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Purpose: Sclerosing lymphocytic lobulitis (SLL) is a rare benign breast condition usually associated with diabetes mellitus and whose imaging features have been assessed in few studies, limiting the adoption of diagnostic guidelines. We aimed to identify the main morphological features associated with SLL on imaging examinations (mainly ultrasound and mammography) and to retrospectively evaluate the role that each method played in the diagnostic workup (detection and indication for biopsy). Methods: A retrospective study was conducted in a high-volume single center, encompassing 51 consecutive patients (100% female; 26-78 y; 43.7 ± 15.5 y) with histopathologically proven SLL (59 lesions; 0.5-6.1 cm). Results: Most lesions (31/59; 53%) were found in asymptomatic individuals. Ultrasound detected 91.1% (51 out of 56 lesions assessed by this modality), of which 94.1% were non-circumscribed masses (BI-RADS® 4). Mammography detected 41.6% (15 out of 36 lesions assessed by this modality), with a predominance (80%) of non-calcified ones (masses, asymmetries and distortion). Two-year follow-up was achieved in 29 lesions (49%), showing complete remission (45%) or stability (41%) in most cases. Conclusions: Most lesions in this retrospective sample have been detected by means of ultrasound and had their need for biopsy indicated by this modality. Female diabetic patients younger than 40 years presenting with a palpable lesion and a non-circumscribed mass on ultrasound could be submitted to core biopsy; histopathologic findings suggestive of SLL should be considered concordant in this scenario, with subsequent conservative treatment.

Objectives to evaluate the probability of survival and failure modes of lithium-disilicate, feldspathic-ceramic, and resin-nanoceramic anterior veneers cemented on dentin analog substrates after sliding-contact step-stress accelerated life testing (SSALT). Methods A virtual incisor tooth preparation was produced with a reduction of 1.5 mm at the incisal edge and of 0.7 mm buccally. A .STL file of the preparation was generated and CAD/CAM based G10 dentin-analog material was used for testing. Laminate veneers were milled in three different materials: lithium-disilicate (LDS, E.max CAD), resin-nanoceramic (RN, Lava Ultimate), and feldspathic-ceramic (FELDS, Vita Blocks). SSALT was employed where a spherical indenter contacted the veneer, slided along its interface with G10 to lift off and start a new cycle at 2 Hz in water. Qualitative fractography was performed. The probability of survival (90% confidence-bounds) was calculated for several load/cycle missions. Results The probability of survival for a mission of 50,000 cycles decreased from 50 up to 150 N equally for all groups and were not different between them. At 200 N, the probability of survival was significantly lower for FELDS (10%) compared to RN veneers (41%), whereas LDS presented intermediate values (22%). The characteristic strength of RN (247 N) was significantly higher than LDS (149 N), and FELDS (151 N). In FELDS and LDS, hackles, wake hackles and twist hackles indicated the direction of crack propagation. In RN, hackles were observed. Conclusions Differences in probability of survival were observed only at 180 and 200 N between groups. Failure modes were similar with veneer fracture down to the tooth-analog substrate.

Background Maturity‐onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. To date, mutations in 11 genes have been frequently associated with this phenotype. In Brazil, few cohorts have been screened for MODY, all using a candidate gene approach, with a high prevalence of undiagnosed cases (MODY‐X). Methods We conducted a next‐generation sequencing target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected, of which 26 had an initial clinical suspicion of MODY‐GCK and 76 were non‐GCK MODY. Results After excluding all benign and likely benign variants and variants of uncertain significance, we were able to assign a genetic cause for 12.7% (13/102) of the probands. Three rare MODY subtypes were identified (PDX1/NEUROD1/ABCC8), and eight variants had not been previously described/mapped in genomic databases. Important clinical findings were evidenced in some cases after genetic diagnosis, such as MODY‐PDX1/HNF1B. Conclusion A multiloci genetic approach allowed the identification of rare MODY subtypes, reducing the large percentage of MODY‐X in Brazilian cases and contributing to a better clinical, therapeutic, and prognostic characterization of these rare phenotypes., Maturity‐onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance and, to date, mutations in 11 genes have been frequently associated with this phenotype. We have conducted a NGS target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected and we were able to assign a genetic cause for 12.7% (13/102) of the probands, with three rare MODY subtypes were identified (PDX1/NEUROD1/ABCC8).

Objective To evaluate the influence of the degree of dentin moisture on interfacial ultramorphology and bond strength (μTBS) of universal adhesives. Materials and methods Futurabond U (FBU), Scotchbond Universal (SBU), Adhese Universal (ADU), and Prime&Bond active (PBA) were used. After acid-etching, moist or over-dried dentin surfaces were tested. Teeth were restored for scanning and transmission electron microscopy (n = 3) and μTBS evaluation (n = 5). μTBS results were analyzed by two-way ANOVA and Tukey. Results For moist dentin, a well-formed hybrid layer (HL) was observed. However, when applied to over-dried dentin, remarkable differences were observed. Defects, gaps, and reduced HL thickness were observed mainly for ADU and FBU. When applied to wet dentin, μTBS values were similar for all adhesives, except for FBU, which was significantly lower. When applied to over-dried dentin, PBA presented the highest μTBS values, followed by SBU, ADU, and FBU. ADU presented significantly lower μTBS when applied to over-dried dentin. Conclusion PBA, SBU, and FBU μTBS values were not sensitive to the degree of moisture. Even though application to over-dried dentin revealed defects, gaps and reduced HL thickness for SBU, ADU, and FBU, μTBS analysis only revealed a significant reduction for ADU. Clinical significance Universal adhesives can be applied in either self-etching or etch-and-rinse mode. However, clinicians are not aware which universal adhesives should be strictly applied on a moist dentin for bonding in the etch-and-rinse mode.

