High anxiety and depressive symptoms in partners of type 1 diabetes persons in a sample of the Brazilian population.

BACKGROUND: Type 1 diabetes (T1D) affects psychologically not only the persons with diabetes themselves but affects their family members. Few studies were conducted to investigate mental health in T1D partners. This study aims: (1) to investigate the frequency of depressive and anxiety symptoms in T1D partners and, (2) to investigate the associations among partners' depressive and anxiety symptoms and their sociodemographic and behavioral characteristics, and (3) to investigate the associations among partners' depressive and anxiety symptoms and clinical, laboratory and demographic characteristics of their T1D spouses in a Brazilian population. METHODS: In a transversal study 72 T1D partners were interviewed. Partners were invited to take part in the study during their T1D spouses' routine consultations. Those who consented to take part in the study signed the consent form. This study followed the principles of the Declaration of Helsinki and was approved by the University Ethics in Research Committee. Inclusion criteria were T1D partners age ≥ 18 and T1D diagnosis > 6 months. Exclusion criteria were cognitive impairment, history of major psychiatric disorders, and severe chronic and terminal diseases. Depressive symptoms were evaluated by the depression subscale of the Hospital Anxiety and Depression scale (HADD) and anxiety symptoms were evaluated by the anxiety subscale of the same instrument (HADA). T1D partners were divided into subgroups according to score ≥ 8 and < 8 in both subscales. Demographic and clinical data were obtained from interview. Descriptive analyses were undertaken using means and percentages, as appropriate. Differences between groups were assessed by the Mann-Whitney test for numerical variables, by the Chi Square test or by Fisher's exact test for categorical variables, as appropriate. All analyses were undertaken using SAS version 9.2 for Windows. Statistical significance was set at 0.05. RESULTS: Of all 72 T1D partners, 72.2% were male, mean age was 42.7 ± 14.1 years old, years of school attendance were 11.8 ± 3.9 years, and 48.5% had income reaching until 3 Brazilian minimal wages. Forty-three percent reported high anxiety symptoms (HADA ≥ 8) and 18.1% reported high depressive symptoms (HADD ≥ 8). Comparing T1D partners group with HADA ≥ 8 and < 8, the first one was associated with CGM use (41.94% vs 19.51%; p = 0.03). Similarly, comparing T1D partners group with HADD ≥ 8 and < 8, the first one was associated with (1) longer duration of T1D of their spouses (28.6 ± 7.1 vs 22.4 ± 12.2; p = 0.02); (2) less years of school attendance of T1D partners (9.3 ± 3.2 vs 12.3 ± 3.8; p = 0.02), and (3) higher number of hypoglycemic episodes requiring other person's intervention (6.3 ± 8.9 vs 2.4 ± 4.7; p = 0.009). Seventy-six percent of partners who helped personally in their spouses' hypoglycemia recovery had HADD ≥ 8 vs 44.7% with HADD < 8 (p = 0.03). Likewise, 84.6% vs 54.2% of partners in which their spouses have T1D chronic complications had HADD ≥ 8 and < 8, respectively (p = 0.04). CONCLUSION: This study showed a high frequency of relevant anxiety and depressive symptoms in this T1D partner population. Several issues related to T1D of their spouses were associated with these symptoms. These results emphasize the need to incorporate the psychological and psychiatric aspects into T1D partners' education and care.

Low empowerment and diabetes regimen distress are related to HbA1c in low income type 1 diabetes patients in a Brazilian tertiary public hospital.

