Long-term Metabolic Consequences Research Articles

Colostrum Supplementation to Rescue Antibiotic-Induced Dysbiosis and Reduce Long-Term Obesity Risk

The prevalence of metabolic disease in the United States has increased from 30.4% to 41.9% in the past decades, with rising rates among children. Emerging evidence implicates intestinal microbiome function as contributing to metabolic disease risk, with dysbiosis being associated with overweight and obese status. While sometimes lifesaving, antibioticssuch as azithromycin cause microbiota ecological instability and are significantly associated with a greater risk ofmetabolic disease and obesity in children. Since antibiotics are often necessary, the identification of nutritional interventions to restore microbial membership and function has a high potential value for millions of patients. Colostrum is the first milk produced by mammals immediately after birth and shapes intestinal colonization patterns, specifically enriching Bifidobacterium, Lactobacillus, and limiting the colonization of Proteobacteria. Bovine colostrum containsimmunomodulators, lactoferrin, oligosaccharides, bioactive compounds, and macronutrients. The compounds are similar across mammalian species. Considering the impact of colostrum in the sterile early-life gut, we hypothesized that bovine colostrum provided as a supplemental nutraceutical therapy would augment gut microbial recolonization following antibiotic exposures and mitigate long-term metabolic consequences. Specific pathogen-free (SPF) C57BL/6 mice (male, three weeks old, Jackson Laboratory) were housed under standard laboratory conditions with a 45% high-fat diet. Tylosintartrate antibiotic (ABX) was administered to some mice in drinking water 3 days/week over three weeks, with four days washout/week. To examine colostrum, some animals were provided colostrum gavage during or immediately following ABX exposures. After intervention, body composition and metabolic phenotypes were monitored for 16 weeks.Compared with ABX alone, colostrum following ABX maintained similar body composition and glucose tolerance as controls, while colostrum during ABX appeared similar to ABX alone. Examination of the gut microbiome showed unique enrichment of Akkermansia and Sutterella with decreased Enterobacteriaceae in mice treated with ABX followed by colostrum. Analysis of the gut mucosa demonstrated ABX decreased goblet cell numbers per villi (7.2/villus) compared with control (9.8/villus), and colostrum following ABX elevated goblet cells (8.6/villus). These data suggest colostrum may stimulate epithelial responses that foster host-microbial symbiosis at the mucosal surface and play a role in intestinal recolonization to benefit long-term homeostasis. Dairy Innovation Hub, UW-Madison. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Preconceptional maternal hyperandrogenism and metabolic syndrome risk in male offspring: a long-term population-based study.

There is limited research on the effects of maternal hyperandrogenism (MHA) on cardiometabolic risk factors in male offspring. We aimed to compare the risk of metabolic syndrome (MetS) in sons of women with preconceptional hyperandrogenism (HA) to those of non-HA women in later life. Using data obtained from the Tehran Lipid and Glucose Cohort Study, with an average of 20years follow-up, 1913 sons were divided into two groups based on their MHA status, sons with MHA (n = 523) and sons without MHA (controls n = 1390). The study groups were monitored from the baseline until either the incidence of events, censoring, or the end of the study period, depending on which occurred first. Age-scaled unadjusted and adjusted Cox regression models were utilized to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in their sons. There was no significant association between MHA and HR of MetS in sons with MHA compared to controls, even after adjustment (unadjusted HR (95% CI) 0.94 (0.80-1.11), P = 0.5) and (adjusted HR (95% CI) 0.98 (0.81-1.18),P = 0.8). Sons with MHA showed a HR of 1.35 for developing high fasting blood sugar compared to controls (unadjusted HR (95% CI) 1.35 (1.01-1.81), P = 0.04), however, after adjustment this association did not remain significant (adjusted HR (95% CI) 1.25 (0.90-1.74), P = 0.1). The results suggest that preconceptional MHA doesn't increase the risk of developing MetS in sons in later life. According to this suggestion, preconceptional MHA may not have long-term metabolic consequences in male offspring.

Childhood maltreatment and the risk of impaired glucose metabolism or type 2 diabetes in young adults: Findings from the Lifelines Cohort Study.

We examined the associations between childhood maltreatment and the risk of impaired glucose metabolism (IGM) or type 2 diabetes (T2D) in young adults aged 18-35. Participants (N = 8506) from the Lifelines Cohort Study without IGM or diabetes at baseline (2007-2013) were included. Childhood maltreatment was assessed by the Childhood Trauma Questionnaire (CTQ) and incident IGM/T2D was assessed by haemoglobin A1c levels (≥5.7%) in 2014-2017. There were 223 (2.6%) cases of IGM/T2D during the follow-up period. After adjusting for sociodemographic and health/lifestyle covariates and follow-up time, only the CTQ Sexual Abuse subscale was significantly associated with IGM/T2D (RR = 1.05 [95% CI = 1.01, 1.10]). The association remained when additionally accounting for depressive and anxiety symptoms (RR = 1.05 [95% CI = 1.00, 1.09]). Childhood sexual abuse was associated with an increased risk of IGM/T2D in young adults, highlighting the long-term metabolic consequences of childhood maltreatment.

A review of dolutegravir-associated weight gain and secondary metabolic comorbidities.

Dolutegravir is an integrase inhibitor and is recommended by the World Health Organization as the preferred first-line and second-line human immunodeficiency virus treatment in all populations. Excessive weight gain associated with dolutegravir-based regimens is an emerging issue; however, the long-term metabolic consequences of this effect have not been fully understood. Growing evidence shows that this leads to a higher incidence of hyperglycemia, hypertension, and metabolic syndrome, along with elevated cardiovascular risk. Dolutegravir-based regimens, also associated with greater adipocyte differentiation and greater expression of markers associated with lipid storage, continue to be a problem among patients living with human immunodeficiency virus. The mechanisms by which certain antiretroviral therapy agents differentially contribute to weight gain remain unknown. Some clinical investigators speculate that dolutegravir could interfere with central nervous system appetite regulation (melanocortin-4 receptor) and insulin signaling, or may have better penetration of adipose tissue where they could exert a direct impact on adipose tissue adipogenesis, fibrosis, and insulin resistance. This review summarizes our current understanding of weight gain and fat changes associated with dolutegravir and its possible secondary metabolic comorbidities.

The Role of the FGF19 Family in the Pathogenesis of Gestational Diabetes: A Narrative Review.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. Understanding the pathogenesis and appropriate diagnosis of GDM enables the implementation of early interventions during pregnancy that reduce the risk of maternal and fetal complications. At the same time, it provides opportunities to prevent diabetes, metabolic syndrome, and cardiovascular diseases in women with GDM and their offspring in the future. Fibroblast growth factors (FGFs) represent a heterogeneous family of signaling proteins which play a vital role in cell proliferation and differentiation, repair of damaged tissues, wound healing, angiogenesis, and mitogenesis and also affect the regulation of carbohydrate, lipid, and hormone metabolism. Abnormalities in the signaling function of FGFs may lead to numerous pathological conditions, including metabolic diseases. The FGF19 subfamily, also known as atypical FGFs, which includes FGF19, FGF21, and FGF23, is essential in regulating metabolic homeostasis and acts as a hormone while entering the systemic circulation. Many studies have pointed to the involvement of the FGF19 subfamily in the pathogenesis of metabolic diseases, including GDM, although the results are inconclusive. FGF19 and FGF21 are thought to be associated with insulin resistance, an essential element in the pathogenesis of GDM. FGF21 may influence placental metabolism and thus contribute to fetal growth and metabolism regulation. The observed relationship between FGF21 and increased birth weight could suggest a potential role for FGF21 in predicting future metabolic abnormalities in children born to women with GDM. In this group of patients, different mechanisms may contribute to an increased risk of cardiovascular diseases in women in later life, and FGF23 appears to be their promising early predictor. This study aims to present a comprehensive review of the FGF19 subfamily, emphasizing its role in GDM and predicting its long-term metabolic consequences for mothers and their offspring.

AAV5-mediated manipulation of insulin expression in choroid plexus has long-term metabolic and behavioral consequences

The choroid plexus (CP) is a source of trophic factors for the developing and mature brain. Insulin is produced in epithelial cells of the CP (EChPs), and its secretion is stimulated by Htr2c-mediated signaling. We modulated insulin expression in EChPs with intracerebroventricular injections of AAV5. Insulin overexpression in CP decelerates food intake, whereas its knockdown has the opposite effect. Insulin overexpression also results in reduced anxious behavior. Transcriptomic changes in the hypothalamus, especially in synapse-related processes, are also seen in mice overexpressing insulin in CP. Last, activation of Gq signaling in CP leads to acute Akt phosphorylation in neurons of the arcuate nucleus, indicating a direct action of CP-derived insulin on the hypothalamus. Taken together, our findings signify that CP is a relevant source of insulin in the central nervous system and that CP-derived insulin should be taken into consideration in future work pertaining to insulin actions in the brain.

Short- and long-term cognitive and metabolic effects of medium-chain triglyceride supplementation in rats

Medium-chain triglycerides (MCT) possess neuroprotective properties. However, the long-term metabolic consequences of supplementing a regular diet with cognition-enhancing doses of MCT are largely unknown. We studied the effects of chronic (28 days) supplementation of regular diet with different doses of MCT oil (1, 3, or 6 g/kg/day) or water (control) on working memory (Y-maze), behavior in the Open Field, spatial learning (Morris water maze), and weight of internal organs in male Wistar 2.5-m.o. Rats. In a separate experiment, we evaluated acute (single gavage) and chronic (28 days) effects of MCT or lard supplementation (3 g/kg) on blood biochemical parameters. MCT-1 and MCT-3 doses improved working memory in YM. In MWM, MCT-6 treatment improved spatial memory. Chronic MCT-1 or MCT-3 treatment did not affect internal organ weight, while MCT-6 dose increased liver weight and the brown/white adipose tissue ratio. Acutely, MCT administration elevated blood β-hydroxybutyrate and malondialdehyde levels. Chronic MCT administration (3 g/kg) did not affect the blood levels of glucose, lactate, pyruvate, acetoacetate, β-hydroxybutyrate, total and HDL cholesterol, triglycerides, malondialdehyde, and aspartate transaminase and alanine transaminase activities. Therefore, daily supplementation of standard feed with MCT resulted in mild intermittent ketosis. It improved working memory at lower concentrations without significant adverse side effects. At higher concentrations, it improved long-term spatial memory but also resulted in organ weight changes and is likely unsafe. These results highlight the importance of monitoring the metabolic effects of MCT supplementation alongside cognitive assessment in future studies of MCT's neuroprotective properties.

P089 Medical co-morbidities among Indigenous patients with OSA

Abstract Introduction Obstructive sleep apnoea is being increasingly recognised among Indigenous Australian adults. Moreover, other medical co-morbidities are also highly prevalent among Indigenous Australians. The bidirectional relationship between OSA and long-term metabolic consequences and its linkage to chronic medical conditions such as cardiovascular disease, hypertension and diabetes is well recognised. However, literature pertaining to presence of medical co-morbidities among Indigenous patients diagnosed with OSA is sparce. We therefore aimed to document the medical co-morbidities among Indigenous patients diagnosed to have OSA. Methods Demographic characteristics, clinical characteristics and presence of medical co-morbidities among patients diagnosed to have OSA with an AHI >5/hour were assessed. Results Of a total 741 Indigenous patients who underwent a diagnostic sleep study between 2011- 2020, 662/741 (89%) were diagnosed to have OSA. At least one comorbidity was reported in 79% of patients, of which Hypertension was the most common in 52%, followed by diabetes in 39% and heart disease including coronary artery disease in 37%. Among patients with a comorbidity, 58% had three or more recorded. The prevalence of comorbidity and multimorbidity did not significantly differ by severity of OSA, aside from hypertension which was noted in 57% of patients with severe OSA compared to 46% with mild OSA. Furthermore, patients who have severe OSA were more likely to be male. Discussion Medical co-morbidities are highly prevalent among Indigenous patients diagnosed to have OSA, especially presence of hypertension, diabetes and heart disease. The long-term consequences are not known. Hence, further studies are warranted.

IGF1R is a mediator of sex-specific metabolism in mice: Effects of age and high-fat diet.

We aimed to investigate the short and long-term metabolic consequences of IGF1R systemic gene deficiency in mice. UBC-CreERT2, Igf1rfl/fl mutant mice were used to suppress IGF1R signaling in adult tissues by inducing postnatal generalized Igf1r deletion with tamoxifen. Animals were analyzed at two different ages: i) 13-weeks old young mice, and ii) 12-months old middle-aged mice. In addition, the effects of 10 weeks-long high-fat diet (HFD) were investigated in middle-aged mice. Young IGF1R-deficient mice were insulin-resistant, with high IGF1, growth hormone (GH) and IGFBP3, as well as low IGFBP2 circulating levels. Males also presented increased triglycerides in liver. In contrast, middle-aged mice did not clearly show all of these alterations, suggesting possible compensatory effects. Middle-aged IGF1R-deficient male mice were able to counteract the negative effects induced by aging and HFD in adiposity, inflammation and glucose metabolism. A metabolic sexual dimorphism dependent on IGF1R was observed, especially in middle-aged mice. These results demonstrate that IGF1R is involved in metabolic homeostasis, with effects modulated by diet-induced obesity and aging in a sex dependent manner. Thus, IGF1R deficiency in mice is proposed as a useful tool to understand metabolic alterations observed in patients with IGF1R gene deletions.

Cardiovascular diseases in HIV patients

New and more effective antiretroviral therapy regimens have increased viral suppression and improved immune function recovery, leading to the extension of the lifespan of people living with HIV (PLWH). The extended lifespan of PLWH has recently been reported as a significant factor associated with diabetes mellitus, dyslipidemia, and long-term metabolic consequences, such as cardiovascular diseases. Therefore, this article briefly reviews the epidemiology and risk factors of cardiovascular diseases, including dyslipidemia and diabetes mellitus, in PLWH.

Intrauterine Growth-Restricted Piglets Are Predisposed to Develop Metabolic Disorders in Adulthood When Fed With Parenteral Nutrition in the Neonatal Period

ObjectivesTotal parenteral nutrition (TPN) is lifesaving yet non-normal nutrition regimen during the neonatal period. However, studies have shown that TPN feeding early in life can permanently alter metabolism at later ages. Moreover, intrauterine growth restricted (IUGR) neonates also have a higher risk of developing metabolic diseases (such as obesity and dyslipidemia) in later life. Because a substantial proportion of IUGR neonates receive TPN in early life, we wondered if the metabolic effects of feeding TPN early in life would exacerbate these effects of IUGR? We hypothesized that feeding TPN to IUGR neonates would aggravate the risk of developing obesity and dyslipidemia in adulthood.MethodsSixteen normal weight female piglets (7 d old) were randomized to sow-fed (SF) or early TPN (TPN-CON); 8 (IUGR or runt) piglets were fed TPN as a third group (TPN-IUGR). After 2 weeks of TPN or suckling, all pigs were fed a normal grower diet for 8 mo. At 8 mo, catheters were implanted and in vivo metabolic tests were conducted.ResultsTPN-IUGR pigs demonstrated catch-up growth by 4 mo, and body weights were not different among groups at 8 mo. The metabolic effects of feeding TPN persisted into adulthood, as indicated by higher postprandial plasma triglycerides (TG) and fasting plasma non-esterified fatty acids (NEFA), compared to SF (P < 0.05). IUGR exacerbated TPN-induced risk for diseases by worsening obesity outcomes with greater subcutaneous fat deposition (P < 0.05) and greater ectopic TG deposition in the liver (P < 0.05) and muscle (P < 0.05). Furthermore, IUGR led to dyslipidemia as indicated by higher cholesterol in fasted plasma LDL (P < 0.05), slower postprandial TG clearance (P < 0.05), higher fasting plasma NEFA (P < 0.001) and higher plasma dimethylglycine (P < 0.05), compared to the TPN-CON. IUGR pigs had greater VLDL secretion, as suggested by higher microsomal transfer protein mRNA (P < 0.05). Early TPN programmed reduced lipogenesis, as indicated by lower fatty acid synthase mRNA (P < 0.05), compared to SF.ConclusionsCollectively, these findings conclude that although TPN is a lifesaving measure, feeding TPN to IUGR neonates has long-term metabolic consequences predisposing them to develop metabolic disorders in adulthood.Funding SourcesCanadian Institutes of Health Research.

Identification of the Key Pathways and Genes in Hypoxia Pulmonary Arterial Hypertension Following Intrauterine Growth Retardation.

High-throughput sequencing and weighted gene co-expression network analysis (WGCNA) were used to identify susceptibility modules and genes in liver tissue for the hypoxic pulmonary arterial hypertension (PAH) animal model following intrauterine growth retardation (IUGR). A total of 5,000 genes were clustered into eight co-expression modules via WGCNA. Module blue was mostly significantly correlated with the IUGR–hypoxia group. Gene Ontology analysis showed that genes in the module blue were mainly enriched in the fatty acid metabolic process, lipid modification, and fatty acid catabolic process. The Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the genes in module blue were mainly associated with fatty acid metabolism, PPAR signaling pathway, and biosynthesis of unsaturated fatty acids. In addition, the maximal clique centrality method was used to identify the hub genes in the subnetworks, and the obtained results were verified using real-time quantitative PCR. Finally, we identified that four genes including Cyp2f4, Lipc, Acadl, and Hacl1 were significantly associated with IUGR-hypoxia. Our study identified a module and several key genes that acted as essential components in the etiology of the long-term metabolic consequences in hypoxia PAH following IUGR.

Organ-Sparing Pancreatectomy for Benign or Low-Grade Malignant Pancreatic Tumors: A Single-Center Experience with 101 Consecutive Patients.

BackgroundPancreaticoduodenectomy (PD) and distal pancreatectomy with splenectomy (DPS) are considered the standard procedures for pancreatic lesions. However, long-term metabolic consequences of PD and DPS applied for benign or low-grade malignant tumors need to be addressed. This study aimed to investigate the short- and long-term outcomes of organ-sparing pancreatectomy for benign or low-grade malignant pancreatic tumors in our institution.Material/MethodsThe clinical data of 101 patients with benign or low-grade malignant pancreatic tumors who underwent organ-sparing pancreatectomy from January 2009 to September 2021 were retrospectively analyzed, including 40 tumor enucleations (EN), 22 central pancreatectomies (CP), 25 spleen-preserving distal pancreatectomies (SPDP), 7 pylorus-preserving pancreaticoduodenectomies (PPPD) and 7 duodenum-preserving pancreatic head resections (DPPHR).ResultsThe mean operative time, intraoperative blood loss, and length of hospital stay were 182.9±74.6 min, 191.9±127.8 mL, and 11.6±8.1 days, respectively. EN had the shortest operative time, while DPPHR had the longest operative time. The mean intraoperative blood loss of DPPHR and PPPD was significantly greater than the others (all P<0.05). The length of hospital stay of PPPD was longest. The overall morbidity was 33.6%. The reoperation rate was 1.0% and there was no mortality. The incidence of pancreatic endocrine insufficiency and exocrine insufficiency were 5.9% and 6.9%, respectively. None patients had tumor recurrence during the follow-up period.ConclusionsOrgan-sparing pancreatectomy is associated with acceptable perioperative risk and postoperative complications and better long-term outcomes in the aspects of preservation of function and curability in benign or low-grade malignant pancreatic tumors.

The Origins of NAFLD: The Potential Implication of Intrauterine Life and Early Postnatal Period.

Fetal life and the first few months after birth represent a plastic age, defined as a “window of opportunity”, as the organism is particularly susceptible to environmental pressures and has to adapt to environmental conditions. Several perturbations in pregnancy, such as excessive weight gain, obesity, gestational diabetes mellitus and an inadequate or high-fat diet, have been associated with long-term metabolic consequences in offspring, even without affecting birth weight. Moreover, great interest has also been focused on the relationship between the gut microbiome of early infants and health status in later life. Consistently, in various epidemiological studies, a condition of dysbiosis has been associated with an increased inflammatory response and metabolic alterations in the host, with important consequences on the intestinal and systemic health of the unborn child. This review aims to summarize the current knowledge on the origins of NAFLD, with particular attention to the potential implications of intrauterine life and the early postnatal period. Due to the well-known association between gut microbiota and the risk of NAFLD, a specific focus will be devoted to factors affecting early microbiota formation/composition.

Weight Gain and Metabolic Syndrome in Human Immunodeficiency Virus Patients.

While human immunodeficiency virus (HIV)-associated wasting has declined with significant advances in antiretroviral therapy (ART), weight gain and metabolic syndrome (MetS) are now becoming a problem for people living with HIV (PLWH) worldwide. The development of a new and more effective ART regimen has increased viral suppression and improved immunologic function recovery, leading to the extension of the lifespan of PLWH. It has recently been reported as one of the significant factors associated with weight gain, obesity, and long-term metabolic consequences in PLWH. This article reviewed the epidemiology of overweight and MetS among PLWH and the known risk factors for weight gain and its major comorbidities, such as dyslipidemia, diabetes mellitus, cardiovascular diseases, neurocognitive disorders, and liver diseases, in PLWH. In addition, reports on the pharmacological and surgical management of overweight and obesity in PLWH has been briefly summarized.

Veritable evaluation and inspection of PCOS and its apropos medicaments

Polycystic Ovary Syndrome (PCOS) is a vastly familial, prevalent yet complicated endocrine disorder seen in 5 to 15% of premenopausal women. An estimated one in five ~ 20% Indian women suffer from PCOS. In India, PCOS is a tabooed disorder; If neglected, the condition can prove fatal. However, the past decade has seen the changing discourse in India. PCOS negatively affects reproduction, general health, sexual health, and quality of life. Genetic predisposition of hormonal and non-hormonal factors influence ovary functioning and are responsible for the onset of the syndrome. Hormonal imbalance, metabolic abnormality, and insulin resistance are characteristic features that significantly increase the risk of anovulatory infertility, type 2 diabetes, and cardiovascular diseases. The underlying cause of the path physiology of PCOS is still under the radar, but the derangement of the hypothalamic-pituitary-ovarian axis could be the sweeping reason for the same. PCOS management should address on healthy lifestyle with symptomatic medical therapy and psychological bearing with special emphasis on far reaching side effects and long-term metabolic consequences This review article gives a comprehensive overview of PCOS and the morbidities hooked up with it. It has a notable emphasis on the PCOS guidelines, diagnosis, non-pharmacological, and pharmacological treatments.

879. Evaluation of the Incidence of Hypertension, Diabetes, and Hyperlipidemia in Patients on Antiretroviral Therapy

Abstract Background Although integrase inhibitor (INSTI)-based regimens have been associated with weight gain, there is limited data on whether INSTIs cause long-term metabolic consequences. This study evaluated the effect of INSTIs on the development of metabolic comorbidities compared to non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)-based therapies in patients in the Illinois Department of Corrections. Methods This retrospective cohort study consisted of incarcerated adult patients living with HIV and receiving a guideline-recommended regimen between 7/12/10 and 12/31/19. Patients with a pre-existing diagnosis of diabetes, hypertension, or hyperlipidemia, or lack of medical follow-up data were excluded. The primary outcome was to compare the incidence of a metabolic comorbidity between regimens. Secondary outcomes compared the incidence of weight gain, diabetes, hypertension, and hyperlipidemia as separate outcomes between drug classes. Demographics and pertinent labs were collected. Data was analyzed with ANOVA, chi-squared, and paired t-tests. The primary outcome was adjusted for age, race, use of antipsychotic medications, and family history of metabolic comorbidities. Results A total of 206 patients were included in the analysis with mean follow-up time of 31.5 ± 19.4 months. Majority of patients were Black (69%) and male (91%). A total of 42 patients developed a metabolic comorbidity (Table 1). After adjustment for confounding factors, there was a significant difference in the development of comorbidities between the treatment groups (p=0.031) with INSTI use being more likely to develop a comorbidity than NNRTI (p=0.004). No difference was found between INSTI and PI use (p=0.518). Development of hypertension was significantly higher in the INSTI group than NNRTI group (p=0.014), while the development of diabetes and hyperlipidemia were not. Weight and BMI were significantly higher regardless of antiretroviral (Table 2). No differences were found in the primary outcome between agents within the same drug class or between 1st or 2nd generation INSTIs. Table 1. Results of Primary and Secondary Outcomes Table 2. Impact of HIV regimen on weight and BMI after 1 year Conclusion All antiretrovirals were linked to weight gain but INSTIs were associated with increased incidence of hypertension. Disclosures All Authors: No reported disclosures

The effect of distance on the adherence to postpartum follow-up in women with gestational diabetes

Despite the increasing prevalence of gestational diabetes mellitus and well-known long-term metabolic consequences, a low rate of postpartum screening in this population is reported. Few studies focused on environmental factors of attending and performing blood glucose screening tests in women with gestational diabetes. This work aimed to assess the proportion of uptake of postpartum follow-up after the first recall and to study the adherence-related factors in women with gestational diabetes. All women with gestational diabetes were recalled for postpartum screening in a tertiary care center as the center of the cohort study in 2016. The postal addresses were geocoded, and precise spatial (x, y) was provided for each mother's home location. SPSS and GIS were used for data analysis. The incidence rate of gestational diabetes was 8.5% (826/9630). Of women with gestational diabetes, 21.3% accepted to return and completed postpartum screening tests in the first recall. The distance from the cohort center, history of diabetes in the family, and a number of pregnancies were significant predictors for return to follow-up using binary logistic regression (P < 0.01). The first 25% of patients had a distance of 2346 m from the cohort center, and all of the mothers referred to the hospital were 0 to 5 km away, i.e., those who did not return were more than 5 km away (95% confidence interval). Overall screening uptake rate was low. Distance from the center of the screening was an essential factor in deciding to return and adhere to postpartum care in women with gestational diabetes. Geographic inequalities must be considered as a risk factor of visiting the healthcare center in addition to individual contributors. A more accessible center may improve the postpartum follow-up rate in women with a history of gestational diabetes.

Exploring new treatment options for polycystic ovary syndrome: Review of a novel antidiabetic agent SGLT2 inhibitor.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age associated with long-term metabolic and cardiovascular consequences. A plethora of symptoms and their severity differentiate on an individual level, giving the syndrome numerous phenotypes. Due to menstrual cycle abnormalities, women suffer from irregular menstrual bleeding, difficulty in conception, and infertility. Furthermore, the risk of pregnancy complications such as gestational diabetes mellitus, hypertensive disorders of pregnancy, and preterm birth are higher in women with PCOS than in the general population. Often, women with PCOS have comorbidities such as dyslipidemia, obesity, glucose intolerance or diabetes type 2, non-alcoholic fatty liver disease, and metabolic syndrome, which all influence the treatment plan. Historic insulin-sensitizing agents, although good for some of the metabolic derangements, do not offer long-term cardiovascular benefits; therefore, new treatment options are of paramount importance. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors, a new class of antidiabetic agents with beneficial cardiovascular, bodyweight, and antihyperglycemic effects, although not approved for the treatment of PCOS, might be an attractive therapeutic addition in the PCOS armamentarium. Namely, recent studies with SGLT-2 inhibitors showed promising improvements in anthropometric parameters and body composition in patients with PCOS. It is important to further explore the SGLT-2 inhibitors potential as an early therapeutic option because of the PCOS-related risk of metabolic, reproductive, and psychological consequences.

Prognostic impact of conservative surgery for pancreatic IPMNs

BackgroundThe extent of pancreatic resection for intraductal papillary mucinous neoplasms (IPMNs) remains an unresolved issue. The study aims at analyzing the prognostic impact of conservative surgery (CS) i.e. of pancreatoduodenectomy or distal pancreatectomy, versus total pancreatectomy (TP), for pancreatic IPMNs. MethodsWe retrospectively analyzed and compared data of patients who had undergone pancreatic resection for IPMNs at our center between November 2007 and April 2019. Patients were divided into two main groups based on the extent of surgery: TP-group and CS-group. Subsequently, the perioperative and the long-term outcomes were compared. Moreover, a sub-group analysis of patients with IPMN alone and patients with malignant IPMN, based on preoperative indications to surgery and post-operative histopathological findings, was also performed. ResultsFifty-three patients were included in the TP-group and 73 in the CS-group. In 50 (39.7%) cases the frozen section changed the pre-operative surgical planning, with an extension of the pancreatic resection, in 43 (34.1%) cases up to a total pancreatectomy. Twenty-six patients (20.6%) with low-grade dysplasia at the frozen section underwent CS, while twenty (15.8%) underwent TP. Comparing these two sub-groups no differences were found in surgical IPMN recurrence, nor progression. The rate of overall postoperative complications was 56.6% in the TP-group and 57.5% in the CS-group (p = 0.940). Fifteen patients (20.5%) developed diabetes in the CS-group.None of the patients treated with CS developed a surgical IPMN recurrence or progression during the follow-up period. Comparing OS and DFS of the two groups, we did not find any statistically significant difference (p = 0.619 and 0.315). ConclusionA timely CS can be considered an appropriate and valid strategy in the surgical treatment of the majority of pancreatic IPMNs, as it can avoid the serious long-term metabolic consequences of TP in patients with a long-life expectancy. On the contrary, TP remains mandatory in case of PDAC or high-risk features involving the entire gland.