Aims Maturity-Onset Diabetes of the Young (MODY) caused by glucokinase (GCK) mutations is characterized by lifelong mild non-progressive hyperglycemia, with low frequency of coronary artery disease (CAD) compared to other types of diabetes. The aim of this study is to estimate cardiovascular risk by coronary artery calcification (CAC) score in this group. Materials and methods Twenty-nine GCK-MODY cases, 26 normoglycemic controls (recruited among non-affected relatives/spouses of GCK mutation carriers), and 24 unrelated individuals with type 2 diabetes were studied. Patients underwent CAC score evaluation by computed tomography and were classified by Agatston score ≥ or Results Median [interquartile range] CAC score in GCK-MODY was 0 [0,0], similar to controls (0 [0,0], P = 0.49), but lower than type 2 diabetes (39 [0, 126], P = 2.6 × 10-5). A CAC score ≥ 10 was seen in 6.9% of the GCK group, 7.7% of Controls (P = 1.0), and 54.2% of individuals with type 2 diabetes (P = 0.0006). Median Framingham risk score was lower in GCK than type 2 diabetes (3% vs. 13%, P = 4 × 10-6), but similar to controls (3% vs. 4%, P = 0.66). Conclusions CAC score in GCK-MODY is similar to control individuals from the same family and/or household and is significantly lower than type 2 diabetes. Besides demonstrating low risk of CAD in GCK-MODY, these findings may contribute to understanding the specific effect of hyperglycemia in CAD.

Aims Maturity-Onset Diabetes of the Young (MODY) comprises a heterogeneous group of monogenic forms of diabetes caused by mutations in at least 14 genes, but mostly by mutations in Glucokinase ( GCK ) and hepatocyte nuclear factor-1 homeobox A ( HNF1A ). This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. Methods 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report. Results 72 individuals had GCK mutations, 9 described in Brazilian individuals for the first time. One previously unpublished novel GCK mutation, Gly178Ala, was found in one family. 31 individuals had HNF1A mutations, 2 described for the first time in Brazilian individuals. Comparisons of GCK probands vs HNF1A : age 16 ± 11 vs 35 ± 20 years; age at diagnosis 11 ± 8 vs 21 ± 7 years; BMI 19 ± 6 vs 25 ± 6 kg/m 2 ; sulfonylurea users 5 vs 83%; insulin users 5 vs 17%; presence of arterial hypertension 0 vs. 33%, all p Conclusions Most MODY cases in Brazil are due to GCK mutations. In agreement with other studied populations, novel mutations are common. Only 14% of patients with familial diabetes carry a HNF1A mutation. Diagnosis of other rare forms of MODY is still a challenge in Brazilian population, as well as adequate strategies to screen individuals for molecular diagnosis.

Thirty-two patients with diabetes negative for point mutations in GCK and HNF1A underwent further molecular screening of GCK, HNF1A, HNF4A, and HNF1B by MLPA analysis. We described the first Brazilian case of MODY5 due to a heterozygous whole-gene deletion in HNF1B, who developed rapidly progressive renal failure and death.

Adiponectin (APN), an adipose tissue-released adipokine with demonstrated anti-inflammatory and anti-atherogenic properties, is encoded by a gene whose polymorphisms are associated with presence of coronary artery disease (CAD). Serum APN levels are inversely related with presence and complexity of CAD. Within this context, we sought to compare levels of total APN and its high molecular weight form (HMW APN) according to clinical presentation and extent of CAD in patients undergoing elective cardiac catheterization. From March 2008 to June 2010, clinical data and blood samples for APN and HMW APN measurements were collected from 415 subjects undergoing cardiac catheterization at two tertiary centers. CAD extent was estimated by the number of coronary arteries with significant stenosis (≥70% obstruction in a major coronary artery) and by Duke Jeopardy Score (DJS). Serum APN levels were similar between groups with stable or unstable CAD (APN 9.20±5.88 vs 9.47±6.23 μg/mL, P=0.738, and HMW APN 5.31±3.72 vs 5.91±4.16 μg/mL, P=0.255), even after stratification by the number of arteries involved (single-vessel vs multivessel disease: APN 9.39±5.76 vs 9.26±6.27 μg/mL, P=0.871; HMW APN 5.29±3.79 vs 5.83±4.04 μg/mL, P=0.306) and DJS score (APN, P=0.718; HMW APN, P=0.276). We conclude that APN and HMW APN serum levels are similar across clinical presentations and different extents of CAD, despite being significantly lower in the presence of obstructive CAD.

Different dietary interventions have been identified as potential modifiers of adiponectin concentrations, and they may be influenced by lipid intake. We identified studies investigating the effect of dietary lipids (type/amount) on adiponectin concentrations in a systematic review with meta-analysis. A literature search was conducted until July 2013 using databases such as Medline, Embase and Scopus (MeSH terms: ‘adiponectin’, ‘dietary lipid’, ‘randomized controlled trials (RCT)’). Inclusion criteria were RCT in adults analysing adiponectin concentrations with modification of dietary lipids. Among the 4930 studies retrieved, fifty-three fulfilled the inclusion criteria and were grouped as follows: (1) total dietary lipid intake; (2) dietary/supplementary n-3 PUFA; (3) conjugated linoleic acid (CLA) supplementation; (4) other dietary lipid interventions. Diets with a low fat content in comparison to diets with a high-fat content were not associated with positive changes in adiponectin concentrations (twelve studies; pooled estimate of the difference in means: − 0·04 (95 % CI − 0·82, 0·74) μg/ml). A modest increase in adiponectin concentrations with n-3 PUFA supplementation was observed (thirteen studies; 0·27 (95 % CI 0·07, 0·47) μg/ml). Publication bias was found by using Egger's test (P= 0·01) and funnel plot asymmetry. In contrast, CLA supplementation reduced the circulating concentrations of adiponectin compared with unsaturated fat supplementation (seven studies; − 0·74 (95 % CI − 1·38, − 0·10) μg/ml). However, important sources of heterogeneity were found as revealed by the meta-regression analyses of both n-3 PUFA and CLA supplementation. Results of new RCT would be necessary to confirm these findings.