BACKGROUND: Adults with type 1 diabetes (T1D) have a high risk of developing depressive symptoms and diabetes-related distress (DD). Low socioeconomic level is associated with increased risk of poor self-management, treatment difficulties and psychological distress. The goals of this study were to document the frequency of major depressive disorder (MDD), high depressive symptoms and high DD, to assess levels of empowerment and to determine the association with each of these measures and glycemic control in a low-income Brazilian sample of adults with T1D. METHODS: In a cross-sectional study, inclusion criteria were age > 18 years and diagnosis of T1D > 6 months. Exclusion criteria were cognitive impairment, history of major psychiatric disorders, severe diabetes-related complications and pregnancy. Diagnoses of MDD were made using interview-based DSM-5 criteria. Depressive symptoms were evaluated by the depression subscale of the Hospital Anxiety and Depression Scale (HAD-D). The Diabetes Distress Scale (DDS) assessed DD. Empowerment levels were evaluated by the Diabetes Empowerment Scale short form (DES-SF). Glycemic control was measured by HbA1c. The latest lipid panel results were recorded. Number of complications was obtained from medical records. RESULTS: Of the 63 T1D patients recruited, 36.5% were male, mean age was 31.5 (± 8.9), mean number of complications was 1 (± 1.1), and mean HbA1c was 10.0% (± 2). Frequency of MDD was 34.9% and 34.9% reported high depressive symptoms. Fifty-seven percent reported clinically meaningful DD. High diabetes regimen distress and low empowerment were associated to HbA1c (p = 0.003; p = 0.01, respectively). In multivariate analyses, lower empowerment levels were associated to higher HbA1c (beta - 1.11; r-partial 0.09; p value 0.0126). MDD and depressive symptoms were not significantly correlated with HbA1c in this expected direction (p = 0.72; p = 0.97, respectively). CONCLUSIONS: This study showed high rates of MDD, high depressive symptoms and high DD and low levels of empowerment in this low income population. Empowerment and diabetes regimen distress were linked to glycemic control. The results emphasize the need to incorporate the psychological and psychosocial side of diabetes into strategies of care and education for T1D patients.

Relatively young T1D adults using fixed doses of insulin have higher diabetes distress levels in a sample of patients from a Brazilian tertiary hospital.

BACKGROUND: Elevated rates of anxiety and depressive symptoms in Type 1 Diabetes patients (T1D) and high rates of diabetes-specific distress (DD) have been shown. Several factors may be responsible for increase the DD levels such as age, life changes, lack of familiar support, education, insulin regimens (IRs) and chronic complications. The goals of this study were: 1-to compare DD levels, anxiety and depressive symptoms according to age (< and ≥ 25 years old), 2-to evaluate the association between DD levels, anxiety and depressive symptoms and IRs, and 3-to evaluate the association between DD levels, anxiety and depressive symptoms and chronic complications. METHODS: In a cross-sectional study, T1D patients receiving outpatient care at Unicamp tertiary hospital were included. Inclusion criteria were age at least 18 years old and diagnosis of T1D for 6 months. Exclusion criteria were cognitive impairment, major psychiatric disorders, severe diabetes-related complications, and pregnancy. Depressive symptoms were evaluated by the depression subscale of the Hospital Anxiety and Depression Scale (HAD-D) and the anxiety symptoms by the anxiety subscale of the same instrument (HAD-A). DDS scale assessed DD. Glycemic control was evaluated by HbA1C. The latest lipid panel results were recorded and IRs and chronic complications were obtained through chart review. RESULTS: Of all 70 patients, 70% were younger than 25 years old. No differences were found between two groups according to gender, education, and income (p = 0.39, p = 0.87, and p = 0.52, respectively). HbA1c mean was 10% in both groups (p = 0.15). Older patients had higher levels of total DD and physician DD than younger (p = 0.0048 and p = 0.0413; respectively).Total DD and DD on subscales 1 and 2 were higher in patients using fixed doses of insulin compared to variable doses according to carbohydrates count (p = 0.0392, p = 0.0383 and p = 0.0043, respectively). No differences were found between anxiety and depressive symptoms and age and IRs. Similarly, no differences were found among DD levels, anxiety and depressive symptoms in patients with and without chronic complications. CONCLUSIONS: When providing education and care for T1D patients, health providers should consider age, patient's developmental stage, with its related demands and the burden of insulin regimen.

Translation and cultural adaptation into Brazilian culture of type 1 diabetes distress scale.

