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ERROR: type should be string, got "https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvMjEzOTA3My1vdmVydmlldw==\nDrugs & Diseases > Endocrinology\nAuthor: Se Min Kim, MD; Chief Editor: George T Griffing, MD more...\nSections Insulin Pumps\nClinical Trial Evidence\nClinical Implementation\nFollow-up/Monitoring\nSince the first human trials of insulin pumps in the late 1970s, [1] insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII), has been used for more than 30 years. As technology has developed, insulin pumps have become more user-friendly and smaller. Modern pumps weigh less than 4 ounces and are the size of a pager or cell phone.\nThe number of patients using CSII has been increasing. The US Food and Drug Administration (FDA) reported that approximately 375,000 adults with type 1 diabetes used external insulin infusion pumps in 2007, compared to 130,000 in 2002. [2]\nThe FDA classifies insulin infusion pumps as class II devices, which need more than “general controls” (ie, provisions that relate to controlling the quality of the device, preventing issues such as adulteration or misbranding, and tracking components and devices) to ensure reasonable safety and effectiveness. [2] As with any class II device, the “special controls” required may include additional labeling requirements, mandatory performance standards, and postmarket surveillance. [2]\nThe chief benefit of insulin pump therapy is customized flexible basal and bolus dosing to meet patients’ individual requirements. Insulin pumps allow users to program different basal rates to allow for variations in lifestyle and bolus doses to allow for variations in diet. Insulin delivery via a pump is more consistent and precise than via syringe or injection pen. [3]\nThere are newer electronics with complex algorithms capable of calculating insulin bolus doses necessary to maintain glucose level within a set range as measured by a continuous glucose monitor (CGM). Ultimately, this technology will likely lead to an “artificial pancreas” that automatically senses glucose level and its rate of change and adjusts insulin dosing accordingly. However, this technology is still under development and is not ready for clinical use.\nAccu-check Spirit (Roche Insulin Delivery system)\nDana Diabecare IIS (Sooil Development)\nMinimed Paradigm Real-Time Revel (Medtronic Diabetes)\nOmnipod (Insulet Corp)\nOneTouch Ping (Animas Corp)\nMost insulin pumps on the market consist of 3 parts: the pump itself (which is a programmable electronic device that includes a user interface, electronic processor, worm screw to control dosing, and batteries), a disposable reservoir that stores the insulin, and a disposable infusion set (which is the tubing that connects to the reservoir and which terminates in a cannula or needle through which the insulin is infused). The needle or cannula is inserted under the skin, and the insulin pump itself is worn externally. Newer pumps have convenient features to track trends of glucose levels; some also have lighted screens or audio cues for patients with visual impairment.\nOther insulin pump features\nThe latest models of insulin pumps include new features to help patients manage insulin delivery.\nBolus calculator\nThe physician prescribes bolus insulin based on the carbohydrate content of a meal and for the correction of any elevation of blood sugar levels. An insulin-to-carbohydrate ratio is usually programmed into the pump (eg, 1 unit of insulin per 15 g of carbohydrate). However, the patient must estimate the carbohydrate content of the meal.\nSimilarly, correction insulin can be programmed into the pump (eg, 1 unit of insulin for every 50 mg/dL glucose >100 mg/dL). The patient tests his or her blood sugar level, and the glucose level is either entered manually or automatically communicated to the pump, depending on the pump model. The calculator can also adjust the bolus amount based the amount of insulin still in the patient’s system from a previous bolus.\nAlarms can be set to remind the user if a bolus was missed (eg, if no bolus is given at the usual lunch time, the pump will alert the user), if a timed glucose test was missed, or if various other user-defined parameters are met or unmet.\nAssociated glucose meters\nSome insulin pumps facilitate direct communication between the patient’s glucose meter and insulin pump.