Melanie Rodacki

NK cells and type 1 diabetes

Type 1 diabetes (T1D) is characterized by an immuno-mediated progressive destruction of the pancreatic β cells. Due to the ability of NK cells to kill target cells as well as to interact with antigen-presenting and T cells, it has been suggested that they could be involved in one or multiple steps of the immune-mediated attack that leads to T1D. Abnormalities in the frequency and activity of NK cells have been described both in animal models and patients with T1D. Some of these alterations are linked to its onset while others seem to be a consequence of the disease. Here, we discuss the main characteristics of NK cells and review the studies that investigated the role of NK cells in T1D, both in mouse models and humans.

Regional differences in clinical care among patients with type 1 diabetes in Brazil: Brazilian Type 1 Diabetes Study Group

BackgroundTo determine the characteristics of clinical care offered to type 1 diabetic patients across the four distinct regions of Brazil, with geographic and contrasting socioeconomic differences. Glycemic control, prevalence of cardiovascular risk factors, screening for chronic complications and the frequency that the recommended treatment goals were met using the American Diabetes Association guidelines were evaluated.MethodsThis was a cross-sectional, multicenter study conducted from December 2008 to December 2010 in 28 secondary and tertiary care public clinics in 20 Brazilian cities in north/northeast, mid-west, southeast and south regions. The data were obtained from 3,591 patients (56.0% females and 57.1% Caucasians) aged 21.2 ± 11.7 years with a disease duration of 9.6 ± 8.1 years (<1 to 50 years).ResultsOverall, 18.4% patients had HbA1c levels <7.0%, and 47.5% patients had HbA1c levels ≥ 9%. HbA1c levels were associated with lower economic status, female gender, age and the daily frequency of self-blood glucose monitoring (SBGM) but not with insulin regimen and geographic region. Hypertension was more frequent in the mid-west (32%) and north/northeast (25%) than in the southeast (19%) and south (17%) regions (p<0.001). More patients from the southeast region achieved LDL cholesterol goals and were treated with statins (p<0.001). Fewer patients from the north/northeast and mid-west regions were screened for retinopathy and nephropathy, compared with patients from the south and southeast. Patients from the south/southeast regions had more intensive insulin regimens than patients from the north/northeast and mid-west regions (p<0.001). The most common insulin therapy combination was intermediate-acting with regular human insulin, mainly in the north/northeast region (p<0.001). The combination of insulin glargine with lispro and glulisine was more frequently used in the mid-west region (p<0.001). Patients from the north/northeast region were younger, non-Caucasian, from lower economic status, used less continuous subcutaneous insulin infusion, performed less SBGM and were less overweight/obese (p<0.001).ConclusionsA majority of patients, mainly in the north/northeast and mid-west regions, did not meet metabolic control goals and were not screened for diabetes-related chronic complications. These results should guide governmental health policy decisions, specific to each geographic region, to improve diabetes care and decrease the negative impact diabetes has on the public health system.

Diabetic ketoacidosis in adults: update of an old complication

Diabetic ketoacidosis is an acute complication of Diabetes Mellitus characterized by hyperglycemia, metabolic acidosis, dehydration, and ketosis, in patients with profound insulin deficiency. It occurs predominantly in patients with type 1 diabetes and is frequently precipitated by infections, insulin withdrawal or undiagnosed type 1 diabetes. The authors review its pathophysiology, diagnostic criteria and treatment options in adults, as well as its complications.

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.

Precocious markers of cardiovascular risk and vascular damage in apparently healthy women with previous gestational diabetes

AbstractPrevious gestational diabetes mellitus (pGDM) indicates future risk for type 2 diabetes (T2DM). Insulin resistance (IR) may precede T2DM in many years and is associated with an increased risk for cardiovascular diseases.AimThis study aims to identify endothelial dysfunction and cardiovascular risk factors in women with pGDM.MethodsThis cross-sectional analysis included 45 non diabetic women, 20 pGDM and 25 controls, at least one year after delivery. Body mass index (BMI), abdominal circumference (AC), blood pressure, serum lipids, liver enzymes, uric acid, nonesterified fatty acids, C-reactive protein and plasma glucose, insulin, fibrinogen and plasminogen activator inhibitor 1 were measured. HOMA IR and β were calculated. Pre and post induced ischemia videocapillaroscopy was performed in hand nailfold to evaluate microvascular morphologic aspect and functional response.ResultsAC and fasting glucose were significantly higher in pGDM (p = 0.01 and p = 0.002 respectively). Women with pGDM and BMI < 25 kg/m2 had significantly higher levels of fasting insulin and HOMA IR than controls (p = 0.008 and 0.05 respectively). Abnormal morphologic findings were more frequent and papillae rectification were 3.3 times more prevalent in pGDM (p = 0.003). Other microvascular parameters did not differ between groups.ConclusionCardiovascular risk factors and a microcirculation abnormality (papillae rectification) were significantly increased in young non-diabetic women with pGDM.

