[Show abstract][Hide abstract] ABSTRACT: Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene - KCNJ11:c1001G>7 (p.Gly334Val) - and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.
[Show abstract][Hide abstract] ABSTRACT: Background:
The aim of this study was to assess the relationship between health-related quality of life (HRQoL) and the presence or absence of hypertension and diabetes-related chronic complications in type 2 diabetes, and also the association between HRQoL and the number of chronic complications.
One hundred patients with type 2 diabetes were interviewed. HRQoL was evaluated using the age-adjusted Short-Form 36 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health).
The mean age of the study population was 62.7±8.7 years; 54.0% were male, and 51.0% were receiving only oral hypoglycemic agents. Chronic complications were related to worse HRQoL in different dimensions: peripheral neuropathy and cardiovascular disease (all, except bodily pain), retinopathy (physical functioning, general health, vitality, and mental health), peripheral arterial disease (physical functioning, role-physical, and general health), and nephropathy (general health and vitality). Hypertension was related to worse general health and vitality. An increased number of chronic complications was associated with worse HRQoL in all dimensions of Short-Form 36 except for the bodily pain dimension.
The presence and increased number of diabetes-related chronic complications, and the presence of hypertension were related to worse age-adjusted HRQoL. Peripheral neuropathy and cardiovascular disease were more strongly related to age-adjusted HRQoL.
Full-text · Article · Aug 2015 · Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
[Show abstract][Hide abstract] ABSTRACT: Bariatric surgery improves lipid profile. A still unanswered question is whether this improvement is merely weight-dependent or also results from factors inherent to specificities of the bariatric procedure. We aimed to study lipid profile 1 year after bariatric surgery and compare its changes between the different procedures in patients matched for initial weight and weight loss.
We retrospectively analysed patients submitted to Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB) or sleeve gastrectomy (SG) between 2010 and 2013. Patients were matched for age (±5 years), sex, pre-surgery body mass index (BMI) (±2 Kg/m(2)) and excess weight loss (EWL) (±5 %). Baseline and 1-year lipid profile, its variation and percentage of variation was compared between surgeries.
We analysed 229 patients: 72 pairs RYGB-AGB, 47 pairs RYGB-SG and 33 pairs AGB-SG. The median age was 41 (35-52) years and 11.8 % were male. Pre-operative BMI was 44.0 ± 4.6 and 32.1 ± 4.4 Kg/m(2) at 1 year. EWL at 1 year was 64.2 ± 18.9 %. There were no differences in baseline lipid profile between patients submitted to different types of bariatric surgery. At 1 year, high-density lipoprotein cholesterol (HDL) and triglycerides (TG) improved similarly with all surgeries. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) at 1 year decreased significantly more in patients submitted to RYGB than in weight-matched patients undergoing AGB or SG.
RYGB is the only bariatric surgery that reduces TC and LDL in age-, sex-, BMI- and EWL-matched patients. All three procedures improved TG and HDL similarly when the confounding effect of weight loss is eliminated.
[Show abstract][Hide abstract] ABSTRACT: PROP1 (Prophet of POUF1) mutations are the most frequent genetic cause of combined pituitary hormone deficiency, a condition associated with a deficiency or inadequate production of hormones of the anterior pituitary. The PROP1 gene encodes a transcription factor involved in the ontogeny, differentiation and function of somatotrophs, lactotrophs and thyrotrophs. These mutations are characterized by a remarkable clinical variability, including time of onset of hormonal deficiencies, hypophyseal dimensions and secretion of cortisol.
[Show abstract][Hide abstract] ABSTRACT: AbstrAct Obesity and type 2 diabetes are metabolic diseases that have reached epidemic proportions worldwide. Although their etiology is complex, both result from interplay between behaviour, environment and genetic factors. Within ambient determinants, human overall gut bacteria have been identified as a crucial mediator of obesity and its consequences. Gut microbiota plays a crucial role in gastro-intestinal mucosa permeability and regulates the fermentation and absorption of dietary polyssacharides, which may explain its importance in the regulation of fat accumulation and the resultant development of obesity-related diseases. The main objective of this review is to address the pathogenic association between gut microbiota and obesity and to explore related innovative therapeutic targets. New insights into the role of the small bowel and gut microbiota in diabetes and obesity may make possible the development of integrated strategies to prevent and treat these metabolic disorders.
