ABSTRACT Objective: To investigate the association of the rs741301 polymorphism in the ELMO1 gene with diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Materials and methods: This study analyzed 350 patients with T2DM and DR (cases) and 234 patients with T2DM without this complication but with more than 10 years of diabetes mellitus (DM) (controls). DR was diagnosed by indirect fundoscopy. Genotyping was performed by allelic discrimination real-time PCR. Results: The frequency of the C/C genotype of the rs741301 polymorphism in the ELMO1 gene was 26.9% in cases and 17.9% in controls (P = 0.011). After adjustment for covariables, the C/C genotype was associated with an increased risk of DR [odds ratio (OR) = 1.805, 95%CI 1.101–2.961; P = 0.019]. This association remained significant in dominant and additive inheritance models after adjustment for the same variables [OR = 1.597, 95%CI 1.089-2.343; P = 0.017; and OR = 1.818, 95%CI 1.099-3.007; P = 0.020]. Conclusion: This study demonstrated an association between the presence of the C allele of the ELMO1 rs741301 polymorphism and an increased risk of DR in patients with T2DM from Southern Brazil. Objective rs rs74130 ELMO (DR T2DM. TDM . T DM (T2DM) methods 35 (cases 23 1 (DM controls. (controls) fundoscopy realtime real time PCR Results CC 269 26 9 26.9 179 17 17.9 0.011. 0011 0.011 0 011 0.011) covariables odds (OR 1805 805 1.805 95CI CI 95 1.101–2.961 11012961 101 961 0.019. 0019 0.019 019 0.019] 1597 597 1.597 1.0892.343 10892343 1.089 2.343 089 343 1.089-2.343 0.017 0017 017 1818 818 1.818 1.0993.007 10993007 1.099 3.007 099 3 007 1.099-3.007 0.020. 0020 0.020 020 0.020] Conclusion Brazil rs7413 (T2DM (controls 26. 17. 001 0.01 01 180 80 1.80 1.101–2.96 1101296 96 159 59 1.59 0892 1.0892.34 1089234 1089 1.08 2343 2.34 08 34 1.089-2.34 181 81 1.81 0993 1.0993.00 1099300 1099 1.09 3007 3.00 09 00 1.099-3.00 002 0.02 02 rs741 0.0 18 8 1.8 1.101–2.9 110129 15 5 1.5 1.0892.3 108923 108 1.0 2.3 1.089-2.3 1.0993.0 109930 109 300 3.0 1.099-3.0 rs74 0. 1. 1.101–2. 11012 1.0892. 10892 2. 1.089-2. 1.0993. 10993 30 3. 1.099-3. rs7 1.101–2 1101 1.0892 1.089-2 1.0993 1.099-3 1.101– 110 1.089- 1.099- 1.101 11 1.10 1.1

ABSTRACT Objective: To investigate the association between the long noncoding RNAs (lncRNAs) maternally expressed gene 3 (MEG3) rs7158663 polymorphism and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Subjects and methods: The study included 628 patients with T2DM and DR ("case group," including 283 with proliferative DR [PDR] and 345 with nonproliferative DR [NPDR]), and 381 patients with T2DM but no DR ("control group"). The diagnosis of DR was established using indirect ophthalmoscopy. The rs7158663 A/G polymorphism was genotyped using real-time polymerase chain reaction (PCR) with TaqMan probes. Results: Patients with DR, compared with those without DR, had lower frequencies of both the G/G genotype (17.5% and 23.6%, respectively, p = 0.044) and the G allele (p = 0.017). When only patients with PDR were compared with controls, the G/G genotype was associated with increased protection against PDR after adjustment (odds ratio 0.551, 95% confidence interval 0.314–0.966, p = 0.038). This association also remained in the dominant (p = 0.036) and additive (p = 0.031) genetic models. Conclusion: This study reveals, for the first time, that the G/G genotype of the lncRNA MEG3 rs7158663 single-nucleotide polymorphism is associated with a protective effect against advanced-stage DR in patients with T2DM. Additional studies are warranted to validate this finding. Objective lncRNAs (lncRNAs MEG (MEG3 rs rs715866 (DR TDM . T DM (T2DM) methods 62 case group, group 28 [PDR 34 NPDR, NPDR , [NPDR]) 38 control group. group") ophthalmoscopy AG A realtime real time PCR (PCR probes Results GG 17.5% 175 17 5 (17.5 236 23 6 23.6% respectively 0.044 0044 0 044 0.017. 0017 0.017 017 0.017) controls odds 0551 551 0.551 95 03140966 314 966 0.314–0.966 0.038. 0038 0.038 038 0.038) 0.036 0036 036 0.031 0031 031 models Conclusion reveals singlenucleotide single nucleotide advancedstage advanced stage finding (MEG rs71586 (T2DM [NPDR] group" 17.5 1 (17. 23.6 0.04 004 04 001 0.01 01 055 55 0.55 9 0314096 31 96 0.314–0.96 003 0.03 03 rs7158 [NPDR 17. (17 23. 0.0 00 05 0.5 031409 0.314–0.9 rs715 (1 0. 03140 0.314–0. rs71 ( 0314 0.314–0 rs7 0.314– 0.314 0.31 0.3

