Portomesenteric vein thrombosis following sleeve gastrectomy: Case report focusing on the role of pathogenetic factors.

INTRODUCTION: Sleeve gastrectomy has currently become the most commonly performed bariatric. procedure worldwide according to the last IFSO survey, overtaking gastric bypass with. a share of more than 50% of all primary bariatric-metabolic surgery. Gastric leak, intraluminal bleeding, bleeding from the staple-line and strictures are the most common complications. Portomesenteric vein thrombosis (PMVT)after sleeve gastrectomy is. another complication that has been increasingly reported in case-series in recent.years, although it remains uncommon. In this case report is described an extended portomesenteric vein thrombosis after. sleeve gastrectomy interesting splenic vein too with a favorable course and an. uneventful follow-up. We try to search in this case for pathogenetic factors involved in. this complication. CASE REPORT: A 42-year old man, with a body mass index (BMI) of 45 kg/m2, with a medical history of Obstructive Sleep Apnea Sindrome (OSAS) underwent laparoscopic sleeve gastrectomy. Early postoperative course was uneventful. Six days after discharge he complained abdominal pain and was admitted at the Emergency Department. A CT scan with intravenous contrast showed an occlusion of the portal vein, of the intrahepatic major branches and an extension to the superior mesenteric vein and the splenic vein. The patient received heparin and oral anticoagulation together with intravenous hydration and proton pump inhibitors. Considering the favourable course the patient was discharged after six days with long-term oral anticoagulation therapy. Anticoagulation with acenocumarol was continued for six months after a CT scan showed resolution of the PMVT without cavernoma. He had no recurrence of symptoms. DISCUSSION: Porto-mesenteric thrombosis after sleeve gastrectomy is a rare complication but it has been increasingly reported over the last 10 years along with the extensive use of sleeve gastrectomy. Because PMVT is closely associated with sleeve gastrectomy in comparison with other bariatric procedures, we need to investigate what pathogenetic factors are involved in sleeve gastrectomy. Thrombophylic state, prolonged duration of surgery, high levels of pneumoperitoneum, thermal injury of the gastroepiploic vessels during greater curvature dissection, high intragastric pressure, inadequate antithrombotic prophylaxis and delayed mobilization of the patient after surgery have been reported as pathogenetic factors of portmesenteric vein thrombosis. Most of the cases presented in the literature such as our clinical case resolve with medical therapy, although portal vein thrombus extends into the superior mesenteric vein and the splenic vein. CONCLUSION: Portomesenteric venous thrombosis is a rare but serious complication of bariatric surgery, especially associated with sleeve gastrectomy. Diagnosis is based on CT examination with intravenous contrast, and initial therapy is anticoagulation. Etiologic factors reported in the literature include a long duration of surgery, a high degree of pneumoperitoneum, high intragastric pressure after sleeve gastrectomy and thermal injury to the short gastric vessels and gastroepiploic arcade. Limited operative time, controlled values of pneumoperitoneum, careful dissection with energy device of gastric greater curvature, appropriate prophylaxis with low molecular weight heparin may be useful tools to prevent and limit this complication. Nonetheless we have to search which factors may condition the evolution of an extended PMVT as that described in this case towards resolution or to a further worsening clinical state. Early diagnosis? Correct treatment? Undiscovered patientrelated factors?

[Management of myelodysplastic syndromes in 2019: An update]. / Prise en charge des syndromes myélodysplasiques en 2019 : mise au point.