Six Brazilian families with mild familial hyperglycaemia have been screened for glucokinase (GCK) mutations. All had mutations that co-segregated with the phenotype. One of the mutations, the deletion 96_98delAAG (p.Lys32del), had not been previously described, reinforcing the worldwide prevalence of GCK MODY and widespread existence of undetected new mutations.

Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.

We investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study. We studied 5,110 unrelated French men and women who participated in the prospective Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Additional cross-sectional analyses were performed on 4,472 French individuals with type 2 diabetes and 3,065 controls. Three single nucleotide polymorphisms (SNPs) were genotyped: rs10010131, rs1801213/rs7672995 and rs734312. We observed statistically significant associations between the major alleles of the three variants and prevalent type 2 diabetes in the DESIR cohort at baseline. Cox analyses showed an association between the G-allele of rs10010131 and incident type 2 diabetes (HR 1.34, 95% CI 1.08–1.70, p = 0.007). Similar results were observed for the G-allele of rs1801213 and the A-allele of rs734312. The GGA haplotype was associated with an increased risk of diabetes as compared with the ACG haplotype (HR 1.26, 95% CI 1.04–1.42, p = 0.02). We also observed statistically significant associations of the three SNPs with plasma glucose, HbA1c levels and insulin secretion at baseline and throughout the study in individuals with type 2 diabetes or at risk of developing diabetes. However, no association was observed in those who remained normoglycaemic at the end of the follow-up. Associations between the three variants and type 2 diabetes were replicated in cross-sectional studies of type 2 diabetic patients in comparison with a non-diabetic control group. The most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.

Wolcott-Rallison syndrome (WRS, OMIM 226980) is a rare autosomal recessive disorder characterized by permanent neonatal diabetes mellitus, epiphyseal dysplasia, and other multisystemic clinical manifestations. We described two novel mutations in the EIF2AK3 gene in two consanguineous families with WRS from Brazil and Morocco. We have observed in case 1 a homozygous C > T replacement at base pair c.1192 at exon 7, generating a stop codon at position 398 (Gln398Stop). Both of his parents were found to be heterozygous for the mutation. We detected in both parents of case 2, a deceased Moroccan girl, a duplication of base pair c.851A at exon 5 (c.851dupA) leading to a frameshift and a stop codon at position 285 (p.Pro285AlafsX3). Both cases 1 and 2 had neonatal diabetes mellitus, multiple epiphyseal dysplasia, and growth delay, and presented episodes of acute hepatic dysfunction. Case 1 presented central hypothyroidism, developmental delay, and mild mental retardation. Case 2 presented a fatal episode of acute renal failure. The clinical phenotype associated with the syndrome can be variable, but a combination of infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, and hepatic and/or renal dysfunction is the mainstay of diagnosis.

Diabetic patients have a threefold higher risk of developing atherosclerosis and its clinical complications compared with nondiabetic individuals. Part of the cardiovascular risk associated with diabetes is probably due to genetic determinants influencing both glucose homeostasis and the development of atherosclerosis. However, type 2 diabetes frequently coexists with other cardiovascular risk factors such as arterial hypertension, central obesity, and dyslipidemia. Genetic variability affects many areas, such as lipid and energy metabolisms, hypertension and hemodynamic mechanisms, blood clotting homeostasis, inflammation, and matrix turnover in the vascular wall, and will have an impact on the development of macrovascular complications in diabetic patients. These individual susceptibility factors each contribute only a small increased risk interacting with environmental determinants.

The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Brazilian population and test the capability of a low resolution full-house DR-DQ typing method to find subjects at diabetes risk. Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients. Genotypes with two risk haplotypes or a combination of a susceptibility associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control subjects (P< 0.0001). Insulin gene −2221 C/T polymorphism was also associated with diabetes risk: CC genotype was found among 83.1% of patients compared to 69.3% of healthy controls (P= 0.0369, OR 1.98) but CTLA-4 gene +49 A/G polymorphism did not significantly differ between patients and controls. Despite the diversity of the Brazilian population the screening sensitivity and specificity of the used method for T1D risk was similar to that obtained in Europe.

The Vitamin D endocrine system regulates multiple aspects of calcium metabolism and cellular differentiation and replication in the immune system, endocrine pancreas, liver, skeletal muscles and adipocytes. It plays an important role in glucose homeostasis, notably, in the mechanism of insulin release. Actions of vitamin D are mediated by the binding of 1, 25-(OH)2D3 to a specific cytosolic/nuclear vitamin D receptor (VDR), a member of the steroid/thyroid hormone receptor superfamily. Several frequent polymorphisms are found in the VDR gene and were reported to be associated with a variety of physiological and pathological phenotypes in many populations. In this paper, we will review the evidences suggesting associations of allelic variations in the VDR gene and phenotypes related to body weight, glucose homeostasis, diabetes and its vascular complications.

Genetic factors play an important role in various forms of diabetes mellitus (DM), but inheritance is complex and interacts with environmental factors. Although in most cases type 2 DM (T2DM) and T1DM are polygenic disorders, several monogenic forms have been identified. Among them, maturity-onset diabetes of the young (MODY) has been the most intensively investigated. MODY is a group of six different forms of monogenic diabetes, characterized by insulin secretion defects in pancreatic beta-cells, supposed to be responsible for 2-5% of all cases of diabetes. The most common are MODY2 and MODY3, caused by mutations in the genes encoding glucokinase and hepatocyte nuclear factor 1-alpha respectively. MODY2 is characterized by glucose sensing defects, leading to an increase in insulin secretion threshold. This causes lifelong sustained and mild hyperglycaemia from birth, most often in non-diabetic levels. Diagnosis is incidental in most cases. These patients are asymptomatic, seldom need treatment and rarely present chronic complications. MODY3 is characterized by a severe insulin secretion defect in response to glucose. Diagnosis is made usually in adolescence and early adulthood, often by osmotic symptoms. Hyperglycaemia is progressive, and patients frequently need treatment with oral drugs or insulin some time in their follow up. This group seems to have a marked sensitivity to sulphonylureas compared to other types of diabetes. The recognition of MODY as a monogenic disorder and a thorough understanding of its pathophysiology are important for correct diagnosis and treatment, with great impact on prognosis. Besides, the study of these forms of diabetes brings important contributions to the understanding of glucose homeostasis as a whole.

