Using trend arrows in continuous glucose monitoring systems for insulin adjustment in clinical practice: Brazilian Diabetes Society Position Statement.

This manuscript reports the Brazilian Diabetes Society Position Statement for insulin adjustments based on trend arrows observed in continuous glucose monitoring systems. The Brazilian Diabetes Society supports the utilization of trend arrows for insulin dose adjustments in patients with diabetes on basal-bolus insulin therapy, both with multiple daily insulin doses or insulin pumps without closed-loop features. For those on insulin pumps with predictive low-glucose suspend feature, we suggest that only upward trend arrows should be used for adjustments. In this paper, tables for insulin adjustment based on sensitivity factors are provided and strategies to optimize the use of trend arrows in clinical practice are discussed.

HbA1c variability and long-term glycemic control are linked to peripheral neuropathy in patients with type 1 diabetes.

BACKGROUND: HbA1c variability has been linked to retinopathy, renal disease and autonomic neuropathy in patients with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D). Although the same relationship has been demonstrated for diabetic peripheral neuropathy (DPN) in patients with T2D, data for T1D are still lacking. METHODS: Patients older than 17 years of age with ≥ 10 years of T1D duration and follow-up were included. All patients underwent nerve conduction studies and neurological examination. Laboratorial data was retrospectively extracted from chart review. Mean HbA1c (mHbA1c) over 10 years was calculated, as well as HbA1c variability estimated by standard deviation (HbA1c-SD) and coefficient of variation (HbA1c-CV). RESULTS: Fifty patients with T1D were included (30 females and 21 non-caucasians), with mean age and T1D duration of 25.6 ± 5.0 and 17.9 ± 6.1 years, respectively. The frequency of DPN was 24%. Higher mHbA1c (10.4 ± % vs 8.1 ± %; p < 0.001), HbA1c-SD (1.8 ± 0.8 vs 0.9 ± 0.4; p < 0.001), and HbA1c-CV (1.7 ± 0.8 vs 1.2 ± 1.1; p = 0.006) were observed in patients with DPN compared to others. SD-HbA1c and HbA1c-CV were associated with DPN, diagnosed by either clinical or NCS criteria, independent of mHbA1c, age and gender. CONCLUSIONS: Not only long-term glycemic control, but also its variability is associated with DPN in patients with T1D. Larger studies are required to confirm this finding.

The potential effect of ultra-long insulin degludec on glycemic variability.

Despite the therapeutic advances in the treatment of diabetes, metabolic control instability due to glycemic variability (GV) is frequently observed in patients with diabetes on intensive insulin therapy and is associated with hyperglycemic peaks and hypoglycemic episodes. Hyperglycemia associated with GV has been implicated in the development of chronic complications due to its pro-oxidative consequences. On the other hand, hypoglycemia can be associated with increased cardiovascular risk secondarily to adrenergic activation. The ultra-long-acting insulin analogue, insulin degludec (IDeg), presents a flat and stable glucose-lowering effect both in Type 1 and Type 2 diabetes patients. In pharmacodynamic studies, IDeg has been associated with a lower variability in its insulin action than other alternatives for basal insulin, which might have clinical advantages for the stability of the glycemic control. The main objective of this review is to present pharmacological and clinical data regarding the efficacy and safety of IDeg for the treatment of diabetes focusing on its effects on GV and on hypoglycemia frequency.

Insulin mediated improvement in glycemic control in elderly with type 2 diabetes mellitus can improve depressive symptoms and does not seem to impair health-related quality of life.

