Persistent post-bariatric-surgery hypoglycemia: A long-term follow-up reassessment.

BACKGROUND AND AIM: Post-bariatric-surgery hypoglycemia (PBH) is a serious complication of bariatric surgery (BS). In our previous study about three quarters of the patients developed PBH. However long-term follow-up data is lacking to determine whether this condition improves with time. The aim of the current study was to re-assess post-BS patients who participated in our previous study and determine whether there are changes in the frequency and/or severity of hypoglycemic events. METHODS AND RESULTS: Twenty-four post-BS, post Roux-en-Y gastric-bypass (RYGB = 10), post omega-loop gastric-bypass (OLGB = 9) and post sleeve-gastrectomy (SG = 5) individuals were reevaluated in a follow-up study 34.4 ± 4 months after their previous assessment and 67 ± 17 months since surgery. The evaluation included: a dietitian assessment, a questionnaire, meal-tolerance test (MTT) and a one-week masked continuous glucose monitoring (CGM). Hypoglycemia and severe hypoglycemia were defined by glucose levels ≤54 mg/dl and ≤40 mg/dl, respectively. Thirteen patients reported questionnaire meal-related complaints, mainly non-specific. During MTT, hypoglycemia occurred in 75% of the patients, and severe hypoglycemia in a third, but none was associated with specific complaints. During CGM, 66% of patients developed hypoglycemia and 37% had severe hypoglycemia. We did not observe significant improvements in hypoglycemic events compared to the previous assessment. Despite the high frequency of hypoglycemia, it did not necessitate hospitalizations or lead to death. CONCLUSIONS: PBH did not resolve within long-term follow-up. Intriguingly, most patient were unaware of these events which can lead to underestimation by the medical staff. Further studies are needed to determine possible long term sequela of repeated hypoglycemia.

Protein tyrosine phosphatase alpha inhibits hypothalamic leptin receptor signaling and regulates body weight in vivo.

Understanding how body weight is regulated at the molecular level is essential for treating obesity. We show that female mice genetically lacking protein tyrosine phosphatase (PTP) receptor type α (PTPRA) exhibit reduced weight and adiposity and increased energy expenditure, and are more resistant to diet-induced obesity than matched wild-type control mice. These mice also exhibit reduced levels of circulating leptin and are leptin hypersensitive, suggesting that PTPRA inhibits leptin signaling in the hypothalamus. Male and female PTPRA-deficient mice fed a high-fat diet were leaner and displayed increased metabolic rates and lower circulating leptin levels, indicating that the effects of loss of PTPRA persist in the obese state. Molecularly, PTPRA down-regulates leptin receptor signaling by dephosphorylating the receptor-associated kinase JAK2, with which the phosphatase associates constitutively. In contrast to the closely related tyrosine phosphatase ε, leptin induces only weak phosphorylation of PTPRA at its C-terminal regulatory site Y789, and this does not affect the activity of PTPRA toward JAK2. PTPRA is therefore an inhibitor of hypothalamic leptin signaling in vivo and may prevent premature activation of leptin signaling, as well as return signaling to baseline after exposure to leptin.-Cohen-Sharir, Y., Kuperman, Y., Apelblat, D., den Hertog, J., Spiegel, I., Knobler, H., Elson, A. Protein tyrosine phosphatase alpha inhibits hypothalamic leptin receptor signaling and regulates body weight in vivo.

The effect of a low-carbohydrate high-fat diet and ethnicity on daily glucose profile in type 2 diabetes determined by continuous glucose monitoring.

BACKGROUND AND AIMS: Nutrition is an integral part of type 2 diabetes (T2DM) treatment, but the optimal macronutrient composition is still debated and previous studies have not addressed the role of ethnicity in dietary response. The current study aims were to compare the effect of short-term glycemic response to low-carbohydrate high-fat (LC-HF) diet vs. high-carbohydrate low-fat (HC-LF) diet using continuous glucose monitoring (CGM) and to evaluate the response of individuals with T2DM of Yemenite (Y-DM) and non-Yemenite origin (NY-DM). METHODS: Twenty T2DM males, ten Y-DM and ten NY-DM underwent meal tolerance test and indexes of insulin resistance and secretion were calculated. Subsequently, patients were connected to CGM to assess daily glycemic control and glucose variability in response to isocaloric HC-LF or LC-HF diet, receiving each diet for 2 days by providing prepared meals. Daily glucose levels, area under the glucose curve (G-AUC) and parameters of glucose variability [standard deviation (SD), mean amplitude of glycemic excursions (MAGE) and mean absolute glucose (MAG)] were evaluated. RESULTS: The LC-HF resulted in a significantly lower G-AUC (p < 0.001) and in lower variability parameters (p < 0.001) vs. the HC-LF diet. However, Y-DM showed less reduction in glucose variability indices upon diet-switching vs. NY-DM; MAGE decreased, respectively, by 69% vs. 89%, p = 0.043 and MAG by 34% vs. 45%, p = 0.007 in Y-DM compared to NY-DM. CONCLUSIONS: These results suggest that LC-HF diet is effective in reducing glycemic fluctuation in T2DM and that ethnicity may have a role in the response to dietary regime.

