ABSTRACT Objective Sex differences in lipid metabolism associated with prevalent small dense (S-) low-density lipoprotein (LDL) cholesterol particles are not elucidated. An LDL to apolipoprotein B (ApoB) ratio < 1.2 can estimate how prevalent S-LDL particles are and, thus, reflect cardiovascular risk. The aim of this study was to evaluate the sex distribution of LDL/ApoB ratio among patients with type 2 diabetes (DM) and to assess, in both sexes, the correlations between key lipid parameters and LDL/ApoB < 1.2. Subjects and methods The study included 190 Caucasian participants (mean age 51.8 ± 6.4 years) with DM (DM group) or without DM (control group) divided into subgroups according to sex. The participants were examined for levels of several lipid parameters, selected lipid-related oxidative stress markers, and estimated S-LDL prevalence. Results An LDL/ApoB < 1.2 (p < 0.05) was observed in 67% of male and female patients with DM. Although triglyceride levels did not differ between men and women, women had higher levels of total cholesterol (p < 0.05) and LDL cholesterol (p < 0.01) than men. Among women with LDL/ApoB < 1.2, strong correlations were observed between values of lipid hydroperoxides (LOOH) and atherogenic index of plasma (p < 0.005) and between levels of triglycerides and LOOH (p < 0.005) and ApoB (p < 0.0001). Conclusions The findings indicate that women with LDL/ApoB < 1.2 tend to have a higher cardiovascular risk than men. Additionally, LDL/ApoB < 1.2 can be a surrogate marker for estimating the S-LDL prevalence in individuals with potentially increased cardiovascular risk. S (S- lowdensity low density (LDL elucidated (ApoB 12 1 1. SLDL thus LDLApoB assess sexes 19 mean 518 51 8 51. 64 6 4 6. years group control lipidrelated related markers p 0.05 005 0 05 67 0.01 001 01 (LOOH 0.005 0005 0.0001. 00001 0.0001 . 0001 0.0001) Additionally (S 5 0.0 00 0.00 000 0000 0.000 0.

ABSTRACT Objective We examined the accuracy of novel anthropometric indices in predicting the progression of prediabetes to diabetes. Subjects and methods This study was performed on the pre-diabetic sub-population from Isfahan Cohort Study (ICS). Participants were followed up from 2001 to 2013. During every 5-year follow-up survey, patients’ data regarding the incidence and time of incidence of diabetes were recorded. We evaluated the association between the risk of developing diabetes and novel anthropometric indices including: visceral adiposity index (VAI), lipid accumulation products (LAP), deep abdominal adipose tissue (DAAT), abdominal volume index (AVI), A body shape index (ABSI), body roundness index (BRI) and weight-adjusted waist index (WWI). We categorized the indices into two groups according to the median value of each index in the population. We used Cox regression analysis to obtain hazard ratios (HR) using the first group as the reference category and used receiver operating characteristics (ROC) curve analysis for comparing the predictive performance of the indices. Results From 215 included subjects, 79 developed diabetes during the 13-year follow-up. AVI, LAP, BRI, and VAI indicated statistically significant HR in crude and adjusted regression models. LAP had the greatest association with the development of diabetes HR = 2.18 (1.36-3.50) in multivariable analysis. ROC curve analysis indicated that LAP has the greatest predictive performance among indices (area under the curve = 0.627). Conclusion Regardless of baseline confounding variables, prediabetic patients with a higher LAP index may be at significantly higher risk for developing diabetes. pre diabetic subpopulation sub population ICS. ICS . (ICS) 200 2013 5year year 5 followup follow survey recorded including VAI, , (VAI) (LAP) DAAT, DAAT (DAAT) AVI (AVI) ABSI, ABSI (ABSI) BRI (BRI weightadjusted weight WWI. WWI (WWI) (HR (ROC 21 subjects 7 13year 13 followup. up. models 218 2 18 2.1 1.363.50 136350 1.36 3.50 1 36 3 50 (1.36-3.50 area 0.627. 