BACKGROUND AND OBJECTIVES: Type 2 diabetes (T2D) is very prevalent among the elderly. Insulin therapy is often required for glycemic control. The association of starting this therapy with depressive symptoms as well the health-related quality of life (HRQoL) is unknown among the elderly patients. AIMS: Evaluate the association of starting insulin therapy depressive symptoms as well with HRQoL of elderly people with T2D. METHODS: 36 T2D participants (67.9 % females, age 66.5 years ± 5.1) were recruited, 26 of whom completed the follow-up. Generic (Short-Form 36 Health Survey - SF-36) and specific (Problem Areas in Diabetes - PAID) HRQoL questionnaires, Beck Depression Inventory (BDI), clinical, laboratorial and socio-demographic data were recorded on baseline and 6 months after the beginning of insulin treatment. RESULTS: There was a reduction in the BDI score after the use of insulin, which means an improvement in depressive symptoms (Before/After: median - 10.5 / 7; p = 0008). There were no statistically significant differences in HRQoL scores between the two time periods There was also a reduction in HbA1c (Before/After: median - 8.7/7.9). Otherwise, there were no statistically significant differences in: BMI (28.1/28.3); Abdominal circumference:(100.5/99.5) and chronic complications status. CONCLUSION: Insulin therapy in elderly people with type 2 diabetes can lead to an improvement of depressive symptoms and does not seem to affect negatively HRQoL of the participants.

Prospective evaluation of glutamine and phospholipids levels in first degree relatives of patients with Type 1 Diabetes from a multiethnic population.

BACKGROUND: A dysregulation in the metabolism of lipids may be an early marker of autoimmunity in Type 1 Diabetes (T1D). It would be of general importance to identify metabolic patterns that would predict the risk for T1D later in life. The aim of this study was to perform a prospective evaluation of glutamine and phospholipids levels in Brazilian first degree relatives (FDR) of patients with T1D in a mean interval of 5 years. FINDINGS: Brazilian FDR (n = 30) of patients with T1D were evaluated and blood was sampled to measure the levels of glutamine and phospholipids in the fasting serum by quantitative colorimetric method. The tests were repeated after a mean interval of 5 years and compared to a control group (n = 20). The FDR presented lower levels of phospholipids than controls (p = 0.028), but not of glutamine (p = 0.075). Phospholipids levels decreased over time (p = 0.028) in FDR and were associated with Glutamic acid decarboxylase autoantibody (GADA) titers (p = 0.045), autoantibody positivity (p = 0.008) and PTPN22 polymorphisms (p = 0.014). CONCLUSIONS: In this Brazilian multiethnic population, there was a significant decrease in phospholipids levels in FDR in patients with T1D during a 5-year prospective follow-up, as well as a significant association between these metabolite, GADA and PTPN22 polymorphisms. For Glutamine no difference was found. These findings suggest that a dysregulation in the metabolism of lipids may precede the onset of the autoimmunity in T1D.

Should thyroid-stimulating hormone goals be reviewed in patients with type 1 diabetes mellitus? Results from the Brazilian Type 1 Diabetes Study Group.

AIMS: To investigate if thyroid-stimulating hormone (TSH) levels are associated with any differences in glycaemic control or diabetes-related complications in individuals with Type 1 diabetes. METHODS: This observational, cross-sectional and multicentre study included patients with Type 1 diabetes for ≥ 5 years, with a recent TSH measurement and without a known previous thyroid disease. Patients were divided into three groups according to TSH levels: 0.4-2.5 mU/l; 2.5-4.4 mU/l; and ≥ 4.5 mU/l. RESULTS: We included 1205 individuals with a mean ± sd age of 23.8 ± 11.3 years. Seven patients had TSH levels <0.4 mU/l and were excluded from the comparison between groups. HbA1c levels, systolic and diastolic blood pressure, LDL cholesterol and disease duration were similar in all groups (P = 0.893, P = 0.548, P = 0.461, P = 0.575 and P = 0.764, respectively). The rates of diabetic retinopathy and GFR < 60/mL/min/1.73 m(2) differed between groups (P = 0.006 and P < 0.001, respectively) and were lower in those with lower TSH levels. Multivariate analysis confirmed these associations. The frequencies of retinopathy and GFR < 60 mL/min/1.73 m(2) were higher not only in patients with TSH ≥ 4.5 mU/l (odds ratio 1.878 and 2.271, respectively) but also in those with TSH levels of 2.5-4.4 mU/l (odds ratio 1.493 and 2.286, respectively), when compared with patients with TSH levels of 0.4-2.5 mU/l. CONCLUSIONS: TSH levels of 0.4-2.5 mU/l are associated with a lower risk of diabetic retinopathy and renal failure in individuals with Type 1 diabetes, independently of glycaemic control and duration of the disease.