Myelodysplastic syndromes are a heterogeneous group of clonal myeloid disorders characterized by peripheral cytopenias and an increased risk of progression to acute myeloid leukemia. Inflammatory, auto-immune or syndromic symptoms can make the diagnosis difficult. Diagnosis is currently based on bone marrow cytology but cytogenetics and molecular features are currently overpassing their initial prognostic function (allowing early diagnosis and prediction of therapeutic response). The prognostic classification is based on the Revised International Prognostic Scoring System, which also provides guidance for therapeutic management. The treatment of low-risk myelodysplastic syndromes is based on the correction of cytopenias (erythropoiesis stimulating agents, transfusions, lenalidomide, etc.), whereas in high-risk group, the goal is the control of the leukemic clone (hypomethylating agents, allograft of hematopoietic stem cell transplantation). Other molecules are used to manage complications of cytopenias or transfusion (anti-infectious prophylaxis and treatments, martial chelation). New molecules are being studied with some interesting results (luspatercept, venetoclax). This article aims to provide an update on the knowledge that an internist should know for the practical management of myelodysplastic syndromes in 2019.

Oncogenic FLT3-ITD supports autophagy via ATF4 in acute myeloid leukemia.

In acute myeloid leukemia (AML), internal tandem duplication mutations in the FLT3 tyrosine kinase receptor (FLT3-ITD) account for up to 25% of cases and are associated with a poor outcome. In order to better target this AML subtype, a comprehensive view of how FLT3-ITD impacts AML cell biology is required. Here, we found that FLT3-ITD expression increased basal autophagy in AML cells, and that both pharmacological and genetic inhibition of the receptor reduced autophagy in primary AML samples and cell lines. Conditional expression of shRNAs against key autophagy proteins demonstrated that autophagy is required for AML cell proliferation in vitro and for leukemic cells survival in a mouse model of xenograft. Importantly, autophagy inhibition also overcame FLT3 inhibitor resistance both in vitro and in vivo. The transcription factor ATF4 was identified as an essential actor of FLT3-ITD-induced autophagy. Cellular levels of ATF4 were highly dependent on FLT3-ITD activity, and downregulation of ATF4 inhibited autophagy-dependent AML cell proliferation and improved overall mouse survival similarly to autophagy inhibition. These results suggest that targeting autophagy or ATF4 in patients expressing FLT3 mutations may represent a novel promising and innovative therapeutic strategy for AML.

Association between ratio indexes of body composition phenotypes and metabolic risk in Italian adults.

The ratio between fat mass (FM) and fat-free mass (FFM) has been used to discriminate individual differences in body composition and improve prediction of metabolic risk. Here, we evaluated whether the use of a visceral adipose tissue-to-fat-free mass index (VAT:FFMI) ratio was a better predictor of metabolic risk than a fat mass index to fat-free mass index (FMI:FFMI) ratio. This is a cross-sectional study including 3441 adult participants (age range 18-81; men/women: 977/2464). FM and FFM were measured by bioelectrical impedance analysis and VAT by ultrasonography. A continuous metabolic risk Z score and harmonised international criteria were used to define cumulative metabolic risk and metabolic syndrome (MetS), respectively. Multivariate logistic and linear regression models were used to test associations between body composition indexes and metabolic risk. In unadjusted models, VAT:FFMI was a better predictor of MetS (OR 8.03, 95%CI 6.69-9.65) compared to FMI:FFMI (OR 2.91, 95%CI 2.45-3.46). However, the strength of association of VAT:FFMI and FMI:FFMI became comparable when models were adjusted for age, gender, clinical and sociodemographic factors (OR 4.06, 95%CI 3.31-4.97; OR 4.25, 95%CI 3.42-5.27, respectively). A similar pattern was observed for the association of the two indexes with the metabolic risk Z score (VAT:FFMI: unadjusted b = 0.69 ± 0.03, adjusted b = 0.36 ± 0.03; FMI:FFMI: unadjusted b = 0.28 ± 0.028, adjusted b = 0.38 ± 0.02). Our results suggest that there is no real advantage in using either VAT:FFMI or FMI:FFMI ratios as a predictor of metabolic risk in adults. However, these results warrant confirmation in longitudinal studies.

Electric field control of magnetic properties and electron transport in BaTiO3-based multiferroic heterostructures.

