[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: 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.
Obesity Surgery 07/2015; DOI:10.1007/s11695-015-1825-1 · 3.75 Impact Factor
[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.
BioMed Research International 06/2015; 2015. DOI:10.1155/2015/979515 · 2.71 Impact Factor
[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.
BMC Research Notes 04/2015; 8(1):140. DOI:10.1186/s13104-015-1065-4
[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.
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 04/2015; 8:219-226. DOI:10.2147/DMSO.S80472
[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.
[Show abstract][Hide abstract] ABSTRACT: Introduction: Obesity is associated with an increased risk of type 2 Diabetes
Mellitus (DM). Oral glucose tolerance test (OGTT), fasting plasma
glucose (FPG) and A1c test can be use to diagnose the condition. As the
OGTT is more expensive and time consuming than alternative tests is
questionable to perform the test in all obese patients. Objective: To compare
OGTT with A1c and FPG in the diagnosis of DM in obese patients.
Methods: Cross-sectional study of a population of 717 morbidly obese
adults evaluated in a Multidisciplinary Assessment of Surgical Treatment
of Morbid Obesity between January/2010-December/2013. Demographic,
anthropometric and metabolic parameters were evaluated. Diabetes was
defined according to ADA criteria.
Results: In a cohort of 717 patients, 629 (87.7%) were female, with a median
age of 41 years (IQR 35–51) and a median BMI of 43.5kg/m2 (IQR
40.6–47.1). Of 707 patients who performed FPG, 18 (2.5%) met DM criteria;
of 657 patients who underwent OGTT, 37 (5.6%) fulfilled DM criteria;
of 673 who performed A1c, 25 patients (3.7%) had DM by this criterion.
629 patients performed the three diagnostic tests. Of those, 18 patients
(2.9%) did not meet criteria for DM by A1c or FPG, but they were diagnosed
by OGTT. The FPG and A1c diagnosed DM in 12 patients (1.9%)
with a normal OGTT. The FPG and A1c test showed a specificity of 98%
and a sensitivity of 48.6% for the identification of patients with DM compared
Conclusion: OGTT diagnosed diabetes in patients with normal FPG and
A1C. FPG or A1c showed a low diagnostic sensitivity, which highlights
the importance of performing OGTT in obese patients, in order to reduce
the number of undiagnosed cases of diabetes.
[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: Background
HIV-infected patients may be at increased risk of cardiovascular (CV) events, and lipodystrophy is generally associated with proatherogenic metabolic disturbances. Carotid intima-media thickness (cIMT) has been used as a surrogate marker for atherosclerosis and it has been shown to be an independent risk factor for CV disease. Our objective was to evaluate cIMT in HIV-infected patients on combined anti-retroviral therapy (cART) with and without lipodystrophy defined by fat mass ratio (L-FMR), and to determine the association of lipodystrophy and visceral obesity [(visceral (VAT), subcutaneous adipose tissue (SAT) volume and VAT/SAT ratio, objectively evaluated by CT scan] with cIMT.
Cross-sectional study of 199 HIV-infected patients. Body composition by DXA and abdominal CT, lipids, blood pressure, inflammatory markers, and cIMT by ultrasonography were performed. L-FMR was defined as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared using the chi-square or Fisher’s exact test. Spearman correlation coefficients were estimated to study the association between cIMT and clinical and metabolic characteristics. Means of cIMT, adjusted for age, were calculated, using generalized linear models.
L-FMR was present in 41.2% of patients and cIMT was higher in these patients [0.81 (0.24) vs. 0.76 (0.25); p = 0.037)]. Lipodystrophic patients had higher VAT and VAT/SAT ratio and lower SAT. cIMT was associated with lipodystrophy evaluated by FMR, trunk fat, total abdominal fat, VAT and VAT/SAT ratio. No association was observed between cIMT and leg fat mass. Using generalized linear models, cIMT means were adjusted for age and no significant differences remained after this adjustment. The adjusted mean of cIMT was 0.787 (95% CI: 0.751-0.823) in patients without lipodystrophy, and 0.775 (95% CI: 0.732-0.817) in those with lipodystrophy (p = 0.671).
HIV-infected patients on cART with lipodystrophy defined by FMR, had a significantly higher cIMT. Carotid IMT was also associated with classical cardiovascular risk factors. In these patients, visceral adipose tissue had a significant impact on cIMT, although age was the strongest associated factor.