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Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.

Introduction: Parkinson's disease affects 2% of the population aged over 65 years and is the second most common neurodegenerative disorder in the general population. The appearance of motor symptoms is associated with the degeneration of dopaminergic neurons in the nigrostriatal pathway. Clinically significant nonmotor symptoms are also important for severe disability with disease progression. Pharmacological treatment with levodopa, which involves dopamine restitution, results in a temporary improvement in motor symptoms. Among the mechanisms underlying the pathogenesis of the disease are exacerbated oxidative stress, mitochondrial dysfunction, and neuroinflammation. A phytochemical prospecting study showed that the aqueous extract of the leaves from Swietenia macrophylla (Melineaceae), known as mahogany, has polyphenols with antioxidant and anti-inflammatory capacity in a significantly higher percentage than leaf extracts from other Amazonian plants. Furthermore, the antioxidant and anti-inflammatory capacity of aqueous extract of mahogany leaf has already been demonstrated in an in vitro model. In this study, we hypothesized that the aqueous extract of mahogany leaf (AEML) has a neuroprotective effect in a murine model of Parkinson's disease induced by 6-hydroxidopamine (6-OHDA), due to antioxidant and anti-inflammatory properties of its phenolic compounds., Methods: Mice were treated daily with the mahogany extract at a dose of 50 mg/kg, starting 7 days before 6-OHDA infusion until post-surgery day 7., Results and Discussion: The animals from the 6-OHDA/mahogany group, which corresponds to animals injected with the toxin and treated with aqueous extract of the mahogany leaf, presented distinct behavioral phenotypes after apomorphine challenge and were therefore subdivided into 2 groups, 6-OHDA/mahogany F1 and 6-OHDA/mahogany F2. The F1 group showed a significant increase in contralateral rotations, whereas the F2 group did not show rotations after the apomorphine stimulus. In the F1 group, there was an increase, although not significant, in motor performance in the open field and elevated plus maze tests, whereas in the F2 group, there was significant improvement, which may be related to the lesser degree of injury to the nigrostriatal dopaminergic pathway. The TH+ histopathological analysis, a dopaminergic neuron marker, confirmed that the lesion to the nigrostriatal dopaminergic pathway was more pronounced in 6-OHDA/mahogany F1 than in 6-OHDA/mahogany F2. Our main result consisted of signs of improvement in the inflammatory profile in both the F1 and F2 6-OHDA/mahogany groups, such as a lower number of IBA-1+ microglial cells in the ventral striatum and substantia nigra pars compacta and a reduction in GFAP+ expression, an astrocyte marker, in the dorsal striatum. In this study, several bioactive compounds in the aqueous extract of mahogany leaf may have contributed to the observed beneficial effects. Further studies are necessary to better characterize their applicability for treating chronic degenerative diseases with inflammatory and oxidative bases, such as Parkinson's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cardoso, Valente-Amaral, Monteiro, Meira, de Meira, da Silva, Pinheiro, Bastos, Felício and Yamada.)

Background: Considering the potential role of miRNAs as biomarkers and their interaction with both nuclear and mitochondrial genes, we investigated the miRNA expression profile in type 1 diabetes (T1DM) patients, including the pathways in which they are involved considering both nuclear and mitochondrial functions., Methods: We analyzed samples of T1DM patients and control individuals (normal glucose tolerance) by high throughput miRNA sequencing (miRNome). Next, five miRNAs - hsa-miR-26b-5p , hsa-let-7i-5p , hsa-miR-143-3p , hsa-miR-501-3p and hsa-miR-100-5p - were validated by RT-qPCR. The identification of target genes was extracted from miRTarBase and mitoXplorer database. We also performed receiver operating characteristic (ROC) curves and miRNAs that had an AUC > 0.85 were considered potential biomarkers., Results: Overall, 41 miRNAs were differentially expressed in T1DM patients compared to control. Hsa-miR-21-5p had the highest number of predicted target genes and was associated with several pathways, including insulin signaling and apoptosis. 34.1% (14/41) of the differentially expressed miRNAs also targeted mitochondrial genes, and 80.5% (33/41) of them targeted nuclear genes involved in the mitochondrial metabolism. All five validated miRNAs were upregulated in T1DM. Among them, hsa-miR-26b-5p showed AUC>0.85, being suggested as potential biomarker to T1DM., Conclusion: Our results demonstrated 41 DE miRNAs that had a great accuracy in discriminating T1DM and control group. Furthermore, we demonstrate the influence of these miRNAs on numerous metabolic pathways, including mitochondrial metabolism. Hsa-miR-26b-5p and hsa-miR-21-5p were highlighted in our results, possibly acting on nuclear and mitochondrial dysfunction and, subsequently, T1DM dysregulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ferraz, Santos, da-Silva-Cruz, Braga-da-Silva, Magalhães, Ribeiro-dos-Santos, Vidal, Vinasco-Sandoval, Reis-das-Mercês, Sena-dos-Santos, Pereira, Silva, Melo, Souza, Leal, Figueiredo, Neto, Moraes, Lemos, Queiroz, Felício, Cavalcante, Ribeiro-dos-Santos and Felício.)

To control glycemic variability in people with Type 1 diabetes mellitus (T1DM), it is essential to perform carbohydrate counting (CC), a strategy that ensures better quality of life for these patients. Thus, this study aims to analyze potential factors associated with adherence to CC in adults with T1DM during social distancing due to COVID-19 in Brazil. This was a single cross-sectional study carried out in July 2020. An online form was used to collect sociodemographic and economic data on the purchasing of supplies and food, as well as social distancing. The Chi-square test was performed with adjusted residuals analysis and a binomial logistic regression analysis (p < 0.05). Of 472 adults, 37.71% reported performing CC in the same frequency as before social distancing. There was an association between performance of CC and the type of city (p = 0.027), family income (p = 0.000), use of financial emergency aid (p = 0.045), type of insulin administration and glycemic monitoring (p < 0.000), and cooking more (p = 0.012). Participants who maintained or reduced consumption of ultra-processed foods were 0.62 times more likely to adhere to CC (OR 0.626, 95% IC: 0.419−0.935) and participants who cooked more were 1.67 times more likely to adhere to CC (OR 1.67, 95% CI: 1.146−2.447). There are still people with T1DM who did not know about and did not use CC method, which highlights the need for diabetes education.