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

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.

Anti-parietal cell antibodies and pernicious anemia in patients with type 1 diabetes mellitus and multiethnic background

Anti-parietal cell (APC) antibodies and pernicious anemia (PA) were evaluated in patients with type 1 diabetes (n=75) and in controls. A higher frequency of APC (13.3%) and PA (4%) was found in cases than in controls (p=0.003), associated with other autoimmune diseases (p=0.003), but not with insulin or PTPN22 polymorphisms.

C-peptide residual secretion makes difference on type 1 diabetes management?

Type 1 diabetes is a chronic disease characterized by progressive destruction of the pancreatic beta cells, what leads to insulin deficiency and hyperglycemia. However, a significant secretory function may persist for long periods in a few patients, what is clinically evident through the detection of serum C peptide. This phenomenon might reduce the risk of chronic complications, severe hypoglycemias and allow easier metabolic control. It is possible that these advantages are caused, at least partially, by C peptide itself, acting directly in its target tissues.

Hereditary Pancreatitis Associated With the N29T Mutation of the PRSS1 Gene in a Brazilian Family: A Case-Control Study.

Abstract Hereditary pancreatitis (HP) is an autosomal-dominant disease with incomplete penetrance manifesting as early-onset chronic relapsing pancreatitis. A mutation in the PRSS1 gene is present in greater than 70% of HP kindreds and leads to a gain-of-function characterized by the increased autocatalytic conversion of trypsinogen to active trypsin, promoting autodigestion and damage to acinar cells. Other genetic defects observed in the pathogenic mechanism of pancreatitis include mutations in the genes encoding SPINK1, CTRC, and CPA1. There are few reports of HP in Latin America, and no families have been investigated in Brazil. A case-control observational study was conducted at Clementino Fraga Filho University Hospital in Brazil. Patients with suspected HP and healthy controls were enrolled in this study, and a detailed questionnaire was administered to patients with HP. PRSS1 and SPINK1 genes were analyzed by DNA sequencing, and a family that fit the HP diagnostic criteria was identified. The neutral polymorphism c.88-352A > G in the SPINK1 gene was found to be prevalent in the individuals studied, but no important alterations were found in this gene. Ten out of 16 individuals in this family carried the N29T mutation in the PRSS1 gene, with 2 clinically unaffected mutation carriers. The median age of HP onset was 6 years. Pancreatic exocrine failure occurred in 6 patients, 5 of whom also had diabetes mellitus. Surgical procedures were performed on 3 affected members, and no cases of pancreatic cancer have been reported thus far. This study identified the first PRSS1 gene mutation in a Brazilian family with HP.

Impact of advanced and basic carbohydrate counting methods on metabolic control in patients with type 1 diabetes

OBJECTIVE Diets based on carbohydrate counting remain a key strategy for improving glycemic control in patients with type 1 diabetes. However, these diets may promote weight gain because of the flexibility in food choices. The aim of this study was to compare carbohydrate counting methods regarding anthropometric, biochemical, and dietary variables in individuals with type 1 diabetes, as well as to evaluate their knowledge about nutrition. METHODS Participants were allocated in basic or advanced groups. After 3 mo of the nutritional counseling, dietary intake, anthropometric variables, lipemia, and glycemic control were compared between groups. A questionnaire regarding carbohydrate counting, sucrose intake, nutritional knowledge, and diabetes and nutrition taboos also was administered. RESULTS Ten (30%) participants had already used advanced carbohydrate counting before the nutritional counseling and these individuals had a higher body mass index (BMI) (P < 0.01) and waist circumference (WC) (P = 0.01) than others (n = 23; 69.7%). After 3 mo of follow-up, although participants in the advanced group (n = 17; 51.52%) presented higher BMI (P < 0.01) and WC (P = 0.03), those in the basic group (n = 16; 48.48%) showed a higher fat intake (P < 0.01). The majority of participants reported no difficulty in following carbohydrate counting (62.5% and 88% for basic and advanced groups, respectively) and a greater flexibility in terms of food choices (>90% with both methods). CONCLUSIONS Advanced carbohydrate counting did not affect lipemic and glycemic control in individuals with type 1 diabetes, however, it may increase food intake, and consequently the BMI and WC, when compared to basic carbohydrate counting. Furthermore, carbohydrate counting promoted greater food flexibility.