Splenic Abscess in an Adolescent due to Salmonella enterica Conservatively Treated with Ultrasound-Guided Fine-Needle Aspiration.

Background: Splenic abscesses are rare and potentially fatal. Diagnosis is often delayed due to vague symptoms, and laboratory findings are varying and often nonspecific. Ultrasound and computed tomography have a high sensitivity in detecting splenic abscesses. Splenectomy was previously considered the gold standard for treatment, but in recent years, a shift has been seen towards a more conservative approach, i.e., ultrasound-guided aspiration or drainage in combination with adequate antibiotics in selected cases. Case Report. A previously healthy adolescent complained of left-sided chest pain, pain in the left clavicular region for three weeks, and recent fever. Ultrasound and computed tomography demonstrated an intrasplenic abscess. The patient was successfully treated with two percutaneous fine-needle punctures and adequate antibiotics for six weeks. Salmonella enterica serotype Poona was grown from the aspirate. At one-year follow-up, the patient remained healthy without signs of recurrence. Conclusion: The present case report demonstrates that ultrasound-guided aspiration and subsequent treatment with antibiotics may be an effective alternative to splenectomy in patients with a splenic abscess.

Comparable Effects of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass on Basal Fuel Metabolism and Insulin Sensitivity in Individuals with Obesity and Type 2 Diabetes.

Aim: Bariatric surgery improves insulin sensitivity and glucose tolerance in obese individuals with type 2 diabetes (T2D), but there is a lack of data comparing the underlying metabolic mechanisms after the 2 most common surgical procedures Roux-en-Y gastric bypass surgery (RYGB) and sleeve gastrectomy (SG). This study was designed to assess and compare the effects of RYGB and SG on fuel metabolism in the basal state and insulin sensitivity during a two-step euglycemic glucose clamp. Materials and Methods: 16 obese individuals with T2D undergoing either RYGB (n = 9) or SG (n = 7) were investigated before and 2 months after surgery, and 8 healthy individuals without obesity and T2D served as controls. All underwent a 2 h basal study followed by a 5 h 2-step hyperinsulinemic euglycemic glucose clamp at insulin infusion rates of 0.5 and 1.0 mU/kg LBM/min. Results: RYGB and SG induced comparable 15% weight losses, normalized HbA1c, fasting glucose, fasting insulin, and decreased energy expenditure. In parallel, we recorded similar increments (about 100%) in overall insulin sensitivity (M-value) and glucose disposal and similar decrements (about 50%) in endogenous glucose production and FFA levels during the clamp; likewise, basal glucose and insulin concentrations decreased proportionally. Conclusion: Our data suggest that RYGB and SG improve basal fuel metabolism and two-step insulin sensitivity in the liver, muscle, and fat and seem equally favourable when investigated 2 months after surgery. This trial is registered with NCT02713555.

[Acute appendicitis after colonoscopy].

Severe complications following colonoscopy are rare. This is a case report of a 44-year-old woman, who presented to an emergency department (ED) 24 hours following an uncomplicated colonoscopy performed in an out-patient clinic. Acute contrast-enhanced CT (CECT) was performed, showing acute appendicitis, which was later confirmed by a laparoscopy and histology. Weeks prior, the patient had been admitted to the ED with lower abdominal pain. On this occasion, CECT was performed, showing acute inflammation of the sigmoid colon.

[Acute abdominal vasculitis in rheumatic diseases].

Mesenteric vasculitis is the most common abdominal manifestation of vasculitis and can present as acute abdominal pain. Mesenteric vasculitis is most frequent in systemic lupus erythematosus and polyarteritis nodosa in adulthood and immunoglobulin A-vasculitis in childhood. Involvement of other organs is also seen. The diagnosis can be challenging, but detailed clinical assessment in combination with diagnostic tests often identifies the underlying cause. Medical treatment is used, when the abdominal manifestation is considered reversible, while surgery is used in unstable patients or patients with non-reversible conditions.

[Overweight and gastro-oesophageal reflux disease].