[Show abstract][Hide abstract] ABSTRACT: As alterações da função tiroideia são comuns nos doentes infetados pelo vírus da imunodeficiência humana (VIH). A prevalência de condições geralmente assintomáticas (como o hipotiroidismo subclínico) está aumentada e a doença de Graves pode ocorrer durante a reconstituição imune associada à terapêutica antirretrovírica combinada (TARC).
[Show abstract][Hide abstract] ABSTRACT: Nonalcoholic fatty liver disease is the hepatic expression of metabolic syndrome, being frequently associated with obesity, insulin resistance, and dyslipidemia. Recent lines of evidence have demonstrated a role of gut microbiota in insulin resistance, obesity, and associated metabolic disturbances, raising the interest in its relationship with NAFLD pathogenesis. Therefore, intestinal microbiota has emerged as a potential factor involved in NAFLD, through different pathways, including its influence in energy storage, lipid and choline metabolism, ethanol production, immune balance, and inflammation. The main objective of this review is to address the pathogenic association of gut microbiota to NAFLD. This comprehension may allow the development of integrated strategies to modulate intestinal microbiota in order to treat NAFLD.
Full-text · Article · Jun 2015 · BioMed Research International
[Show abstract][Hide abstract] ABSTRACT: Background HIV-infected patients are at high risk of fragility fractures as they experience early decline in muscle mass and in bone mineral density (BMD), which is the most important independent risk factor for bone fragility. Several tools have been developed to identify subgroups at highest risk of low BMD. Most of them include well established determinants of BMD, as age and weight, but in the last years the potential independent role of lean mass has been speculated. Middle upper arm circumference (MUAC) highly correlates to skeletal muscle mass in HIV-infected males and EPIPOST , a tool developed to identify men in the general population with low BMD, supports that lean mass, indirectly measured by MUAC, is the best predictor of low BMD. We hypothesize that as HIV-infected patients experience sarcopenia, EPIPOST may be more suitable to identify low BMD in this population.
Objectives To evaluate the discriminatory capacity of Osteoporosis Screening Tool (OST; based on weight and age) and EPISPOT (based on MUAC) to identify low bone mineral density HIV-infected men.
Methods Cross-sectional evaluation of 118 HIV-infected Caucasian men, on combination antiretroviral therapy, followed in the Endocrinology outpatient clinic of São João Hospital Centre. Data on gender, age, weight, height, MUAC and femoral neck BMD (LUNAR EXPERT-XL) was collected. T-scores were calculated as recommended by the World Health Organization (the number of standard deviations (SD) by which an individual measurement differs from the mean value for healthy adult female population aged 30 years; the reference population were obtained from the NHANES III study). Patients with T-score <-1.0 were classified as having low BMD. Determination of the area under the ROC curve (AUC) was estimated to evaluate the discriminatory capacity of OST and EPIPOST. Sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) were calculated to the cut-off points suggested for the general Portuguese population .
Results Mean (SD) age was 48.5 (10.70) years-old and the prevalence of low BMD was 7.6% (n=9). The AUC for OST was 0.725 (p=0.025) and for EPIPOST was 0.776 (p=0.006). At the suggested cut-off points, OST (OST≤2) had a SE of 33.3%, a SP of 79.8%, a PPV of 12.0% and a NPV of 93.5%. At the suggested cut-off (EPIPOST> -2), EPIPOST had a SE of 100%, a SP of 3.6%, a PPV of 7.8% and a NPV of 100%.
Conclusions We conclude that, even though both tools show reasonable performance, EPIPOST has better discriminatory capacity than OST to identify HIV men with low bone mineral density. Although as screening tests both tools should identify the maximum of positive cases, the very high SE observed in EPIPOST is associated with an unacceptable specificity. This unbalance calls for calibration and determination of new EPIPOST cut-offs for HIV-infected men.
