Thyroid morphology in lethal non-thyroidal illness: a post-mortem study

OBJECTIVE: Non-thyroidal illness (NTI) is associated with alterations in thyroid hormone metabolism. Whether morphological changes of the thyroid gland accompany NTI is unknown. The aim of the present study was to describe thyroid morphology in patients with lethal non-thyroidal disease. DESIGN: In an autopsy study 267 cases have been examined. METHODS: Clinical data were obtained from medical records. Subjects were patients with chronic disease (group A), intensive care patients (group B) or persons who had died suddenly without pre-existing illnesses (group C). Patients (n = 93) who did not fit into one of these categories and subjects with pre-existing thyroid disorders were excluded. Thyroid histology was assessed semi-quantitatively: grade I <25%, grade II 25--50% or grade III >75% occupation of the thyroid gland by follicles with a diameter <200 microm. RESULTS: Mean thyroid weight was 19.9 g in group A (n=75, age 19--96 (median 75) years, 48 males); 25.7 g in group B (n=64, age 24--93 (median 69) years, 43 males); and 26.0 g in group C (n=35, age 31--89 (median 69) years, 22 males) (P<0.0005, A vs B/C). Grade I thyroid histology was present in 6 out of 75 patients with chronic illness, in 3 out of 64 intensive care patients and in 33 out of 35 sudden-death subjects. Grade III thyroid histology occurred in 30 out of 75 chronically ill patients, in 17 out of 64 intensive care patients and in 0 out of 35 sudden-death subjects (P<0.0005, C vs A/B). CONCLUSIONS: NTI is associated with reduced thyroid follicular size that is accompanied by lower thyroid weight in chronically ill patients but not significantly in intensive care patients

Dyslipidemia in Obesity: Mechanisms and Potential Targets

Obesity has become a major worldwide health problem. In every single country in the world, the incidence of obesity is rising continuously and therefore, the associated morbidity, mortality and both medical and economical costs are expected to increase as well. The majority of these complications are related to co-morbid conditions that include coronary artery disease, hypertension, type 2 diabetes mellitus, respiratory disorders and dyslipidemia. Obesity increases cardiovascular risk through risk factors such as increased fasting plasma triglycerides, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels and high blood pressure. Novel lipid dependent, metabolic risk factors associated to obesity are the presence of the small dense LDL phenotype, postprandial hyperlipidemia with accumulation of atherogenic remnants and hepatic overproduction of apoB containing lipoproteins. All these lipid abnormalities are typical features of the metabolic syndrome and may be associated to a pro-inflammatory gradient which in part may originate in the adipose tissue itself and directly affect the endothelium. An important link between obesity, the metabolic syndrome and dyslipidemia, seems to be the development of insulin resistance in peripheral tissues leading to an enhanced hepatic flux of fatty acids from dietary sources, intravascular lipolysis and from adipose tissue resistant to the antilipolytic effects of insulin. The current review will focus on these aspects of lipid metabolism in obesity and potential interventions to treat the obesity related dyslipidemia

Diurnal Triglyceridemia in Relation to Alcohol Intake in Men

__Abstract__ Fasting and postprandial triglyceride concentrations largely depend on dietary and lifestyle factors. Alcohol intake is associated with triglycerides, but the effect of alcohol on diurnal triglyceridemia in a free living situation is unknown. During three days, 139 men (range: 18-80 years) measured their own capillary triglyceride (cTG) concentrations daily on six fixed time-points before and after meals, and the total daily alcohol intake was recorded. The impact of daily alcohol intake (none; low, 30 g/day) on diurnal triglyceridemia was analyzed by the incremental area under the cTG curve (∆cTG-AUC) reflecting the mean of the six different time-points. Fasting cTG were similar between the alcohol groups, but a trend of increased cTG was observed in men with moderate and high alcohol intake after dinner and at bedtime (p for trend <0.001) which persisted after adjustment for age, smoking and body mass index. The ∆cTG-AUC was significantly lower in males with low alcohol intake (3.0 ± 1.9 mmol·h/L) (n = 27) compared to males with no (7.0 ± 1.8 mmol·h/L) (n = 34), moderate (6.5 ± 1.8 mmol·h/L) (n = 54) or high alcohol intake (7.2 ± 2.2 mmol·h/L) (n = 24), when adjusted for age, smoking and body mass index (adjusted p value < 0.05). In males, low alcohol intake was associated with decreased diurnal triglyceridemia, whereas moderate and high alcohol intake was associated with increased triglycerides after dinner and at bed time