The increase in the prevalence of obesity is paralleled by an increase in gastro-oesophageal reflux disease (GERD), and several mechanisms link GERD and obesity, so weight loss is a cornerstone in the treatment of GERD. Sustained weight loss often requires surgery, and fundoplication is the first surgical choice among normal weight patients with reflux; however, reflux complications increase with increasing BMI. Therefore, patients with obesity and GERD should be treated with gastric bypass surgery. The aim of this article is to discuss the relationship between overweight and GERD and outline treatment options of this disease.

Genetic alterations within the DENND1A gene in patients with polycystic ovary syndrome (PCOS).

Polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs) in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene in white patients with PCOS to identify possible alterations that may be implicated in the PCOS pathogenesis. Patients were referred with PCOS and/or hirsutism between 1998 and 2011 (n = 261). PCOS was diagnosed according to the Rotterdam criteria (n = 165). Sequence analysis was performed in 10 patients with PCOS. Additional patients (n = 251) and healthy female controls (n = 248) were included for SNP genotyping. Patients underwent clinical examination including Ferriman-Gallwey score (FG-score), biochemical analyses and transvaginal ultrasound. Mutation analysis was carried out by bidirectional sequencing. SNP genotyping was tested by allelic discrimination in real-time PCR in the additional patients and controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not known to be associated with any diseases. One missense SNP was detected (rs189947178, A/C), potentially altering the structural conformation of the DENND1A protein. SNP genotyping of rs189947178 showed significantly more carriers among patients with PCOS and moderate hirsutism compared to controls. However, due to small sample size and lack of multiple regression analysis supporting an association between rs189947178 and FG-score or PCOS diagnosis, this could be a false positive finding. In conclusion, sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis, but a missense SNP (rs189947178) was identified in one patient and significantly more carriers of rs189947178 were found among patients with PCOS and moderate hirsutism vs. controls. Additional studies with independent cohort are needed to confirm this due to the small sample size of this study.

Increased action of pulsatile compared to non-pulsatile insulin delivery during a meal-like glucose exposure simulated by computerized infusion in healthy humans.

It has previously been demonstrated that pulsatile insulin has a greater hypoglycemic effect than non-pulsatile insulin during euglycemic conditions. The aim of the present study was to examine the effect of pulsatile versus non-pulsatile insulin delivery during a meal-like iv-glucose challenge. Ten healthy young subjects were examined on two occasions. A pancreatic-pituitary clamp was maintained with somatostatin infusion and replacement of glucagon and growth hormone at baseline levels. During the first three hours on both study days, insulin was infused in a pulsatile manner. Hereafter glucose and insulin were infused by computer-controlled pumps for four hours in a pattern mimicking the postprandial glucose and insulin profiles. At one study day, insulin infusion was done in a continuous manner, while at the other study day this profile was done in a pulsatile pattern. The hypoglycemic effect of insulin was measured as the integrated area under the curve of glucose during the four-hour infusion period. The mean insulin concentration measured as the integrated area under the curve was identical (P > .9). The hypoglycemic effect of insulin was significantly augmented by 13% during pulsatile delivery as compared to continuous delivery (P = .015). Likewise was the maximal glucose concentration significantly lower at the day of the pulsatile profile (9.9 ± 1.0 vs. 11.4 ± 2.3 mmol/l, P = .036). Pulsatile insulin release plays an important role in the postprandial glucose homeostasis. The disturbed insulin pulsatility in type 2 diabetes mellitus may contribute to the postprandial hyperglycemia.

Normalisation of insulin-like growth factor-I does not improve insulin action in cirrhosis.