Background: Little is known about the evolution of peripheral arterial disease (PAD) since diagnosis and its association with glycemic and lipid control in patients with Type 2 Diabetes Mellitus (T2DM)., Objective: Evaluate the actual criteria to start screening PAD with ankle-brachial index (ABI) in T2DM patients and assess its progression and relationship with glycemic and lipid control since diagnosis., Methods: We performed a 3-year prospective cohort study with two groups: group 1 (978 individuals with T2DM undergoing drug treatment) and group 2 [221 newly diagnosed drug-naive (< 3 months) patients with T2DM]. PAD diagnosis was by ABI ≤ 0.90, regardless any symptoms., Results: As expected, abnormal ABI prevalence was higher in group 1 vs. Group 2 (87% vs. 60%, p < 0.001). However, abnormal ABI prevalence did not differ between patients over and under 50 years in both groups. Our drug-naive group stabilizes ABI (0.9 ± 0.1 vs 0.9 ± 0.1, p = NS) and improved glycemic and lipid control during follow-up [glycated hemoglobin (HbA1c) = 8.9 ± 2.1 vs 8.4 ± 2.3%, p < 0.05; LDL = 132 ± 45 vs 113 ± 38 mg/dL, p < 0.01, respectively]. When compared, patients who evolved with normalization or maintained normal ABI levels at the end [Group A, N = 60 (42%)] with those who decreased ABI to abnormal levels (ABI basal 1.0 ± 0.1 vs final 0.85 ± 0.1, p < 0.001) [Group B, N = 26 (18%)], an improvement in HbA1c (9 ± 2 vs 8 ± 2%, p < 0.05) and a correlation between the final HbA1c with ABI (r = - 0.3, p = 0.01) was found only in the first. In addition, a correlation was found between albuminuria variation and ABI solely in group A (r = - 0.3; p < 0.05)., Conclusion: Our study suggests that ABI should be measured at diagnosis in T2DM patients, indicating that current criteria to select patients to screen PAD with ABI must be simplified. An improvement in albuminuria and glycemic and lipid control could be related with ABI normalization in newly diagnosed T2DM drug-naive patients., (© 2022. The Author(s).)

We aimed to investigate the relationship between HLA alleles in patients with type 1 diabetes from an admixed population and the reported race/skin color of their relatives. This cross-sectional, multicenter study was conducted in public clinics in nine Brazilian cities and included 662 patients with type 1 diabetes and their relatives. Demographic data for patients and information on the race/skin color and birthplace of their relatives were obtained. Typing of the HLA-DRB1, -DQA1, and -DQB1 genes was performed. Most studied patients reported having a White relative (95.17%), and the most frequently observed allele among them was DRB1*03:01. Increased odds of presenting this allele were found only in those patients who reported having all White relatives. Considering that most of the patients reported having a White relative and that the most frequent observed allele was DRB1*03:01 (probably a European-derived allele), regardless of the race/skin color of their relatives, we conclude that the type 1 diabetes genotype comes probably from European, Caucasian ethnicity. However, future studies with other ancestry markers are needed to fill the knowledge gap regarding the genetic origin of the type 1 diabetes genotype in admixed populations such as the Brazilian.

Background: Type 1 Diabetes Mellitus (T1DM) impacts health-related quality of life (HRQoL). Cross-sectional studies suggest that low levels of vitamin D (VD) may impair HRQoL, however, the effect of VD supplementation on quality of life in T1DM patients has not yet been clarified. Our study evaluated the effects of high-dose VD supplementation on HRQoL in T1DM., Methods: We performed a prospective study with 64 patients receiving cholecalciferol (4000 IU/day for patients with 25-OH-vitamin D [25(OH)D] between 30 and 60 ng/mL, and 10,000 IU/day for those with 25(OH)D below 30 ng/mL) for 12 weeks, as part of a research protocol. HRQoL was assessed with EuroQol instruments (EQ-5D and EQ-VAS)., Results: There was an improvement in global EQ-5D index, and analysing specifically the EQ-5D domains, we observed an improvement in mobility (1.3 ± 0.6 versus 1.1 ± 0.3, p < 0.01). Evaluating possible outcome influencing variables, we detected a reduction in albuminuria at the end of the trial, without changes in BMI, lipids, blood pressure, glycemic control and insulin doses. We found correlations between final albuminuria and the dimensions: mobility (r = 0.6; p < 0.01), personal care (r = 0.7; p < 0.01), pain and discomfort (r = 0.6; p < 0.01) and habitual activities (r = 0.6; p < 0.01), suggesting an association between albuminuria reduction and the impact of VD supplementation on HRQoL., Conclusion: Our data showed that high doses of cholecalciferol supplementation can improve HRQoL in patients with T1DM, and the reduction of albuminuria seems to be an important factor in this context., Trial Registration: (ISRCTN32601947), 03/06/2017 retrospectively registered., (© 2022. The Author(s).)

Vitamin D has been considered a strong contributing factor to type 1 diabetes mellitus (T1DM). Many studies have investigated polymorphisms in the VDR gene in association with T1DM in different populations, but there are still conflicting findings. This study aimed to evaluate the association of four variants in the VDR gene (rs7975232, rs1544410, rs731236, and rs2228570) with T1DM risk and vitamin D levels within a population from North Region, Brazil, as well as the influence of genomic ancestry on T1DM. A total of 65 T1DM patients and 83 non-T1DM patients were enrolled in this study. VDR gene polymorphisms were assessed using Sanger sequencing analysis. Genomic ancestry was analyzed using a set of 61 ancestry-informative markers. T1DM patients showed higher European genomic contribution and lower Native American genomic contribution when compared to non-T1DM patients. T1DM patients with AA genotype in rs1544410 or CC genotype in rs731236 had significantly lower 25(OH)D levels compared to the other two genotypes ( p = 0.013 and p = 0.02, respectively), while T1DM with TT genotype in rs2228570 had higher 25(OH)D levels compared to CC + TC in the same polymorphism ( p = 0.011). Our findings suggest that the association between 25(OH)D and T1DM may be modified by VDR variants, possibly influencing the development of this autoimmune disease.

