High-dose Vitamin D Supplementation on Type 1 Diabetes Mellitus Patients: Is there an Improvement in Glycemic Control?

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.

Association Between 25(OH)Vitamin D, HbA1c and Albuminuria in Diabetes Mellitus: Data From a Population-Based Study (VIDAMAZON).

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.

Association of Soy and Exclusive Breastfeeding With Central Precocious Puberty: A Case-Control Study.

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.

High-dose Cholecalciferol Supplementation Reducing Morning Blood Pressure in Normotensive DM1 Patients.

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.

Improvement in Cardiovascular Autonomic Neuropathy After High-Dose Vitamin D Supplementation in Patients With Type 1 Diabetes.

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.

Diagnosis of Idiopathic GHD in Children Based on Response to rhGH Treatment: The Importance of GH Provocative Tests and IGF-1.

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.

Cochlear dysfunction and microvascular complications in patients with type 1 diabetes mellitus.

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.

Albuminuria Reduction after High Dose of Vitamin D in Patients with Type 1 Diabetes Mellitus: A Pilot Study.

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.

Central nervous system tumours profile at a referral center in the Brazilian Amazon region, 1997-2014.

Tumours of the Central Nervous System (CNS) are an important cause of mortality from cancer. Epidemiological data on neoplams affecting the CNS are scarce in Brazil, especially in the Amazon region. The study aims at describing the histopathological profile of CNS tumours cases at a high-complexity referral cancer center. This study has described a 17-year-series profile of CNS tumours, registered at a high-complexity referral cancer center in Pará state, from January 1997 until July 2014 in the Brazilian Amazon Region. Data was gathered from histopathology reports kept in the hospital's cancer registry and 949 cases of CNS tumours were analyzed. The most common histopathology were neuroepithelial tumours (approx. 40%) and meningioma was the most frequent especific tumor histologic subtype (22.2%). Neuroepithelial tumours were more frequent in patients with ages ranging from less than a year to 19 years, whereas metastatic tumours were prevalent in patients over 40 years of age. It was not found temporal trends during the studied period. The knowledge of these tumours profile is valuable for the understanding of cancer epidemiology in the region, since its prevalence is currently underreported and more awareness on the disease is needed.

Vitamin D on Early Stages of Diabetic Kidney Disease: A Cross-sectional Study in Patients with Type 1 Diabetes Mellitus.

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 (log10) = 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 r2 = 0.2 and p < 0.01. CONCLUSION: Our data suggest an association between reduced levels of VD and the presence and severity of DKD.