BACKGROUND & AIMS: Cirrhosis of the liver is characterised by insulin resistance and low levels of insulin-like growth factor I (IGF-I). Lack of IGF-I may contribute to this insulin resistance, as IGF-I increases insulin sensitivity. This study aimed to determine the effects of normalisation of IGF-I on insulin action in cirrhosis. METHODS: This article is a randomised sequence-crossover placebo controlled study. Eight patients with cirrhosis and eight controls were studied following treatment with IGF-I (50 µg/kg twice daily) or saline. Insulin action, glucose utilisation and endogenous glucose production were measured during the euglycaemic hyperinsulinaemic clamp. RESULTS: The patients with cirrhosis had normal fasting glucose level, but increased levels of insulin (P < 0.05) and C-peptide (P < 0.05). Insulin resistance resulted from a defect in glycogen synthesis, whereas insulin-mediated suppression of glucose production was unaltered. In cirrhosis, IGF-I treatment normalised free (from 0.07 ± 0.01 to 0.26 ± 0.05 µg/L) and total IGF-I (from 73 ± 6 to 250 ± 39 µg/L), whereas in controls, the IGF-I level increased into the upper physiological range (free IGF-I from 0.23 ± 0.02 to 0.61 ± 0.06 µg/L; total IGF-I from 200 ± 19 to 500 ± 50 µg/L) (all P-values < 0.05). In cirrhosis, IGF-I treatment did not change fasting glucose, insulin or C-peptide levels (P > 0.05). In the controls, insulin and C-peptide levels decreased (P < 0.05). IGF-I treatment did not improve insulin sensitivity in cirrhosis. CONCLUSIONS: Because normalisation of IGF-I levels did not affect insulin sensitivity lack of IGF-I is unlikely to result in insulin resistance in cirrhosis. IGF-I supplementation is therefore unlikely to improve insulin action in patients with cirrhosis.

Muscle GLUT4 in cirrhosis.

BACKGROUND/AIMS: The insulin-dependent glucose transporter GLUT4 mediates 50-80% of whole body glucose uptake, but its relation to the frequent glucose intolerance in patients with liver cirrhosis is unknown. METHODS: Thirty patients and seven healthy controls underwent a 2-h oral glucose tolerance test and later a muscle biopsy. Levels of GLUT4 total protein and mRNA content were determined in muscle biopsies by polyclonal antibody labelling and RT-PCR, respectively. RESULTS: GLUT4 protein content in the cirrhosis group was not different from that of the controls, but at variance with the control subjects it correlated closely with measures of glucose tolerance (R(2)=0.45; p=0.003). GLUT4 mRNA of the patients with cirrhosis was reduced to 56% of control value (95% ci: 27-86%; p=0.015) and was inversely related to the level of basal hyper-insulinemia (R(2)=0.39; p=0.004). CONCLUSIONS: In cirrhosis GLUT4 protein content was quantitatively intact, while limiting glucose tolerance. This indicates loss of redundancy of the major glucose transport system, possibly related to the markedly decreased expression of its gene. Hyper-insulinemia may be a primary event. Our findings implicate the muscular GLUT4 system in the glucose intolerance of liver cirrhosis by a mechanism different from that in diabetes.

Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis.

OBJECTIVE: Liver cirrhosis is characterized by reduced circulating IGF-I and this has been linked to an adverse clinical outcome. Therefore, we investigated the dynamic changes in circulating total, free, and bioactive IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-2, and IGFBP-1-bound IGF-I (binary complex) during an oral glucose tolerance test (OGTT) in patients with liver cirrhosis. METHODS: Seven Caucasian males with liver cirrhosis and seven healthy males matched for age (54.4+/-3.2 vs 54.6+/-4.4 years) and body mass index (25.3+/-1.2 vs 25.9+/-1.3 kg/m2) were studied. Blood samples were drawn at 0, 30, 60, 90, 120, 150, and 180 min for determination of serum total and free IGF-I, IGFBP-1, IGFBP-2, and binary complex, while bioactive IGF-I was measured at 0, 30, 60, 120, and 180 min. RESULTS: In comparison with healthy subjects, baseline levels of total (47%), free (36%), and bioactive IGF-I (51%) were lower, while IGFBP-1 (268%) was higher (P<0.05), IGFBP-2 (172%) tended to be higher (P>0.05), and the binary complex unchanged (approximately 100%) in cirrhotic patients. Serum total and free IGF-I, and IGFBP-2 remained unchanged in both study groups during the OGTT. Bioactive IGF-I decreased by 29% from baseline to 60 min in cirrhotic patients and remained low at the end of the OGTT (P<0.05). A similar tendency was observed in healthy controls (P=0.052). Concomitantly, IGFBP-1, binary complex, and IGFBP-1 saturation index decreased significantly in both groups. The disappearance of the binary complex was about twofold faster than that of IGFBP-1 (P < 0.05). CONCLUSION: Despite unchanged concentrations of total and free IGF-I, bioactive IGF-I declined significantly after an oral glucose load in patients with liver cirrhosis and the same tendency was observed in healthy subjects. We speculate that the reduction in bioactive IGF-I may be related to the higher levels of free IGFBP-1 and the faster disappearance of IGFBP-1-bound IGF-I.