Background: Some authors evaluated the effect of VD on hyperglycemia in T1DM, but the results remain controversial. This study aims to analyze the effects of high-dose VD supplementation on T1DM patients' glycemic levels, maintaining stable doses of insulin., Methods: Prospective, 12-week clinical trial including 67 T1DM patients, supplemented with high doses of cholecalciferol according to participants' VD value. Patients with VD levels below 30 ng/mL received 10,000 IU/day; those with levels between 30-60 ng/mL received 4,000 IU/day. Patients who had not achieved 25(OH)D levels > 30 ng/ml or presented insulin dose variation during the study were not analyzed., Results: Only 46 out of 67 patients accomplished the criteria at the end of the study. There was no general improvement in the glycemic control evaluated by HbA1c (9.4 ± 2.4 vs 9.4 ± 2.6, p=NS) after VD supplementation. However, a post-hoc analysis, based on HbA1c variation, identified patients who had HbA1c reduced at least 0.6% (group 1, N = 13 (28%)). In addition, a correlation between 25(OH)D levels with HbA1c and total insulin dose at the end of the study was observed (r = -0.3, p<0.05; r=-0.4, p<0.05, respectively), and a regression model demonstrated that 25(OH)D was independent of BMI, duration of T1DM and final total insulin dose, being capable of determining 9.2% of HbA1c final levels (Unstandardized B coefficient = -0.033 (CI 95%: -0.064 to -0.002), r2 = 0.1, p <0.05)., Conclusion: Our data suggest that VD is not widely recommended for glycemic control. Nevertheless, specific patients might benefit from this approach., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The effect of glycemic control on diabetic kidney disease (DKD) is well known. Recent evidence has suggested that Vitamin D (VD) may have a nephroprotective effect in diabetes, but the relationship between VD, glycemic control, and albuminuria has yet to be clarified., Objective: Evaluate the relationship between 25-hydroxy-vitamin D [25(OH)D], HbA1c, and albuminuria in Diabetes Mellitus (DM)., Patients and Methods: Cross-sectional study with 1576 individuals with DM who had 25(OH)D, HbA1c, and albuminuria levels measured. Patients with abnormal creatinine levels were excluded, in order to avoid interference on VD levels by impaired kidney function., Results: Patients with HbA1c ≥7% had lower 25(OH)D when compared to patients with HbA1c <7% (29.7 ± 10.2 vs 28.1 ± 9.9 ng/ml, p = 0.003) and 25(OH)D levels seems to predict 1.5% of HbA1c behavior. The 25(OH)D concentrations in patients with normoalbuminuria were higher than the levels observed in those with micro or macroalbuminuria (29.8 ± 9.0 vs 26.8 ± 8.6 and 25.1 ± 7.6, respectively, p = 0.001), patients who had 25(OH)D <20 ng/ml and 25(OH)D <30 ng/ml were at a higher risk of presenting albuminuria [OR = 2.8 (95% CI = 1.6 - 4.9), p<0.001, and OR = 2.1 (95% CI = 1.3 - 4.6), p<0.001, respectively]. In our regression model, albuminuria was influenced by HbA1c (r² = 0.076, p<0.00001) and 25(OH)D (r² = 0.018, p = 0.002) independently., Conclusion: Our study found an association between vitamin D levels, HbA1c and DKD. Additionally, our data suggest that the association between urinary albumin excretion and vitamin D levels is independent of glycemic control in patients with diabetes. Even though our patients presented normal creatinine levels, it is necessary further prospective studies to confirm if this association precedes or not the loss of renal function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Felício, de Rider Britto, Cortez, de Souza Resende, de Lemos, de Moraes, de Aquino, de Souza Parente, de Queiroz, Abrahão Neto, de Alcântara, da Silva, de Souza Neto, Freire Piani, de Souza, Silva, de Oliveira, Said, Nascimento de Lemos, de Melo, Gomes, Contente Braga de Souza, de Sá Oliveira dos Reis, Leal, Lobato and Felício.)

Introduction: While soy is suggested as a possible risk factor, exclusive breastfeeding (EBF) has a likely protective effect in precocious puberty. Our aim was to evaluate the association between both of these variables with central precocious puberty (CPP)., Methods: We performed a retrospective, case-control study. A total of 161 girls were divided into two groups: 84 patients diagnosed with CPP composed the case group and 77 patients without the diagnosis of CPP (had gone through normal onset of puberty) were the control group., Results: Our control group had a higher presence of EBF >6 months, which was an important protective factor for CPP (OR: 0.5; IC 95%: 0.3-0.9, p = 0.05) and also correlated negatively with the presence of it (r = -0.2; p < 0.05). Oppositely, the use of soy was significantly higher in the CPP group, (OR: 3.8; IC 95%: 1.5-6, p < 0.05) and positively correlating (r = 0.2; p < 0.01) with the presence of CPP. Duration of soy intake (years) correlated with bone age (r = 0.415; p < 0.05). A logistic regression was performed to evaluate the effects of EBF duration and soy on CPP. The model was significant (x² (2) = 20,715, p = <0.001) and explained 12.2% (Nagelkerke R2) of the variance, correctly classifying 62.5% of cases. EBF was associated with a reduction of likelihood of having CPP [OR = 0,187 (CI = 0.055-0,635); Wald = 7,222, p = 0.007], while soy intake increased the risk [OR = 3.505 (CI) = 1,688-7,279, Wald = 11,319, p = 0.001]., Conclusion: Our data found the use of soy was associated with CPP. Additionally, EBF was pointed as a protective factor. However, future prospective studies are needed to clarify this issue., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Felício, de Alcântara, Janaú, de Moraes, de Oliveira, de Lemos, de Souza Neto, Neto, da Silva, de Souza, Said, de Lemos, Vieira, Khayat, Santos, de Queiroz, de Sousa, Santos, de Melo, Piani and Felício.)

Background: Vitamin D (VD) deficiency has been related to several endocrine metabolic and cardiovascular diseases. The effect of VD supplementation on blood pressure (BP) in patients with diabetes is controversial., Objective: The aim of this study was to evaluate high-dose vitamin D supplementation effects on blood pressure of normotensive patients with diabetes mellitus 1 (DM1) patients by 24-hour ambulatory blood pressure monitoring (ABPM)., Methods: We performed a clinical trial including 35 DM1 normotensive patients, who received doses of 4,000 or 10,000 IU/day of cholecalciferol for 12 weeks according to previous VD levels. They underwent 24-hour ABPM, along with glycated hemoglobin, creatine, lipids profile and PCRus dosage before and after VD supplementation., Results: We found an expressive reduction of systolic and diastolic morning blood pressures (117±14 vs 112±14, p<0,05; 74±9 vs 70±10 mmHg, p<0,05, respectively) with no changes in other pressoric markers. Besides, we noticed a relationship between levels of VD after supplementation and diastolic morning blood pressure (r= -0,4; p<0.05)., Conclusion: Our study suggests an association between supplementation of high doses of vitamin D and the reduction of morning blood pressure in normotensive DM1 patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Cardiovascular autonomic neuropathy (CAN) is associated with diabetes mellitus , increasing morbidity and mortality. Some cross-sectional studies associated CAN with low 25-hydroxyvitamin D levels. The aim of our study was to evaluate the effect of high-dose vitamin D (VD) supplementation on CAN in Type 1 Diabetes Mellitus (T1DM) patients., Methods: We performed a prospective study with 23 patients diagnosed with T1DM and CAN. Subjects with VD levels <30 ng/ml received 10,000 IU/day; the ones with VD levels between 30-60 ng/ml were given 4,000 IU/day for 12 weeks., Results: There was an improvement in CAN parameters related to resting heart rate variability, such as time domain parameters [Maximum RR interval (0.77 ± 0.11 vs 0.94 ± 0.51 s, p <0.05), Mean length of regular RR intervals (0.71 ± 0.10 vs 0.76 ± 0.09 s, p <0.05) and Standard deviation of all NN intervals (0.02 ± 0.01 vs 0.03 ± 0.02 s; p <0.01)] and frequency domain parameters [Low Frequency (1.9 ± 0.5 vs 2.5 ± 0.9 s, p < 0.001), Total Power (2.5 ± 0.4 vs 2.8 ± 0.6 s, p <0.05)]. In addition, there was a correlation between absolute VD level variation and posttreatment High Frequency (%), as well as among percent variation in VD level and end-of-study Low Frequency/High Frequency ratio (r=0.6, p<0.01; r= -0.5, p<0.05, respectively)., Conclusion: Our pilot study is the first to suggest a strong association between high-dose vitamin D supplementation and improved cardiovascular autonomic neuropathy in T1DM patients. It occurred without any variation in HbA1C, blood pressure levels, lipids, and insulin dose., Clinical Trial Registration: http://www.isrctn.com/ISRCTN32601947, identifier ISRCTN32601947., (Copyright © 2020 Silva, de Queiroz, de Melo, Abrahão Neto, Janaú, de Souza Neto, de Lemos, de Oliveira, de Alcântara, de Moraes, da Silva, de Souza, Said, de Lemos, Felício, Santos, Motta, dos Reis, Lobato, de Figueiredo, de Souza, Piani and Felício.)