0627 0.627 0 627 0.627) variables (ICS 20 201 (VAI (LAP (DAAT (AVI (ABSI (WWI 2. 363 1.363.5 13635 136 1.3 350 3.5 (1.36-3.5 062 0.62 62 1.363. 1363 1. 35 3. (1.36-3. 06 0.6 6 1.363 (1.36-3 0. (1.36- (1.36 (1.3 (1. (1 (

ABSTRACT Objective This study aimed to evaluate the association of detectable C-peptide levels with various continuous glucose monitoring (CGM) metrics and diabetes complications in patients with type 1 diabetes mellitus (T1DM). Subjects and methods Retrospective, descriptive study of 112 patients with T1DM undergoing intensive insulin therapy, categorized according to fasting C-peptide level into undetectable (<0.05 ng/mL) and detectable (≥0.05 ng/mL) groups. Results The patients’ median age at diagnosis was 22 (12-34) years and the median T1DM duration was 18.5 (12-29) years. Patients with detectable versus undetectable C-peptide levels were older (27.5 [16.5-38.5] versus 17.5 [9.8-28.8] years, respectively, p = 0.002) and had shorter disease duration (14 [9-24] versus 20 [14-32] years, respectively, p = 0.004). After adjustment for covariates (sex, disease duration, body mass index, and use of continuous subcutaneous insulin infusion), detectable C-peptide level was associated with lower time above range (TAR; aβ -11.03, p = 0.002), glucose management indicator (GMI, aβ -0.55, p = 0.024), and average glucose (aβ -14.48, p = 0.045) and HbA1c (aβ -0.41, p = 0.035) levels. Patients with detectable versus those with undetectable C-peptide level had significantly higher time in range (TIR) before (β = 7.13, p = 0.044) and after (aβ = 11.42, p = 0.001) adjustments. Detectable C-peptide level was not associated with lower time below range (TBR), coefficient of variation (CV), or prevalence of chronic microvascular and macrovascular complications. Conclusions Persistent C-peptide secretion in patients with T1DM was associated with significantly better metabolic control reflected by different glucose metrics, namely, TIR, TAR, GMI, and HbA1c. Cpeptide C peptide CGM (CGM T1DM. TDM . T DM (T1DM) Retrospective 11 therapy <0.05 005 0 05 (<0.0 ng/mL ngmL ng mL ≥0.05 (≥0.0 groups 2 1234 12 34 (12-34 185 18 5 18. 1229 29 (12-29 27.5 275 27 (27. 16.538.5 165385 16.5 38.5 16 38 [16.5-38.5 175 17 17. 9.828.8 98288 9.8 28.8 9 8 28 [9.8-28.8 respectively 0.002 0002 002 14 (1 924 24 [9-24 1432 32 [14-32 0.004. 0004 0.004 004 0.004) sex, sex (sex index infusion, infusion , infusion) TAR (TAR 11.03, 1103 03 -11.03 0.002, GMI (GMI 0.55, 055 55 -0.55 0.024, 0024 0.024 024 0.024) 14.48, 1448 48 -14.48 0.045 0045 045 HbAc HbA c 0.41, 041 41 -0.41 0.035 0035 035 TIR (TIR β 713 7 13 7.13 0.044 0044 044 1142 42 11.42 0.001 0001 001 adjustments TBR, TBR (TBR) CV, CV (CV) namely (T1DM <0.0 00 (<0. ≥0.0 (≥0. 123 3 (12-3 122 (12-2 27. (27 538 16.538. 16538 165 16. 385 38. [16.5-38. 828 9.828. 9828 98 9. 288 28. [9.8-28. 0.00 000 ( 92 [9-2 143 [14-3 11.03 110 -11.0 0.55 -0.5 0.02 02 14.48 144 4 -14.4 0.04 04 0.41 -0.4 0.03 003 71 7.1 114 11.4 (TBR (CV <0. (<0 ≥0. (≥0 (12- (2 53 16.538 1653 [16.5-38 82 9.828 982 [9.8-28 0.0 [9- [14- 11.0 -11. 0.5 -0. 14.4 -14. 0.4 7. 11. <0 (< ≥0 (≥ (12 16.53 [16.5-3 9.82 [9.8-2 0. [9 [14 -11 -0 14. -14 < ≥ [16.5- [9.8- [ [1 -1 - [16.5 [9.8 [16. [9. [16

