Hyperinsulinemic-Euglycemic Clamp Strengthens the Insulin Resistance in Nonclassical Congenital Adrenal Hyperplasia.

OBJECTIVE: Insulin sensitivity evaluation by hyperinsulinemic-euglycemic clamp in nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxilase deficiency. DESIGN AND SETTING: Cross-sectional study at university hospital outpatient clinics. PATIENTS AND METHODS: NC-CAH patients (25 females, 6 males; 24 ± 10 years) subdivided into C/NC (compound heterozygous for 1 classical and 1 nonclassical allele) and NC/NC (2 nonclassical alleles) genotypes were compared to controls. RESULTS: At diagnosis, C/NC patients presented higher basal and adrenocorticotropin-stimulated 17-hydroxyprogesterone and androstenedione levels than NC/NC genotype. Patients and controls presented similar weight, body mass index, abdominal circumference, and total fat body mass. NC-CAH patients showed higher waist-to-hip ratio, lower adiponectin and lower high-density lipoprotein cholesterol levels with no changes in fasting plasma glucose, glycated hemoglobin, homeostatic model assessment for insulin resistance, leptin, interleukin 6, tumor necrosis factor alpha, C-reactive protein, and carotid-intima-media thickness. All patients had used glucocorticoid (mean time of 73 months). Among the 22 patients with successful clamp, 13 were still receiving glucocorticoid-3 patients using cortisone acetate, 9 dexamethasone, and 1 prednisone (hydrocortisone equivalent dose of 5.5mg/m²/day), while 9 patients were off glucocorticoid but had previously used (hydrocortisone equivalent dose of 5.9mg/m2/day). The NC-CAH patients presented lower Mffm than controls (31 ± 20 vs 55 ± 23µmol/min-1/kg-1, P = 0.002). The Mffm values were inversely correlated with the duration of glucocorticoid treatment (r = -0.44, P = 0.04). There was association of insulin resistance and glucocorticoid type but not with androgen levels. CONCLUSION: Using the gold standard method, the hyperinsulinemic-euglycemic clamp, insulin resistance was present in NC-CAH patients and related to prolonged use and long-acting glucocorticoid treatment. Glucocorticoid replacement and cardiometabolic risks should be monitored regularly in NC-CAH.

Endoplasmic reticulum stress activation in adipose tissue induces metabolic syndrome in individuals with familial partial lipodystrophy of the Dunnigan type.

BACKGROUND: Familial partial lipodystrophy of the Dunnigan type is one of the most common inherited lipodystrophies variables. These individuals have important metabolic disorders that cause predisposition to various diseases. In this study we aimed to demonstrate the relation between the metabolic abnormalities, inflammatory profile and the expression of genes involved in the activation of the endoplasmic reticulum stress (ERS) in subjects with FPLD. METHODS: We evaluated 14 female FPLD patients and compared with 13 female healthy individuals. The subjects were paired with their respective BMI and age and categorized into two groups: Familial partial lipodystrophy of the Dunnigan type (FPLD) and control. Patients were fasted for 12 h before blood collection for measurement of HbA1c, glucose, insulin, lipids and inflammatory markers. Subcutâneous adipose tissue was collected by puncture aspiration of submental region during ambulatorial surgical aesthetic procedure. RESULTS: We demonstrate that patients with FPLD show increased HbA1c (p < 0.01), fasting glucose (p < 0.002) and triglycerides (p < 0.005) while HDL/cholesterol (p < 0.001) was lower when compared to healthy individuals. We found that 64.2% FPLD patients had metabolic syndrome according to International Diabetes Federation definition. We also observe increased AUC of glucose (p < 0.001) and insulin during oGTT, featuring a frame of hyperglycemia and hyperinsulinemia, suggesting insulin resistance. Also we found hyperactivation of several genes responsible for ERS such as ATF-4 (p < 0.01), ATF-6 (p < 0.01), EIF2α3K (p < 0.005), CCT4 (p < 0.001), CHOP (p < 0.01), CALR (p < 0.001) and CANX (p < 0.005), that corroborate the idea that diabetes mellitus and metabolic syndrome are associated with direct damage to the endoplasmic reticulum homeostasis. Ultimately, we note that individuals with lipodystrophy have an increase in serum interleukins, keys of the inflammatory process, as IL-1ß, TNF-α and IL-6 (p < 0.05 all), compared with healthy individuals, which can be the trigger to insulin resistance in this population. CONCLUSION: Individuals with FPLD besides having typical dysfunctions of metabolic syndrome, show a hyperactivation of ERS associated with increased systemic inflammatory profile, which together may explain the complex clinical aspect of this diseases.Trial registration HCRP no 6711/2012.

Supplementation of α-linolenic acid improves serum adiponectin levels and insulin sensitivity in patients with type 2 diabetes.