Objective: Investigate the prevalence of vitamin D deficiency in an equatorial population through a large-sample study., Methods: Cross-sectional study with 30,224 healthy individuals from the North Region, in Brazil (Amazônia - state of Pará), who had 25-hydroxy-vitamin D (25(OH)D) and intact parathyroid hormone (PTH) serum levels measured by immunoassay method. Those with history of acute or chronic diseases were excluded. Abnormal levels of calcium, creatinine, glycemia and albumin were also exclusion criteria., Results: 25(OH)D levels were 29.1 ± 8.2 ng/mL and values <12.7 ng/mL were equal to < -2 s.d. below average. Hypovitaminosis D was present in 10% of subjects according to the Institute of Medicine (values <20 ng/mL) and in 59%, in consonance with Endocrine Society (values 20-30 ng/mL as insufficiency and <20 ng/mL as deficiency) criteria. Individuals were divided according to four age brackets: children, adolescents, adults and elderly, and their 25(OH)D levels were: 33 ± 9; 28.5 ± 7.4; 28.3 ± 7.7; 29.3 ± 8.5 ng/mL, respectively. All groups differed in 25(OH)D, except adolescents vs adults. Regression model showed BMI, sex, living zone (urban or rural) and age as independent variables to 25(OH)D levels. Comparing subjects with vitamin D deficiency (<20 ng/mL) to those with vitamin D insufficiency (20-30 ng/mL), a difference between PTH levels in these two groups was observed (95.9 ± 24.7 pg/mL vs 44.2 ± 64.5 pg/mL; P < 0.01). Additionally, the most accurate predictive vitamin D level for subclinical hyperparathyroidism in ROC curve was 26 ng/mL., Conclusion: Our equatorial population showed low prevalence of vitamin D hypovitaminosis ranging with age bracket. The insufficient category by Endocrine Society was corroborated by our PTH data.

Background: Evogliptin (EVO) is a potent and selective dipeptidyl peptidase-4 inhibitor (DPP4i) developed for the treatment of type 2 diabetes mellitus (T2DM). DPP4is are known to exhibit a better glucose-lowering effect in Asians compared to other ethnic groups. Once EVO's clinical development program was conducted in Asian patients, this bridging study was designed to validate for the Brazilian population the efficacy and safety of the approved dose regimen (once-daily 5.0 mg)., Methods: In this randomized, double-blind, double-dummy, parallel trial, 146 patients with T2DM with inadequate glycemic control on diet and exercise (7.5% ≤ HbA1c ≤ 10.5%) were randomly assigned to a 12-week once-daily treatment with EVO 2.5 mg (N = 35), EVO 5 mg (N = 36), EVO 10 mg (N = 36), or sitagliptin (SITA) 100 mg (N = 39). Absolute changes (Week 12-baseline) in HbA1c, fasting plasma glucose (FPG) and body weight (BW) were obtained. One-sided one sample t test was used to determine if mean HbA1c reduction in each group was < - 0.5% (beneficial metabolic response). An analysis of covariance estimated the change in HbA1c and FPG adjusted by baseline HbA1c, FPG, body mass index (BMI) and study site. Response rates to treatment were also established. No between-group statistical comparisons were planned., Results: HbA1c mean reductions were - 1.26% (90% CI - 1.7%, - 0.8%), - 1.12% (90% CI - 1.4%, - 0.8%), - 1.29% (90% CI - 1.6%, - 1.0%), and - 1.15% (90% CI - 1.5%, - 0.8%) in groups EVO 2.5 mg, EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. FPG levels showed a mean increase of 10.89 mg/dL in group EVO 2.5 mg, with significant mean reductions of - 18.94 mg/dL, - 21.17 mg/dL, and - 39.90 mg/dL in those treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. BW showed significant reductions of approximately 1 kg in patients treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg. Mean adjusted reductions of HbA1c and FPG levels confirmed the significant clinical benefit of all study treatments. The clinical benefit of EVO's "target" dose (5 mg) was confirmed. No safety concerns were identified., Conclusions: These results validate for the Brazilian population the approved dose regimen of EVO (once-daily 5 mg). Trial registration ClinicalTrials.gov Identifier: NCT02689362 (first posted on 02/23/2016)., Competing Interests: Competing interestsACF, JSF, JLCB, CC—Received financial support for the research and is a speaker for Eurofarma Laboratórios S.A. LATR, JS, PM, TB, ARC, FE—Received financial support for the research., (© The Author(s) 2019.)