ABSTRACT Objective This pilot study investigated whether single nucleotide polymorphisms (SNP) in the NOX5 gene (NADPH oxidase 5) are associated with the type 2 diabetes (T2D) risk. Subjects and methods A total of 1579 patients with T2D and 1627 age- and sex-matched healthy subjects were recruited for this study. Genotyping of common SNPs, namely rs35672233, rs3743093, rs2036343, rs311886, and rs438866, was performed using the MassArray-4 system. Results SNP rs35672233 was associated with an increased risk of T2D (OR = 1.67, 95% CI 1.29-2.17, FDR = 0.003). The H3 haplotype (rs35672233T-rs3743093G-rs2036343A-rs311886C-rs438866C) increased T2D risk (OR = 1.65, 95% CI 1.27-2.13, FDR = 0.001). The rs35672233 polymorphism and H3 haplotype were found to have an association with T2D risk only in subjects with a body mass index greater than 25 kg/m2 (FDR < 0.01). Environmental risk factors, such as chronic psycho-emotional stress, sedentary lifestyle, high-calorie diet and SNP rs35672233 were jointly associated with T2D susceptibility. A haplotype comprising the allele rs35672233-C and conferring protection against T2D, was associated with elevated levels of antioxidants such as total glutathione and uric acid, as well as reduced levels of two-hour postprandial glucose in the plasma of patients. The NOX5 polymorphisms showed no associations with diabetic complications. Conclusion The present study is the first to establish associations between polymorphisms in NOX5 and the risk of type 2 diabetes mellitus, and provides a new line of evidence for the crucial role of oxidative stress-related genes in disease susceptibility. (SNP NOX NADPH 5 TD T D (T2D 157 162 age sexmatched sex matched SNPs rs rs3743093 rs2036343 rs311886 rs438866 MassArray4 MassArray 4 MassArray- system rs3567223 OR 167 1 67 1.67 95 1.292.17, 129217 1.29 2.17, 29 17 1.29-2.17 0.003. 0003 0.003 . 0 003 0.003) H rs35672233Trs3743093Grs2036343Ars311886Crs438866C rsTrsGrsArsCrsC rs35672233T rs3743093G rs2036343A rs311886C rs438866C G C (rs35672233T-rs3743093G-rs2036343A-rs311886C-rs438866C 165 65 1.65 1.272.13, 127213 1.27 2.13, 27 13 1.27-2.13 0.001. 0001 0.001 001 0.001) kgm2 kgm kg m2 m kg/m 0.01. 0.01 01 0.01) factors psychoemotional psycho emotional stress lifestyle highcalorie high calorie susceptibility rs35672233C rsC acid twohour two hour complications mellitus stressrelated related 15 16 rs374309 rs203634 rs31188 rs43886 rs356722 6 1.6 9 292 1.292.17 12921 129 1.2 217 2.17 1.29-2.1 000 0.00 00 Trs Grs Ars Crs rsT rsG rsA 272 1.272.13 12721 127 213 2.13 1.27-2.1 0.0 rs37430 rs20363 rs3118 rs4388 rs35672 1. 1.292.1 1292 12 21 2.1 1.29-2. 1.272.1 1272 1.27-2. 0. rs3743 rs2036 rs311 rs438 rs3567 1.292. 2. 1.29-2 1.272. 1.27-2 rs374 rs203 rs31 rs43 rs356 1.292 1.29- 1.272 1.27- rs37 rs20 rs3 rs4 rs35 rs2

ABSTRACT Objective: Fasting insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) index are relatively simple and reliable noninvasive markers of insulin resistance (IR). Given the relevance of correctly diagnosing IR, we emphasize the importance of establishing reliable reference intervals (RIs) for these markers. This study aimed to determine the RIs of fasting insulin and HOMA-IR index in adults living in Rio de Janeiro and, secondarily, to verify potential RI differences between sexes. Subjects and methods: Serum insulin levels of 146,497 individuals (ages 20-60 years) who underwent blood sampling in the state of Rio de Janeiro were obtained retrospectively through access to an extensive laboratory database. Insulin was measured using the electrochemiluminescence