\nThe Medtronic Minimed Paradigm series of pumps can receive data transmitted wirelessly from a glucometer (Lifescan in the United States; Bayer in the rest of the world), which then allows the pump to use glucose measurements to calculate boluses.\nThe Accu-Chek Combo Insulin Pump System allows the glucometer to be used to control the pump itself, as well as to communicate glucose readings to the pump. The Insulet OmniPod remote has an integrated glucometer, which allows the remote to calculate boluses based on glucose readings and then transmit them to the pod connected to the patient’s body.\nThe DANA Diabecare IISG pump works similarly but has a glucometer integrated into the pump itself.\nThe Medtronic Minimed Paradigm series of pumps can interact with the Guardian Real-Time CGM, which is a device that takes real-time measurements of the glucose concentration in the subcutaneous fluid; this parallels the serum glucose levels. The CGM can then wirelessly communicate measurements to its associated insulin pump, which then displays the blood glucose and its rate of change. Alarms can also be set to warn the user when glucose levels are too high or too low or are changing too quickly. Although other CGM systems exist, the Guardian Real-Time is the only CGM that communicates with an insulin pump.\nCGM technology has been gaining prominence in optimized CSII, although frequent self-monitored blood glucose (SMBG) using a glucometer remains the foundation of optimized insulin therapy.\nCGM has a potential role to revolutionize insulin delivery via a closed-loop insulin delivery system, the so-called “artificial pancreas.” Closed-loop systems were shown to reduce the risk of nocturnal hypoglycemia in children and adolescents with type 1 diabetes and improved overall glycemic control.\nThree randomized studies of overnight closed-loop systems were performed in young patients with type 1 diabetes. An analysis of pooled data showed that CGM increased patients’ duration of normal glucose levels and decreased hypoglycemic episodes. [4] A study in adult patients demonstrated similar findings. The same study group performed a randomized crossover study with eating-in and eating-out scenarios in adult type 1 DM. The amount of time patients spent in the target glucose range increased to 77%, compared to 51% in the conventional CSII group. The amount of time patients spent in a hypoglycemia state overnight was also significantly reduced. [5]\nHowever, closed-loop control during waking hours is complicated by various factors, such as diet, lifestyle, and the intrinsic limitation of current technologies. Safety during the postprandial period is an issue because of the delays in rapid-acting insulin analogue absorption. A study comparing fully closed-loop control to hybrid closed-loop control that used small manual premeal “priming” boluses in addition to dosing via the closed-loop system found that the hybrid closed-loop system improved daytime and postprandial glycemic control in patients with type 1 diabetes. [6]\nOverall, closed-loop insulin delivery systems are currently limited and are still under development. CGM devices should be used to complement SMBG until the FDA approves them as a replacement for SMBG.\nCommunication with personal computers\nMany insulin pumps have mechanisms to transmit and receive data between the pump and a personal computer. The computer interface can be used to manage pump settings and/or to document and analyze data from the pumps and associated glucose meters. They can also assist physicians in monitoring patients’ glycemic control and behavior related to managing diabetes.\n2016 guidelines on diabetes insulin pumps by the Endocrine Society with the American Association for Clinical Chemistry, American Association of Diabetes Educators, and European Society of Endocrinology recommend the following [7] :\nContinuous subcutaneous insulin infusion (CSII) recommended over analog-based basal-bolus multiple daily injections (MDI) in patients with type 1 diabetes mellitus (T1DM) who have not achieved their A1C goal, as long as the patient and caregivers are willing and able to use the device.\nCSII recommended over analog-based basal-bolus MDI in patients with T1DM who have achieved their A1C goal but continue to experience severe hypoglycemia or high glucose variability, as long as the patient and caregivers are willing and able to use the device.\nCSII recommended in patients with T1DM who require increased insulin delivery flexibility or improved satisfaction and are capable of using the device.