BACKGROUND: Diabetes related distress is common in type 1 diabetes patients (T1D). High levels of diabetes distress are related to poor metabolic control. An instrument to evaluate diabetes distress in T1D patients is "type 1 diabetes scale-T1DDS". The aim of this study was to translate and culturally adapt the T1DDS into Brazilian culture. METHODS: T1DDS scale was translated into Portuguese. Back translation was performed and evaluated by a specialists committee. Pre-test was performed with 40 T1D outpatients at State University of Campinas hospital. Internal consistency, external consistency and re-test were performed. RESULTS: 72% women, mean age: 32, 1 ± 9, 7 years, mean diabetes duration: 15, 8 ± 9, 1 years, mean scholarity: 11, 5 ± 3, 6, glycosylated hemoglobin mean: 9 ± 2%. Internal consistency: Cronbach alpha of T1DDS Brazilian version was 0.93. External consistency: Spearman's coefficient between T1DDS and PAID, Brazilian version, was 0.7781; (p < 0.0001). CONCLUSIONS: The T1DDS Brazilian version is a reliable tool to evaluate diabetes distress in T1D patients in the Brazilian Population. This tool can be useful in clinical care and to identify patiens at risk and in need for psychosocial intervention.

Expression of Mcl-1 and Ki-67 in Papillary Thyroid Carcinomas.

UNLABELLED: Studying molecules that are differentially expressed in cancers as well as benign and normal tissues is crucial for identifying novel biomarkers for cancer immunotherapy. This study aimed to investigate the clinical utility of the immunochemical expression of the proliferative cell marker Ki-67 and the apoptotic blocker Mcl-1 in papillary thyroid carcinoma (PTC). METHODS: We built a tissue microarray with 282 thyroid specimens. There were 59 PTCs including 35 classic (CPTC), 3 tall cell (TCPTC) and 21 follicular variants (FVPTC); 79 benign thyroid diseases (22 follicular adenomas; 57 adenomatoid hyperplasia); 33 Hashimoto's thyroiditis (HT) specimens; and 111 normal thyroid tissues. Clinical history and ultrasound data were retrospectively obtained by chart review. RESULTS: Mcl-1 overexpression was evident in 66.7% of the PTC tissues compared to 32% of the benign thyroid diseases. Mcl-1 strong staining distinguished benign from malignant thyroid lesions (sensitivity=61.3%; specificity=72.8%; negative predictive value, NPV=68%; positive predictive value, PPV=66.7% and 67.5% accuracy). Positive nuclear Ki-67 staining was observed in 34% of PTCs vs. 19% of thyroid adenomas (P=0.031). Strong Mcl-1 and Ki-67 co-expression was identified in 57.5% of PTCs with a higher PPV (75.8%). Mcl-1 and Ki-67 expression was not associated with any clinicopathological feature of malignancy. No deaths occurred during the follow-up. CONCLUSIONS: Mcl-1 immunochemical overexpression allowed differentiating low-risk PTC from the benign thyroid lesions. We suggest that Mcl-1 expression may help differentiate follicular patterned thyroid lesions. The influence of the Mcl-1 expression on several features of tumor aggressiveness has to be studied in large series of high-risk thyroid carcinomas.

Relationship of thyroid hormone levels and cardiovascular events in patients with type 2 diabetes.