immunoassay method. After applying exclusion criteria, 21,684 individuals (18,576 [86%] women) were included. The RIs were estimated using a computational mining approach that integrates a selection of R packages. Results: The 95% RIs in women and men and in the overall population were, respectively, 2.54-13.30 μU/mL (15.3-80.12 pmol/L), 2.43-11.89 μU/mL (14.6-71.7 pmol/L), and 2.52-13.14 μU/mL (15.2-79.2 pmol/L) for fasting insulin levels and 0.39-2.86, 0.38-2.81, and 0.39-2.86 for HOMA-IR values. Despite significant differences in insulin levels and HOMA-IR index between men and women, the use of sex-specific RIs was not justified. Conclusion: The RIs of fasting insulin levels and HOMA-IR values found in the overall population can be applied to both sexes. Thus, for our population, we suggest the RIs of 2.52-13.14 μU/mL (15.1-78.8 pmol/L) for fasting insulin and 0.39-2.86 for the HOMA-IR index. Objective HOMAIR HOMA IR (HOMA-IR IR. . (IR) (RIs secondarily sexes methods 146497 146 497 146,49 ages 2060 20 60 20-6 years database method criteria 21684 21 684 21,68 18,576 18576 18 576 (18,57 86% 86 [86% included packages Results 95 respectively 2.5413.30 2541330 2.54 13.30 2 54 13 30 2.54-13.3 μUmL μU mL 15.380.12 1538012 15.3 80.12 15 3 80 12 (15.3-80.1 pmol/L, pmolL pmol/L , pmol L 2.4311.89 2431189 2.43 11.89 43 11 89 2.43-11.8 14.671.7 146717 14.6 71.7 14 6 71 7 (14.6-71. 2.5213.14 2521314 2.52 13.14 52 2.52-13.1 15.279.2 152792 15.2 79.2 79 (15.2-79. 0.392.86, 039286 0.39 2.86, 0 39 0.382.81, 038281 0.38 2.81, 38 81 0.38-2.81 0.392.86 2.86 0.39-2.8 sexspecific sex specific justified Conclusion Thus 15.178.8 151788 15.1 78.8 1 78 8 (15.1-78. (IR 14649 49 146,4 206 20- 2168 68 21,6 18,57 1857 57 (18,5 [86 9 5413 2.5413.3 254133 254 2.5 1330 13.3 5 2.54-13. 380 15.380.1 153801 153 15. 8012 80.1 (15.3-80. 4311 2.4311.8 243118 243 2.4 1189 11.8 4 2.43-11. 671 14.671. 14671 14. 717 71. (14.6-71 5213 2.5213.1 252131 252 1314 13.1 2.52-13. 279 15.279. 15279 152 792 79. (15.2-79 392 03928 039 0.3 286 382 0.382.81 03828 038 281 2.81 0.38-2.8 0.392.8 2.8 0.39-2. 178 15.178. 15178 151 788 78. (15.1-78 1464 146, 216 21, 18,5 185 (18, [8 541 2.5413. 25413 25 2. 133 13. 2.54-13 15.380. 15380 801 80. (15.3-80 431 2.4311. 24311 24 118 11. 2.43-11 67 14.671 1467 (14.6-7 521 2.5213. 25213 131 2.52-13 27 15.279 1527 (15.2-7 0392 03 0. 28 0.382.8 0382 0.38-2. 0.392. 0.39-2 17 15.178 1517 (15.1-7 18, (18 [ 2.5413 2541 2.54-1 15.380 1538 (15.3-8 2.4311 2431 2.43-1 14.67 (14.6- 2.5213 2521 2.52-1 15.27 (15.2- 0.382. 0.38-2 0.392 0.39- 15.17 (15.1- (1 2.541 2.54- 15.38 (15.3- 2.431 2.43- (14.6 2.521 2.52- (15.2 0.382 0.38- (15.1 ( (15.3 (14. (15. (14 (15

SUMMARY Denosumab is a potent antiresorptive medication, commonly used in the treatment of osteoporosis, as well as in a variety of other diseases. Potential adverse rebound effects after its cessation include a loss in bone mineral density and an increased risk of osteoporotic fractures. Hypercalcemia is a less frequently reported rebound phenomenon after denosumab discontinuation, that may pose a diagnostic challenge to physicians as a rare non-parathyroid hormone (PTH) dependent cause of hypercalcemia. In our case, a 47-year-old male presented with rebound hypercalcemia after denosumab cessation during follow-up after surgical treatment for parathyroid carcinoma. This non-PTH-dependent hypercalcemia resolved after re-initiation of denosumab. We performed a systematic literature review on rebound hypercalcemia after denosumab cessation and identified 52 individual patient cases. Children appear to be more prone