In this paper, we report on a purely electric mechanism for achieving the electric control of the interfacial spin polarization and magnetoresistance in multiferroic tunneling junctions. We investigate micrometric devices based on the Co/Fe/BaTiO3/La0.7Sr0.3MnO3 heterostructure, where Co/Fe and La0.7Sr0.3MnO3 are the magnetic electrodes and BaTiO3 acts both as a ferroelectric element and tunneling barrier. We show that, at 20 K, devices with a 2 nm thick BaTiO3 barrier present both tunneling electroresistance (TER = 12 ± 0.1%) and tunneling magnetoresistance (TMR). The latter depends on the direction of the BaTiO3 polarization, displaying a sizable change of the TMR from -0.32 ± 0.05% for the polarization pointing towards Fe, to -0.12 ± 0.05% for the opposite direction. This is consistent with the on-off switching of the Fe magnetization at the Fe/BaTiO3 interface, driven by the BaTiO3 polarization, we have previously demonstrated in x-ray magnetic circular dichroism experiments.

Accuracy of three novel predictive methods for measurements of fat mass in healthy older subjects.

UNLABELLED: This study evaluated the agreement of novel anthropometric equations and established indirect methods (skinfold thickness and bioimpedance analysis) with reference methods [dual X-ray absorptiometry (DXA) and air displacement plethysmography (ADP)] for fat mass assessment (FM) in older subjects. METHODS: Forty subjects (M/F = 15/25, age = 61-84 years, BMI = 18-37 kg/m(2)) were recruited. The agreement of the following predictive equations was evaluated: body adiposity index (BAI), BAI-Fels and Clínica Universidad de Navarra-body adiposity estimator (CUN-BAE). RESULTS: BAI estimates were comparable to DXA (Δ ± 2SD = 0.4 ± 6.0 kg, p > 0.05) but not to ADP (Δ ± 2SD = -2.8 ± 7.2 kg, p < 0.001); BAI-Fels estimates were comparable to DXA (Δ ± 2SD = 0.8 ± 5.5 kg, p > 0.05) but not to ADP (Δ ± 2SD = -4.0 ± 6.9 kg, p < 0.001). The difference between CUN-BAE and ADP was not significant (Δ ± 2SD = -0.4 ± 5.6 kg, p > 0.05), whereas it significantly overestimated DXA (Δ ± 2SD = 2.8 ± 5.4 kg, p < 0.001). ADP significantly overestimated FM compared to DXA (Δ ± 2SD = 3.2 ± 5.4 kg, p < 0.001) and the measurement bias was significantly correlated with BMI in men (p = 0.004). CONCLUSIONS: The accuracy of the three anthropometric indexes is dependent on the choice of the reference method. The variability of the FM estimates was large and these indexes cannot be recommended for the assessment of FM in older subjects.

Accuracy of predictive equations for the measurement of resting energy expenditure in older subjects.

BACKGROUND AND AIMS: The measurement of resting energy expenditure (REE) is important to assess individual total energy requirements in older subjects. The validity of REE prediction equations in this population has not been thoroughly evaluated and therefore the main aim of this analysis was to assess the accuracy of REE prediction equations in older subjects. METHODS: Weight, height and body mass index (BMI) were measured. REE was measured by indirect calorimetry (IC) in 68 older subjects (age: 60-94 years, M/F: 13/55, BMI: 26.3 ± 5.0 kg/m(2)). Measured REE was compared to 14 equations for the calculation of REE estimates. In addition, two novel approaches (Aggregate model and meta-regression equations) for the prediction of REE were evaluated. Paired t test and Bland-Altman method were used to assess the agreement of the equations. RESULTS: The average measured REE was 1298 ± 264 kcal/day. The equation with the smallest bias was proposed by Muller (Bias ± 2SD = +3 ± 294 kcal/day) whereas the Mifflin equation was associated with the largest error (Bias ± 2SD = -172 ± 282 kcal/day). The Aggregate, Muller, Harris-Benedict and Fredrix equations were characterised by a prediction within ±10% of measured REE in more than 60% of subjects. Of the four algorithms, only the Aggregate equation did not show a significant association of the measurement bias with age, BMI and gender. CONCLUSIONS: The Aggregate algorithm was characterised by a higher, overall accuracy for the prediction of REE in older subjects and its use should be advocated in older subjects. However, due to the large variability of the estimates, the measurement of REE by IC is still recommended for an accurate assessment of individual REE.