SYMPTOMATIC AND ASYMPTOMATIC HYPOGLYCEMIA POST THREE DIFFERENT BARIATRIC PROCEDURES: A COMMON AND SEVERE COMPLICATION.

Background: The prevalence of post-bariatric surgery hypoglycemia (PBH) remains unclear due to diagnostic criteria variability, types of bariatric procedures and possible unawareness. Objective: To determine the frequency, pattern and severity of symptomatic and asymptomatic hypoglycemia in subjects post three different bariatric procedures performed >1 year before evaluation and a group of obese subjects before surgery. Design and Setting: Observational cohort study. Fifty-one consecutive patients participated: post Roux-en-Y gastric-bypass (RYGB) (n=16), post omega-loop gastric-bypass (OLGB) (n=12), post sleeve-gastrectomy (SG) (n=15), obese subjects before surgery (controls) (n=8). Hypoglycemic events (glucose ≤54 mg/dL) and severe hypoglycemia (glucose ≤40 mg/dL) were evaluated by symptoms' questionnaire, mixed-meal tolerance test (MMTT) and continuous glucose monitoring (CGM). Results: According to questionnaires, meal-related complaints were reported in 11 (26%) of the surgical group and in one control subject. During MMTT, 88%, 82% and 67% experienced hypoglycemia in RYGB, OMGB and SG groups, respectively, vs. none of the controls (P<0.001). Severe hypoglycemia occurred in 38%, 45% and 7% in RYGB, OMGB and SG groups, respectively (P=0.025), but only 10 of the total operated patients (24%) reported any symptoms. During CGM, fasting hypoglycemic events occurred more in RYGB and OLGB vs. SG group: 55%, 63% and 17% respectively (P=0.036). Conclusions: PBH is very common after RYGB, OMGB and SG and can be severe especially following bypass procedures. Our results show that hypoglycemia occurs not only postprandially but also in the fasting state, especially following bypass procedures. In most cases, there were no specific complaints, possibly leading to its underestimation.

Holocaust Survival and the Long-term Risk of Cardiovascular Disease in the Elderly.

BACKGROUND: Reports of longevity in Holocaust survivors (HS) conflict with excess prevalence of chronic diseases described among them. However, data on their long-term risk of cardiovascular diseases (CVD) are limited. Clinical data on large representative groups of HS who were exposed to severe persecution are also limited. OBJECTIVES: To determine the prevalence of CVD and the risk factors in a large cohort of elderly HS compared to elderly individuals who were not exposed to the Holocaust (NHS). METHODS: CVD prevalence rates and risk factors data from the computerized system of the central district of Clalit Health Services, the largest Israeli health maintenance organization (HMO) in Israel were evaluated in a retrospective observational study. The study was comprised of 4004 elderly HS who underwent direct severe persecution. They were randomly matched by identification numbers to 4004 elderly NHS. RESULTS: HS were older than NHS and 51% of them were older than 85 years. The prevalence rate of ischemic heart disease (IHD) was significantly higher among HS. HS underwent significantly more cardiac interventions (20% vs. 15.7%, P < 0.05). HS status was an independent risk factor for increased IHD and for more coronary interventions. CONCLUSIONS: Despite having a higher prevalence of CVD, a substantial number of HS live long lives. This finding may imply both unique resilience and ability to cope with chronic illness of the survivors as well as adjusted medical services for this population. These findings may help in planning the treatment of other mass trauma survivors.

THE EFFECT OF PHLEBOTOMY-INDUCED HEMOLYSIS ON INSULIN LEVEL DETERMINATION.