Abstract Long non-coding RNAs (lncRNAs) are RNAs with >200 nucleotides that are unable to encode proteins and are involved in gene expression regulation. LncRNAs have a key role in many physiological and pathological processes and, consequently, they have been associated with several human diseases, including diabetes chronic complications, such as diabetes kidney disease (DKD). In this context, some studies have identified the dysregulation of the lncRNAs MALAT1 and TUG1 in patients with DKD; nevertheless, available data are still contradictory. Thus, the objective of this study was to compare MALAT1 and TUG1 expressions in urine of patients with type 1 diabetes mellitus (T1DM) categorized according to DKD presence. This study comprised 18 T1DM patients with DKD (cases) and 9 long-duration T1DM patients without DKD (controls). MALAT1 and TUG1 were analyzed using qPCR. Bioinformatics analyses were done to identify both lncRNA target genes and the signaling pathways under their regulation. The lncRNA MALAT1 was upregulated in urine of T1DM patients with DKD vs. T1DM controls (P = 0.007). The expression of lncRNA TUG1 did not differ between groups (P = 0.815). Bioinformatics analysis showed these two lncRNAs take part in metabolism-related pathways. The present study shows that the lncRNA MALAT1 is upregulated in T1DM patients presenting DKD. noncoding non coding (lncRNAs 200 >20 regulation consequently diseases complications . (DKD) context MALAT TUG nevertheless contradictory Thus TDM T DM (T1DM presence cases (cases longduration long duration controls. (controls) qPCR vs P 0.007. 0007 0.007 0 007 0.007) 0.815. 0815 0.815 815 0.815) metabolismrelated metabolism related 20 >2 (DKD (controls 000 0.00 00 081 0.81 81 2 > 0.0 08 0.8 8 0.

ABSTRACT Objective: The objective of this study was to investigate the association between SNPs in the TIE2 and ANGPT-1 genes and diabetic retinopathy (DR). Subjects and methods: This study comprised 603 patients with type 2 diabetes mellitus (T2DM) and DR (cases) and 388 patients with T2DM for more than 10 years and without DR (controls). The TIE2 rs639225 (A/G) and rs638203 (A/G) SNPs and the ANGPT-1 rs4324901 (G/T) and rs2507800 (T/A) SNPs were genotyped by real-time PCR using TaqMan MGB probes. Results: The G/G genotype of the rs639225/TIE2, the G/G genotype of the rs638203/TIE2 and the T allele of the rs4324901/ANGPT-1 SNPs were associated with protection against DR after adjustment for age, glycated hemoglobin, gender, and presence of hypertension (P = 0.042, P = 0.003, and P = 0.028, respectively). No association was found between the rs2507800/ANGPT-1 SNP and DR. Conclusion: We demonstrated, for the first time, the association of TIE2 rs638203 and rsrs939225 SNPs and ANGPT-1 rs4324901 SNP with protection against DR in a Brazilian population. Objective TIE ANGPT1 ANGPT 1 ANGPT- . (DR) methods 60 TDM DM (T2DM cases (cases 38 controls. controls (controls) rs rs63922 A/G AG A G (A/G rs63820 rs432490 G/T GT (G/T rs250780 T/A TA (T/A realtime real time probes Results GG rs639225TIE2 rsTIE rs639225/TIE2 rs638203TIE2 rs638203/TIE rs4324901/ANGPT1 rs4324901ANGPT1 rsANGPT rs4324901/ANGPT rs4324901/ANGPT- age hemoglobin gender 0042 0 042 0.042 0003 003 0.003 0028 028 0.028 respectively. respectively respectively) rs2507800/ANGPT1 rs2507800ANGPT1 rs2507800/ANGPT rs2507800/ANGPT- Conclusion demonstrated rsrs rsrs93922 population (DR 6 3 (controls rs6392 rs6382 rs43249 rs25078 rs639225TIE rs639225/TIE rs638203TIE rs4324901ANGPT 004 04 0.04 000 00 0.00 002 02 0.02 rs2507800ANGPT rsrs9392 rs639 rs638 rs4324 rs2507 0.0 rsrs939 rs63 rs432 rs250 0. rsrs93 rs6 rs43 rs25 rsrs9 rs4 rs2