\nCSII with good adherence to monitoring and dosing recommended in patients with type 2 diabetes mellitus (T2DM) who have poor glycemic control despite intensive insulin therapy, oral agents, other injectable therapy, and lifestyle modifications.\nReal-time continuous glucose monitoring (RT-CGM) devices recommended for adult patients with T1DM who have A1C levels above target and who are willing and able to use these devices on a nearly daily basis.\nUse of short-term, intermittent RT-CGM suggested for adult patients with T2DM (not on prandial insulin) who have A1C levels ≥7% and are willing and able to use the device.\nThe American Diabetes Association (ADA) published a position statement in 2004, [8] and the American Association of Diabetes Educators (AADE) published its Guideline for Successful Outcomes in 2009. [3] The American Academy of Pediatrics published its position statement in 2006. [9] In 2010, the American Association of Clinical Endocrinologists (AACE) released a statement regarding CSII. [10]\nThere is a consensus that appropriate patient selection is critical and is a key to realizing the potential advantages of CSII, since insulin pump therapy requires more training than other forms of insulin delivery. Patients must be motivated and willing to work with providers to succeed in using this complex therapy.\nThe AADE recommends considering an insulin pump in the following patients: [3]\nPatients whose hemoglobin A1c (HbA1c) level is greater than 7%, accompanied by frequent severe hypoglycemia (< 55 mg/dL)\nPatients who have hypoglycemic events that require third-party assistance or that interfere with work, school, or family obligations\nPatients with frequent and unpredictable fluctuations in blood glucose levels\nPatients who perceive that diabetes management impedes the pursuit of personal or professional goals\nProspective pump users or caregivers must be able to handle infusion pumps and must be prepared to troubleshoot problems. [3] In addition, they should be competent in assessing the nutritional value of meals and monitoring blood glucose levels frequently (preferably 6-8 times but at least 4 times per day). [3]\nThe psychological aspect of insulin pump use is also important. One study showed that patients who feel more responsible for the process of CSII achieve better glycemic control than patients who feel less responsible. [11] The patient’s emotional maturity and the stability of his or her life situation need to be considered before starting insulin pump therapy. [10]\nClinically suitable insulin pump candidates\nThe 2010 AACE statement proposed the following patients as clinically suitable insulin pump candidates. [10]\nPatients are classified as class 1 if they have type 1 diabetes mellitus (DM) and do not reach glycemic goals despite adherence to a maximum multiple daily injection (MDI) and are on a non-CSII program (≥4 insulin injections and ≥4 self-monitored blood glucose measurements daily), especially if they have the following:\nVery labile DM (erratic and wide glycemic excursions, including recurrent diabetic ketoacidosis [DKA])\nFrequent severe hypoglycemia and/or hypoglycemia unawareness\nSignificant “dawn phenomenon” (increase in blood glucose levels, usually from 2 am to 8 am, resulting from increased secretion of counter-regulatory hormones, particularly growth hormone)\nExtreme insulin sensitivity\nSpecial circumstance (eg, preconception, pregnancy, children, adolescents with eating problems, competitive athletes)\nPatients are classified as class 2 if they have type 1 DM and are on a maximized basal-bolus MDI insulin regimen, defined as more than 3 daily injections, regardless of their level of glycemic control and who, after investigation and careful consideration, feel that CSII would be helpful or more suitable for lifestyle reasons.