OBJECTIVE: To examine the effect of phlebotomy-induced hemolysis on serum insulin and C-peptide measurement by an immunochemiluminometric assay. METHODS: As part of a study designed to evaluate ß-cell function in a group of adults with newly diagnosed type 2 diabetes, we tested insulin and C-peptide levels in 1,048 samples. In order to evaluate the effect of phlebotomy-induced hemolysis, we determined insulin and C-peptide levels simultaneously in hemolyzed and nonhemolyzed samples. RESULTS: Forty-seven (4.5%) of the 1,048 samples were affected by hemolysis. In 26 cases, we had paired hemolyzed and nonhemolyzed serum samples that allowed a simultaneous comparison. We found that all degrees of hemolysis led to a significant decrease in insulin level. In hemolyzed serum, the median (interquartile range) of the insulin was 5.6 (1.8 to 24.3) mIU/L, versus 21.3 (11.4 to 48.5) mIU/L in nonhemolyzed serum, representing a 25 to 98% loss. This phenomenon was not found for C-peptide levels. CONCLUSION: Clinicians have to be aware that even a mild degree of phlebotomy-induced hemolysis has a significant effect on serum insulin level determination, which can lead to misinterpretation of test results. This finding has important implications, especially in the evaluation of suspected cases of hyperinsulinemic hypoglycemia.

[ISRAELI GUIDELINES FOR THE TREATMENT OF HYPERLIPIDEMIA - 2014 UPDATE].

Atherosclerosis is one of the leading causes of morbidity and mortality in the world, including in Israel. This document updates the clinical recommendations of the Israeli medical societies (The Society for Research, Prevention and Treatment of Atherosclerosis, The Israel Heart Society, The Israel Association of Family Physicians, The Israel Society of Internal Medicine) from 2012. The need for an update stems from new studies and from the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. These recommendations take into account the guidelines of leading medical organizations in the world, as well as the specific circumstances and needs of the medical system in Israel.

Prebiotic Treatment in Patients with Nonalcoholic Fatty Liver Disease (NAFLD)-A Randomized Pilot Trial.

Several studies show that gut microbiotas in patients with nonalcoholic fatty liver disease (NAFLD) differ from those in a healthy population, suggesting that this alteration plays a role in NAFLD pathogenesis. We investigated whether prebiotic administration affects liver fat content and/or liver-related and metabolic parameters. Patients with NAFLD and metabolic syndrome (age: 50 ± 11; 79% men) were randomized to receive either 16 g/day of prebiotic (ITFs-inulin-type fructans) (n = 8) or placebo (maltodextrin) (n = 11) for 12 weeks. Patients were instructed to maintain a stable weight throughout the study. Liver fat content (measured by H1MRS), fecal microbiota, and metabolic, inflammatory, and liver parameters were determined before and after intervention. Fecal samples from patients who received the prebiotic had an increased content of Bifidobacterium (p = 0.025), which was not observed with the placebo. However, the baseline and end-of-study liver fat contents did not change significantly in the prebiotic and placebo groups, neither did the liver function tests' metabolic and inflammatory mediators, including fibroblast growth factor-19 and lipopolysaccharide-binding protein. Body weight remained stable in both groups. These findings suggest that prebiotic treatment without weight reduction is insufficient to improve NAFLD.

Prenatal Breastfeeding Counseling Intervention in Women with Pre-Gestational Diabetes Mellitus-A Randomized Controlled Trial.

BACKGROUND: Data on breastfeeding rates and targeted interventions in women with pre-gestational diabetes mellitus are inconclusive. The aim of the study was to evaluate breastfeeding rates up to one year postpartum and whether targeted counseling towards the end of pregnancy can impact breastfeeding rates and duration. An additional goal was to evaluate whether counseling affected women's perceptions regarding breastfeeding. METHODS: Women with pre-gestational diabetes mellitus were cluster-randomized between 32 and 36 weeks of gestation, either to face-to-face instruction with a certified lactation consultant or to receive written information on breastfeeding. Thirty-eight women without diabetes served as controls and were given written information on breastfeeding. All women filled out a questionnaire regarding intended breastfeeding duration, exclusivity, and perceptions, before intervention and at three, six, and twelve months post-partum. RESULTS: Fifty-two women with pre-gestational diabetes mellitus consented to participate. All completed the questionnaires, 26 in each group. At three, six, and twelve months postpartum, rates of any breastfeeding were around 60%, 50%, and 30%, respectively. Approximately one-third breastfed exclusively in each group at three and six months. No significant difference in breastfeeding rates was noted between face-to-face instruction, written information, and controls. End-of-pregnancy counseling improved confidence in breastfeeding knowledge and confidence in being able to manage blood glucose. CONCLUSIONS: Breastfeeding rates in pre-gestational diabetes mellitus were comparable to those of women without diabetes and were unchanged by mode of instruction at the end of pregnancy. However, targeted diabetes-oriented breastfeeding instruction at the end of pregnancy improved knowledge and confidence among women with pre-gestational diabetes mellitus.