Pim kinases phosphorylate Chk1 and regulate its functions in acute myeloid leukemia.

Phosphorylation by Akt on Ser 280 was reported to induce cytoplasmic retention and inactivation of CHK1 with consequent genetic instability in PTEN-/- cells. In acute myeloid leukemia cells carrying the FLT3-internal tandem duplication (ITD) mutation, we observed high rates of FLT3-ITD-dependent CHK1 Ser 280 phosphorylation. Pharmacological inhibition and RNA interference identified Pim1/2, not Akt, as effectors of this phosphorylation. Pim1 catalyzed Ser 280 phosphorylation in vitro and ectopic expression of Pim1/2-induced CHK1 phosphorylation. Ser 280 phosphorylation did not modify CHK1 localization, but facilitated its cell cycle and resistance functions in leukemic cells. FLT3, PIM or CHK1 inhibitors synergized with DNA-damaging agents to induce apoptosis, allowing cells to bypass the etoposide-induced G2/M arrest. Consistently, etoposide-induced CHK1-dependent phosphorylations of CDC25C on Ser 216 and histone H3 on Thr11 were decreased upon FLT3 inhibition. Accordingly, ectopic expression of CHK1 improved the resistance of FLT3-ITD cells and maintained histone H3 phosphorylation in response to DNA damage, whereas expression of unphosphorylated Ser 280Ala mutant did not. Finally, FLT3- and Pim-dependent phosphorylation of CHK1 on Ser 280 was confirmed in primary blasts from patients. These results identify a new pathway involved in the resistance of FLT3-ITD leukemic cells to genotoxic agents, and they constitute the first report of CHK1 Ser 280 regulation in myeloid malignancies.

The short form of RON is expressed in acute myeloid leukemia and sensitizes leukemic cells to cMET inhibitors.

Several receptor tyrosine kinases (TKs) are involved in the pathogenesis of acute myeloid leukemia (AML). Here, we have assessed the expression of the Recepteur d'Origine Nantais (RON) in leukemic cell lines and samples from AML patients. In a series of 86 AML patients, we show that both the full length and/or the short form (sf) of RON are expressed in 51% and 43% of cases, respectively. Interestingly, sfRON is not expressed in normal CD34+ hematopoietic cells and induces part of its oncogenic signaling through interaction with the Src kinase Lyn. sfRON-mediated signaling in leukemic cells also involves mTORC1, the proapoptotic bcl2-family member, BAD, but not the phosphatidylinositol 3-kinase/Akt pathway. Furthermore, the expression of sfRON was specifically downregulated by 5-azacytidine (AZA). Conversely, AZA could induce the expression of sfRON in sfRON-negative leukemic cells suggesting that the activity of this drug in AML and myelodysplastic syndromes could involve modulation of TKs. cMET/RON inhibitors exhibited an antileukemic activity exclusively in AML samples and cell lines expressing sfRON. These results might support clinical trials evaluating cMET/RON inhibitors in AML patients expressing sfRON.

Estimated height from knee-height in Caucasian elderly: implications on nutritional status by mini nutritional assessment.