to developing rebound hypercalcemia, which could be attributed to their higher baseline bone turnover, underlying conditions, or denosumab dosage regimens. In most cases, patients initially presented with acute and often severe symptoms of hypercalcemia that occur from 1.75 to 9 months after denosumab cessation (4 to 9 months in adults). Most effective treatment approaches to sufficiently decrease serum calcium levels were bisphosphonates or re-administration of denosumab. A watch and wait strategy may be sufficient in asymptomatic cases, which are less common and probably underdiagnosed. Subsequent antiresorptive treatment after denosumab cessation, which is a common practice in osteoporosis treatment, may reduce the risk of rebound hypercalcemia. As denosumab is a frequently used drug in patients with advanced malignant diseases and rebound hypercalcemia with low PTH levels may raise the suspicion for skeletal metastases, awareness of this rebound effect may be for particular relevance in such settings. medication fractures discontinuation nonparathyroid non (PTH case 47yearold yearold 47 year old followup follow up carcinoma nonPTHdependent reinitiation re initiation 5 cases turnover conditions regimens 175 1 75 1.7 4 ( adults. adults . adults) readministration administration underdiagnosed metastases settings 17 7 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 Objective This study aimed to evaluate the association of detectable C-peptide levels with various continuous glucose monitoring (CGM) metrics and diabetes complications in patients with type 1 diabetes mellitus (T1DM). Subjects and methods Retrospective, descriptive study of 112 patients with T1DM undergoing intensive insulin therapy, categorized according to fasting C-peptide level into undetectable (<0.05 ng/mL) and detectable (≥0.05 ng/mL) groups. Results The patients’ median age at diagnosis was 22 (12-34) years and the median T1DM duration was 18.5 (12-29) years. Patients with detectable versus undetectable C-peptide levels were older (27.5 [16.5-38.5] versus 17.5 [9.8-28.8] years, respectively, p = 0.002) and had shorter disease duration (14 [9-24] versus 20 [14-32] years, respectively, p = 0.004). After adjustment for covariates (sex, disease duration, body mass index, and use of continuous subcutaneous insulin infusion), detectable C-peptide level was associated with lower time above range (TAR; aβ -11.03, p = 0.002), glucose management indicator (GMI, aβ -0.55, p = 0.024), and average glucose (aβ -14.48, p = 0.045) and HbA1c (aβ -0.41, p = 0.035) levels. Patients with detectable versus those with undetectable C-peptide level had significantly higher time in range (TIR) before (β = 7.13, p = 0.044) and after (aβ = 11.42, p = 0.001) adjustments. Detectable C-peptide level was not associated with lower time below range (TBR), coefficient of variation (CV), or prevalence of chronic microvascular and macrovascular complications. Conclusions Persistent C-peptide secretion in patients with T1DM was associated with significantly better metabolic control reflected by different glucose metrics, namely, TIR, TAR, GMI, and HbA1c. Cpeptide C peptide CGM (CGM T1DM. TDM . T DM (T1DM) Retrospective 11 therapy <0.05 005 0 05 (<0.0 ng/mL ngmL ng mL ≥0.05 (≥0.0 groups 2 1234 12 34 (12-34 185 18 5 18. 1229 29 (12-29 27.5 275 27 (27. 16.538.5 165385 16.5 38.5 16 38 [16.5-38.5 175 17 17. 9.828.8 98288 9.8 28.8 9 8 28 [9.8-28.8 respectively 0.002 0002 002 14 (1 924 24 [9-24 1432 32 [14-32 0.004. 