Determinants of self-monitoring of blood glucose in patients with Type 1 diabetes: a multi-centre study in Brazil.

AIM: The aim of this study was to determine the relationship between the daily frequency of self-monitoring of blood glucose and glycaemic control, demographic and socio-economic status in patients with Type 1 diabetes under routine clinical care in Brazil. METHODS: This was a cross-sectional, multi-centre study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The data were obtained from 3176 patients, aged 22 ± 11.8 years, of whom 56.3% were female and 57.4% were Caucasian. The mean time since diabetes diagnosis was 11.7 ± 8.1 years. RESULTS: The prevalence of self-monitoring of blood glucose was 88.5%. There was a significant increase in self-monitoring frequency associated with female gender, lower ages, more intensive diabetes management and higher socio-economic status. A correlation between HbA(1c) levels and the daily frequency of self-monitoring was observed (r(s) = -0.13; P = 0.001). The mean HbA1c levels were related to the daily frequency of self-monitoring (P < 0.001) without additional benefit to patients who performed self-monitoring more than four times daily (9.2, 11.2, 10.2,15.2 and 15% for one, two, three, four, five or more self-monitoring tests daily, respectively; P < 0.0001). CONCLUSIONS: The majority of our patients (88.5%) performed three or more self-monitoring tests daily, with more frequent testing reported by females, younger patients, those on intensive insulin regimens and of higher socio-economic status. No additional benefit was found in patients who performed self-monitoring more than four times daily. The diabetes care team must improve patients' education regarding self-monitoring of blood glucose and its benefits.

Pancreatic autoantibodies, HLA DR and PTPN22 polymorphisms in first degree relatives of patients with type 1 diabetes and multiethnic background.

AIM: To evaluate the prevalence of pancreatic auto-antibodies (PAb) as well as its relationship with HLA DR B1 and PTPN22 polymorphisms in first degree relatives (FDR) of Brazilian patients with Type 1 diabetes (T1D) and multiethnic background. METHODS: FDR of patients with T1D were interviewed and blood was sampled for PAb measurement, HLA DRB1 and PTPN22 genotyping. Genotyping was also performed in index cases. RESULTS: In FDR (n=78), 16.7% presented at least one PAb. These individuals had a higher prevalence of HLA DRB1* 03 than others (p=0.03), without differences in PTPN22 genotyping. While the genetic profile was similar in FDR with PAb and their index cases, those without PAb had a lower frequency of HLA DR B1 * 03 than their correspondent patients (p=0.009). CONCLUSION: In this multiethnic population, a significant proportion of FDR of T1D patients had PAb, which was associated with HLA DR B1 * 03 but not with the PTPN22 polymorphism.

Family history of type 2 diabetes is increased in patients with type 1 diabetes.

It has been suggested that type 1 (T1D) and type 2 diabetes (T2D) might share some susceptibility risk factors. A higher prevalence of T2D has been reported in families of Caucasian T1D children than in the general population, although data in adults and multiethnic groups is still lacking. Our goal was to compare the prevalence of T2D family history between adults with T1D from a multiethnic population and a non-diabetic control group. We performed a cross-sectional analysis of 145 adults with T1D and 141 healthy adults (control group) that included an interview and a review of the medical charts. Groups were matched for age, sex, ethnicity and body mass index (BMI). We found a higher prevalence of not only T1D but also T2D in first-degree relatives of patients than in controls (p<0.001 and p=0.042, respectively). These differences were not observed for second/third-degree relatives. When subjects were stratified according to their ethnicity, the higher frequency of T2D in FDR of patients than controls became more striking in non-white (p=0.002) and disappeared in white individuals (p=0.85). To conclude, the prevalence of T1D and T2D was higher in first-degree relatives of patients with T1D than of controls. The difference in T2D family history between patients and controls was specially striking among non-whites, which may represent a peculiarity of T1D in this group.

Diffuse vertebral body edema due to calcified intraspongious disk herniation.