\nPatients are classified as class 3 if they have insulin-requiring type 2 DM and satisfy any or all of the following:\nPositive C-peptide results but with suboptimal control on a maximal program of basal/bolus injections\nSubstantial “dawn phenomenon”\nErratic lifestyle (eg, frequent long-distance travel, shift work, unpredictable schedules that disrupt maintaining timing of meals)\nSevere insulin resistance, candidate for U500 insulin via CSII (eg, type A and type B insulin resistance syndrome, congenital and acquired generalized lipodystrophy, hyperandrogenism–insulin resistance–acanthosis nigricans [HAIR-AN], Rabson-Mendenhall syndrome)\nSelected patients with other DM types (eg, DM due to pancreatectomy)\nThe following patient factors contraindicate insulin pumps:\nUnable or unwilling to perform multiple daily insulin injections (≥3 daily), frequent blood glucose monitoring (≥4 daily), or carbohydrate counting\nLack of motivation to achieve tighter glucose control and/or history of nonadherence to insulin injection protocols\nHistory of serious psychological or psychiatric condition(s) (eg, psychosis, severe anxiety, depression)\nReservations about pump usage interfering with lifestyle (eg, contact sports or sexual activity)\nUnrealistic expectations of pump therapy (eg, belief that it eliminates the need to be responsible for diabetes management)\nIn 1993, the Diabetes Control and Complications Trial (DCCT) demonstrated the beneficial effects of intensive glycemic control in type 1 diabetes with an insulin pump or multidose insulin in slowing the progression of microvascular complications, such as retinopathy, nephropathy, and neuropathy. [12]\nSince then, numerous randomized and nonrandomized studies have supported the efficacy and safety of CSII.\nThe large “5 Nations Trials,” including 272 patients in 11 European centers, also showed a statistically significant difference in HbA1 reduction (-0.23%, P< 0.001) in the CSII group compared to MDI with neutral protamine hagedorn (NPH) as a bolus insulin. CSII treatment resulted in lower HbA1c levels (7.45% vs 7.67%, P< 0.001) and less fluctuation in blood glucose levels than MDI. [13]\nOther randomized trials by Hanaire-Broutin et al, DeVries et al, and Weintrob et al also reported that CSII yielded better glycemic control than MDI. [14, 15, 16]\nA meta-analysis from 2008 assessed 12 randomized trials with adult type 1 diabetes and showed a statistically significant difference of HbA1c reduction (-0.6%; 95% CI, -0.87 to -0.22) in favor of CSII over MDI. [17] However, all of the studies included in this meta-analysis used NPH rather than long-acting insulin analogues in the MDI group.\nIn 2010, a Cochrane review [18] compared CSII with MDI in type 1 DM. This review included 23 randomized studies involving 976 participants. Of 23 studies, 5 trials compared CSII to MDI with a long-acting insulin analogue (glargine) and short-acting insulin analogue (lispro or aspart). There was a statistically significant difference in HbA1c favoring CSII (weighted difference, -0.3%; 95% CI, -0.1 to -0.4). In addition, reduced severe hypoglycemia was reported in those using CSII, and CSII users demonstrated greater improvement in quality-of-life measures.\nMDI with a long-acting insulin analogue was also compared with CSII. One randomized study compared a group using MDI with once-daily glargine and premeal/snack insulin aspart and another using CSII with insulin aspart. This study demonstrated that the CSII group achieved lower HbA1c level, from 8.1% to 7.2% after 16 weeks of therapy (P< 0.02 vs baseline and P< 0.05 vs glargine group). Premeal and bedtime glucose levels were significantly higher in the MDI group, although fasting glucose levels did not differ in the two groups. [19]\nThis short-term study showed that a lack of compliance may be the intrinsic obstacle that contributes to poorer glycemic control in the MDI group. This would be consistent with the findings from a long-term study by Schiaffini et al in which both MDI and CSII improved glycemic control, but the improved HbA1c levels lasted longer in the CSII group. [20]\nHowever, other studies showed that MDI with glargine as the basal insulin was not inferior to CSII, even though the insulin requirement in the CSII group was significantly less than in the MDI group. [21, 22]\nThe psychosocial benefit of CSII has been also noted. Parent-reported or self-reported diabetic-specific quality of life increased significantly with CSII use. [23] One study also reported that the improvement in glycemic control with CSII was accompanied by improvements in mood, behavior, and cognition in children with type 1 DM. [24]\nThe use of CSII in type 2 DM is not well established. Two randomized trials showed similar efficacy of CSII to MDI in terms of HbA1c reduction. Those studies used NPH with aspart and glargine with lispro, respectively. [25, 26]\nHowever, patients on CSII showed a lower incidence of hyperglycemic excursions and achieved more consistent glucose control. [25] A small randomized crossover study showed a reduced hyperglycemic period