Abstract The transforming growth factor beta 1 (TGFB1) is a pro-inflammatory cytokine that plays a key role in the mechanisms of angiogenesis and breakdown of the blood-retina barrier, which are implicated in the pathogenesis of diabetic retinopathy (DR). Polymorphisms in the TGFB1 gene have been associated with DR; however, results are still contradictory. Therefore, the aim of this study was to investigate the potential association between two TGFB1 polymorphisms and DR. This study included 992 patients with diabetes mellitus (DM): 546 patients with DR (cases) and 446 patients without DR and with ≥10 years of DM (controls). The TGFB1 rs1800469 and rs1800470 polymorphisms were genotyped by real-time PCR. Frequency of rs1800469 T/T genotype was higher in controls compared to DR cases (18.3% vs. 12.7%, P= 0.022). This genotype remained associated with protection for DR, adjusting for covariables (OR= 0.604; 95% CI 0.395 - 0.923; P= 0.020, recessive model). The rs1800470 C/C genotype was observed in 25.4% of the controls and 18.0% of the cases (P= 0.015); thus, being associated with protection against DR under the recessive model (OR= 0.589; 95% CI 0.405 - 0.857; P= 0.006), adjusting for covariables. In conclusion, the TGFB1 rs1800469 and rs1800470 polymorphisms are associated with protection against DR in DM patients from Southern Brazil. TGFB (TGFB1 proinflammatory pro inflammatory bloodretina blood retina barrier . (DR) however contradictory Therefore 99 (DM) 54 (cases 44 10 ≥1 controls. (controls) rs rs180046 rs180047 realtime real time PCR TT T 18.3% 183 18 3 (18.3 vs 127 12 7 12.7% P 0.022. 0022 0.022 0 022 0.022) OR= OR (OR 0.604 0604 604 95 0395 395 0.39 0.923 0923 923 0020 020 0.020 model. model) CC C 254 25 4 25.4 180 18.0 (P 0.015 0015 015 0.015) thus 0.589 0589 589 0405 405 0.40 0.857 0857 857 0.006, 0006 0.006 , 006 0.006) conclusion Brazil (TGFB (DR 9 (DM 5 ≥ (controls rs18004 18.3 (18. 12.7 002 0.02 02 0.60 060 60 039 39 0.3 0.92 092 92 2 25. 18. 0.01 001 01 0.58 058 58 040 40 0.4 0.85 085 85 000 0.00 00 rs1800 (18 12. 0.0 0.6 06 6 03 0. 0.9 09 0.5 05 04 0.8 08 8 rs180 (1 rs18 ( rs1

ABSTRACT Objective: The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. Materials and methods: The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years’ duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Results: Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Conclusion: Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.