E Duplus is in the Neurobiologie des processus adaptatifs laboratory from 2003; Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) is the key enzyme in glyceroneogenesis, an important metabolic pathway in adipocytes for reesterification of fatty acids during fasting. Dysregulation of glyceroneogenesis could play a role in the increase in plasma non-esterified fatty acids that accompanies type 2 diabetes. In rodent adipocyte transcription of the PEPCK-C gene is induced by thiazolidinediones (TZDs) through an element, named PCK2, in its promoter. PCK2 binds a peroxisome proliferator activated receptor gamma (PPARgamma), retinoid X receptor alpha (RXRalpha) heterodimer. We demonstrated that in cultured human subcutaneous adipose tissue explants, PEPCK-C specific activity and mRNA were induced by 1 microM of the TZD rosiglitazone, respectively, about twofold in 8 h and fivefold in 5 h. Using gel shift experiments, we show that this effect is likely to involve the human PCK2 (hPCK2) element, which binds a protein complex that contains PPARgamma and RXRalpha. We analyzed hPCK2 (position -1031 to -1015 base pairs) and nearby sequences in the PEPCK-C promoter in 403 subjects with type 2 diabetes and 123 non-diabetic controls. The sequence of hPCK2 was not polymorphic, but we detected two C/T single nucleotide polymorphisms (SNPs), in complete linkage disequilibrium, at positions -1097 and -967 bp. Allele and genotype frequencies were not significantly different in patients and controls. However, our results suggest co-dominant effects of C and T-alleles on fasting plasma glucose and glycosylated hemoglobin A1c levels in obese type 2 diabetic patients.

Summary objective A single nucleotide polymorphism (A1220G; N363S) in exon 2 of the glucocorticoid receptor gene (NR3C1), associated with increased sensitivity to glucocorticoids, was shown to be associated with obesity in nondiabetic subjects. Here, we investigated the impact of this variant on traits related to obesity and hyperglycaemia in subjects with type 2 diabetes mellitus. patients and measurements The N363S variant was screened by restriction fragment length polymorphism technique following DNA amplification by polymerase chain reaction in 369 French Caucasians with type 2 diabetes mellitus. results Twenty subjects were found to be heterozygous for the variant (AG genotype frequency 0·0542). The prevalence of overweight [body mass index (BMI) > 25 kg/m2] was higher in AG carriers than in AA carriers (100%vs. 73%, P = 0·003). Moreover, the mean body weight and the BMI were higher in AG as compared to AA carriers, although only the body weight was significantly different between groups. However, when only the men were considered, a significantly higher BMI was observed in AG as compared to AA carriers: 30·0 ± 4·8 vs. 27·3 ± 4·6 kg/m2 (BMI Z-score 1·28 ± 1·38 vs. 0·55 ± 1·17; P = 0·035). No evidence was found for an association of the N363S variant with parameters related to the severity of hyperglycaemia. conclusions The 363S allele of the N363S variant of NR3C1 is associated with the susceptibility to overweight in subjects with type 2 diabetes mellitus.

Estima-se que perto de 5% dos indivíduos classificados como portadores de diabetes mellitus (DM) tipo 2 e 10% daqueles considerados como tipo 1 (anteriormente classificado como juvenil) sejam, na verdade, portadores de mutações MODY. Nesta forma de DM ocorre uma co-segregação evidente de algumas mutações com a hiperglicemia, fato este reproduzido em inúmeras famílias estudadas em várias populações do mundo. Caracteriza-se por ser uma das poucas causas de DM cujo modo de transmissão da predisposição genética ocorre de uma forma autossômica-dominante, compondo o grupo chamado de DM monogênicos, onde os outros representantes têm uma prevalência bastante rara. As mutações nos genes MODY, mesmo no estado heterozigoto, apresentam um forte impacto no fenótipo (alta penetrância), sendo que 95% dos indivíduos nascidos com alguma mutação MODY serão diabéticos ou apresentarão alterações no âmbito do metabolismo glicídico antes dos 55 anos de idade. Este trabalho objetiva a discussão desta forma de DM, enfatizando suas características clínicas e genéticas mais relevantes. A pesquisa sistemática de mutações MODY começa a ser feita de forma rotineira em vários países, havendo uma tendência de se colocar este recurso diagnóstico como um exame na prática da diabetologia. It is estimated that close to 5% of the individuals classified as having type 2 diabetes mellitus (DM) and about 10% of those considered type 1 DM (previously categorized as juvenile type) are actual carriers of a MODY mutation. In this form of DM, there is evident co-segregation of some mutations and the advent of hyperglycemia, this fact having been reproduced by the study of several families of different populations. Its main characteristic is being one of the few causes of DM in which the transmission of the genetic susceptibility is due to an autossomical dominant inheritance, making part of the group classified as monogenic DM, where the other members are very rare. Mutations occurring in MODY genes, even in the heterozygous form, lead to a profound phenotypic impact (high penetrance), in that 95% of the individual carriers of a MODY mutation will be diabetic or will have altered glicemic metabolism before the age of 55 years. In this paper we approach this form of DM, emphasizing its most relevant clinical and genetic characteristics. The systematic search for MODY mutations is beginning to take place regularly in many countries, and there is a tendency to add this diagnostic tool to the routine exams in the practice of diabetology.