We describe the case of a patient with a recent history of high back pain, with magnetic resonance imaging (MRI) of the thoracic spine showing intervertebral disk herniation into the spongious bone of the vertebral body of T9 that might have caused diffuse, low signal intensity on fluid-attenuated inversion recovery T1-weighted (FLAIR-T1W) images, high signal intensity magnetic resonance (MR) on T2-weighted (T2W) images and T2-weighted fat-suppressed images (T2W-FSIs) and marked enhancement on the vertebral body of T9 with gadolinium on T1-weighted fat-suppressed images (T1W-FSIs) images. Those findings suggested diffuse edema and might be indistinguishable from tumoral or inflammatory diseases, but the plain films and the reformatted sagittal computed tomography scans of the thoracic spine were helpful to show a calcified part of the intervertebral disk migrating into the vertebral body of T9. The patient made full recovery from the symptoms after conservative treatment and at the follow-up MRI showed normalization of the bone marrow signal intensity of the vertebral body of T9.

Relationship between the prevalence of anti-glutamic acid decarboxylase autoantibodies and duration of type 1 diabetes mellitus in Brazilian patients.

The objective of the present study was to determine whether the duration of disease has any influence on the prevalence of glutamic acid decarboxylase autoantibodies (GADA) in Brazilian patients with type 1 diabetes (T1D) and variable disease duration. We evaluated 83 patients with T1D. All participants were interviewed and blood was obtained for GADA measurement by a commercial radioimmunoassay (RSR Limited, Cardiff, UK). Four groups of patients were established according to disease duration: A) 1-5 years of disease (N = 24), B) 6-10 years of disease (N = 19), C) 11-15 years of disease (N = 25), and D) >15 years of disease (N = 15). GADA prevalence and its titers were determined in each group. GADA was positive in 38 patients (45.8%) and its frequency did not differ between the groups. The prevalence was 11/24 (45.8%), 8/19 (42.1%), 13/25 (52%), and 6/15 (40%) in groups A, B, C, and D, respectively (P = 0.874). Mean GADA titer was 12.54 +/- 11.33 U/ml for the sample as a whole and 11.95 +/- 11.8, 12.85 +/- 12.07, 10.57 +/- 8.35, and 17.45 +/- 16.1 U/ml for groups A, B, C, and D, respectively (P = 0.686). Sex, age at diagnosis or ethnic background had no significant effect on GADA (+) frequency. In conclusion, in this transversal study, duration of disease did not affect significantly the prevalence of GADA or its titers in patients with T1D after one year of diagnosis. This was the first study to report this finding in the Brazilian population.

Relationship between the prevalence of anti-glutamic acid decarboxylase autoantibodies and duration of type 1 diabetes mellitus in Brazilian patients

The objective of the present study was to determine whether the duration of disease has any influence on the prevalence of glutamic acid decarboxylase autoantibodies (GADA) in Brazilian patients with type 1 diabetes (T1D) and variable disease duration. We evaluated 83 patients with T1D. All participants were interviewed and blood was obtained for GADA measurement by a commercial radioimmunoassay (RSR Limited, Cardiff, UK). Four groups of patients were established according to disease duration: A) 1-5 years of disease (N = 24), B) 6-10 years of disease (N = 19), C) 11-15 years of disease (N = 25), and D) >15 years of disease (N = 15). GADA prevalence and its titers were determined in each group. GADA was positive in 38 patients (45.8 percent) and its frequency did not differ between the groups. The prevalence was 11/24 (45.8 percent), 8/19 (42.1 percent), 13/25 (52 percent), and 6/15 (40 percent) in groups A, B, C, and D, respectively (P = 0.874). Mean GADA titer was 12.54 ± 11.33 U/ml for the sample as a whole and 11.95 ± 11.8, 12.85 ± 12.07, 10.57 ± 8.35, and 17.45 ± 16.1 U/ml for groups A, B, C, and D, respectively (P = 0.686). Sex, age at diagnosis or ethnic background had no significant effect on GADA (+) frequency. In conclusion, in this transversal study, duration of disease did not affect significantly the prevalence of GADA or its titers in patients with T1D after one year of diagnosis. This was the first study to report this finding in the Brazilian population.