OBJECTIVES: To investigate if the use of estimated height (EH) by currently available prediction formulas might affect the screening and outcome prediction attitudes of both the Mini Nutritional Assessment (MNA) and its short-form version (MNA-SF). DESIGN: A 6-month observational study. SETTING: Two long-term cares of the province of Como. PARTICIPANTS: 266 resident elderly (102 men, 164 women; mean age +/- SD: 80.4 +/- 8.6 years). MEASUREMENTS: Subjects were studied by anthropometry (weight, standing height, knee-height, arm and calf circumferences, triceps skinfold) and biochemistry (albumin and prealbumin). Nutritional status was assessed using both MNA and MNA-SF. At 6 months, major outcome were: death, infections and bedsores. RESULTS: In overall population, prediction formulas significantly underestimated real height. The bias by Italian-specific equation was higher than that by nationally-representative formulas for white Americans. The use of EHs produced significant differences in body mass index (BMI) but these did not affect nutritional status scoring by MNA and MNA-SF (r > or =0.99, p < 0.0001). Cohen's kappa statistic also showed an almost perfect concordance (kappa > 0.9). Moreover, similar degrees of correlation were found between nutritional parameters and both MNA and MNA-SF scores by BMI from SH and EHs. After 6 months, major complications occurred in twenty-eight patients (11.6%). The use EHs did not affect the distribution of events among MNA and MNA-SF nutritional classes. CONCLUSION: In Italian elderly, height prediction by nationally representative equations for white Americans should be preferred to that by ethnic-specifc formula. However, the use of both models does not seem to affect nutritional screening and outcome prediction by MNA and MNA-SF.

Metabolic consequences of peritoneal dialysis treatment.

Energy and protein metabolism are both altered in chronic kidney disease (CKD) from its early stages. Patients undergoing peritoneal dialysis (PD) use peritoneal solutions with glucose as osmotic agent, which exposes them to an increased glucose load (40-80 g/day) and during PD there is a net loss of proteins through the peritoneum (4-8 g/day). Insulin resistance may lead to a reduction of the anabolic effects of insulin, while its proliferative effects on adipose tissue are potentially enhanced. Insulin resistance is also an important factor in the development of hypertriglyceridemia in PD patients: it increases free fatty acid availability, which then stimulates the release of large triglyceride-rich VLDL. Moreover, inhibitors of lipolytic enzymes (apoC-III, inflammation, oxidative modification and carbamoylation of apolipoproteins) may reduce lipid clearance, contributing to the development of dyslipidemia. Inflammatory molecules also play an important role in regulating glucose metabolism, and the excessive activation of inflammatory pathways may represent a fundamental step in the development of insulin resistance, including an over-expression of cytokines. Frequently, protein intake is reduced in PD because of under-dialysis, glucose load, abdominal discomfort and abnormal hormones levels, leading to a complex "protein-energy malnutrition". Optimization of dialysis dose, correction of acidosis and anemia and nutritional counseling, together with "non-traditional" management strategies, such as the use of PD solutions without glucose, like icodextrin and amino acid based solutions, represent the best strategies to prevent and correct malnutrition in PD patients. The mainstay of therapy is a reduction of glucose-based PD solutions and a correct dietary prescription.

[Vascular access in the elderly: AVF vs CVC. A comment]. / L'accesso vascolare nell'anziano: confronto FAV versus CVCp, commento.

The aging population starting hemodialysis treatment raises the question as to which is the best vascular access in an older patient with multiple complications. The center effect is an important element in the choice of a vascular access, as shown by the DOPPS data and by a recent audit held in Lombardy. However, other data show an increase in the use of permanent CVCs in the last years and other factors must be taken into account in this clinical choice. Also the timing of proposing a vascular access to a patient has changed over the years (see K-DOQI 2006 vs 2000). Most of the literature agrees on the strategy of a global clinical evaluation of the patient to decide when to place a vascular access and which type of access to use. Native and prosthetic fistulas are considered superior to CVCs although the latter have certain advantages in selected patients, such as those with severe cardiac problems. The nephrologist has a major role in vascular access management as part of a team made up also by a vascular surgeon and an interventional radiologist. Only in a center where both native and prosthetic fistulas can be constructed and permanent CVCs be placed can a nephrologist choose the most appropriate vascular access for individual patients after evaluation not only of their renal function but their cardiovascular risk as well.