Purpose: Serum IGF-1 (Insulin like growth factor 1) and Growth Hormone (GH) provocative tests are reasonable tools for screening and diagnosis of idiopathic GH Deficiency (IGHD). However, the average cut-off points applied on these tests have a lower level of evidence and produce large amounts of false results. The aim of this study is to evaluate the sensitivity, specificity, and accuracy of IGF-1 and GH stimulation tests as diagnostic tools for IGHD, using clinical response to recombinant human GH (rhGH) treatment as diagnostic standard [increase of at least 0.3 in height standard deviation (H-SD) in 1 year]. Methods: We performed a prospective study with 115 children and adolescents presenting short stature (SS), without secondary SS etiologies such as organic lesions, genetic syndromes, thyroid disorders. They were separated into Group 1 [patients with familial SS or constitutional delay of growth and puberty (CDGP), not treated with rhGH], Group 2 (patients with suspicion of IGHD with clinical response to rhGH treatment), and Group 3 (patients with suspicion of IGHD without growth response to rhGH treatment). Then, they were assessed for diagnostic performance of IGF-1, Insulin Tolerance Test (ITT) and clonidine test (CT) alone and combined at different cut-off points. Results: Based on the ROC curve, the best cut-off points found for IGF-1, ITT, and CT when they were used isolated were -0.492 SDS (sensitivity: 50%; specificity: 53.8%; accuracy: 46.5%), 4.515 μg/L (sensitivity: 75.5%; specificity: 45.5%; accuracy: 52.7%), and 4.095 μg/L (sensitivity: 54.5%; specificity: 52.6%; accuracy: 56.9%), respectively. When we had combined IGF-1 with-2SD as cut-off alongside ITT or CT, we found 7 μg/L as the best cut-off point. In this situation, ITT had sensitivity, specificity and accuracy of 93.9, 81.8, and 90.1%, while CT had 93.2, 68.4, and 85.7%, respectively. Conclusion: Our data suggest that diagnosis of IGHD should be established based on a combination of clinical expertise, auxologic, radiologic, and laboratorial data, using IGF-1 at the -2SD threshold combined, with ITT or CT at the cut-off point of 7 μg/L. Additional studies, similar to ours, are imperative to establish cut-off points based on therapeutic response to rhGH in IGHD, which would be directly related to a better treatment outcome., (Copyright © 2019 Felício, Janaú, Moraes, Zahalan, de Souza Resende, de Lemos, de Souza Neto, Farias de Franco, Leitão, Silva, de Oliveira, de Alcântara, Contente Braga de Souza, da Silva, dos Santos, de Queiroz, de Moraes, de Figueiredo, Farinassi, Farias, da Silva, Felício and Abrahão Neto.)

Background: Peripheral arterial disease in patients with type 2 diabetes mellitus is an important risk factor for vascular events. Recommendations about whether ankle-brachial index should be performed differ depending on the source; therefore, it is necessary to re-evaluate the most important risk factors associated with peripheral arterial disease and whether it is useful to perform ankle-brachial index in newly diagnosed and drug-naïve patients with diabetes, independent of age or peripheral arterial disease symptoms., Methods: A total of 711 subjects were divided into groups: group 1, 600 type 2 diabetes mellitus patients, symptomatic or not for peripheral arterial disease; group 2, 61 type 2 diabetes mellitus patients newly diagnosed and drug naïve; and group 3, 50 subjects without diabetes. Ankle-brachial index, medical records and physical examination were performed in all patients, accessing cardiovascular risk factors., Results: Analysing group 1 asymptomatic patient to peripheral arterial disease, we found abnormal ankle-brachial index in 49% (77/156) ⩾50 years and 42% (16/38) <50 years ( p  = not significant). Considering drug-naïve patients, a peripheral arterial disease prevalence of 39% (24/61) was found; among these, 48% (13/27) were <50 years and 32% (11/34) were ⩾50 years ( p  = not significant). A forward stepwise regression model was developed, with type 2 diabetes mellitus duration ( r 2  = 0.12) and sedentary lifestyle ( r 2  = 0.14) found as independent variable predictors of severity of peripheral arterial disease, related to ankle-brachial index., Conclusion: We suggest that, in type 2 diabetes mellitus, ankle-brachial index should be measured at diagnosis. In addition, sedentary lifestyle was strongly associated with presence and severity of peripheral arterial disease.

Sensorineural hearing impairment has been associated with DM, and it is probably linked to the same pathophysiological mechanisms as well-established in microvascular diabetes complications. The study of otoacoustic emissions (OAEs) is useful to identify subclinical cochlear dysfunction. Therefore, the aim of this study was to evaluate the association between abnormal OAEs responses, diabetic kidney disease (DKD) and diabetic cardiac autonomic neuropathy (CAN). We performed a cross-sectional study with 37 type 1 DM patients without auditory symptoms, submitted to the study of Distortion Product Otoacoustic Emissions (DPOAEs) and screened for DKD and CAN. The otoacoustic emissions responses were considered abnormal in 27/37 (73%) patients. A correlation was found between abnormal OAEs responses and presence of DKD (r = 0.36, p < 0.05), and 14/16 (88%) patients with a lower amplitude of OAEs in 8 kHz frequency band presented DKD. Abnormal OAEs responses in the 6 kHz frequency band were correlated with the presence (r = 0.41, p = 0.01) and severity of CAN (r = 0.44, p < 0.001). Additionally, 7/9 (78%) patients with abnormal OAE responses in this frequency also presented abnormal CAN scores. Our results suggest that abnormal otoacoustic emissions responses in high frequency bands are associated with diabetes microvascular complications and could be a risk marker for DKD and CAN, presenting low sensitivity and high specificity. Therefore, assuming that hearing impairment is a pre-clinical stage of hearing loss, performing distortion product otoacoustic emissions in T1DM patients with microvascular complications could be useful to identify those who would be benefit with regular audiologic follow up and tighter diabetes control.

Background In the EXSCEL (Exenatide Study of Cardiovascular Event Lowering), exenatide once-weekly resulted in a nonsignificant reduction in major adverse cardiovascular events ( MACEs ) and a nominal 14% reduction in all-cause mortality in 14 752 patients with type 2 diabetes mellitus (T2 DM ) with and without cardiovascular disease. Whether patients at increased risk for events experienced a comparatively greater treatment benefit with exenatide is unknown. Methods and Results In the EXSCEL population, we created risk scores for MACEs and all-cause mortality using step-wise selection of baseline characteristics. A risk score was calculated for each patient, and a time-to-event model for each end point was developed including the risk score, treatment assignment, and risk-treatment interaction. Interaction P values evaluating for a differential treatment effect by baseline risk were reported. Over a median follow-up of 3.2 years (interquartile range, 2.2, 4.4), 1091 (7.4%) patients died and 1744 (11.8%) experienced a MACE . Independent predictors of MACEs and all-cause mortality included age, sex, comorbidities (eg, previous cardiovascular event), body mass index, blood pressure, hemoglobin A1c, and estimated glomerular filtration rate. The all-cause mortality and MACE risk models had modest discrimination with optimism-corrected c-indices of 0.73 and 0.71, respectively. No interaction was observed between treatment effect and risk profile for either end point (both interactions, P>0.1). Conclusions Baseline characteristics (eg, age, previous cardiovascular events) and routine laboratory values (eg, hemoglobin A1c, estimated glomerular filtration rate) provided modest prognostic value for mortality and MACEs in a broad population of patients with type 2 diabetes mellitus. Exenatide's effects on mortality and MACEs were consistent across the spectrum of baseline risk. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 01144338.