ABSTRACT Objective: As studies have reported the involvement of angiopoietin-2 (ANGPT-2) in the pathogenesis of diabetic retinopathy (DR), the aim of this study was to investigate the association between the ANGPT-2 rs2442598 polymorphism and DR. Materials and methods: This case-control study comprised 107 patients with type 1 diabetes mellitus (T1DM) and DR (cases) and 129 patients with T1DM without DR (controls) and with ≥ 10 years of DM. The ANGPT-2 rs2442598 (G/A) polymorphism was genotyped by real-time PCR using TaqMan MGB probes. Results: Genotype distributions of this polymorphism were consistent with the Hardy-Weinberg equilibrium. The frequency of the rs2442598 A allele was higher in cases compared to controls (p = 0.011). Moreover, the A/A genotype was more frequent in cases than in controls (p = 0.017) and was associated with risk for DR after adjustments for duration of DM, HbA1c, triglycerides, estimated glomerular filtration rate, and hypertension (odds ratio [OR] = 5.19, 95% confidence interval [CI] 1.21-22.27). This association was maintained under recessive (OR = 4.78, 95% CI 1.14-19.99) and additive (OR = 6.861, 95% CI 1.45-32.38) inheritance models. Conclusion: Our data demonstrated, for the first time, an association between the ANGPT-2 rs2442598 A allele and risk for DR in T1DM patients from southern Brazil. Additional studies are necessary to replicate this association in other populations.

Type 1 diabetes mellitus (T1DM) is a chronic, progressive autoimmune disease characterized by metabolic decompensation often leading to dehydration and ketoacidosis. Viral agents seem to play an important role in triggering the autoimmune destruction that leads to the development of T1DM. Among several viral strains investigated so far, the enterovirus family has been consistently associated with the onset of T1DM in humans. One of the mediators of viral damage is the double-stranded RNA (dsRNA) generated during replication and transcription of viral RNA and DNA. The Toll-like receptor 3 (TLR3) gene codes for an endoplasmic receptor of the pattern-recognition receptors (PRRs) family that recognizes dsRNA, plays an important role in the innate immune response triggered by viral infection. Binding of dsRNA to the TLR3 triggers the release of proinflammatory cytokines, such as interferons, which exhibit potent antiviral action; thus, protecting uninfected cells and inducing apoptosis of infected ones. Therefore, the TLR3 gene is a good candidate for the development of T1DM. Within this context, the objective of the present review was to address the role of the TLR3 gene in the development of T1DM. Arch Endocrinol Metab. 2015;59(1):4-12

Objetivo: Avaliar a associação do polimorfismo rs1893217 no gene PTPN2 com DM1 e/ou suas características clínicas e laboratoriais em uma população de brancos do Sul do Brasil. Sujeitos e métodos: Quatrocentos e oitenta e seis pacientes com DM1 e 484 indivíduos não diabéticos foram incluídos no estudo. A genotipagem do PTPN2 rs1893217 foi realizada por PCR em tempo real. Resultados: As frequências genotípicas não diferiram entre os pacientes com DM1 e indivíduos não diabéticos (p = 0,265). O alelo C foi observado em 14,5% da amostra com DM1 e 12,2% no grupo de não diabéticos (p = 0,152). Além disso, as frequências dessa variante não diferiram estatisticamente entre os pacientes com DM1 e indivíduos não diabéticos considerando-se os modelos de herança recessivo, dominante ou aditivo. As características clínicas e laboratoriais dos pacientes com DM1 também não diferiram significativamente entre os três genótipos do polimorfismo rs1893217. Conclusão: O polimorfismo rs1893217 do gene PTPN2 não está associado com DM1 em brancos do Sul do Brasil.

Objective: To evaluate the association of the PTPN2 rs1893217 polymorphism with T1DM and/or its clinical and laboratory characteristics in a Caucasian population from Southern Brazil. Subjects and methods: Four hundred and eighty six patients with T1DM and 484 non-diabetic subjects were included in the study. Genotyping of the PTPN2 rs1893217 was performed by real-time PCR. Results: Genotype frequencies did not differ between T1DM patients and non-diabetic subjects (P = 0.265). The C allele was observed in 14.5% of the T1DM sample and 12.2% of the non-diabetic group (P = 0.152). Moreover, the frequencies of this variant did not differ statistically between T1DM patients and non-diabetic subjects when assuming recessive, dominant, or additive inheritance models. The clinical and laboratory characteristics of T1DM patients did not differ significantly among the three genotypes of the rs1893217 polymorphism, either. Conclusion: The PTPN2 rs1893217 polymorphism is not significantly associated with T1DM in Caucasian subjects from Southern Brazil.