0004 0.004 004 0.004) sex, sex (sex index infusion, infusion , infusion) TAR (TAR 11.03, 1103 03 -11.03 0.002, GMI (GMI 0.55, 055 55 -0.55 0.024, 0024 0.024 024 0.024) 14.48, 1448 48 -14.48 0.045 0045 045 HbAc HbA c 0.41, 041 41 -0.41 0.035 0035 035 TIR (TIR β 713 7 13 7.13 0.044 0044 044 1142 42 11.42 0.001 0001 001 adjustments TBR, TBR (TBR) CV, CV (CV) namely (T1DM <0.0 00 (<0. ≥0.0 (≥0. 123 3 (12-3 122 (12-2 27. (27 538 16.538. 16538 165 16. 385 38. [16.5-38. 828 9.828. 9828 98 9. 288 28. [9.8-28. 0.00 000 ( 92 [9-2 143 [14-3 11.03 110 -11.0 0.55 -0.5 0.02 02 14.48 144 4 -14.4 0.04 04 0.41 -0.4 0.03 003 71 7.1 114 11.4 (TBR (CV <0. (<0 ≥0. (≥0 (12- (2 53 16.538 1653 [16.5-38 82 9.828 982 [9.8-28 0.0 [9- [14- 11.0 -11. 0.5 -0. 14.4 -14. 0.4 7. 11. <0 (< ≥0 (≥ (12 16.53 [16.5-3 9.82 [9.8-2 0. [9 [14 -11 -0 14. -14 < ≥ [16.5- [9.8- [ [1 -1 - [16.5 [9.8 [16. [9. [16

ABSTRACT Objective This pilot study investigated whether single nucleotide polymorphisms (SNP) in the NOX5 gene (NADPH oxidase 5) are associated with the type 2 diabetes (T2D) risk. Subjects and methods A total of 1579 patients with T2D and 1627 age- and sex-matched healthy subjects were recruited for this study. Genotyping of common SNPs, namely rs35672233, rs3743093, rs2036343, rs311886, and rs438866, was performed using the MassArray-4 system. Results SNP rs35672233 was associated with an increased risk of T2D (OR = 1.67, 95% CI 1.29-2.17, FDR = 0.003). The H3 haplotype (rs35672233T-rs3743093G-rs2036343A-rs311886C-rs438866C) increased T2D risk (OR = 1.65, 95% CI 1.27-2.13, FDR = 0.001). The rs35672233 polymorphism and H3 haplotype were found to have an association with T2D risk only in subjects with a body mass index greater than 25 kg/m2 (FDR < 0.01). Environmental risk factors, such as chronic psycho-emotional stress, sedentary lifestyle, high-calorie diet and SNP rs35672233 were jointly associated with T2D susceptibility. A haplotype comprising the allele rs35672233-C and conferring protection against T2D, was associated with elevated levels of antioxidants such as total glutathione and uric acid, as well as reduced levels of two-hour postprandial glucose in the plasma of patients. The NOX5 polymorphisms showed no associations with diabetic complications. Conclusion The present study is the first to establish associations between polymorphisms in NOX5 and the risk of type 2 diabetes mellitus, and provides a new line of evidence for the crucial role of oxidative stress-related genes in disease susceptibility. (SNP NOX NADPH 5 TD T D (T2D 157 162 age sexmatched sex matched SNPs rs rs3743093 rs2036343 rs311886 rs438866 MassArray4 MassArray 4 MassArray- system rs3567223 OR 167 1 67 1.67 95 1.292.17, 129217 1.29 2.17, 29 17 1.29-2.17 0.003. 0003 0.003 . 0 003 0.003) H rs35672233Trs3743093Grs2036343Ars311886Crs438866C rsTrsGrsArsCrsC rs35672233T rs3743093G rs2036343A rs311886C rs438866C G C (rs35672233T-rs3743093G-rs2036343A-rs311886C-rs438866C 165 65 1.65 1.272.13, 127213 1.27 2.13, 27 13 1.27-2.13 0.001. 0001 0.001 001 0.001) kgm2 kgm kg m2 m kg/m 0.01. 0.01 01 0.01) factors psychoemotional psycho emotional stress lifestyle highcalorie high calorie susceptibility rs35672233C rsC acid twohour two hour complications mellitus stressrelated related 15 16 rs374309 rs203634 rs31188 rs43886 rs356722 6 1.6 9 292 1.292.17 12921 129 1.2 217 2.17 1.29-2.1 000 0.00 00 Trs Grs Ars Crs rsT rsG rsA 272 1.272.13 12721 127 213 2.13 1.27-2.1 0.0 rs37430 rs20363 rs3118 rs4388 rs35672 1. 1.292.1 1292 12 21 2.1 1.29-2. 1.272.1 1272 1.27-2. 0. rs3743 rs2036 rs311 rs438 rs3567 1.292. 2. 1.29-2 1.272. 1.27-2 rs374 rs203 rs31 rs43 rs356 1.292 1.29- 1.272 1.27- rs37 rs20 rs3 rs4 rs35 rs2