Contribution of defects in glucose uptake to carbohydrate intolerance in liver cirrhosis: assessment during physiological glucose and insulin concentrations.

It is well established that subjects with liver cirrhosis are insulin resistant, but the contribution of defects in insulin secretion and/or action to glucose intolerance remains unresolved. Healthy individuals and subjects with liver cirrhosis were studied on two occasions: 1) an oral glucose tolerance test was performed, and 2) insulin secretion was inhibited and glucose was infused in a pattern and amount mimicking the systemic delivery rate of glucose after a carbohydrate meal. Insulin was concurrently infused to mimic a healthy postprandial insulin profile. Postabsorptive glucose concentrations were equal (5.36 +/- 0.12 vs. 5.40 +/- 0.25 mmol/l, P = 0.89), despite higher insulin (P < 0.01), C-peptide (P < 0.01), and free fatty acid (P = 0.05) concentrations in cirrhotic than in control subjects. Endogenous glucose release (EGR; 11.50 +/- 0.50 vs. 11.73 +/- 1.00 mumol.kg(-1).min(-1), P = 0.84) and the contribution of gluconeogenesis to EGR (6.60 +/- 0.47 vs. 6.28 +/- 0.64 mumol.kg(-1).min(-1), P = 0.70) were unaltered by cirrhosis. A minimal model recently developed for the oral glucose tolerance test demonstrated an impaired insulin sensitivity index (P < 0.05), whereas the beta-cell response to glucose was unaltered (P = 0.72). During prandial glucose and insulin infusions, the integrated glycemic response was greater in cirrhotic than in control subjects (P < 0.05). EGR decreased promptly and comparably in both groups, but glucose disappearance was insufficient at the prevailing glucose concentration (P < 0.05). Moreover, identical rates of [3-(3)H]glucose infusion produced higher tracer concentrations in cirrhotic than in control subjects (P < 0.05), implying a defect in glucose uptake. In conclusion, carbohydrate intolerance in liver cirrhosis is determined by insulin resistance and the ability of glucose to stimulate insulin secretion. During prandial glucose and insulin concentrations, EGR suppression was unaltered, but glucose uptake was impaired, which demonstrates that intolerance can be ascribed to a defect in glucose uptake, rather than abnormalities in glucose production or beta-cell function. Although insulin secretion ameliorates glucose intolerance, impaired glucose uptake during physiological glucose and insulin concentrations produces marked and sustained hyperglycemia, despite concurrent abnormalities in glucose production or insulin secretion.

Evidence of increased visceral obesity and reduced physical fitness in healthy insulin-resistant first-degree relatives of type 2 diabetic patients.