Background: Some studies suggest an association between diabetic kidney disease (DKD) and vitamin D (VD), but there is no data about the effect of high dose of VD on DKD in type 1 diabetes mellitus (T1DM). Our pilot study aims to evaluate albuminuria reduction in patients with T1DM supplemented with high dose of VD., Methods: 22 patients received doses of 4,000 and 10,000 IU/day of cholecalciferol for 12 weeks according to patient's previous VD levels. They were submitted to continuous glucose monitoring system, 24 hours ambulatory blood pressure monitoring and urine albumin-to-creatinine ratio before and after VD supplementation., Results: There was a reduction of DKD prevalence at the end of the study (68 vs 32%; p  = 0.05), with no changes on insulin doses, glycated hemoglobin, glycemic variability and blood pressure values. A correlation between percentage variation of VD levels (ΔVD) and albuminuria at the end of the study was presented ( r  = -0.5; p  < 0.05). Among T1DM patients with DKD at the beginning of the study, 8/13 (62%) had their DKD stage improved, while the other five ones (38%) showed no changes ( p  < 0.05)., Conclusion: Our pilot study suggests an association between VD high dose supplementation, lower prevalence and improvement in stages of DKD in T1DM.

Context: Genetic and environmental factors are involved in the pathogenesis of type 1 diabetes mellitus (T1DM), and vitamin D (VD) deficiency appears as a candidate to risk factor for developing diabetic kidney disease (DKD)., Objective: The purpose of study was to evaluate the existence of an association between low levels of VD and the presence and degree of DKD in T1DM., Patients and Methods: We performed a cross-sectional study, between November 2014 and December 2015. Levels of 25(OH)D and albuminuria were analyzed in 37 patients with T1DM and normal glomerular filtration rate. Thirty-six subjects were evaluated as a control group., Results: Patients with T1DM and hypovitaminosis D had higher levels of albuminuria compared to those with normal VD levels [albuminuria (log 10 ) = 1.92 vs. 1.44; p  < 0.05]. When we have separated the group of patients according to stage of DKD in patients with normo, micro, and macroalbuminuria, there are lower levels of 25(OH)D in the last when compared to the first two groups (26.7 ± 6.2, 24.8 ± 7.0, and 15.9 ± 7.6 ng/ml; p  < 0.05, respectively). In T1DM group, we have found correlations between VD levels and both albuminuria and DKD stages ( r  = -0.5; p  < 0.01 and r  = -0.4; p  < 0.05, respectively). A simple linear regression model, with albuminuria as the dependent variable and VD as an independent variable, showed r 2 = 0.2 and p  < 0.01., Conclusion: Our data suggest an association between reduced levels of VD and the presence and severity of DKD.

Mycobacterium avium complex (MAC) is a heterogeneous group of species found in several environmental sources and that exhibit variable degrees of pathogenicity. Among the MAC members, Mycobacterium colombiense has been related to pulmonary disease and disseminated infection in HIV-infected patients in Colombia. Lymphadenopathy cases have also been reported. We have described a fatal case of M. colombiense pulmonary disease in a Brazilian patient without evidence of HIV infection or other known causes of immunosuppression., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Context: Ultrasound (US)-guided percutaneous ethanol injection (PEI) has been proposed for treatment of benign thyroid nodules (TNs). However, there is no consensus for the optimal amount of ethanol injection, number of applications, and time to re-evaluation in order to achieve maximum volume reduction with minimum adverse effects., Objective: The purpose of the present study was to analyze the effectiveness of an US-guided PEI protocol to treat solid and mixed TNs based on a new target outcome., Patients and Methods: We performed a prospective study evaluating the results of PEI in 52 patients with benign solid and mixed TNs. The ethanol dose was fixed in 30% of the nodular volume per session. Patients returned 1 month after each session for US re-evaluation. Therapeutic success was defined as volume reduction of at least 30% associated with disappearance of clinical symptoms and a complete esthetic satisfaction reported by the patient., Results: We performed a mean of 2.8 ± 1.9 PEI sessions, with an average total volume of ethanol injected of 9.1 ± 10.3 ml, and a follow-up time of 10.0 ± 8.7 months. There was a reduction of at least 50% of the initial nodular volume in 33 patients (63.5%). In 11 patients (21.2%), the reduction did not reach 50% (mean reduction of 31 ± 11%), but 6 of them reported esthetically satisfactory results and treatment was stopped. Our therapeutic success rate considering the patients with esthetic improvement was 75%. There were no severe complications., Conclusion: Our protocol is effective and safe to treat solid and mixed benign TNs based on our established outcome.

The pathogenesis of diabetic cardiomyopathy (DCM) is partially understood and is likely to be multifactorial, involving metabolic disturbances, hypertension and cardiovascular autonomic neuropathy (CAN). Therefore, an important need remains to further delineate the basic mechanisms of diabetic cardiomyopathy and to apply them to daily clinical practice. We attempt to detail some of these underlying mechanisms, focusing in the clinical features and management. The novelty of this review is the role of CAN and reduction of blood pressure descent during sleep in the development of DCM. Evidence has suggested that CAN might precede left ventricular hypertrophy and diastolic dysfunction in normotensive patients with type 2 diabetes, serving as an early marker for the evaluation of preclinical cardiac abnormalities. Additionally, a prospective study demonstrated that an elevation of nocturnal systolic blood pressure and a loss of nocturnal blood pressure fall might precede the onset of abnormal albuminuria and cardiovascular events in hypertensive normoalbuminuric patients with type 2 diabetes. Therefore, existing microalbuminuria could imply the presence of myocardium abnormalities. Considering that DCM could be asymptomatic for a long period and progress to irreversible cardiac damage, early recognition and treatment of the preclinical cardiac abnormalities are essential to avoid severe cardiovascular outcomes. In this sense, we recommend that all type 2 diabetic patients, especially those with microalbuminuria, should be regularly submitted to CAN tests, Ambulatory Blood Pressure Monitoring and echocardiography, and treated for any abnormalities in these tests in the attempt of reducing cardiovascular morbidity and mortality.

Background: Type 1 Diabetes Mellitus (Type 1 DM) affects the psychological and emotional well-being of patients and their families. This study aims to evaluate the health- related quality of life (HRQoL) of people with Type 1 DM in Brazil, a country of continental proportions, using the EuroQol questionnaires., Methods: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group, by analyzing EuroQol scores from 3,005 participants with Type 1 DM, in 28 public clinics in Brazil. Data on demography, economical status, chronic complications, glycemic control and lipid profile were also collected., Results: The assessment of HRQoL by the EuroQol showed that the average score assigned to general health in Brazil is markedly lower than those found in two other Type 1 DM population-based studies conducted in Europe (EQ-VAS from the Netherlands, the United Kingdom and Brazil were 80.8 ± 15.2, 75.1 ± 18.4 and 72.5 ± 22, respectively). Additionally, our data suggest that a better glycemic control could positively impact the HRQoL of people with Type 1 DM, implying that each 1 % reduction in glycated haemoglobin might lead to an increase of 1.5 points in general health status assessed by the EuroQol., Conclusions: This is a population-based study evaluating the HRQoL of people with Type 1 DM in Brazil. Our data indicate a worse quality of health of people with Type 1 DM in Brazil in comparison to Europe, and suggest that a better glycemic control could positively impact the HRQoL of these individuals. However, this study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of these people.