using continuous glucose monitoring. In this study, CSII with lispro was slightly more efficacious than MDI with NPH as the bolus insulin, and HbA1c levels decreased from 9±1.6% to 8.6±1.6% with multiple injections and to 7.7±0.8% when using an insulin pump (P< 0.03). [27]\nIn pregnant women with diabetes, CSII has been compared with MDI to evaluate decreases in neonatal complications associated with DM, especially macrosomia (neonates born at >90th percentile of weight for gestational age or sex or >2 standard deviations). A few studies have suggested that CSII is safe and effective during pregnancy with type 1 DM. [28, 29] However, a Cochrane review in 2007 reported that a significant increase in mean birth weight was associated with CSII, although the authors concluded that the result is not clinically significant since the difference in the rate of macrosomia was not significant. [30]\nMore robust evidence is needed to assess the advantages of CSII over MDI in pregnancy, but there are anecdotal observations from healthcare professionals that women who have been very troubled by hypoglycemia during pregnancy have improved by a switch to CSII. [31]\nInsulin pumps differ from manufacturer to manufacturer, and even models from the same manufacturer may have substantial differences. Thus, patients need to be trained on the use of their specific pump.\nAn important consideration in prescribing an insulin pump is the patient’s (or caregiver’s) willingness and ability to perform diabetes self-management, because, once patients are trained in how to use an insulin pump, daily management of the pump needs to be under the control of the patients themselves or their caregivers. The physician’s role is to provide guidance on pump settings and other aspects of diabetes care.\nFor the successful use of CSII, there must be regular communication between the patient and the healthcare team. Thorough evaluation and training is needed before initiating this therapy to ensure that the patient is a suitable candidate for insulin pump use and that he or she has the knowledge needed to manage the device safely and effectively.\nAs with any technology, insulin pumps have advantages and disadvantages. While insulin pumps are not appropriate for all patients, they offer tremendous benefits for the right candidates—improved glycemic control, reduction of hypoglycemic events, and increased flexibility in managing diabetes. This explains the increasing use of CSII technology.\nInsulin for the pump\nTo use the insulin pump, the patient must first fill the reservoir with insulin, typically a rapid-acting insulin analog such as glulisine, lispro, or aspart. Some insulin pumps use a prefilled cartridge. For all pumps except the Insulet OmniPod, the reservoir is then attached to the infusion set. The infusion set is primed by the insulin pump to load insulin to the end of the cannula. This is done with the pump disconnected from the body to prevent unintended insulin delivery. The cannula surrounds a stainless steel needle.\nThe infusion set is inserted into the infusion site, typically a site on the patient’s abdomen, buttock, or thigh, and the needle is removed, leaving the cannula taped down in place at the infusion site. Again, with the exception of the Insulet OmniPod, the specifics of filling the reservoir, connecting the infusion set, and inserting the device at the infusion site vary among different manufacturer’s products, but the basic process remains similar.\nThe Insulet OmniPod consists of two components—a “pod,” which injects the insulin it contains into a subcutaneous infusion site, and a separate electronic device that wirelessly controls how the pod delivers insulin. Unlike other insulin pumps on the market, the OmniPod connects directly to the body instead of connecting via an infusion set. To prepare the OmniPod, the reservoir within the pod is filled via a syringe. The pod is then attached at the infusion site via adhesive. The patient then initiates pumping by pressing Start on the electronic controller, and the pod automatically inserts a cannula subcutaneously and begins pumping.\nInsulin dosing\nConceptually, there are two different dosing regimens administered via insulin pump: basal and bolus insulin. Both use the same rapid-acting insulin contained in the pump’s reservoir.