[Prevention and treatment of atherosclerosis and cardiovascular diseases].

Atherosclerosis is one of the main causes of morbidity and mortality world-wide and specifically in Israel. These guidelines update the previous guidelines of the Israeli Society for Research, Prevention and Treatment of Atherosclerosis, published in 2005. The need for an update is based on new scientific data published in recent years necessitating changes in the recommendations for preventing and treating atherosclerosis. These guidelines were written in collaboration between all the societies outlined here and the content of this statement was approved by the delegates of these societies. The recommendations were written taking into consideration guidelines published by other international medical societies and also the specific needs of the Israeli medical system. Due to limitations of space, in the current paper we present: assessment of cardiovascular risk, smoking cessation and the treatment of dyslipidemia. Other sections including: recommendations to the general population, nutritional and physical activity recommendations, treatment of hypertension, prevention of ischemic stroke and the metabolic syndrome are available at http://www.ima.org.il/harefuah.

Is Telemedicine the Preferred Visit Modality in Patients with Type 1 Diabetes?

BACKGROUND: The COVID-19 pandemic limits access to diabetes clinics. Remote communication by phone calls and WhatsApp messages became available in the past years. However, the current need to avoid face-to-face meetings necessitates further expansion of telemedicine services. There are limited data whether the option of virtual meetings is a preferred therapeutic modality for patients with type 1 diabetes (T1D). OBJECTIVE: To assess in a cohort of T1D patients, their preference and perception of telemedicine. METHODS: T1D patients who are followed in a hospital-affiliated diabetes clinic were asked to fill a structured questionnaire aimed to determine their attitude towards telemedicine and their preference of virtual versus conventional visits. The questionnaire was offered to consecutive T1D patients who visited the clinic between August to October 2020. RESULTS: Seventy one T1D patients that fulfilled the questionnaire were included. Median age was 38 years, 39% were male, and median duration of diabetes was 18 years. Fourteen percent of the participants preferred only virtual visits, 24% only conventional visits and 62% preferred a combination of these modalities. Sex, origin, education, duration of diabetes, mode of insulin treatment and distance from the clinic were not associated with patients' preference, but older patients (≥ 61 years) tended to prefer conventional visits. Sixty-six percent felt confident in their ability to download data from their personal medical devices. CONCLUSIONS: Patients from a wide range of treatment modalities are willing to use telemedicine. However, virtual meetings cannot fully replace conventional visits in T1D especially in the older age group.

Seasonal Variation of Testosterone Levels in a Large Cohort of Men.

Objectives: The aim of the study was to evaluate in a large cohort of males with a wide range of age, metabolic status, and coexistent morbidities whether month of blood test performance was associated with total and bioavailable testosterone levels independent of age, body mass index (BMI), existing cardiovascular disease (CVD), and CVD risk factors. Methods: Cross-sectional study includes data from computerized medical records of 27,328 men aged 20-70, treated by the largest healthcare organization in Israel, who had undergone testosterone measurement. In 7,940 subjects with available sex-hormone-binding globulin levels, bioavailable testosterone was calculated. Results: Total and bioavailable testosterone levels gradually decreased with age and BMI (P < 0.001) and were significantly lower in men with diabetes, hypertension, hyperlipidemia, and known CVD, but were higher in current smokers compared with nonsmokers (P < 0.001). Hormone levels were highest in August-October declined after and lowest in March. Overall, both total and bioavailable testosterone levels were significantly lower in March compared to August-October (P < 0.001). In a linear regression analysis, age, BMI, current smoking, and month of testing were independently associated with total (P < 0.001) and bioavailable testosterone levels (P=0.002), and diabetes was associated with total testosterone (P < 0.001). Conclusion: In a large cohort of men with a wide range of age, BMI, and comorbidities, month of testing was independently associated with total and bioavailable testosterone levels. These data provide strong evidence that seasonal variation has to be considered in clinical practice.

Subacute Thyroiditis-Still a Diagnostic Challenge: Data from an Observational Study.