Background: In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities., Methods: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected., Results: We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North-Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined., Conclusions: Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.

Context: The supervised 72-h fast remains the gold standard test for the diagnosis of endogenous hyperinsulinism and has recently been suggested to be shortened or even avoided., Objective: This study aimed to evaluate whether measurement of blood glucose, insulin and C-peptide levels after a 12 h overnight fast (mini-fasting test), in at least 3 consecutive days, could allow making or ruling out diagnosis of endogenous hyperinsulinism, according to the Endocrine Society's recent guidelines., Patients and Methods: We performed 12 h mini-fasting test in at least 3 consecutive days, dosing blood glucose, insulin and C-peptide levels in 26 inpatient patients with pathologically proven endogenous hyperinsulinism., Results: In our series, 100% of patients showed insulin levels of at least 3 μU/ml and C-peptide levels of at least 0.6 ng/ml concomitant with symptomatic hypoglycemia (≤ 55 mg/dl)., Conclusion: It leads to the conclusion that mini-fasting test might avoid, in most cases, prolonged fasting test for the diagnosis of hypoglycemia due to endogenous hyperinsulinism., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Objective. This study evaluated the prevalence, awareness, and type of treatment for hypertension in Brazil in patients with type 1 diabetes (T1D). Methods. This was a cross-sectional, multicenter study that was conducted from December 2008 to December 2010 in 28 public clinics located in 20 Brazilian cities. Results. A total of 3,591 patients were studied, 56% female, average age 21.2 ± 11.7 years, with a median duration of diabetes 9.6 ± 8.1 years. Blood pressure levels were available for a total of 3,323 patients and 689 (19.2%) patients were hypertensive. Hypertensive patients were older, exhibited longer duration of diabetes, and had higher body mass index (BMI), total cholesterol, triglycerides, and LDL-C values (P < 0.001, for all comparisons), but only 370 (53.7%) received treatment. Patient awareness of hypertension was documented in 453 (65.5%) patients. However, only 76 (22.9%) of the treated patients attained the target systolic (sBP) and diastolic blood pressures (dBP). Conclusions. Our results demonstrate that a large number of T1D patients with hypertension do not receive appropriate treatment; few of the treated T1D patients achieved the target sBP and dBP values. Greater attention should be paid to blood pressure evaluation, hypertension diagnosis, and treatment of T1D patients in Brazil.

Objective: To determine the prevalence of patients with type 1 diabetes mellitus who meet the glycemic and cardiovascular (CV) risk factors goals and the frequency of screening for diabetic complications in Brazil according to the American Diabetes Association guidelines., Research Design and Methods: This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 1774 adult patients (56.8% females, 57.2% Caucasians) aged 30.3 ± 9.8 years with diabetes duration of 14.3 ± 8.8 years., Results: Systolic blood pressure was at goal in 40.3% and diastolic blood pressure was at goal in 26.6% of hypertensive patients. LDL cholesterol and HbA1c were at the goal in 45.2% and 13.2% of the patients, respectively. Overweight was presented in 25.6% and obesity in 6.9%. Among those with more than 5 years of disease, screening for retinopathy was performed in the preceding year in 70.1%. Nephropathy and feet complications were screened in 63.1% and 65.1%, respectively., Conclusions: The majority of patients did not meet metabolic control goals and a substantial proportion was not screened for diabetic complications. These issues may increase the risk of chronic complications and negatively impact public health., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Diagnosis of endogenous hyperinsulinism caused by insulinoma is based on confirmation of hypoglycemia during the symptoms associated to elevated insulin levels. Patients with insulinoma may demonstrate an excessive insulin response and subsequent hypoglycemia after 1 mg of glucagon iv injection. Glucagon test was performed in 11 patients with insulinoma before therapy and in 4 after therapy. Our study suggests that the presence of plasma glucose levels less than 55 mg/dl and below baseline at time 120 min of glucagon test strongly reinforce the diagnosis of insulinoma.

Hypoglycemia due to endogenous hyperinsulinism (EH) is diagnosed in a symptomatic patient with low levels of plasma glucose concomitant with elevated plasma insulin and C-peptide. Causes of EH are pancreatic islet-cells disease, use of insulin secretagogues, and autoimmune hypoglycemia. In this review, the authors studied 24 patients with hypoglycemia due to endogenous hyperinsulinism in order to describe aspects of diagnosis and treatment. Our study demonstrated that after 12 hours of fasting (mini-fasting test; at least three samples), all patients presented the diagnostic criteria for EH. Additionally, we found that 11 of 12 patients (91.7%) who underwent glucagon test achieved glucose levels less than 50 mg/dL and below baseline after 120 minutes. Mini-fasting (3 samples) and glucagon test may be useful to prevent prolonged fasting test to clarify the diagnosis of endogenous hyperinsulinism.

Spinal epidural abscess (SEA) is an uncommon condition and its most important predisposing factor is diabetes mellitus. Although the treatment of choice is prompt surgical abscess evacuation, followed by antibiotic therapy, successful conservative treatment of SEA has been reported in some cases. We describe a SEA case in a 23-year old white woman with diabetes for 14 years, who was successfully treated only with antibiotics, and achieved full recovery at the fourth month of follow-up.

Background: Hypertensive patients with reduced blood pressure fall (BPF) at night are at higher risk of cardiovascular events (CVE)., Methods: We evaluated in hypertensive diabetic patients, if a reduced nocturnal BPF can precedes the development of diabetic nephropathy (DN). We followed 70 patients with normal urinary albumin excretion (UAE) for two years. We performed 24-hours ambulatory BP monitoring in baseline and at the end of the study., Results: Fourteen (20%) patients (GI) developed DN (N = 11) and/or CVE (n = 4). Compared to the remaining 56 patients (GII) in baseline, GI had similar diurnal systolic (SBP) and diastolic BP (DBP), but higher nocturnal SBP (138 +/- 15 vs 129 +/- 16 mmHg; p < 0.05) and DBP (83 +/- 12 vs 75 +/- 11 mmHg; p < 0,05). Basal nocturnal SBP correlated with occurrence of DN and CVE (R = 0.26; P < 0.05) and with UAE at the end of the study (r = 0.3; p < 0.05). Basal BPF (%) correlated with final UAE (r = -0.31; p < 0.05). In patients who developed DN, reductions occurred in nocturnal systolic BPF (12 +/- 5 vs 3 +/- 6%, p < 0,01) and diastolic BPF (15 +/- 8 vs 4 +/- 10%, p < 0,01) while no changes were observed in diurnal SBP (153 +/- 17 vs 156 +/- 16 mmHg, NS) and DBP (91 +/- 9 vs 90 +/- 7 mmHg, NS). Patients with final UAE < 20 microg/min, had no changes in nocturnal and diurnal BP., Conclusions: Our results suggests that elevations in nocturnal BP precedes DN and increases the risk to develop CVE in hypertensive patients with T2DM.