\nBasal insulin is given at a specified (usually hourly) rate over time. As with long- and intermediate-acting insulins, basal insulins are intended to meet the insulin requirements that the body has for basal activities. The dose of insulin administered by most pumps can be calibrated and varied hour by hour. Thus, unlike long-acting insulins, in which the dose of insulin is fixed for the day, the basal rate of an insulin pump can be set to change throughout the day to account for variations in the patient’s metabolic needs.\nIn theory, a well-calibrated basal rate should maintain the patient’s glucose level with minimal variation as long as the patient does not eat or undergo activities that would change the serum glucose level. For example, early in the morning, many patients require more insulin because of the normal physiologic rise of cortisol and growth hormone (“the dawn phenomenon”). Settings on the pump can be set to account for this variability in basal insulin needs. Contemporary insulin pumps also allow users to set a temporary higher or lower basal rate for when their insulin needs differ from the norm (eg, during exercise or illness). Once the device is programmed, basal insulin runs automatically.\nBolus insulin is given to cover the food that a patient eats or to correct elevated blood glucose levels. A standard bolus is infused in less than a minute, similarly to a typical subcutaneous rapid-acting insulin injection. Unlike basal insulin, which is given automatically once dosing parameters are set, bolus insulin must be manually entered by the patient for each bolus given.\nMany pumps also allow what is called an “extended” or “square wave” bolus, which pumps the dose over an extended period, with the time range typically lasting from a half hour to 3 hours, depending on how the patient sets the bolus. This is useful for high-fat, high-protein meals, which take longer to digest and which raise the blood glucose level for an extended period. It can also be useful in patients who digest their food more slowly, such as in those with gastroparesis. Combination standard/extended boluses are also possible to help manage high-carbohydrate, high-fat meals.\nInsulin pumps are generally used to prevent complications associated with insulin injections (ie, frequent hyperglycemia or hypoglycemia). However, patients who use insulin pumps can also still become hyperglycemic or hypoglycemic. In addition, insulin pumps present unique complications of their own.\nMultiple studies have shown that insulin pumps reduce the frequency of severe hypoglycemic events relative to multiple daily insulin injections. This has been shown in randomized control trials [13, 16, 32, 33] and in before/after studies. [34, 35, 36] This reduction largely results from the patient no longer needing to use long- or, especially, intermediate-acting insulins, which require the patient to predict caloric intake, activity, and other issues that affect serum glucose levels ahead of time. Intermediate-acting insulin can especially be problematic overnight, when its activity peaks at a time when the patient is not eating.\nHowever, despite the advantages of insulin pump use, hypoglycemia may still occur on an insulin pump if the patient is given too large a bolus or the basal rate is set too high. These problems can occur with human error in programming the pump or with device malfunction leading to excess insulin delivery. There has been concern expressed about unintentional and uncontrolled insulin delivery, or “pump runaway.” Although this has occurred, [37] improvements in insulin pump technology and alarms on modern pumps mean that it is an extremely unlikely event, and no cases of this have been reported in the United States in more than decade.\nHyperglycemia and diabetic ketoacidosis\nStudies have also shown improved glycemic control in patients using insulin pumps compared with patients using multiple daily insulin injections. [19, 38] Another study showed that the incidence of DKA is equivalent for pump users and patients on MDIs. [39] In particular, nocturnal and predawn glycemic control is improved on insulin pump therapy, as hour-by-hour preprogrammed basal rate changes facilitated by the pump help counteract prebreakfast blood glucose increases (the “dawn phenomenon”) that are not easily addressed with injection therapy.\nHowever, hyperglycemia and DKA can occur with insulin pump use, whether due to user error in programming or to device malfunction. Studies show that device problems leading to hyperglycemia include diminished insulin delivery due to a depleted or malpositioned battery, occlusion or crimping of the cannula, disruption of the infusion set (eg, via torn tubing), or complete pump failure. DKA in particular occurs more frequently early after starting insulin pump use, suggesting that acclimation to the device has a learning curve.