Está bem estabelecido que fatores genéticos têm papel importante no desenvolvimento do diabetes melito tipo 2 (DM2) e obesidade e que indivíduos suscetíveis geneticamente podem desenvolver essas doenças metabólicas após exposição a fatores de risco ambientais. Assim, grandes esforços têm sido feitos para a identificação de genes associados ao DM2 e/ou à obesidade. A proteína desacopladora 1 (UCP1) é principalmente expressa no tecido adiposo marrom e atua na termogênese, regulação do gasto energético e proteção contra o estresse oxidativo, mecanismos associados tanto à patogênese do DM2 como à obesidade. Portanto, UCP1 é um gene candidato para o desenvolvimento dessas doenças. De fato, diversos estudos relataram que os polimorfismos -3826A/G, -1766A/G e -112A/C na região promotora, Ala64Thr no éxon 2 e Met299Leu no éxon 5 do gene UCP1 estão possivelmente associados à obesidade e/ou ao DM2. Entretanto, os resultados são ainda controversos em diferentes populações. Então, o objetivo deste estudo foi revisar o papel da UCP1 no desenvolvimento dessas doenças metabólicas.

It is well established that genetic factors play an important role in the development of both type 2 diabetes mellitus (DM2) and obesity, and that genetically susceptible subjects can develop these metabolic diseases after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2 and/or obesity. Uncoupling protein 1 (UCP1) is mainly expressed in brown adipose tissue, and acts in thermogenesis, regulation of energy expenditure, and protection against oxidative stress. All these mechanisms are associated with the pathogenesis of DM2 and obesity. Hence, UCP1 is a candidate gene for the development of these disorders. Indeed, several studies have reported that polymorphisms -3826A/G, -1766A/G and -112A/C in the promoter region, Ala64Thr in exon 2 and Met299Leu in exon 5 of UCP1 gene are possibly associated with obesity and/or DM2. However, results are still controversial in different populations. Thus, the aim of this study was to review the role of UCP1 in the development of these metabolic diseases.

Está bem estabelecido que fatores genéticos têm papel importante no desenvolvimento do diabetes melito tipo 2 (DM2) bem como de suas complicações crônicas e que indivíduos geneticamente suscetíveis podem desenvolver essa doença após exposição a fatores de risco ambientais. Assim, grandes esforços têm sido feitos para a identificação de genes associados ao DM2. A proteína desacopladora 2 (UCP2) é expressa em diversos tecidos e atua na proteção contra o estresse oxidativo, na regulação negativa da secreção de insulina pelas células-beta e no metabolismo dos ácidos graxos, mecanismos associados tanto à patogênese do DM2 como a suas complicações crônicas. Portanto, o gene UCP2 é um gene candidato para o desenvolvimento dessas doenças. De fato, diversos estudos têm relatado que três polimorfismos comuns no gene UCP2 estão possivelmente associados ao DM2 e/ou à obesidade. Apenas poucos estudos investigaram esses polimorfismos em relação às complicações crônicas do diabetes, obtendo resultados pouco conclusivos.

It is well established that genetic factors play an important role in the development of type 2 diabetes mellitus (DM2) and its chronic complications, and that genetically susceptible subjects can develop the disease after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2. Uncoupling protein 2 (UCP2) is expressed in several tissues, and acts in the protection against oxidative stress; in the negative regulation of insulin secretion by beta cells, and in fatty acid metabolism. All these mechanisms are associated with DM2 pathogenesis and its chronic complications. Therefore, UCP2 is a candidate gene for the development of these disorders. Indeed, several studies have reported that three common polymorphisms in UCP2 gene are possibly associated with DM2 and/or obesity. Only a few studies investigated these polymorphisms in relation to chronic complications of diabetes, with inconclusive results.

A retinopatia diabética (RD) é uma complicação microvascular do diabetes melito, sendo importante causa de cegueira adquirida. Fatores angiogênicos, como o vascular endothelial growth factor (VEGF), estão envolvidos na patogênese da RD. O VEGF-A é uma citocina potente e multifuncional que atua por meio dos receptores VEGFR-1 e VEGFR-2 expressos no endotélio vascular causando aumento da permeabilidade vascular e estímulo à neovascularização em processos fisiológicos e patológicos. O VEGFR-2 é o principal mediador mitogênico, angiogênico e do aumento da permeabilidade vascular. Alguns polimorfismos do VEGF têm sido estudados na suscetibilidade e risco de progressão da RD. Importante associação entre o polimorfismo 634C/G e a presença de RD é relatada principalmente em relação ao alelo C. A homozigose CC estaria relacionada à RD proliferativa (RDP) e a níveis sérico e vítreo aumentados de VEGF, sugerindo que a presença do alelo C seja um fator de risco independente para RD. Os conhecimentos sobre o VEGF levaram ao desenvolvimento de agentes antiVEGF com o objetivo de inibir a neovascularização patológica e são uma realidade na prática médica do tratamento da RD.

