 +/- 9.8 years with a duration of diabetes of 5 (1-21) years, without clinical chronic complications and 66 non-diabetic subjects (26 males) aged 23.1 +/- 10.9 years. Inclusion criteria were normoalbuminuria, normal eye fundoscopy, and no evidence of cardiovascular disease or neuropathy. RESULTS: High CRP [0.23 (0.01-2.90 l) vs (0.14 (0.01-2.41l) mg/dl p=0.01] and AGP [53.5(40-78) vs 40.0(40-115) mg/dl p=0.0001] levels were found in patients with type 1 diabetes compared to nondiabetic subjects. In the pooled group studied, AGP was correlated with CRP, HbA(1c), fasting plasma glucose (FBG) and AER and CRP was correlated with HbA(1c) and AER. The correlation of AGP and CRP with AER persisted after controlling for HbA(1c) and FBG. Stepwise multiple regression with AGP as the dependent variable showed that FBG and HbA(1c) were the significant independent variables. No correlation between AFP and HBA(1c) and FBG was observed in the diabetic group. CONCLUSIONS: According to our results, AFP, a known marker of low-grade chronic inflammation, are increased in patients with type 1 diabetes probably independently of glycemic control and the presence of clinical microvascular or macrovascular disease. The influence of AFP on the development of chronic complications in patients with type 1 diabetes must be addressed in prospective studies.

Early alterations of blood pressure in normotensive and normoalbuminuric Type 1 diabetic patients.

With the objective to examine patterns of blood pressure (BP) in normotensive and normoalbuminuric Type 1 diabetic patients during 24 h ambulatory blood pressure monitoring (ABPM) we studied 28 Type 1 diabetic patients aged 27+/-7.1 years with a disease duration of 9+/-6.6 years, and 28 non-diabetic normotensive subjects aged 25+/-6.5 years matched to the diabetic group for age, gender, skin color, weight, height, body mass index, clinic BP and absence of microalbuminuria. Systolic BP (sBP) and diastolic BP (dBP) were recorded for 24 h, daytime and nighttime. SBP and dBP burden, night/day BP ratios and percent nighttime BP fall were determined. Subjects with a nocturnal fall in either sBP or dBP of less than 10% of daytime values were classified as non-dippers. Both sBP (111+/-7.1 vs. 104+/-9 mmHg; P=0.003) and dBP nighttime (66+/-6.1 vs. 61+/-5.3 mmHg; P=0.001) were higher in diabetic patients than non-diabetic subjects. Night/day ratios for sBP (0.93+/-0.04 vs. 0.89+/-0.05; P=0.006) and dBP (0.86+/-0.06 vs. 0.82+/-0.06; P=0.007) were higher in diabetics. The loss of a fall in sBP was more prevalent in diabetic subjects (78 vs. 39%; P=0.007). Non-dippers for sBP and dBP in the diabetic group had higher BP burden during the nighttime (21.4+/-16.6 vs. 3.2+/-3.9%; P=0.01 and 21.9+/-10 vs. 3.7+/-5.5%; P<0.001, respectively). Our data demonstrate higher sBP and dBP during the nighttime and loss of the nocturnal fall in BP in Type 1 diabetic patients. Further prospective studies are needed to define if high BP burden in diabetic non-dippers during the night could represent a risk for nephropathy and cardiovascular disease.

Is there a physiological variability for albumin excretion rate? Study in patients with diabetes type 1 and non-diabetic individuals.

BACKGROUND: To determine the intraindividual coefficient of variation (CV(i)) of albumin excretion rate (AER). METHOD: We studied 76 patients with type 1diabetes and 66 non-diabetic subjects (ND) under routine clinical conditions providing three timed overnight urine samples for urinary albumin determination by radioimmunoassay. RESULTS: Patients and ND had similar CV(i) of AER (50.7+/-33.3 vs. 58.1+/-33.2% P=0.12). Intermittent microalbuminuric subjects (one out of 3 AER >20 microg/min) had higher CV(i) of AER than normoalbuminuric and persistent microalbuminuric patients, [84.9 (37.1-145. 3) vs. 39.8 (4.9-124.8) vs. 34.6 (12.1-116.5)% P=0.0007] without difference between the two latter groups. In patients, the independent factor associated with the CV(i) of AER in multiple regression analysis was age (r(2)=0.08; P=0.01). Sensitivity (95% CL) and specificity of first AER for diagnosing microalbuminuria was 85.7% (42.0-99.2) and 91.3% (81.4-96.4). CONCLUIONS: Our findings suggest the variability of AER was physiological, unrelated to diabetic condition. First AER could be used for screening of microalbuminuria followed by a second one when the patient has AER >20 microg/min in the first. This would result in low cost for screening and diagnosis of microalbuminuria, that is not always feasible in routine clinical practice in developing countries using three urine samples.