OBJECTIVE: First-degree relatives (FDR) of type 2 diabetic patients are often insulin resistant. Visceral obesity is closely linked to both insulin resistance and type 2 diabetes. We therefore hypothesized that the inheritance of an increased tendency to store fat in visceral fat depots may be a characteristic phenotypic feature in FDR contributing to their insulin resistance. DESIGN AND METHODS: We measured fat distribution in 20 FDR and 14 age-, gender- and body mass index (BMI)-matched controls employing dual energy X-ray absorbtiometry (DEXA)- and computed tomography (CT)-scanning. Insulin-stimulated glucose uptake (ISGU) was determined by a hyperinsulinemic clamp and maximal aerobic work capacity (VO2 max) by a bicycle ergometer test. Baseline lipolysis was measured using [3H]palmitate. The activity level of the hypothalamic-pituitary-adrenal axis was assessed as the 24 h urinary (u)-cortisol/creatinine ratio. RESULTS: All subjects had a normal oral glucose tolerance test (OGTT), but FDR were insulin resistant (ISGU: 6.64+/-0.48 vs 9.12+/-0.98 mg/kg ffm/min, P=0.01). Despite similar BMI (25.2+/-0.5 vs 24.8+/-0.7 kg/m2, P=0.61) and overall fat mass (26.4+/-1.6 vs 24.2+/-2.1%, P=0.41) in FDR vs controls, the amount of visceral adipose tissue was substantially increased (65.9+/-10.0 vs 40.1+/-11.3 cm2, P<0.05) and VO2 max was reduced (52.2+/-3.1 vs 63.3+/-3.9 ml/kg ffm/min, P<0.05) in FDR. Visceral adiposity was inversely correlated with ISGU (FDR: r=-0.52, P<0.05; controls: r=-0.65, P<0.01) and in multiple regression analysis visceral adiposity (P<0.01), VO2 max (P<0.001) and a family history of type 2 diabetes (P<0.05) (r2=0.64) all significantly and independently contributed to the level of ISGU. Baseline palmitate appearance (145+/-10 vs 139+/-15 micromol/min, P=0.74) and the 24 h u-cortisol/creatinine ratio ((24.9+/-1.3 vs 27.4+/-2.0).10(-6), P=0.28) were both comparable in the two groups. CONCLUSION: Healthy but insulin-resistant FDR have enhanced visceral obesity and reduced VO2 max compared with people without a family history of diabetes, despite similar BMI and overall fat mass. Both the visceral adiposity and reduced aerobic fitness are strongly associated with and may contribute to their insulin resistance.

Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects.

Excess cortisol has been demonstrated to impair hepatic and extrahepatic insulin action. To determine whether glucose effectiveness and, in terms of endogenous glucose release (EGR), gluconeogenesis, also are altered by hypercortisolemia, eight healthy subjects were studied after overnight infusion with hydrocortisone or saline. Glucose effectiveness was assessed by a combined somatostatin and insulin infusion protocol to maintain insulin concentration at basal level in the presence of prandial glucose infusions. Despite elevated insulin concentrations (P < 0.05), hypercortisolemia resulted in higher glucose (P < 0.05) and free fatty acid concentrations (P < 0.05). Furthermore, basal insulin concentrations were higher during hydrocortisone than during saline infusion (P < 0.01), indicating the presence of steroid-induced insulin resistance. Postabsorptive glucose production (P = 0.64) and the fractional contribution of gluconeogenesis to EGR (P = 0.33) did not differ on the two study days. During the prandial glucose infusion, the integrated glycemic response above baseline was higher in the presence of hydrocortisone than during saline infusion (P < 0.05), implying a decrease in net glucose effectiveness (4.42 +/- 0.52 vs. 6.65 +/- 0.83 ml.kg-1.min-1; P < 0.05). To determine whether this defect is attributable to an impaired ability of glucose to suppress glucose production, to stimulate its own uptake, or both, glucose turnover and "hot" (labeled) indexes of glucose effectiveness (GE) were calculated. Hepatic GE was lower during cortisol than during saline infusion (2.39 +/- 0.24 vs. 3.82 +/- 0.51 ml.kg-1.min-1; P < 0.05), indicating a defect in the ability of glucose to restrain its own production. In addition, in the presence of excess cortisol, glucose disappearance was inappropriate for the prevailing glucose concentration, implying a decrease in glucose clearance (P < 0.05). The decrease in glucose clearance was confirmed by the higher increment in [3-3H]glucose during hydrocortisone than during saline infusion (P < 0.05), despite the administration of identical tracer infusion rates. In conclusion, short-term hypercortisolemia in healthy individuals with normal beta-cell function decreases insulin action but does not alter rates of EGR and gluconeogenesis. In addition, cortisol impairs the ability of glucose to suppress its own production, which due to accumulation of glucose in the glucose space results in impaired peripheral glucose clearance. These results suggest that cortisol excess impairs glucose tolerance by decreasing both insulin action and glucose effectiveness.