OBJECTIVE: ω-3 Polyunsaturated α-linolenic acid (ALA) supplementation has not been studied in the setting of adiponectin levels and insulin sensitivity (IS) improvements in patients with type 2 diabetes mellitus (T2DM) by hyperinsulinemic-euglycemic clamp (HEC). The aim of this study was to examine the influence of ω-3 ALA on IS and adiponectin. METHODS: We conducted a randomized study in patients with T2DM and assessed IS using HEC. Twenty patients with T2DM were included and randomly assigned to receive 3 g/d of ALA or placebo for 60 d, in a double-blind design. The assessment of IS by HEC was performed at baseline and after 60 d in all patients; blood samples were taken for the measurement of serum lipids, glucose, insulin, adiponectin, and cytokines. The primary outcome variables were an increase of both glucose infusion rate (GIR) in steady state and glucose metabolization (M) by HEC. The secondary outcomes were an increase in adiponectin levels and a decrease in fasting plasma glucose, glycated hemoglobin, homeostasis model assessment-estimated insulin resistance (HOMA-IR) index, lipids and cytokines. The study was conducted at an academic medical center. RESULTS: The ALA group improved IS corrected for fat-free mass (M/FFM; P = 0.04). Both groups showed increased adiponectin after 60 d (P = 0.01), however, the increase for the ALA group was greater (P = 0.04). In the ALA group, adiponectin was positively correlated with GIR (r = 0.76; P = 0.01) and M/FFM (r = 0.62; P = 0.06), and negatively correlated with HOMA-IR (r = -0.61; P = 0.03). CONCLUSION: ω-3 ALA supplementation improved glucose homeostasis and was associated with an increase in adiponectin. Improvement in the overall metabolic profile with ω-3 ALA suggests a potential clinical utility for this agent and requires further investigation.

Prevalence of the metabolic syndrome using two proposed definitions in a Japanese-Brazilians community.

Metabolic Syndrome (MetS) is associated with increased risk of morbi-mortality, thus the characterization of the population magnitude of this syndrome is critical for allocating health care. However, prevalence estimates of MetS in the same population could differ depending on the definition used. Therefore, we compared the prevalence of the MetS using definitions proposed by: National Cholesterol Education Panel Revised (NCEP) and International Diabetes Federation (IDF) 2009 in a Japanese-Brazilians community (131 individuals, age 57 ± 16 years, 1st and 2nd generation). All individuals went through a clinical and laboratorial evaluation for assessment of weigh, height, waist circumference, blood pressure, triglycerides, HDL-cholesterol and fasting plasma glucose. The prevalence of MetS was 26.7% (n = 35) and 37.4% (n = 49) under the NCEP and IDF definitions, respectively. Despite higher blood pressure measurements, waist circumference and serum triglyceride levels and lower HDL cholesterol levels (p < 0.01), individuals identified with MetS did not show increased blood glucose levels. IDF definition classified 14 individuals (10.7%) with MetS that were not classified under the NCEP and 35 individuals were identified with MetS by both criteria. We observed, in this group, more severe lipid disorders, compared to individuals identified only under the IDF definition, and the BMI and waist circumference (p = 0.01; p = 0.006, respectively) were lower. In conclusion, the IDF revised criteria, probably because of the ethnic specific values of waist circumference, was able to identify a larger number of individuals with MetS. However, our data suggesting that additional studies are necessary to define best MetS diagnostic criteria in this population.

Controle da hiperglicemia intra-hospitalar em pacientes críticos e não-críticos / Control of hyperglycemia intra-hospital in critical and non-critical patients

Hiperglicemia é uma condição frequente encontrada no ambiente intra-hospitalar. Quando presente em pacientes críticos internados pode levar a maior morbi-mortalidade, comprometendo o tratamento da doença de base. Essa revisão tem por objetivo padronizar a conduta terapêutica na hiper e hipoglicemias nos pacientes internados em ambiente hospitalar, de forma a reduzir tempo de internação e mortalidade...

Hyperglycemia is a common condition found in-hospital environment. When present in critically ill patients admitted can lead to increased morbidity and mortality, affecting the treatment of the underlying disease. This protocol aims to standardize the therapeutic approach in hyper-and hypoglycemia in patients admitted to hospital in order to reduce length of stay and mortality...

Production and regulation of lipase activity from Penicillium restrictum in submerged and solid-state fermentations.

Different carbon (C) sources, mainly carbohydrates and lipids, have been screened for their capacity to support growth and lipase production by Penicillium restrictum in submerged fermentation (SmF) and in solid-state fermentation (SSF). Completely different physiological behaviors were observed after the addition of easily (oleic acid and glucose) and complex (olive oil and starch) assimilable C sources to the liquid and solid media. Maximal lipolytic activities (12.1 U/mL and 17.4 U/g) by P. restrictum were obtained with olive oil in SmF and in SSF, respectively. Biomass levels in SmF (12.2-14.1 mg/mL) and SSF (7.0-8.0 mg/g) did not varied greatly with the distinct C sources used. High lipase production (12.3 U/g) using glucose was only attained in SSF, perhaps due to the ability of this fermentation process to minimize catabolite repression.