Thoracic spine arachnoid ossification with and without cord cavitation. Report of three cases.

Thoracic spine arachnoid ossification is a relatively rare disease that affects mainly women and causes sensory, motor, and sphinctal symptoms associated with inferior limb pain. Based on three cases, the authors comment on pathogenic and surgery-related aspects of the disease. The patient in Case 1 was followed over the course of 23 years. Spinal cavitation is highlighted in Case 2, and yellow, gross, half-ring ossification is described in Case 3. Calcium deposits usually occur in the middle and lower thoracic spine where the majority of trabeculated arachnoid cells are located. Operative treatment does not interrupt the ossification process, which continues over time, causing progressive deterioration in the patient. Spinal cavitation can occur due to spinal cord tethering, stretching, and central cord edema formation, accompanied by cerebrospinal fluid blockage and pulse pressure changes. The results of surgical intervention are poor, offering short-term recovery with later deterioration. Multiple pathogenic factors are involved in this clinical syndrome including metabolic changes.

Paracoccidioidomycosis of the central nervous system: CT findings.

A retrospective analysis of six cases of central nervous system paracoccidioidomycosis, all but one proven by biopsy and surgery, was carried out to study the CT and clinical data and pathological correlation. Most of the patients were from the country. Headache, vomiting, seizures and hemiparesis were the most frequent symptoms. Papilloedema was present in four patients with raised intracranial pressure. Five patients had chronic lung disease and two with advanced systemic disease, skin and mucous membrane lesions were also observed. The neurological disturbance was sometimes the presenting features and the diagnosis was discovered incidentally after surgery. Both solitary and multiple parenchymal lesions were observed and the cerebral hemispheres were more commonly involved in four patients. Local meningeal involvement was observed in one with a single cortical granuloma. We emphasise the usefulness of CT, showing a rounded or lobulated mass with an isodense or radiolucent centre after contrast enhancement, surrounded by an irregular wall of varying thickness. There was always moderate oedema, extending peripherally. Other infections or neoplastic diseases may present similar findings. Preoperative diagnosis should rest on integration of clinical data, chest films, laboratory and neuroimaging studies.

CT features of cellulosae and racemosus neurocysticercosis.

Of 210 cases of cerebral neurocysticercosis studied with CT since 1982, three cases proved to be due to the rare Cysticercus racemosus (surgical verification) rather than to the much more prevalent infestation by Cysticercus cellulosae. We attempted to establish CT criteria for differentiating the more severe and always fatal form of C. racemosus. The CT appearance occasionally encountered in C. racemosus resembles a "bunch of grapes"; this appears to be the only criterion of differential value.

Late cerebral arterial spasm: the cerebrovascular response to hypercapnia, induced hypertension and the effect of nimodipine on blood flow autoregulation in experimental subarachnoid hemorrhage in primates.

1. Late cerebral arterial spasm was induced by repeated injections of autologous blood in a total amount of 14-33 ml into the basal cisterns of baboons to mimick subarachnoid hemorrhage (SAH). Regional cerebral blood flow (CBF), sagittal sinus pressure, cerebral arterial caliber from angiograms, and cerebral metabolic rate of oxygen (CMRO2) were measured before and after the experimental SAH to determine responses to hypercapnia and induced hypertension. The effect of the calcium antagonist, Nimodipine, on CBF autoregulation pre- and post-SAH was tested. 2. One week after the blood injections were started there was about 10-20% reduction, depending on territory measured, in the arterial diameter of the carotid and vertebral systems. This was associated with an 18% reduction in CBF and 9% decrease in the brain metabolism. 3. During hypercapnia before and after experimental SAH the flow increased with a mean of 3.7 and 1.8 ml, respectively, for each mm Hg elevation of PaCO2. In control animals, graded angiotensin-induced hypertension did not overtly affect CBF. Following SAH, the CBF autoregulation was impaired in 5 of 6 animals tested. 4. I.v. infusion of Nimodipine markedly curtailed the CBF autoregulation in pre-SAH animals and, to a somewhat slighter extent, also in post-SAH animals.