Diabetic retinopathy (DR), a DM microvascular complication, is the leading cause of blindness. Angiogenic factors such as vascular endothelial growth factor (VEGF) are involved in the pathogenesis of DR. VEGF-A is a potent, multifunctional cytokine that acts through the receptors VEGFR-1 and VEGFR-2 expressed in the vascular endothelium and causing increased vascular permeability and neovascularization stimulation in both physiological and pathological processes. The expression of VEGFR-1 is upregulated by hypoxia and is less responsive to VEGF compared to VEGFR-2 which is the main mediator mitogenic, angiogenic, and increased vascular permeability. VEGF polymorphisms have been studied in DR susceptibility and progression. Significant association between the polymorphism 634C / G and the presence of RD is reported mainly in relation to allele C. The homozygous CC is associated to proliferative RD and to increased vitreous and serum levels of VEGF suggesting that the presence of the C allele is an independent risk factor for RD. The knowledgement of VEGF lead to the development of anti-VEGF drugs (pegaptanib, ranibizumab and bevacizumab) aiming to prevent pathological neovascularization. The anti-VEGF therapy is a reality in practice medical treatment of DR.

O maturity-onset diabetes of the young (MODY) é uma forma monogênica de diabetes melito caracterizada por herança autossômica dominante, de instalação precoce, como disfunção da célula beta pancreática. Mutações heterozigotas em pelo menos sete genes causam MODY. No presente estudo, investigamos a prevalência relativa das mutações da GCK (glucokinase) e HNF1α (hepatocyte nuclear factor 1α), as causas mais freqüentes de MODY, em 13 famílias sul-brasileiras com múltiplos casos de diabetes consistentes com MODY. Variantes heterozigotas nos genes da GCK e HNF1α foram observadas, respectivamente, em uma (7,7%) e em seis (46,2%) famílias. As seis variantes do HNF1α provavelmente causaram o diabetes nas famílias nas quais foram observadas. No entanto, não se pode afirmar que a variante GCK Gly117Ser encontrada em uma família seja a mutação causal. Em conclusão, confirmamos que, em uma população do sul do Brasil, as mutações HNF1α são uma causa comum de diabetes monogênico em adultos selecionados com critérios clínicos diagnósticos estritos.

Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset, and pancreatic beta cell dysfunction. Heterozygous mutations in at least seven genes can cause MODY. In the present study we investigated the relative prevalence of GCK (glucokinase) and HNF1α (hepatocyte nuclear factor 1α) mutations, the more frequent causes of MODY, in 13 South-Brazilian families with multiple cases of diabetes consistent with MODY. Heterozygous variants in GCK and HNF1α genes were observed respectively in one (7.7%), and six (46.2%) families. The six HNF1α variants are likely to cause diabetes in the families where they were observed. However, we could not ascertain whether the GCK Gly117Ser variant found in one family is a causal mutation. In conclusion, we have confirmed in a South-Brazilian population that HNF1α mutations are a common cause of monogenic diabetes in adults selected with strict clinical diagnostic criteria.

OBJETIVO: Avaliar a prevalência de catarata e seus fatores de risco em uma população portadora de diabetes mellitus tipo 1 (DM1). MÉTODOS: Estudo de casos e controles de um banco de dados de 181 pacientes (362 olhos) com diagnóstico de diabetes mellitus tipo 1. Os pacientes foram classificados como casos quando apresentavam diagnóstico de catarata. As variáveis estudadas foram a presença ou não de retinopatia diabética, tratamento com panfotocoagulação, presença de hipertensão arterial sistêmica e neuropatia periférica, colesterol total, triglicerídios séricos, HDL, LDL, índice de massa corporal, creatinina sérica, albuminúria, hemoglobina glicosilada e glicemia de jejum. RESULTADOS: A prevalência de catarata foi de 19,9%. Na análise univariada foi encontrada associação estatisticamente significativa (p<0,005) entre a presença de catarata e retinopatia diabética, neuropatia periférica, creatinina sérica elevada, panfotocoagulação e hipertensão arterial. Após a análise de regressão logística a variável que permaneceu com associação estatisticamente significativa foi a presença de retinopatia diabética. CONCLUSÃO: A prevalência de catarata foi de 19,9%, sendo a presença e a gravidade da retinopatia diabética os principais fatores de risco para desenvolvimento desta.