Background: Subacute thyroiditis (SAT) is a relatively common cause of thyroid disease. However, only a few studies evaluating SAT have been published in recent years with varying diagnostic criteria. We evaluate the clinical presentation and long-term outcome of isotope scan-confirmed SAT. Methods: A retrospective study of 38 patients with isotope scan-confirmed SAT was performed at a single isotope department. All patients were contacted for long-term follow-up. Results: The female/male ratio was 1.4:1, and mean age was 47 ± 14 years and 62 ± 12 years in women and men, respectively (p = 0.002). Almost half of the cases (42%) occurred during the summer. The most common symptoms were neck pain (74%) and weakness (61%). Palpitations, weight loss, heat intolerance, and sweating appeared in 50%, 42%, 21%, and 21%, respectively. Only half of the patients reported fever. TSH level was low in all patients, and mean FT4 and FT3 level were about twice the upper limit of normal range. Elevated CRP and ESR occurred in the majority (88%) of patients. The mean time period between the first clinic visit and performing thyroid function tests was 8 ± 7 days. One-third of the patients initially received a diagnosis of upper respiratory tract infection (URI). NSAIDs and steroids were prescribed to 47% and 8% of patients, respectively. Long-term follow-up of 33.5 months (range 9-52) revealed that 25% remained with subclinical or overt hypothyroidism. Conclusions: These data demonstrate that although SAT is a common entity, there is still a significant delay in diagnosis, and in a third of our patients, the initial diagnosis was URI, with 25% developing long-term hypothyroidism.

Severe post-gastric bypass hypoglycemia in pregnancy.

Post-bariatric surgery hypoglycemia (PBH) is a serious and relatively prevalent complication of bariatric surgery and is often underdiagnosed due to unawareness. PBH can have a profound effect on health and quality of life. Data regarding the natural history and management of PBH during pregnancy are lacking. Here we describe a case of a 34-year-old woman who presented with intractable PBH during the second trimester of her third pregnancy, three years after a Roux-en-Y gastric bypass (RYGB). Treatment with nifedipine showed partial response and eventually intravenous (IV) glucose was needed until birth.

Following the COVID-19 Experience, Many Patients with Type 1 Diabetes Wish to Use Telemedicine in a Hybrid Format.

BACKGROUND: The COVID-19 pandemic has brought to light both challenges and unique opportunities regarding type 1 diabetes (T1D) management, including the usage of telemedicine platforms. METHODS: This study was conducted in a tertiary hospital diabetes clinic. All consecutive T1D patients during March and June 2021 were asked to fill out a structured anonymous questionnaire that aimed to determine their preference regarding continuous use of a virtual platform. RESULTS: In total, 126 T1D patients answered the questionnaire, of whom 51% were under the age of 40, half were men, half used insulin pumps, and 69% used continuous glucose monitoring. During the pandemic, the exposure of patients to virtual visits has grown about twofold, from 29% to 53%. Of the respondents, 49% expressed an interest in future usage of a virtual platform, but most of them preferred use in a hybrid manner. We found an association between preference to use telemedicine in the future and younger age, previous virtual platform experience, and confidence in being able to download data. CONCLUSIONS: Our data demonstrate that the COVID-19 experience has led to a growing interest of T1D patients in using the hybrid format of telemedicine. However, we still need to better understand who will benefit most from this platform and assess its cost-effectiveness and organization.

Skin exposure to UVB light induces a skin-brain-gonad axis and sexual behavior.

Ultraviolet (UV) light affects endocrinological and behavioral aspects of sexuality via an unknown mechanism. Here we discover that ultraviolet B (UVB) exposure enhances the levels of sex-steroid hormones and sexual behavior, which are mediated by the skin. In female mice, UVB exposure increases hypothalamus-pituitary-gonadal axis hormone levels, resulting in larger ovaries; extends estrus days; and increases anti-Mullerian hormone (AMH) expression. UVB exposure also enhances the sexual responsiveness and attractiveness of females and male-female interactions. Conditional knockout of p53 specifically in skin keratinocytes abolishes the effects of UVB. Thus, UVB triggers a skin-brain-gonadal axis through skin p53 activation. In humans, solar exposure enhances romantic passion in both genders and aggressiveness in men, as seen in analysis of individual questionaries, and positively correlates with testosterone level. Our findings suggest opportunities for treatment of sex-steroid-related dysfunctions.