Effects of Metformin on the Regulation of Free Fatty Acids in Insulin Resistance: A Double-Blind, Placebo-Controlled Study

Introduction. Impaired free fatty acid (FFA) metabolism is closely linked to insulin resistance. Our aim was to evaluate plasma FFA changes in insulin resistance in a physiological situation after improvement of insulin sensitivity by metformin. Methods. A double-blind, placebo-controlled intervention with metformin was carried out in patients with insulin resistance. Nineteen patients were randomized to receive metformin 850 mg b.i.d. during 6 weeks or placebo. Participants underwent a mental stress test and an oral glucose tolerance test (OGTT) before and after treatment. Results. Fasting plasma glucose, FFA, and HOMA-IR tended to decrease after metformin, suggesting improved insulin sensitivity. FFA concentrations during the mental stress test showed a similar pattern after metformin, albeit lower at all time points, in contrast to the placebo group. The decrease in fasting plasma FFAs was positively associated to the decrease in HbA1c (; ) and in fasting glucose (; ). The suppression of plasma FFAs during OGTT did not change by metformin or placebo. Conclusion. Metformin in insulin resistance did not lead to improved FFA dynamics despite a trend of improved insulin sensitivity. Metformin most likely decreases plasma FFAs mainly by suppressing fasting FFA concentrations and not by suppression of acute stress-induced lipolysis

Erythrocyte-Bound Apolipoprotein B in Relation to Atherosclerosis, Serum Lipids and ABO Blood Group

Introduction:Erythrocytes carry apolipoprotein B on their membrane, but the determining factors of erythrocyte-bound apolipoprotein B (ery-apoB) are unknown. We aimed to explore the determinants of ery-apoB to gain more insight into potential mechanisms.Methods:Subjects with and without CVD were included (N = 398). Ery-apoB was measured on fresh whole blood samples using flow cytometry. Subjects with ery-apoB levels ≤0.20 a.u. were considered deficient. Carotid intima media thickness (CIMT) was determined as a measure of (subclinical) atherosclerosis.Results:Mean ery-apoB value was 23.2% lower in subjects with increased CIMT (0.80±0.09 mm, N = 140) compared to subjects with a normal CIMT (0.57±0.08 mm, N = 258) (P = 0.007, adjusted P<0.001). CIMT and ery-apoB were inversely correlated (Spearman's r: -0.116, P = 0.021). A total of 55 subjects (13.6%) were considered ery-apoB deficient, which was associated with a medical history of CVD (OR: 1.86, 95% CI 1.04-3.33; adjusted OR: 1.55; 95% CI 0.85-2.82). Discontinuation of statins in 54 subjects did not influence ery-apoB values despite a 58.4% increase in serum apolipoprotein B. Subjects with blood group O had significantly higher ery-apoB values (1.56±0.94 a.u.) when compared to subjects with blood group A (0.89±1.15 a.u), blood group B (0.73±0.1.12 a.u.) or blood group AB (0.69±0.69 a.u.) (P-ANOVA = 0.002).Conclusion:Absence or very low values of ery-apoB are associated with clinical and subclinical atherosclerosis. While serum apolipoprotein B is not associated with ery-apoB, the ABO blood group seems to be a significant determinant

Laparoscopic sleeve gastrectomy with an extensive posterior mobilization: Technique and preliminary results