Nutritional counselling in disabled people: effects on dietary patterns, body composition and cardiovascular risk factors.

AIM: Disabled persons are frequently affected by nutritional status impairment, consequent to quantitative and qualitative inadequacy of diet and physical inactivity, resulting in a significant reduction of fat-free mass and bone mineral density (BMD), and an over-expression of fat mass and an increased number of biochemical risk factors for chronic degenerative diseases. The aim of this study was to analyse the applicability and the efficacy of a nutritional counselling intervention in order to improve dietary intake and nutritional status in disabled people. METHODS: Thirty-seven disabled subjects (24 with physical disability and 13 with both mental retardation and physical disability; age 33.5+/-9.2 years) underwent an assessment of nutritional status, and an intervention with nutritional counselling was proposed to each patient for one year. Anthropometric measurements, indirect calorimetry, dual-energy X-ray absorptiometry, dietary intake, and biochemical analysis at baseline (T0) and after one year (T1) of counselling intervention were performed. RESULTS: Sixty-five percent of patients dropped out. Overall, no significant improvement in cardiovascular risk factors, body composition and dietary patterns was reported at T1 in completer subjects. Six subjects who were obese or overweight at T0, reported significant weight and fat mass (FM) reduction at T1 (P=0.01 and P=0.00, respectively). CONCLUSION: Nutritional counselling seems to be ineffective and poorly applicable to disabled people. Further studies should be directed towards a treatment program associated with careful screening, motivation analysis, and follow-up in this patient population.

Poor agreement between a portable armband and indirect calorimetry in the assessment of resting energy expenditure.

BACKGROUND & AIMS: To evaluate the agreement between resting energy expenditure (REE) estimated by a portable armband and measured by indirect calorimetry. METHODS: One-hundred and twenty-seven women and 42 men with a mean (SD) age of 44 (12) years and a body mass index of 30.2 (5.4) kg/m(2) were studied. REE was estimated using the Sense Wear Pro 2 Armband (SWA), measured using the Sensor Medics 29 metabolic cart (V(max)), and estimated using Schofield's equation. The limits of agreement (LOA) and the concordance correlation coefficient (CCC) were used to evaluate the interchangeability of the methods. RESULTS: The LOA between REE(SWA) and REE(Vmax) were wide in both women (-269 to 378 kcal/day) and men (-330 to 545 kcal/day) and CCC was low (0.579 in females and 0.583 in males, p<0.0001 for both). REE(Schofield) agreed with REE(Vmax) to a similar degree (CCC=0.563 in females and 0.500 in males, p<0.0001 for both). CONCLUSIONS: SWA and indirect calorimetry are not interchangeable methods for the assessment of REE in normal-weight and obese subjects.

Evaluation of air-displacement plethysmography and bioelectrical impedance analysis vs dual-energy X-ray absorptiometry for the assessment of fat-free mass in elderly subjects.

OBJECTIVE: To evaluate air-displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) vs dual-energy X-ray absorptiometry (DXA) for the assessment of fat-free mass (FFM) in healthy elderly subjects. SUBJECTS: Forty-two women and twenty-six men aged 60-84 years. METHODS: FFM was measured by DXA and ADP. Body impedance (Z) was measured by four-polar BIA and the impedance index (ZI) was calculated as stature(2)/Z. Selection of predictors (gender, age, weight and ZI at 5, 50 and 100 kHz) for BIA algorithms was carried out using bootstrapped stepwise linear regression on 1000 samples of 68 subjects. Limits of agreement were used as measures of interchangeability of ADP and BIA with DXA. RESULTS: The limits of agreement of ADP vs DXA were -11.0 to 2.4 kg in males and -4.8 to 2.2 kg in females. Gender, weight and ZI(100) were selected as predictors of FFM by bootstrapped stepwise linear regression. In males, ZI(100) (-12.2 to 12.2 kg) was much less accurate than weight (-6.0 to 6.0 kg) at predicting FFM and their combination did not improve the estimate (-6.0 to 6.0 kg). In females, ZI(100) (-6.8 to 6.8 kg) was less accurate than weight (-5.6 to 5.6 kg) at predicting FFM and their combination improved the estimate only slightly (-5.0 to 5.0 kg). CONCLUSIONS: In healthy elderly subjects, (1) ADP and DXA are not interchangeable for the assessment of FFM, especially in males; and (2) ZI(100) is not superior to weight for the prediction of FFM and their combination is of little advantage and only in females.