PURPOSE: To evaluate the prevalence of cataract and associated risk factors in a diabetic type 1 population. METHODS: 181 patients (362 eyes) were evaluated in a case-control study. Cases were classified when cataract was present at the time of the examination. The studied outcomes were the presence of diabetic retinopathy, retinal panphotocoagulation, high blood pressure, peripheral neuropathy, total cholesterol levels, triglyceride levels, HDL, LDL, body mass index, creatinine levels, albuminuria, glycosylated hemoglobin and glycemia levels. RESULTS: Cataract was present in 19.9% of the studied patients. The association of the presence of cataract and diabetic retinopathy, peripheral neuropathy, elevated levels of creatinine, panphotocoagulation and high blood pressure were statistically significant (univariate analysis). After the logistic regression analysis the presence of cataract was significantly associated with the presence of diabetic retinopathy. CONCLUSION: The prevalence of cataract was 19.9% and the presence and severity of the diabetic retinopathy were the main risk factors for its development.

A nefropatia diabética (ND) é uma importante complicação crônica do diabetes melito (DM), sendo uma das principais causas dos novos casos de diálise e está associada ao aumento da mortalidade. Os principais fatores de risco são a hiperglicemia, a hipertensão arterial sistêmica (HAS), a dislipidemia e a susceptibilidade genética. O sistema renina-angiotensina (SRA) tem papel importante na gênese e na progressão da ND e existem evidências de interação entre este sistema e as endotelinas. As endotelinas são peptídeos com potente ação vasoconstritora que atuam modulando o tono vasomotor, a proliferação celular e a produção hormonal. Estes peptídeos agem por meio de dois receptores (ET-A e ET-B), que são expressos nas células endoteliais e no músculo liso vascular. A ativação destes receptores nas células renais leva à complexa cascata de alterações, resultando proliferação e hipertrofia das células mesangiais, vasoconstrição das arteríolas aferentes e eferentes e acúmulo de matriz extracelular. Essas alterações hemodinâmicas renais estão associadas com o aparecimento e a progressão da doença renal no DM. Níveis plasmáticos elevados de endotelina-1 (ET-1) têm sido relatados em pacientes com DM e há algumas evidências que sugerem que o aumento da produção de ET-1 poderia levar a dano glomerular. O uso de drogas antagonistas do receptor da ET-1 em situações de DM experimental tem mostrado propriedades nefroprotetoras, reforçando a importância deste sistema na ND.

Diabetic Nephropathy (DN) is a major chronic complication of diabetes mellitus (DM), and one of the main causes of new cases for dialysis, being associated with increasing mortality. The main risk factors for DN are hypertension, hyperglycemia, dyslipidemia, and genetic susceptibility. The renin-angiotensin system (RAS) plays an important role in genesis and progression of DN and there is evidence of an interrelationship between this system and the endothelins. Endothelins are powerful vasoconstrictor peptides and act as modulators of vasomotor tone, cell proliferation, and hormone production. These peptides act through two types of receptors (ET-A and ET-B) and are expressed on endothelial cells and vascular smooth-muscle cells. Activation of this receptor in renal cells leads to a complex signaling cascade resultanting in stimulation of mesangial cell hypertrophy, proliferation, contraction, and extracellular matrix accumulation. These hemodinamic renal alterations are associated with the onset and progress of renal disease in DM. Elevated endothelin-1 (ET-1) levels have been reported in patients with DM. There is evidence suggesting that an increase in the production of ET-1 leads to glomerular damage. The use of ET receptor antagonists has been reported as renoprotective, correcting the early hemodynamic abnormalities in experimental DM, reinforcing the importance of this system in DN.