Background: Type 2 diabetes mellitus has well known deleterious effects on coronary artery disease (CAD). the role of milder hyperglycemic states such as prediabetes (PD) on CAD is debatable. Glycated hemoglobin (HbA1c) has recently been advocated as a diagnostic tool for diabetes mellitus (DM) and PD. This study aims to assess the cardiometabolic risk profile and coronary lesions of patients with PD undergoing coronary angiography identified either by fasting plasma glucose (FPG) or HbA1c levels.Methods: We studied 514 individuals without previously known glucose disturbances. Their glycemic status was assessed by FPG and HbA1c (HPLC) and classified according to ADA guidelines, using each parameter independently, as having normal glucose tolerance (N), PD, or DM. CAD was defined as stenosis greater than 50% in one major coronary vessel or branch. Framingham score was calculated.Results: Subjects with PD had a similar frequency of CAD compared do N individuals by both FPG (61 vs. 59.3%) and HbA1c (55.4 vs 61.2%) (p non-significant for linear-by-linear association). PD individuals identified by FPG had worse HOMA2B (mean [95% CI] 65.4 [60.9-69.9] vs. 76.6 [71.4-81.9]) and HOMA2-IR (1.10 [0.98-1.22] vs. 0.80 [0.72-0.89]) when compared to N controls. PD individuals identified by HbA1c had higher frequency of Framingham risk above 20% (25.4 vs 11.8%), arterial hypertension (87.8 vs 72.6%), and dyslipidemia (83.8 vs 72%) compared to N individuals. PD associated with an increased number of coronary lesions only when diagnosed by HbA1c (median [interquartile interval] 2 [0-4] PD versus 1 [0-3.75] N, p = 0.03 for trend).Conclusions: HbA1c was more effective than FPG in identifying individuals with PD associated with high cardiovascular risk profile in a sample of individuals undergoing coronary angiography. Universidade Federal de São Paulo, Endocrinol Unit, Diabet Ctr, São Paulo, Brazil Univ Estado Bahia, Dept Ciencias Vida, Colegiado Med, BR-41150000 Salvador, BA, Brazil Ctr Endocrinol Estado Bahia CEDEBA, Salvador, BA, Brazil Universidade Federal de São Paulo, Endocrinol Unit, Diabet Ctr, São Paulo, Brazil Web of Science

We read with interest the article by Wedrychowicz et al. (1). Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic forms of diabetes. Differential diagnosis with common forms such as type 1 and type 2 diabetes frequently poses a challenge to clinicians, especially in MODY forms caused by transcription factors. Glucokinase ( GCK )-MODY stands out in this regard for displaying a rather constant phenotype (2). We agree with the authors that the incidental association of obesity with GCK mutations can act as a diagnostic confounder. Moreover, coexistence of clinical features of both type 1 and type 2 diabetes is well described in …

Thirty-two Brazilian families with MODY phenotype were screened for GCK and HNF1A mutations. GCK mutations were found in 8 families, all patients with mild asymptomatic hyperglycaemia; 3 of them are novel: p.Asp365Asn, p.Gly81Asp and p.Val253Leu. Previously described mutations in HNF1A were found in 2 families.

OBJECTIVE: Allelic variations in the vitamin D receptor (VDR) gene were reported to modulate insulin secretion in response to glucose. VDR was investigated as a candidate gene for type 2 diabetes mellitus (T2DM). METHOD: Four single nucleotide polymorphisms (SNPs) in intron 8 (BsmI, Tru9I, ApaI) and exon 9 (TaqI) of the VDR gene were examined in 309 unrelated French subjects with T2DM and 143 controls. RESULTS: The distribution of alleles and genotypes of the four SNPs was similar in patients and controls. However, in patients whose age at diagnosis of diabetes was < or =45 years, homozygous subjects for the T-allele of the TaqI SNP had a higher body mass index (BMI) (31.7+/-6.7 kg/m2, P=0.0058) and an increased prevalence of obesity (81%, P=0.005) with respect to heterozygous subjects (27.9+/-5.0 kg/m2; 46%) or homozygous subjects for the t-allele (27.7+/-5.0 kg/m2; 52%). Similar results were observed for homozygous subjects for the b-allele of the BsmI SNP. Logistic regression analysis demonstrated that TT homozygosity was independently associated with obesity in these subjects (odds ratio, 4.64; 95% confidence interval (CI), 1.64-14.76; P=0.0056). CONCLUSION: VDR is not a major gene for T2DM in French Caucasians. However, polymorphisms in the VDR gene are associated with the susceptibility to obesity in subjects with early-onset T2DM. The pathophysiological mechanisms of these associations remain unexplained, but they could be related to a direct effect of vitamin D in adypocyte differentiation and metabolism, or to an indirect effect by modulation of insulin secretion.

O receptor de sulfoniluréia (SUR1) é uma subunidade dos canais de potássio ATP-dependentes expressos nas células beta pancreáticas, O papel deste receptor nos mecanismos de secreção da insulina foi bem demonstrado após a descrição de que mutações no seu gene codificador são responsáveis pela forma neonatal de hiperinsulinismo. O possível envolvimento de variantes deste gene na predisposição genética ao diabetes mellitus tipo 2 também tem sido estudado. Nesta revisão, discutimos os dados da literatura que abordam o envolvimento de alterações genéticas do SUR1 em patologias como o diabetes tipo 2, assim como nos mecanismos de secreção da insulina. The sulfonylurea receptor is a subunit of the ATP-sensitive potassium channel, which is expressed in the pancreatic beta cell. The central role of this receptor in glucose-induced insulin secretion was confirmed by description that mutations in this gene might result in hyperinsulinemic hypoglycemia of infancy. The possible role of SUR1 gene variants in the genetic susceptibility for type 2 diabetes mellitus has been studied. In this review, we discuss the results concerning the genetic variations in SUR1 gene with diseases as type 2 diabetes mellitus and also with the mechanisms of insulin secretion. Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Medicina Institut Cochin de Génétique Moléculaire INSERM U342 UNIFESP, EPM, Depto. de Medicina SciELO

Prevalence of MODY2 and MODY3 mutations has been assessed in 23 Brazilian families with MODY phenotype. Mutations in HNF-1alpha have been found in 3 families (13%) and 2 families (8.7%) had new glucokinase mutations. These genes do not explain the majority of MODY cases in Brazilian population.

Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Endocrinol Unit, Postgrad Fellowship Program Endocrinol, Porto Alegre, RS, Brazil

Background: Adiponectin is a major regulator of glucose and lipid homeostasis by its insulin sensitizer properties. Since decreased insulin sensitivity is linked to metabolic syndrome (MS), decreased adiponectin levels may be related to its development. The purpose of the study was to investigate the relationship between adiponectin levels and MS. Methods: Firstly, we cross-sectionally examined subjects with or without MS submitted to an oral glucose tolerance test at Hospital de Clínicas de Porto Alegre (n = 172). A replication analysis was performed in subjects (n = 422) undergoing cardiac angiography at Hospital São Paulo. Subchronic inflammation (US-CRP), coagulation marker (fibrinogen), insulin sensitivity and resistance (Matsuda ISI and HOMA-IR) were estimated. Plasma total and high molecular weight (HMW) adiponectin were measured. Results: Total and HMW adiponectin levels were lower in MS subjects (P < 0.05). Total adiponectin levels were lower in the presence of high waist circumference, low HDL-cholesterol and elevated triglyceride criteria in both samples and by elevated blood pressure and glucose criteria in Porto Alegre. HMW adiponectin levels were lower in the presence of low HDL-cholesterol, elevated triglycerides, and glucose criteria. Total adiponectin levels were positively related with HDL-cholesterol and ISI Matsuda, negatively related with waist circumference, glucose, triglycerides, HOMA-IR, and US-CRP and not related with blood pressure. While adjusting for sex and age, increased adiponectin levels remained associated with a reduced prevalence ratio for MS in both cohorts (P = 0.001). Conclusions: Adiponectin levels decreased with increasing number of MS criteria, and it is in part determined by its relationship with HDL, triglycerides and abdominal adiposity.

Mutations in the glucokinase gene (GCK) account for many cases of monogenic diabetes featuring maturity-onset diabetes of the young type 2 (MODY2). The clinical pattern of this form of hyperglycemia is rather stable, with a slight elevation in blood glucose, which is usually not progressive. Patients rarely require pharmacological interventions and microvascular complications related to diabetes are unusual. We describe the clinical follow-up of two cases of MODY2 with two different mutations in GCK gene, one in exon 7, p.Glu265Lys (c.793 G> A), which has been previously described, and a novel one, in exon 2, p.Ser69Stop (c. 206C> G). The clinical course of both cases shows similarity in metabolic control of this form of diabetes over the years. Arq Bras Endocrinol Metab. 2012;56(8):490-5 Mutações no gene da glicoquinase (GCK) são determinantes de uma forma de diabetes monogênico denominada de MODY2 (maturity-onset diabetes of the young, tipo 2). O padrão clínico dessa forma de distúrbio glicêmico é bastante estável, com hiperglicemia leve, geralmente não progressiva. Intervenções farmacológicas raramente são necessárias e complicações crônicas secundárias ao diabetes são infrequentes. Descrevemos o acompanhamento clínico de dois casos de MODY2 com duas mutações diferentes, uma no éxon 7, p.Glu265Lys (c.793 G>A) já descrita anteriormente, e outra inédita no éxon 2 p.Ser69Stop (c. 206C>G). A evolução clínica de ambos os casos demonstra uma semelhança no padrão metabólico dessa forma de diabetes ao longo dos anos. Arq Bras Endocrinol Metab. 2012;56(8):490-5

Objective To investigate the association of ADIPOQ variants, total and high molecular weight adiponectin (HMW) adiponectin levels with the prevalence of diabetes mellitus and coronary artery disease (CAD) diagnosed by coronary angiography in Brazilian subjects with high cardiovascular risk. Methods 603 subjects undergoing coronary angiography were studied in regard to their glycemic status and presence of CAD (lesions > 0%). We evaluated baseline concentrations of total and HMW adiponectin and three ADIPOQ variants: − 11391G > A (rs17300539), + 45T > G (rs2241766) and + 276G > T (rs1501299). Results The G-allele of rs2241766 was associated with higher levels of total and HMW adiponectin, and the A-allele of rs17300539 was associated with higher levels of HMW adiponectin. Lower levels of total and HMW adiponectin were independently associated with CAD. The G-allele of rs2241766 (OR 2.45, 95% C.I. 1.05–6.04, p = 0.04) and the G-allele of rs1501299 (OR 1.89, 95% C.I. 1.04–3.45, p = 0.03) were associated with CAD, and these associations were independent of circulating levels of adiponectin. Conclusions In Brazilian subjects with high cardiovascular risk, CAD was associated with lower total and HMW adiponectin levels. The rs2241766 and rs1501299 polymorphisms were associated with CAD. The rs2241766 variant was associated with total and HMW adiponectin levels, while rs17300539 was associated with HMW adiponectin levels.

The relative frequencies of the subtypes of maturity-onset diabetes of the young (MODY) were shown to vary greatly in studies from different populations (1–4). The Brazilian population has mixed ethnic background (African, Asian, European-Caucasian of several different countries of origin, and Indigenous), and little is known about the genetic determinants of diabetes in Brazilians. In this report, we describe the frequencies of the major MODY subtypes in a panel of 12 Brazilian families with autosomal-dominant early-onset type 2 diabetes (Fig. 1). A total of 32 family members were studied. The age at diagnosis of diabetes was

OBJECTIVE: To evaluate the effectiveness of a non-pharmacological intervention for weight gain management in severe mental disorders. METHOD: An open, multicentre interventional study was conducted in 93 mental health services. Patients concerned with weight gain were included in this study and received a 12-week 1-hour group intervention focused on nutrition counseling, lifestyle, physical activity and self-esteem. Weight, waist circumference and blood pressure were measured before and after the intervention. RESULTS: 1,071 patients were enrolled in the study, and 73.9% completed the 12-week intervention. Significant weight loss (Mean difference: 0.41, CI 95%: 0.18 to 0.64, p = 0.001) and a significant BMI reduction (Mean difference: 0.13, CI 95%: 0.04 to 0.22, p = 0.006) were observed. During the intervention 37 (4.4%) patients lost > 7% of their initial weight, 780 (92.5%) maintained their weight, and 26 (3.1%) of the patients had a meaningful weight gain (> 7%). There was a significant increase in the proportion of patients undertaking physical activity after the intervention (70.8%, p < 0.001). CONCLUSION: In this 3-month open study we found a small weight and waist reduction, and increased physical activity practice, suggesting a trend towards anthropometric profile improvement. However, further randomized-controlled trials are necessary to evaluate the efficacy and clinical relevance of this psychosocial intervention for weight gain.