Circulating salicylic acid is related to fruit and vegetable consumption in healthy subjects.

Salicylic acid (SA) is a natural phenolic compound known as the active principle of aspirin. Its presence in vegetal sources suggests that fruit and vegetable (FV) consumption could produce measurable SA serum concentrations in human subjects not taking aspirin. The aim of this study was to investigate the relationship between FV intake and circulating SA in healthy subjects. Thirty-eight volunteers (twenty-two males and sixteen females) were recruited from an Italian university campus. They recorded their food intake for 7 d to evaluate dietary consumption and, in particular, FV intake; fasting blood samples were taken on the morning of the eighth day to measure SA serum concentration, using a sensitive stable isotope dilution and GC-MS method. Median SA serum concentration was 0.124 mumol/l (range 0.028-0.295). Circulating SA was significantly related to FV consumption, both to the mean daily intake (r2 0.13, P = 0.03) and to the last day intake (r2 0.16, P = 0.01). The subjects in the highest FV intake quartile in the preceding day (>4.75 servings) had significantly higher SA concentrations than in the lowest quartile ( < 2.3 servings) (median concentrations 0.188 and 0.112 mumol/l, respectively; P = 0.04). This study proved that, after overnight fast, human subjects not taking aspirin display circulating SA in amounts related to the FV consumption. It is therefore possible that the beneficial effects of regular FV consumption in man could also depend on low chronic SA exposure.

Spontaneous hypoglycemia in patients with cystic fibrosis.

OBJECTIVE: Diabetes frequently complicates cystic fibrosis (CF) without fasting hyperglycemia or despite spontaneous hypoglycemia (anecdotally ascribed to malnutrition), whose prevalence, clinical meaning, and relationship with glucose tolerance and clinical/nutritional status were not previously investigated. The relationship of CF genotype with insulin secretion control is also unclear. DESIGN AND METHODS: A total of 129 CF patients without stable diabetes received 188 oral glucose tolerance tests. Distribution of fasting plasma glucose (FPG), glucose, insulin and C-peptide responses, clinical/nutritional variables, and their relationships were analyzed. RESULTS: FPG < 60 mg/dl (3.3 mmo/l) was detected in 14% of studies and reactive hypoglycemia (PG < 50 mg/dl (2.8 mmo/l)) in 15%. OGTT-based diabetes frequency was similar in the lowest quartile (Q1) and Q2-3 for FPG (10 and 8%), with higher glucose increment and area under the curve in Q1. Insulin and C-peptide levels were similar among FPG quartiles. Class I cystic fibrosis transmembrane conductance regulator mutation carriers had higher insulin concentrations than class II, especially in Q1 for FPG. Age, sex, nutritional, and anthropometric parameters including fat and lean body mass were unrelated to FPG. Lower FPG was associated with more frequent hospitalization rates (P = 0.002) and lower Shwachman scores (P = 0.041). Steroids weaning was accurately evaluated but then excluded as a possible cause of hypoglycemia. CONCLUSIONS/INTERPRETATION: Fasting asymptomatic hypoglycemia is frequent and possibly related to inappropriate insulin secretion control in class I mutation carriers. Low FPG does not exclude impaired glucose tolerance (IGT) and diabetes in CF and reflects worse clinical status.