Disclosure of Interest None declared
No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Familial partial lipodystrophy, Dunnigan variety, is a recognised autosomal dominant disorder which is caused by heterozygous missense mutations in the lamin A/C gene. Dunnigan lipodystrophy is characterised by a variable loss of fat from the extremities and trunk, as well as an excess of subcutaneous fat in the chin and supraclavicular area. The associated metabolic abnormalities include: insulin resistance, diabetes, dyslipidaemia and low leptin levels.
The authors studied the case of a 24-year-old caucasian pregnant woman, with a past medical history of acute pancreatitis, combined dyslipidaemia and diabetes mellitus. At 7 weeks of pregnancy she was referred to the outpatient endocrinology and obstetrics clinic for diabetes care. A physical examination revealed that she presented a loss of fat from the extremities and trunk and also had an excess of subcutaneous fat in the chin. Triglyceride levels were persistently high, and glycaemic control was only achieved through the administration of high doses of insulin (1.8 U/Kg/day). Dunnigan lipodystrophy was suspected and thus a genetic study was requested, which revealed the presence of c.1444C > T (p.Arg482Trp) heterozygote mutation in the lamin A/C gene.
This case is used to illustrate the importance of being able to recognise the clinical signs of this rare lipodystrophic syndrome, which may cause potentially severe consequences, and also the difficulties in treating it during pregnancy.
Full-text · Article · Apr 2015 · BMC Research Notes
[Show abstract][Hide abstract] ABSTRACT: Diabetes mellitus is a chronic metabolic disease, the prevalence of which has registered a considerable increase, mainly in adults and elderly. The purpose of this study was to assess the relationship between health-related quality of life in patients with diabetes and sex, body mass index, type of diabetes and treatment regimens (type 1 diabetes: intensive versus conventional treatment; type 2 diabetes: insulin use versus non-insulin use), and duration of diabetes.
One hundred and twenty-four patients with diabetes were interviewed. Health-related quality of life was evaluated using the age-adjusted Short-Form 36 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health), and related to demographic and clinical variables. Independent samples t-tests and One-Way Analysis of Variance were used to compare means of independent samples. The degree of association between pairs of variables was measured by Pearson's (r) or Spearman's (rs ) correlation coefficients.
The mean age of the study population was 55.7±16.4 years; 54.8% were male, and 77.4% had type 2 diabetes. Females reported worse quality of life than males in all dimensions of the Short-Form 36, except for role-physical and bodily pain. Obese patients had worse physical functioning than normal weight and overweight patients, and worse vitality than their normal weight counterparts. Type 2 diabetic patients taking insulin had lower physical functioning and vitality than those without insulin therapy. Longer duration of diabetes was associated with lower physical functioning, role-physical, general health, vitality, role-emotional, and mental health.
Being female, obese, having type 2 diabetes and taking insulin, and having a longer disease duration are characteristics associated with worse age-adjusted quality of life in patients with diabetes.
Full-text · Article · Apr 2015 · Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
[Show abstract][Hide abstract] ABSTRACT: Combined antiretroviral therapy (cART) for the treatment of HIV-1 infection has been associated with complications, including lipodystrophy. Several interleukins have been implicated in the pathology and physiology of lipodystrophy. The present study aimed to compare the levels of IL-4 and IL-6 in HIV-1 patients under cART with and without, clinically and fat mass ratio defined, lipodystrophy and in four different groups of fat distribution: (1) no lipodystrophy; (2) isolated central fat accumulation; (3) isolated lipoatrophy and (4) mixed forms of lipodystrophy.
In the present cross-sectional study we evaluated IL-4 and IL-6 levels, insulin resistance and insulin sensitivity indexes in 86 HIV-infected adults under cART.
No significant differences in IL-4 and IL-6 levels between the four groups of body composition were observed. Patients with HOMA-IR >4 presented higher levels of IL-6 and lower levels of IL-4, although without statistical significance. No correlation between IL-6, or IL-4, HOMA-IR and quantitative body fat mass distribution was found.
Although there was a tendency for patients with isolated lipoatrophy and isolated fat accumulation to present higher IL-6 levels, these differences were not statistically significant. No differences were found relating IL-4 levels.
Full-text · Article · Feb 2015 · Journal of endocrinological investigation