Moderate Iodine Deficiency Is Common in Pregnancy but Does Not Alter Maternal and Neonatal Thyroid Function Tests.

Introduction: An Israeli national survey found that 85% of pregnant women had urinary iodine content (UIC) levels below the adequacy range (<150 µg/L). Widespread desalinated water usage and no national fortification plan are possible causes. Studies assessing relationships between iodine status and maternal and neonatal thyroid function provided varying results. Our aims were to determine whether iodine deficiency was associated with altered maternal or neonatal thyroid function and the factors leading to iodine deficiency. Methods: A cross-sectional study including 100 healthy women without prior thyroid disease, in their first trimester of a singleton pregnancy were recruited from an HMO clinic in central Israel. The women were followed from their first trimester. All women completed a 24-h dietary recall and life habits questionnaires. We tested for UIC, maternal and neonatal thyroid function, maternal autoantibodies, and neonatal outcomes. Results: Median UIC in our cohort was 49 µg/L [25%-75% interquartile range (IQR) 16-91.5 µg/L], with 84% below adequacy range. No correlation was found between iodine deficiency and maternal or neonatal thyroid function which remained within normal ranges. Antibody status did not differ, but thyroglobulin levels were significantly higher in iodine insufficient subjects. UIC was higher in women consuming an iodine containing supplement. There was no association between UIC and dietary iodine content or water source. Conclusions: Moderate iodine deficiency is common in our healthy pregnant women population. Our data imply that moderate iodine deficiency in pregnancy seem sufficient to maintain normal maternal and neonatal thyroid function.

Single liver metastasis of a follicular variant of papillary thyroid carcinoma: a rare pattern of organ spread.

SUMMARY: Well-differentiated thyroid cancer (WDTC), including papillary, follicular, and Hurthle-cell types, is characterized by a slow course and usually remain localized to the thyroid. However, a minority of these cases develop distant metastases with the most common sites being lungs, bones, and lymph nodes. Liver metastases of WDTC are rare and are usually found along with other distant metastases sites and in a multiple or diffuse pattern of spread. The recognition of distant metastasis in WDTC has a significant impact on the treatment and prognosis. However, because of their low incidence and awareness, distant metastases are often diagnosed late. Herein, we describe a case of a 71 years old woman who during routine surveillance of a follicular variant of papillary thyroid cancer (FV-PTC), 5 years after being treated for her primary thyroid tumor, was found to have a single liver metastasis and underwent liver segmental resection. This case highlights the importance of maintaining vigilant surveillance of patients with WDTC, and illustrates the possibility of unique metastasis at unexpected sites. Further studies are needed to understand the organ tropism of some WDTC leading to distant metastases development and to better prediction of an aggressive course. LEARNING POINTS: WDTC patients with distant metastases have a poor prognosis with a 10-year survival of about 50%. The most common sites of distant metastases are lung, bone and lymph nodes. Liver metastases are rare in WDTC, are usually multiple or diffuse and are found along with other distant metastases sites. Single liver metastasis of WDTC is an unexpected pattern of spread, and very few cases are reported in the literature. Rare sites of distant metastases in WDTC can manifest many years after the primary tumor, stressing the importance of maintaining vigilant surveillance. More studies are needed to predict which WDTC tumors may develop a more aggressive course, allowing clinicians to individualize patient management.

Fecal microbiome signatures of pancreatic cancer patients.

Pancreatic cancer (PC) is a leading cause of cancer-related death in developed countries, and since most patients have incurable disease at the time of diagnosis, developing a screening method for early detection is of high priority. Due to its metabolic importance, alterations in pancreatic functions may affect the composition of the gut microbiota, potentially yielding biomarkers for PC. However, the usefulness of these biomarkers may be limited if they are specific for advanced stages of disease, which may involve comorbidities such as biliary obstruction or diabetes. In this study we analyzed the fecal microbiota of 30 patients with pancreatic adenocarcinoma, 6 patients with pre-cancerous lesions, 13 healthy subjects and 16 with non-alcoholic fatty liver disease, using amplicon sequencing of the bacterial 16S rRNA gene. Fourteen bacterial features discriminated between PC and controls, and several were shared with findings from a recent Chinese cohort. A Random Forest model based on the microbiota classified PC and control samples with an AUC of 82.5%. However, inter-subject variability was high, and only a small part of the PC-associated microbial signals were also observed in patients with pre-cancerous pancreatic lesions, implying that microbiome-based early detection of such lesions will be challenging.