Background: Hypertensive diabetic patients, when compared with essential hypertensive patients, have a higher left ventricular mass index (LVMI) and an impaired cardiac diastolic function (CDF). Autonomic neuropathy (AN) could contribute to this finding., Objective: To evaluate the relationship between AN tests, and LVMI and CDF in normotensive patients with type 2 diabetes mellitus (DM2) and without AN symptoms or left ventricular hypertrophy., Methods: In 21 normotensive patients with DM2 (group 1) and 16 control subjects (group 2), LVMI and CDF were evaluated using atrial deceleration time, isovolumic relaxation time, E wave, A wave and E/A wave ratio. AN tests performed included a deep breathing test, Valsalva manoeuvre and lying-to-standing test., Results: Groups did not differ in clinical and echocardiographic characteristics. None of the patients in either group presented with left ventricular hypertrophy. In group 1, there were correlations between the deep breathing test and LVMI (r=-0.6; P<0.01) and between the deep breathing test and E/A wave ratio (r=0.4; P<0.05). No correlations were found in the control group., Conclusion: In DM2 patients, AN tests correlated with LVMI and CDF before left ventricular hypertrophy, hypertension, impaired CDF and diabetic AN symptoms were present. The present study suggests that AN tests could be regularly performed in DM2 patients. Any abnormalities in tests should be followed by a cardiac evaluation.

The aim of the present study was to evaluate the influence of elevated levels of nocturnal blood pressure (BP) on diabetic retinopathy (DR). A total of 88 diabetic hypertensive patients were divided according to the stage of DR. They underwent 24 h ambulatory BP monitoring and ophthalmological evaluation, and their average level of fasting blood glucose as well as their glycemic control index (percentage of fasting blood glucose higher than 11.2 mmol/L over the previous four years) were calculated. When diabetic patients with retinopathy (n=29) (group 1) were compared with patients without retinopathy (n=59) (group 2), a significant difference was observed in diabetes duration (124 months [range six to 460 months] versus 43 months [range six to 365 months], respectively; P<0.05). In addition, group 1 showed higher levels of nocturnal systolic BP (NSBP) (141 +/- 22 mmHg versus 132+/-18 mmHg; P<0.05). However, no significant differences were found between the two groups (group 1 and group 2) when diurnal pressoric levels were compared (diurnal systolic BP, 153+/-19 mmHg versus 146+/-19 mmHg, P not significant; and diurnal diastolic BP, 91+/-9 mmHg versus 91+/-13 mmHg, P not significant). DR correlated with diabetes duration (r=0.26; P<0.05) and with glycemic control index (r=0.24; P<0.01). Multivariate regression analysis showed NSBP to be an independent predictor of DR (r(2)=0.12; P<0.01). Moreover, patients with severe stages of DR (preproliferative, proliferative or macular edema) showed a lower decrease of NSBP than the other patients (3.9+/-6.0 mmHg versus 9.2+/-6.0 mmHg; P<0.05). The present study suggests that the absence of 24 h normal pressoric rhythm can interfere with the prevalence and severity of DR.

Objective: To evaluate the reproducibility of ambulatory blood pressure monitoring (ABPM) (SpaceLabs-90207) and placebo effect on ABPM., Methods: Blood pressure was measured in the office and over two ABPM periods with an interval from one to ten months (mean 4.9 months), in 26 patients with type 2 diabetes mellitus and hypertension. Eleven patients (G1) had two ABPMs without taking antihypertensive drugs for 15 days, whereas G2 (N=15) had the second ABPM after administration of a placebo for 15 days., Results: In the evaluation of the coefficient of variation (CV) of diurnal (awake) systolic BP (DSBP), of diurnal (awake) diastolic BP (DDBP), of 24-hour systolic BP (24hSBP) and of 24-hour diastolic BP (24hDBP), the values found were 4.6%, 3.9%, 5.0%, 4.0% for G1 and 4.3%, 5.1%, 3.7%, 5.1% for G2 respectively. We also determined the CV of nocturnal (sleep) systolic and diastolic BP (NSBP and NDBP) for G1 (7.7%; 8.2%) and G2 (5.6%; 6.3%). Heart rate CV during alertness and sleep were: G1=5.9% and 9.0%; G2=6.9% and 5.8% respectively. When the total number of 'patients was analyzed, all variables showed a strong correlation between the first and second ABPM measurements (DSBP, r = 0.76; P < 0.001; DDBP, r = 0.65; p < 0.001; 24hSBP, r = 0.77; p < 0.001; 24hDBP, r = 0.70; p < 0.001; NSBP, r = 0.62; p < 0.001; NDBP, r = 0.52; p < 0.01). Office systolic and diastolic BP and 24hSBP and 24hDBP also showed correlation (r = 0.65; p < 0.001; r = 0.57; p < 0.01)., Conclusion: Mean of pressure levels measured by ABPM presented good reproducibility and were not affected by placebo.

Background: The aim of this study was to determine if hypertensive type 2 diabetic patients, when compared to patients with essential hypertension have an increased left ventricular mass index (LVMI) and a worse diastolic function, and if this fact would be related to 24-h pressoric levels changes., Methods: Ninety-one hypertensive patients with type 2 diabetes mellitus (DM) (group-1 [G1]), 59 essential hypertensive patients (group-2 [G2]) and 26 healthy controls (group-3 [G3]) were submitted to 24-h Ambulatory Blood Pressure Monitoring (ABPM) and echocardiography (ECHO) with Doppler. We calculated an average of fasting blood glucose (AFBG) values of G1 from the previous 4.2 years and a glycemic control index (GCI) (percentual of FBG above 200 mg/dl)., Results: G1 and G2 did not differ on average of diurnal systolic and diastolic BP. However, G1 presented worse diastolic function and a higher average of nocturnal systolic BP (NSBP) and LVMI (NSBP = 132 +/- 18 vs 124 +/- 14 mmHg; P < 0.05 and LVMI = 103 +/- 27 vs 89 +/- 17 g/m2; P < 0.05, respectively). In G1, LVMI correlated with NSBP (r = 0.37; P < 0.001) and GCI (r = 0.29; P < 0.05) while NSBP correlated with GCI (r = 0.27; P < 0.05) and AFBG (r = 0.30; P < 0.01). When G1 was divided in tertiles according to NSBP, the subgroup with NSBP> or =140 mmHg showed a higher risk of LVH. Diabetics with NSBP> or =140 mmHg and AFBG>165 mg/dl showed an additional risk of LVH (P < 0.05; odds ratio = 11). In multivariate regression, both GCI and NSBP were independent predictors of LVMI in G1., Conclusion: This study suggests that hyperglycemia and higher NSBP levels should be responsible for an increased prevalence of LVH in hypertensive patients with Type 2 DM.