A crescente elevação na prevalência do diabetes melito (DM) acarretou em um aumento de suas complicações crônicas, entre elas a nefropatia diabética (ND). Além da elevada prevalência, a ND está associada à importante morbidade e mortalidade, principalmente por doenças cardiovasculares. É notória a contribuição genética na patogênese da ND, em que, na presença de fatores ambientais propícios, aqueles indivíduos geneticamente predispostos desenvolverão a doença. Trata-se de uma doença com provável transmissão genética do tipo poligênica e complexa. Duas estratégias principais têm sido utilizadas na busca dos genes associados à ND: a avaliação de genes candidatos e, mais recentemente, a utilização de genoma wide scan. Grande empenho tem sido realizado para identificar os principais genes associados à ND, mas os resultados ainda são heterogêneos com diferentes genes apresentando um efeito pequeno em populações específicas. A identificação dos principais genes permitiria prever os indivíduos de maior risco para o desenvolvimento da ND, além de possibilitar um melhor entendimento fisiopatológico da doença. The increasing prevalence of diabetes mellitus has led to a growing number of chronic complications including diabetic nephropathy (DN). In addition to its high prevalence, DN is associated with high morbidity and mortality especially due to cardiovascular diseases. It is well established that genetic factors play a role in the pathogenesis of DN and genetically susceptible individuals can develop it after being exposed to environmental factors. DN is probably a complex, polygenic disease. Two main strategies have been used to identify genes associated to DN: analysis of candidate genes, and more recently genome-wide scan. Great efforts have been made to identify these main genes, but results are still inconsistent with different genes associated to a small effect in specific populations. The identification of the main genes would allow the detection of those individuals at high risk for DN and better understanding of its pathophysiology as well.

INTRODUÇÃO: Pacientes com esquizofrenia têm maior prevalência de obesidade em comparação à população geral. Esse fato está relacionado a uma alimentação inadequada, ao sedentarismo e ao uso de antipsicóticos. O aumento da obesidade associa-se a diversos distúrbios metabólicos, como o diabetes melito. As intervenções para prevenção e controle do ganho de peso são necessárias nessa população, em especial as intervenções não farmacológicas. OBJETIVO: Revisar os estudos sobre intervenções não farmacológicas para prevenção e controle do ganho de peso em pacientes com esquizofrenia. MÉTODOS: Foram encontrados oito estudos controlados e quatro não controlados sobre intervenções não farmacológicas. Foi feita uma revisãosobre a metodologia e os fatores positivos e limitações dos estudos. CONCLUSÕES: As intervenções não farmacológicas parecem ter um efeito importante em termos de prevenção e controle do ganho de peso e, portanto, devem ser incentivadas e adaptadas à realidade dos pacientes e serviços de saúde. INTRODUCTION: Schizophrenic patients have a higher prevalence of obesity than the general population. There are several factors implicated in weight gain, including poor dietary conditions, sedentary lifestyle and antipsychotic drugs use. Obesity is also associated with metabolic disturbances such as diabetes mellitus. Weight gain interventions are necessary in this population, especially non-pharmacological interventions. OBJECTIVE: To review the non-pharmacological interventions for weight gain management in patients with schizophrenia. METHODS: Eight clinical trials and four open-label studies using these interventions were found. The methodology, strength and limitations of the studies were reviewed. CONCLUSIONS: Non-pharmacological interventions seem to have an important effect on weight gain prevention and control, and should be encouraged and adapted to patients and in mental health institution's reality.

Background Type 2 diabetes mellitus (T2DM) is a genetically heterogeneous disease, hepatocyte nuclear factor-1 homeobox A (HNF1A) single-nucleotide polymorphisms (SNPs) playing a minor role in its pathogenesis. HNF1A is a frequent cause of monogenic diabetes, albeit with early-onset. Some uncommon subgroups like late-onset autosomal dominant diabetes mellitus (LOADDM) may present peculiar inheritance patterns with a stronger familial component. This study aims to investigate the relationship of HNF1A SNPs with cardiovascular risk factors in this group, as well as to characterize them in contrast with classical T2DM (CT2DM). Methods eighteen LOADDM (age at onset > 40 y.o.; diabetes in 3 contiguous generations, uniparental lineage) along with 48 CT2DM patients and 42 normoglycemic controls (N group) have been evaluated for cardiovascular risk factors and SNPs of HNF1A. Results LOADDM showed significantly higher frequencies of SNPs A98V (22.2% vs 2.1%, p = 0.02) and S487N (72.2% vs 43.8%, p = 0.049) of HNF1A compared to CT2DM. I27L did not show significant difference (66.7% vs 45.8%), but associated with lower risk of hypertriglyceridemia (OR 0.16, 95% CI 0.04–0.65, p = 0.01). "Protective effect" was independent from other well-known predictive risk factors for hypertriglyceridemia, such as waist circumference (OR 1.09 per 1 cm increase, p = 0.01) and HDL (OR 0.01 per 1 mmol/l, p = 0.005), after logistic regression. Conclusion Late onset autosomal dominant diabetes mellitus is clinically indistinguishable from classical type 2 diabetes individuals. However, LOADDM group is enriched for common HNF1A polymorphisms A98V and S487N. I27L showed "protective effect" upon hypertriglyceridemia in this sample of individuals, suggesting a role for HNF1A on diabetic individuals' lipid profile. These data contribute to the understanding of the complex interactions between genes, hyperglycemia and cardiovascular risk factors development in type 2 diabetes mellitus.