Background: Laparoscopic sleeve gastrectomy (LSG) is becoming increasingly popular as a stand-alone procedure for the treatment of morbidly obese patients. A direct posterior approach to the angle of His was developed at our department to improve visualization of the difficult dissection of the short gastric vessels and to facilitate proper mobilization of the stomach around the left crus enabling safe realization of a tight sleeve. The technique and its preliminary results are described. Methods: LSG by posterior approach was performed in a consecutive series of 445 (110 male/335 female, age 18-63 years, mean body mass index 46 kg/m2 (range 35-76)) patients between 2007 and 2010. Results: Weight loss defined as mean percent excess weight loss (%EWL) was 71% (±26%) at 1 year, 69% (±25%) at 2 years, and 55% (±27%) at 3 years. Sixteen patients (4%) developed postoperative intra-abdominal hematoma, 8 patients (2%) anastomotic leakage, and 6 patients intra-abdominal abscess (1%), requiring reoperation in 20 patients (4%). Five patients (1%) had pulmonary embolism. Thirty-day mortality rate was 0.2%. Conclusions: LSG by the posterior approach is a safe and effective procedure, enabling a tight sleeve formation leading to satisfactory %EWL results. Since long-term results of LSG are unknown, further studies are needed to define the exact place of the LSG as a stand-alone bariatric proc

Insulin detemir is associated with more predictable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin aspart

WSTĘP. Insulina detemir jest rozpuszczalnym, długodziałającym analogiem insuliny. Cechuje się wyjątkowym, wydłużonym profilem działania, pozwalającym na zmniejszenie zmienności glikemii, związanej ze stosowaniem konwencjonalnych insulin długodziałających. W badaniu porównano insulinę detemir i insulinę NPH pod względem uzyskanej kontroli glikemii, ryzyka hipoglikemii oraz wpływu na masę ciała u chorych na cukrzycę typu 1, otrzymujących przedposiłkowe wstrzyknięcia insuliny krótkodziałającej aspart. MATERIAŁ I METODY. Do badania zakwalifikowano metodą randomizacji 448 chorych na cukrzycę typu 1, którym podawano insulinę detemir lub NPH w stosunku 2:1. Badanie typu otwartego, w którym porównywano równolegle obie grupy pacjentów, trwało 6 miesięcy i było prowadzone w 46 ośrodkach, w 5 krajach. WYNIKI. Po 6 miesiącach badania wartości hemoglobiny glikowanej (HbA1c) w obu grupach były porównywalne. Glikemia na czczo była nieco niższa u chorych leczonych insuliną detemir, jednak różnica ta nie była istotna statystycznie (&#8211;0,76 mmol/l; p = 0,097). Zmienność glikemii na czczo określana na podstawie samokontroli u poszczególnych pacjentów była mniejsza przy stosowaniu insuliny detemir niż insuliny NPH (SD 3,37 vs. 3,78 mmol/l; p < 0,001). Ryzyko niedocukrzenia było o 22% niższe w grupie leczonej insuliną detemir niż w grupie przyjmującej insulinę NPH (p < 0,05); a ryzyko nocnych niedocukrzeń (23.00-06.00) &#8212; o 34% niższe (p < 0,005). Profil glikemii w porze nocnej był bardziej stabilny i stały podczas stosowania insuliny detemir (p = 0,05). Na końcu badania u pacjentów leczonych insuliną detemir zaobserwowano istotnie niższą masę ciała (p < 0,001). WNIOSKI. Leczenie insuliną detemir wiąże się z bardziej przewidywalną kontrolą glikemii, z mniejszymi wahaniami glikemii w ciągu doby oraz istotnym zmniejszeniem ryzyka niedocukrzeń w porównaniu ze stosowaniem insuliny NPH. Zmniejszenie masy ciała podczas terapii insuliną detemir jest dodatkowym, potencjalnie korzystnym efektem. Schematy leczenia oparte na insulinie detemir mogą umożliwić lepszą kontrolę glikemii niż schematy oparte na insulinie NPH.INTRODUCTION. Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals. MATERIAL AND METHODS. This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively. RESULTS. After 6 months, comparable HbA1c levels were found between the two treatment groups. Fasting plasma glucose tended to be lower in patients treated with insulin detemir, but this difference was not statistically significant (&#8211;0.76 mmol/l, P = 0.097). Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin (SD 3.37 vs. 3.78 mmol/l, P < 0.001). Risk of hypoglycemia was 22% lower with insulin detemir than with NPH insulin (P < 0.05) and 34% lower for nocturnal (2300&#8211;0600) hypoglycemia (P < 0.005). Nightly plasma glucose profiles were smoother and more stable with insulin detemir (P < 0.05). Body weight was significantly lower with insulin detemir at the end of the trial (P < 0.001). CONCLUSIONS. Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin