[Swedish Medical Birth Register 50 years - a source for scientific publications]. / Medicinska födelseregistret 50 år.

The nationwide Swedish Medical Birth Register (MBR) includes more than 98% of all births in Sweden since 1973. The MBR is updated annually, and is based on information from antenatal, obstetric, and neonatal records. Maternal information includes self-reported medical history, socio-demographic factors, smoking and snuff use, medication use, height and measured weight. Birth and neonatal/postpartal data include birth date, mode of delivery, singleton or multiple birth, gestational age, stillbirth, birth weight, birth length, head circumference, infant sex, Apgar scores, and maternal and infant diagnoses/procedures. The overall quality of the MBR is very high, partly due to the semi-automated data extraction from the standardized regional electronic health records. The MBR can be linked to other health registers through the unique personal identity numbers of mothers and live-born offspring. More than 1000 scientific publications have used MBR as a data source.

Association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy: prospective, population based cohort study.

Objective: To study the association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy. Design: Prospective, population based cohort study. Setting: All singleton pregnancies after 22 completed gestational weeks registered in the Swedish Pregnancy Register and the Medical Birth Registry of Norway, from 1 March 2020 to 24 May 2022. Participants: 312 456 individuals available for analysis (201 770 in Sweden and 110 686 in Norway), with pregnancies that reached 42 completed gestational weeks by the end of follow-up in the pregnancy registries, excluding individuals with SARS-CoV-2 infection before pregnancy and those with a diagnosis of pre-existing hypertension or onset of hypertension before 20 gestational weeks. Main outcome measures: Newly diagnosed hypertension during pregnancy was defined as a composite outcome of a diagnosis of gestational hypertension, pre-eclampsia, HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome, or eclampsia, from gestational week 20 to one week after delivery. The association between SARS-CoV-2 infection and hypertension during pregnancy was investigated with a stratified Cox proportional hazard model, adjusting for maternal age, body mass index, parity, smoking, region of birth, education, income, coexisting medical conditions, previous hypertension during pregnancy, number of healthcare visits during the past year, and vaccination against SARS-CoV-2. Pre-eclampsia was also analysed as a separate outcome. Results: Of 312 456 individuals available for analysis, 8% (n=24 566) had SARS-CoV-2 infection any time during pregnancy, 6% (n=18 051) had a diagnosis of hypertension during pregnancy, and 3% (9899) had pre-eclampsia. SARS-CoV-2 infection during pregnancy was not associated with an increased risk of hypertension during pregnancy (adjusted hazard ratio 0.99, 95% confidence interval 0.93 to 1.04) or pre-eclampsia (0.98, 0.87 to 1.10). The results were similar for SARS-CoV-2 infection in all gestational trimesters and in different time periods that corresponded to dominance of different variants of the SARS-CoV-2 virus. Conclusions: This population based study did not find any evidence of an association between SARS-CoV-2 infection during pregnancy and an increased risk of hypertension during pregnancy or pre-eclampsia.

Comparing the results from a Swedish pregnancy cohort using data from three automated placental growth factor immunoassay platforms intended for first-trimester preeclampsia prediction.

INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy. MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific. RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4). CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.

The Swedish medical birth register during five decades: documentation of the content and quality of the register.

Pregnancy-related factors are important for short- and long-term health in mothers and offspring. The nationwide population-based Swedish Medical Birth Register (MBR) was established in 1973. The present study describes the content and quality of the MBR, using original MBR data, Swedish-language and international publications based on the MBR.The MBR includes around 98% of all births in Sweden. From 1982 onwards, the MBR is based on prospectively recorded information in standardized antenatal, obstetric, and neonatal records. When the mother and infant are discharged from hospital, this information is forwarded to the MBR, which is updated annually. Maternal data include information from first antenatal visit on self-reported obstetric history, infertility, diseases, medication use, cohabitation status, smoking and snuff use, self-reported height and measured weight, allowing calculation of body mass index. Birth and neonatal data include date and time of birth, mode of delivery, singleton or multiple birth, gestational age, stillbirth, birth weight, birth length, head circumference, infant sex, Apgar scores, and maternal and infant diagnoses/procedures, including neonatal care. The overall quality of the MBR is very high, owing to the semi-automated data extraction from the standardized regional electronic health records, Sweden's universal access to antenatal care, and the possibility to compare mothers and offspring to the Total Population Register in order to identify missing records. Through the unique personal identity numbers of mothers and live-born offspring, the MBR can be linked to other health registers. The Swedish MBR contains high-quality pregnancy-related information on more than 5 million births during five decades.

Placental location and risk of retained placenta in women with a previous cesarean section: A population-based cohort study.

INTRODUCTION: Some studies have shown that women with a previous cesarean section, compared with women with a previous vaginal delivery, have an increased risk of retained placenta during a subsequent vaginal delivery. It is unknown whether this is mediated by anterior placental location, when the placenta might cover the uterine scar. The aim of this study was to evaluate whether the increased risk of retained placenta in women with a previous cesarean section is mediated by anterior placental location. MATERIAL AND METHODS: This is a population-based cohort study, with data from the regional population-based Stockholm-Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The overall study population included 49 598 women with a vaginal second delivery, where adequate information about placental location from the second-trimester ultrasound scan was available. For the main analysis, including the 3921 women with a previous cesarean section, we calculated the relative risk of retained placenta in women with an anterior placental location, using women with non-anterior placental locations as reference. Relative risks were calculated as odds ratios (OR) with 95% CI. In a second model, adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, infant sex, and in vitro fertilization. RESULTS: In the overall study population, the rate of retained placenta at the second delivery was 2.0%. The proportion of women with a retained placenta was higher among women with a previous cesarean compared with those with a previous vaginal delivery (3.4% vs 1.9%; P < .0001). In the main analysis, including women with a previous cesarean section, the risk for retained placenta was not increased with anterior compared with non-anterior placental location (OR 0.84, 95% CI 0.60-1.20). Adjustments did not affect the estimates in a significant way. CONCLUSIONS: The increased risk of retained placenta in women with a previous cesarean section is not mediated by anterior placental location.

Clinical risk assessment in early pregnancy for preeclampsia in nulliparous women: A population based cohort study.

OBJECTIVE: To evaluate the capacity of multivariable prediction of preeclampsia during pregnancy, based on detailed routinely collected early pregnancy data in nulliparous women. DESIGN AND SETTING: A population-based cohort study of 62 562 pregnancies of nulliparous women with deliveries 2008-13 in the Stockholm-Gotland Counties in Sweden. METHODS: Maternal social, reproductive and medical history and medical examinations (including mean arterial pressure, proteinuria, hemoglobin and capillary glucose levels) routinely collected at the first visit in antenatal care, constitute the predictive variables. Predictive models for preeclampsia were created by three methods; logistic regression models using 1) pre-specified variables (similar to the Fetal Medicine Foundation model including maternal factors and mean arterial pressure), 2) backward selection starting from the full suite of variables, and 3) a Random forest model using the same candidate variables. The performance of the British National Institute for Health and Care Excellence (NICE) binary risk classification guidelines for preeclampsia was also evaluated. The outcome measures were diagnosis of preeclampsia with delivery <34, <37, and ≥37 weeks' gestation. RESULTS: A total of 2 773 (4.4%) nulliparous women subsequently developed preeclampsia. The pre-specified variables model was superior the other two models, regarding prediction of preeclampsia with delivery <34 and <37 weeks, both with areas under the curve of 0.68, and sensitivity of 30.6% (95% CI 24.5-37.2) and 29.2% (95% CI 25.2-33.4) at a 10% false positive rate, respectively. The performance of these customizable multivariable models at the chosen false positive rate, was significantly better than the binary NICE-guidelines for preeclampsia with delivery <37 and ≥37 weeks' gestation. CONCLUSION: Multivariable models in early pregnancy had a modest performance, although providing advantages over the NICE-guidelines, in predicting preeclampsia in nulliparous women. Use of a machine learning algorithm (Random forest) did not result in superior prediction.

BRL37344 stimulates GLUT4 translocation and glucose uptake in skeletal muscle via ß2-adrenoceptors without causing classical receptor desensitization.

The type 2 diabetes epidemic makes it important to find insulin-independent ways to improve glucose homeostasis. This study examines the mechanisms activated by a dual ß2-/ß3-adrenoceptor agonist, BRL37344, to increase glucose uptake in skeletal muscle and its effects on glucose homeostasis in vivo. We measured the effect of BRL37344 on glucose uptake, glucose transporter 4 (GLUT4) translocation, cAMP levels, ß2-adrenoceptor desensitization, ß-arrestin recruitment, Akt, AMPK, and mammalian target of rapamycin (mTOR) phosphorylation using L6 skeletal muscle cells as a model. We further tested the ability of BRL37344 to modulate skeletal muscle glucose metabolism in animal models (glucose tolerance tests and in vivo and ex vivo skeletal muscle glucose uptake). In L6 cells, BRL37344 increased GLUT4 translocation and glucose uptake only by activation of ß2-adrenoceptors, with a similar potency and efficacy to that of the nonselective ß-adrenoceptor agonist isoprenaline, despite being a partial agonist with respect to cAMP generation. GLUT4 translocation occurred independently of Akt and AMPK phosphorylation but was dependent on mTORC2. Furthermore, in contrast to isoprenaline, BRL37344 did not promote agonist-mediated desensitization and failed to recruit ß-arrestin1/2 to the ß2-adrenoceptor. In conclusion, BRL37344 improved glucose tolerance and increased glucose uptake into skeletal muscle in vivo and ex vivo through a ß2-adrenoceptor-mediated mechanism independently of Akt. BRL37344 was a partial agonist with respect to cAMP, but a full agonist for glucose uptake, and importantly did not cause classical receptor desensitization or internalization of the receptor.

Placental location and pregnancy outcomes in nulliparous women: A population-based cohort study.

INTRODUCTION: The impact of placenta previa on pregnancy, delivery and infant outcomes has been extensively studied. However, less is known about the possible association of placental location other than previa with pregnancy outcomes. The aim of this study was to investigate if placental location other than previa is associated with adverse pregnancy, delivery and infant outcomes. MATERIAL AND METHODS: This is a population-based cohort study, with data from the regional population-based Stockholm-Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The study population included 74 087 nulliparous women with singleton pregnancies resulting in live-born infants, with information about placental location from the second-trimester ultrasound screening. The association between placental location (fundal, lateral, anterior or posterior) and pregnancy outcomes was estimated using logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated, and adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, sex of the infant and in vitro fertilization. Main outcome measures were pregnancy, delivery and infant outcomes. RESULTS: Compared with posterior placental location, fundal and lateral placental locations were associated with a number of adverse pregnancy outcomes, the most important being: very preterm birth (<32 weeks of gestation) (adjusted OR [aOR] 1.78, 95% CI 1.18-2.63 and aOR 2.12, 95% CI 1.39-2.25, respectively), moderate preterm birth (32-36 weeks of gestation) (aOR 1.23, 95% CI 1.001-1.51 and aOR 1.62, 95% CI 1.32-2.00, respectively), small-for-gestational-age birth (aOR 1.67, 95% CI 1.34-2.07 and aOR 1.77, 95% CI 1.39-2.25, respectively) and manual removal of the placenta in vaginal births (aOR 3.27, 95% CI 2.68-3.99 and aOR 3.27, 95% CI 2.60-4.10, respectively). Additionally, lateral placental location was associated with preeclampsia (aOR 1.30, 95% CI 1.03-1.65) and severe postpartum hemorrhage (aOR 1.42, 95% CI 1.27-1.82). CONCLUSIONS: Compared with posterior placental location, fundal and lateral placental locations are associated with a number of adverse pregnancy, delivery and infant outcomes.

Spontaneous posterior rectus sheath hernia: a case report.

BACKGROUND: Hernias of the posterior rectus sheath are very rare abdominal wall hernias with only a handful of cases reported in the literature to date. As an uncommon disease, it is important to recognize and report this case in order to enhance scientific knowledge of this disease. CASE PRESENTATION: This case report presents a spontaneous posterior rectus sheath herniation in a 79-year-old white man with previous abdominal surgery for appendicitis. His herniation was discovered incidentally during an examination for his chief complaints of lower abdominal pain and diarrhea which were later diagnosed as Salmonella-related gastroenteritis. A computed tomography scan of his abdomen and pelvis showed abdominal wall hernia with loops of small bowel extending into his rectus abdominis muscle. In this case, it was decided to leave the situation alone for now due to no evidence of bowel obstruction and the low risk of this hernia getting strangulated, which otherwise would have warranted urgent surgery. CONCLUSIONS: This report adds to the limited stock of available literature on this unusual issue and strengthens the evidence base on the best approach to support informed clinical decision making. The significant clinical implication of such case reports is increased identification rate of rare clinical conditions which otherwise often go unnoticed.

α1A-Adrenoceptors activate mTOR signalling and glucose uptake in cardiomyocytes.

The capacity of G protein-coupled receptors to modulate mechanistic target of rapamycin (mTOR) activity is a newly emerging paradigm with the potential to link cell surface receptors with cell survival. Cardiomyocyte viability is linked to signalling pathways involving Akt and mTOR, as well as increased glucose uptake and utilization. Our aim was to determine whether the α1A-adrenoceptor (AR) couples to these protective pathways, and increased glucose uptake. We characterised α1A-AR signalling in CHO-K1 cells co-expressing the human α1A-AR and GLUT4 (CHOα1AGLUT4myc) and in neonatal rat ventricular cardiomyocytes (NRVM), and measured glucose uptake, intracellular Ca2+ mobilization, and phosphorylation of mTOR, Akt, 5' adenosine monophosphate-activated kinase (AMPK) and S6 ribosomal protein (S6rp). In both systems, noradrenaline and the α1A-AR selective agonist A61603 stimulated glucose uptake by parallel pathways involving mTOR and AMPK, whereas another α1-AR agonist oxymetazoline increased glucose uptake predominantly by mTOR. All agonists promoted phosphorylation of mTOR at Ser2448 and Ser2481, indicating activation of both mTORC1 and mTORC2, but did not increase Akt phosphorylation. In CHOα1AGLUT4myc cells, siRNA directed against rictor but not raptor suppressed α1A-AR mediated glucose uptake. We have thus identified mTORC2 as a key component in glucose uptake stimulated by α1A-AR agonists. Our findings identify a novel link between the α1A-AR, mTORC2 and glucose uptake, that have been implicated separately in cardiomyocyte survival. Our studies provide an improved framework for examining the utility of α1A-AR selective agonists as tools in the treatment of cardiac dysfunction.

The Duari hernia and recognition of the femoral vein compression sign.

Femoral hernias can be difficult to diagnose and are at high risk of strangulation. This report is of a rare case of an irreducible femoral hernia containing caecum and appendix presenting as an emergency. To the authors' knowledge, there have only been three cases reported, the first described by Duari. This case was incorrectly diagnosed preoperatively as an inguinal hernia, so the CT diagnosis of femoral hernias is reviewed, in particular demonstrating the radiological use of the femoral vein compression sign.

Hyperbilirubinaemia: its utility in non-perforated appendicitis.

BACKGROUND: The diagnosis of acute appendicitis is made using clinical findings and investigations. Recent studies have suggested that serum bilirubin, a cheap and simple biochemical test, is a positive predictor in the diagnosis of appendiceal perforation and may be more specific than C-reactive protein (CRP) and white cell count (WCC). The aim of this study was to investigate the utility of the serum bilirubin level in patients with suspected acute but non-perforative appendicitis. METHODS: A retrospective chart review of 213 patients who presented with suspected appendicitis in a 6-month period to Nambour General Hospital was performed. Serum bilirubin, WCC and CRP were recorded and analysed as to their utility in relation to the final diagnosis. RESULTS: A total of 196 patients underwent an appendicectomy and 41 of these were negative. The specificity of hyperbilirubinaemia for appendicitis overall was 0.83 with a positive predictive value (PPV) of 0.86, compared with CRP (specificity 0.40, PPV 0.75) and WCC (specificity 0.67, PPV 0.85). The area under the receiver operating characteristic curve for bilirubin was 0.6289 compared to 0.6171 for CRP and 0.7219 for WCC. A subgroup analysis of those with complicated appendicitis demonstrated a PPV for bilirubin of 0.66 compared to 0.58 for WCC and 0.34 for CRP in agreement with the literature. Subgroup analysis of hyperbilirubinaemia in simple appendicitis demonstrated a PPV of 0.81 compared to CRP (0.71) and WCC (0.82). CONCLUSION: Bilirubin had a higher specificity than CRP and WCC overall in patients with appendicitis. Hyperbilirubinaemia had a high PPV in patients with simple appendicitis.

Totally Endovascular Management of Popliteal Artery Occlusion and Pseudoaneurysm Formation after Total Knee Replacement.

Injuries to the popliteal artery during total knee arthroplasty (TKA) are rare. We present a case of a 72-year-old man with popliteal artery thrombosis and a pseudoaneurysm presenting immediately after TKA. First-line management of acute limb ischemia is currently transitioning from open surgery to endovascular strategies such as catheter-directed thrombolysis or mechanical thrombectomy. Due to the rarity of acute limb ischemia and pseudoaneurysms after TKA, endovascular management is only reported in a few case studies. This case is distinctive by having both popliteal artery thrombosis and a pseudoaneurysm which were successfully managed entirely endovascular using AngioJet thrombolysis and a flexible covered stent. This case contributes to the evidence supporting endovascular management of this rare complication of TKA.

Popliteal Vein Aneurysm: A Rare Cause of Pulmonary Emboli.

Venous aneurysms are a rare pathology that was first reported in the literature in 1968. Popliteal venous aneurysms (PVAs) are the most common lower limb venous aneurysm and have significant consequences including deep vein thrombosis, pulmonary embolus (PE), and death. A 52-year-old woman presented with chest pain and shortness of breath. A computed tomography (CT) angiography demonstrated bilateral pulmonary emboli, and she was commenced on rivaroxaban. History revealed no significant risk factors, and a thrombophilia screen was negative. However, an aneurysmal popliteal vein as seen on an ultrasound scan that was further clarified with CT venography. She underwent an uncomplicated open tangential resection and lateral venorrhaphy. The diagnosis of PVA is usually made incidentally during investigations for pulmonary embolism or chronic venous insufficiency. Surgery is indicated in all symptomatic patients with PE as anticoagulation alone is inadequate in these patients. Surgery is also recommended in patients with asymptomatic saccular aneurysms or large (>20 mm) fusiform aneurysms. The current mainstay of treatment for PVAs is open surgical management.

Ruptured Left Gastric Artery Aneurysms: Three Cases Managed Successfully with Open Surgical Repair.

INTRODUCTION: Visceral artery aneurysms (VAAs) are an uncommon vascular pathology with an incidence estimated at 0.01-2%. The likely etiology of VAAs is uncertain, which includes atherosclerosis, trauma, and inflammation. VAAs are often asymptomatic until rupture which causes life-threatening hemorrhage and are associated with a high mortality. Gastric artery aneurysms (GAA) form a very small proportion of VAAs (<4%). CASE DESCRIPTION: This is a case series of 3 patients who presented to the Nambour Hospital with a ruptured left gastric aneurysm. They each presented with acute abdominal pain and hemodynamic instability with imaging revealing a ruptured left gastric artery aneurysm and hemoperitoneum. Patients 1 and 2 received open surgical repair in the first instance, while Patient 3 was managed endovascularly initially and proceeded to open repair due to ongoing hemorrhage. DISCUSSION: Management of ruptured VAAs can be by either open surgical or endovascular means. The advantages of open exploration in the emergency setting include the ability to directly inspect the gastric wall and other viscera and to evacuate hematoma. Additionally, it does not require the use of an angiographic suite. We feel that open repair remains an important means of managing a ruptured GAA, particularly in the shocked patient.

Prolonged second stage of labor is associated with low Apgar score.

There is no consensus on the effects of a prolonged second stage of labor on neonatal outcomes. In this large Swedish population-based cohort study, our objective was to investigate prolonged second stage and risk of low Apgar score at 5 min. All nulliparous women (n = 32,796) delivering a live born singleton infant in cephalic presentation at ≥37 completed weeks after spontaneous onset of labor between 2008 and 2012 in the counties of Stockholm and Gotland were included. Data were obtained from computerized records. Exposure was time from fully retracted cervix until delivery. Logistic regression analyses were used to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Adjustments were made for maternal age, height, BMI, smoking, sex, gestational age, sex-specific birth weight for gestational age and head circumference. Epidural analgesia was included in a second model. The primary outcome measure was Apgar score at 5 min <7 and <4. We found that the overall rates of 5 min Apgar score <7 and <4 were 7.0 and 1.3 per 1000 births, respectively. Compared to women with <1 h from retracted cervix to birth, adjusted ORs of Apgar score <7 at 5 min generally increased with length of second stage of labor: 1 to <2 h: OR 1.78 (95% CI 1.19-2.66); 2 to <3 h: OR 1.66 (1.05-2.62); 3 to <4 h: OR 2.08 (1.29-3.35); and ≥4 h: OR 2.71 (1.67-4.40). We conclude that prolonged second stage of labor is associated with an increased risk of low 5 min Apgar score.

Improving type 2 diabetes through a distinct adrenergic signaling pathway involving mTORC2 that mediates glucose uptake in skeletal muscle.

There is an increasing worldwide epidemic of type 2 diabetes that poses major health problems. We have identified a novel physiological system that increases glucose uptake in skeletal muscle but not in white adipocytes. Activation of this system improves glucose tolerance in Goto-Kakizaki rats or mice fed a high-fat diet, which are established models for type 2 diabetes. The pathway involves activation of ß2-adrenoceptors that increase cAMP levels and activate cAMP-dependent protein kinase, which phosphorylates mammalian target of rapamycin complex 2 (mTORC2) at S2481. The active mTORC2 causes translocation of GLUT4 to the plasma membrane and glucose uptake without the involvement of Akt or AS160. Stimulation of glucose uptake into skeletal muscle after activation of the sympathetic nervous system is likely to be of high physiological relevance because mTORC2 activation was observed at the cellular, tissue, and whole-animal level in rodent and human systems. This signaling pathway provides new opportunities for the treatment of type 2 diabetes.