Alterations in thyroid hormone levels are found associated with inflammation in patients with non-thyroidal illness (NTIS) and are common in patients with type 2 diabetes mellitus (T2DM). Inflammation has also been linked with development of cardiovascular events (CVE) in T2DM. Our objective was to assess whether thyroid hormone abnormalities typical of NTIS in patients with T2DM are related to inflammation and CVE. This was a cross-sectional study of 140 subjects; 70 with T2DM and 70 as a control group paired by age, sex and body mass index (BMI). We recorded age, sex, BMI, waist/hip ratio, diabetes duration, HbA1c, CVE history, serum amyloid A (SAA), TSH, total (T) and free (F) T4 and T3, reverse T3 (rT3) and TT3/rT3 ratio. Patients with T2DM had lower levels of TT4 (p = 0.012), TT3 (p < 0.001), FT3 (p < 0.001) and TT3/rT3 (p = 0.002). They also showed higher FT4 (p < 0.001) and similar TSH levels (p = 0.627) compared to the control group. SAA levels correlated positively with rT3 (r = 0.45; p < 0.001) and inversely with TT3/rT3 (r = -0.38; p = 0.001). Patients with T2DM and history of CVE had higher rT3 (p = 0.006) and lower TT3/rT3 (p = 0.002), along with higher SAA levels (p = 0.002) than patients without this characteristic. Multiple logistic regression showed that factors independently associated with CVE were older age (OR = 1.159, 95 % CI 1.011-1.329), male sex (OR = 4.391, 95 % CI 1.081-17.829) and higher TT3/rT3 (OR = 0.993, 95 % CI 0.987-0.999). We have confirmed the presence of NTIS in T2DM. We also showed that thyroid hormone abnormalities are associated to inflammatory activity and to CVE in these patients.

Central hypothyroidism in patients with chronic hepatitis C and relation with interferon-alpha treatment.

OBJECTIVE: Since some authors referred to panhypopituitarism or central hypothyroidism during the treatment of chronic hepatitis C virus (HCV) infection using interferon-α, it is intended to evaluate the prevalence of central hypothyroidism (CH) in HCV patients before and during interferon-α therapy. PATIENTS AND METHODS: We evaluated 308 HCV patients treated with standard interferon-α (IFN) and/or pegylated-interferon-α (PEG-IFN) associated with ribavirin. Free thyroxine (FT4) and thyrotropin (TSH) levels were measured before, during and after treatment. CH was diagnosed when the level of FT4 was lower than normal values with concomitant normal or lower TSH as verified at least in two consecutive measures. RESULTS: Before treatment, 18 (5.8 %) patients presented CH Twelve patients maintained laboratory changes during the treatment and 17 new patients developed central hypothyroidism. Among the 29 patients (9.4 %) with CH, 11 used IFN, six used PEG-IFN and 12 patients used two or more therapeutic schedules. The differences in gender, age, cirrhosis, viral genotype, duration of treatment and the type of interferon used were not statistically significant. The absence of sustained virologic response was associated with central hypothyroidism (OR=3.83). CONCLUSION: HCV patients may develop CH due to viral infection or during the interferon treatment. These patients presented 3.83 times more chance of not obtaining sustained virologic response.

Immunohistochemical study of the pancreatic basement membrane in non obese diabetic mice (NOD) with spontaneous autoimmune insulitis.

The role of the basement membrane as an antigenic structure in autoimmune diseases is controversial. To determine possible structural changes in the endocrine pancreatic basement membrane (PBM) in autoimmune diabetes, we studied the expression of laminin in the islets of 42 NOD mice, aged between 4 to 42 weeks, as an animal model of spontaneous diabetes. Insular lymphocytic inflammatory infiltration of variable intensity was present in 24 of these mice. An immunohistochemical staining using the streptavidin-biotin-peroxidase technique was performed on paraffin-embedded tissue sections, with a polyclonal antilaminin antibody. Staining for laminin was restricted to the basement membrane. In islets with no inflammatory infiltration, laminin was observed as a thin, continuous and uniform brown layer, covering the pericapsular basement membrane of the islets and their capillaries. The continuity of the PBM was lost in the islets with insulitis and the immunostaining showed clearcut interruption and destruction, particularly when the islets were in contact with inflammatory infiltrate. Our findings suggest that the loss of integrity of the PBM in islets with inflammatory infiltrate could facilitate antigenic exposure contributing towards the start o f autoimmune DM in NODmice.

Erythrocyte sodium-lithium countertransport and proliferative diabetic retinopathy.