Schizophrenic patients have a higher prevalence of obesity than the general population. There are several factors implicated in weight gain, including poor dietary conditions, sedentary lifestyle and antipsychotic drugs use. Obesity is also associated with metabolic disturbances such as diabetes mellitus. Weight gain interventions are necessary in this population, especially non-pharmacological interventions.To review the non-pharmacological interventions for weight gain management in patients with schizophrenia.Eight clinical trials and four open-label studies using these interventions were found. The methodology, strength and limitations of the studies were reviewed.Non-pharmacological interventions seem to have an important effect on weight gain prevention and control, and should be encouraged and adapted to patients and in mental health institution's reality.

As mutações ativadoras, heterozigóticas do gene KCNJ11 (Kir6.2) são a causa mais freqüente de diabetes melito neonatal permanente (DMNP) e a terapêutica oral com sulfoniluréias tem sido bem sucedida em muitos destes casos. Relatamos o processo de substituição da insulinoterapia convencional para o tratamento oral com glibenclamida em uma paciente de 4 anos, portadora de DMNP e síndrome DEND devido a uma mutação C166Y no gene KCNJ11. A insulina NPH (0,2 U/kg/dia) foi substituída pela glibenclamida (1 mg/kg/dia e 1,5 mg/kg/dia) durante internação hospitalar. As respostas de glicose e peptídeo-C no teste de tolerância oral à glicose (OGTT), os níveis de hemoglobina glicada, o perfil de glicemias capilares de 8 pontos e a freqüência de hipoglicemias foram comparados antes e durante o tratamento com glibenclamida. Não houve melhora no controle glicêmico, nem no quadro neurológico. Concluímos que a mutação C166Y associa-se a uma forma de DMNP insensível à glibenclamida. Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (PNDM) and several cases have been successfully treated with oral sulfonylureas. We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from subcutaneous NPH insulin (0.2 units/kg/d) to oral glibenclamide (1 mg/kg/d and 1.5 mg/kg/d) was performed. Glucose and C-peptide responses stimulated by oral glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were analyzed, before and during treatment with glibenclamide. Neither diabetes control nor neurological improvements were observed. We concluded that C166Y mutation was associated with a form of PNDM insensitive to glibenclamide. Universidade de São Paulo Faculdade de Medicina Hospital das Clínicas Fleury Medicina e Saúde Ninewells Hospital & Medical School Biomedical Research Institute Royal Devon and Exeter Hospital Centre for Molecular Genetics at the Peninsula Medical School Diabetes Research department Universidade Federal de São Paulo (UNIFESP) Laboratório de Endocrinologia Molecular UNIFESP, Laboratório de Endocrinologia Molecular SciELO

OBJECTIVE-Uncoupling protein 2 (UCP2) is a physiological downregulator of reactive oxygen species generation and plays an antiatherogenic role in the vascular wall. A common variant in the UCP2 promoter (-866G>A) modulates mRNA expression, with increased expression associated with the A allele. We investigated association of this variant with coronary artery disease (CAD) in two cohorts of type 2 diabetic subjects.RESEARCH DESIGN and METHODS-We studied 3,122 subjects from the 6-year prospective Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events, and Ramipril (DIABHYCAR) Study (14.9% of CAD incidence at follow-up). An independent, hospital-based cohort of 335 men, 52% of whom had CAD, was also studied.RESULTS-We observed an inverse association of the A allele with incident cases of CAD in a dominant model (hazard risk 0.88 [95% CI 0.80-0.96]; P = 0.006). Similar results were observed for baseline cases of CAD. Stratification by sex confirmed an allelic association with CAD in men, whereas no association was observed in women. All CAD phenotypes considered-myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), and sudden death-contributed significantly to the association. Results were replicated in a cross-sectional study of an independent cohort (odds ratio 0.47 [95% CI 0.25-0.89]; P = 0.02 for a recessive model).CONCLUSIONS-The A allele of the -866G>A variant of UCP2 was associated with reduced risk of CAD in men with type 2 diabetes in a 6-year prospective study. Decreased risk of myocardial infarction, angina pectoris, CABG, and sudden death contributed individually and significantly to the reduction of CAD risk. This association was independent of other common CAD risk factors. INSERM, Fac Med Xavier Bichat, U695, F-75018 Paris, France Cochin Hosp, AP HP, Dept Immunol & Diabetol, Paris, France Univ São Paulo, Lab Cellular & Mol Endocrinol, São Paulo, Brazil Universidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, Brazil Fed Fac Fdn Med Sci Porto Alegre, Post Grad Program Med Sci, Porto Alegre, RS, Brazil Hop La Pitie Salpetriere, Dept Cardiol, AP HP, Paris, France Univ Paris 07, Paris, France Univ Paris 05, Paris, France Universidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, Brazil Web of Science

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) represent intermediate states between normal fasting glucose (NFG) or normal glucose tolerance (NGT), respectively, and diabetes (1). The regulation of fasting and glucose concentrations after an oral glucose load is dependent on different physiological mechanisms (2), and current evidence suggests that IFG and IGT have different pathophysiologies (3,4). Measurement of fasting plasma glucose (FPG) is the most frequently used screening test for diabetes. However, the oral glucose tolerance test (OGTT) might be a preferable test because FPG underestimates the severity of glucose intolerance (5,6) and because IFG and IGT define two distinct populations with only partial overlap (5,7,8). The present study was undertaken to compare insulin sensitivity and insulin secretion profiles associated with different stages of hyperglycemia as assessed by FPG only or by FPG and 2-h plasma glucose during an OGTT. We analyzed data from 900 subjects without previously known diabetes who underwent an OGTT for diagnostic purposes at Fleury Institute, Sao Paulo, Brazil. A double-glycemic status was determined for each subject. A first set was based on FPG only as follows: NFG (FPG …

Universidade Federal de Sao Paulo (UNIFESP) Escola Paulista de Medicina Laboratory of Molecular Endocrinology