PURPOSE: To investigate whether elevated erythrocyte Na+/Li+ countertransport (Na+/Li+ CT) activity is present in patients with proliferative diabetic retinopathy (PDR). METHODS: The rate of Na+/Li+ CT activity assayed in 21 patients with type 1 diabetes mellitus (DM) presenting PDR was compared with 10 patients with nonproliferative retinopathy (NPDR) and with 11 patients with normal fundi. Twelve normal volunteers with no family history of hypertension were used as a control group. The albumin excretion rate was determined by nephelometry, and the glomerular filtration rate was measured by the plasma clearance of eidetic acid labeled with chromium-51. RESULTS: Patients with PDR showed higher diastolic blood pressure levels (mean +/- SD) compared with those with NPDR or normal fundi (95 +/- 13 versus 90 +/- 09 and 82 +/- 19 mm Hg, P = 0.02, respectively). The albumin excretion rate was higher [geometric mean (range)], and the glomerular filtration rate was lower (mean +/- SD) in patients with PDR than in those with NPDR or normal fundi [333 (2 to 5140) versus 32 (5.9 to 2200) and 6 (1.5 to 306) microg/min, P = 0.01, and 63 +/- 33 versus 99 +/- 37 and 93 +/- 43 ml/min, P = 0.02, respectively]. The mean Na+/Li+ CT in patients with PDR was significantly higher than in patients with NPDR or normal fundi and control group (0.46 +/-0.20 versus 0.32 +/- 0.12, 0.32 +/- 11, and 0.21 +/- 0.07 mM/L red blood cells (RBC)/h, respectively, P = 0.0001). In a multiple logistic regression analysis, with PDR as the dependent variable, Na+/Li+ CT (odds ratio [OR]: 4.7, confidence interval [CI]: 1.2-17.6, P = 0.02), diastolic blood pressure (OR, 3.4; CI, 1.3 to 9.6; P = 0.018), and glomerular filtration rate (OR, 5.1; CI, 1.6-17.7; P = 0.007) were the only variables that were maintained in the equation, indicating that they were the main determinants of PDR. CONCLUSIONS: Patients with type 1 DM and proliferative retinopathy have elevated erythrocyte Na+/Li+ CT.

Distribution of HLA-DRB1 alleles in a mixed population with insulin-dependent diabetes mellitus from the southeast of Brazil.

HLA class II genes are strongly associated with susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM). The present study reports the HLA-DRB1 genotyping of 41 IDDM patients and 99 healthy subjects from the Southeast of Brazil (Campinas region). Both groups consisted of an ethnic mixture of Caucasian, African Negro and Amerindian origin. HLA-DRB1*03 and *04 alleles were found at significantly higher frequencies among IDDM patients compared to the controls (DRB1*03: 48.8% vs 18.2%, P < 0.005, RR = 4.27; DRB1*04: 43.9% vs 15.1%, P < 0.008, RR = 4.37) and were associated with a susceptibility to the disease. DRB1*03/*04 heterozygosity conferred a strong IDDM risk (RR = 5.44). In contrast, the HLA-DRB1*11 allele frequency was lower among IDDM patients (7.3% vs 26.3% in controls), but the difference was not significant. These data agree with those described for other populations and allow genetic characterization of IDDM in Brazil.

Distribution of HLA-DRB1 alleles in a mixed population with insulin-dependent diabetes mellitus from the Southeast of Brazil

HLA class II genes are strongly associated with susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM). The present study reports the HLA-DRB1 genotyping of 41 IDDM patients and 99 healthy subjects from the Southeast of Brazil (Campinas region). Both groups consisted of an ethnic mixture of Caucasian, African Negro and Amerindian origin. HLA-DRB1*03 and *04 alleles were found at significantly higher frequencies among IDDM patients compared to the controls (DRB1*03: 48.8 percent vs 18.2 percent, P<0.005, RR= 4.27); DRB1*04:43.9 percent vs 15.1 percent, P<0.008, RR=4.37) and were associated with a susceptibility to the disease. DRB1*03/*04 heterozygosity conferred a strong IDDM risk (RR=5.44). In contrast, the HLA-DRB1*11 allele frequency was lower among IDDM patients (7.3 percent vs 26.3 percent in controls), but the difference was not significant. These data agree with those described for other populations and allow genetic characterization of IDDM in Brazil.