\nFinally, continuous use of the same infusion set for an extended period (ie, >2.5 days) increases the risk of cannula occlusion and changes the physiochemical environment at the delivery site, altering the rate of insulin absorption [40] and increasing the risk of hyperglycemia, [41] as well as other problems described below. One study has found that there was a slow but steady increase in average daily serum glucose concentrations as patients wore an infusion set continuously beyond 3 days. [41]\nA population-based cohort study by Karges et al that included 30,579 patients of which 14,119 used pump therapy and 16,460 who used insulin injections, reported that pump therapy was associated with lower rates of severe hypoglycemia and diabetic ketoacidosis when compared with injection therapy. The study also found that glycated hemoglobin levels were lower with pump therapy than with injection therapy. [42]\nIrritation and infection at the infusion site\nInsulin pump manufacturers recommend changing infusion sets and infusion sites every 48–72 hours to prevent irritation and/or infection at the infusion site. Wearing an infusion set for an extended period increases the risk of bacterial infection at the site, contact dermatitis from the infusion set adhesive, swelling and erythema at the infusion site, cannula occlusions, and hyperglycemia.\nOne study in which subjects wore an infusion set for increasing durations found that an increasing incidence of these problems began to occur on the third day of infusion set use. [41] According to one prospective descriptive study, with normal use, infected infusion sites occur once in every 27 patient-months. [37]\nInfusion-site infections most often involve Streptococcus bacteria that have been introduced from the skin by insertion of the cannula, but Staphylococcus species and other pathogens may also be involved, particularly in staph carriers. [43]\nPump discontinuation\nA number of studies [44, 45, 46, 47] have examined the rate of discontinuation of insulin pump therapy. Discontinuation rates found in these studies varied widely, from 18%-49% of patients in the studies. The reasons reported for discontinuing insulin pump therapy included interference with lifestyle, lack of improvement in glycemic control, or discomfort/infection at the infusion site.\nSubjects were more likely to discontinue CSII if they were female, were younger, were pregnant, had a shorter duration of diabetes, had more frequent prior episodes of DKA, or had psychological comorbidities. Interestingly, one study [47] found that even the patients who discontinued insulin pump usage had decreased frequency of DKA after discontinuing insulin pump therapy than they had before initiating insulin pump use.\nTamborlane WV, Sherwin RS, Genel M, Felig P. Reduction to normal of plasma glucose in juvenile diabetes by subcutaneous administration of insulin with a portable infusion pump. N Engl J Med. 1979 Mar 15. 300(11):573-8. [Medline].\nInsulin Infusion Pumps Panel Information. US Food and Drug Administration, General Hospital and Personal Use Medical Devices Panel; March 2010.\nScheiner G, Sobel RJ, Smith DE, Pick AJ, Kruger D, King J, et al. Insulin pump therapy: guidelines for successful outcomes. Diabetes Educ. 2009 Mar-Apr. 35 Suppl 2:29S-41S; quiz 28S, 42S-43S. [Medline].\nRenard E. Closed-loop insulin delivery: is the Holy Grail near?. Lancet. 2010 Feb 27. 375(9716):702-3. [Medline].\nHovorka R, Kumareswaran K, Harris J, et al. Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies. BMJ. 2011 Apr 13. 342:d1855. [Medline]. [Full Text].\nWeinzimer SA, Steil GM, Swan KL, Dziura J, Kurtz N, Tamborlane WV. Fully automated closed-loop insulin delivery versus semiautomated hybrid control in pediatric patients with type 1 diabetes using an artificial pancreas. Diabetes Care. 2008 May. 31(5):934-9. [Medline].\nPeters AL, Ahmann AJ, Battelino T, Evert A, Hirsch IB, Murad MH, et al. Diabetes Technology-Continuous Subcutaneous Insulin Infusion Therapy and Continuous Glucose Monitoring in Adults: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 Nov. 101 (11):3922-3937. [Medline].\nContinuous subcutaneous insulin infusion. Diabetes Care. 2004 Jan. 27 Suppl 1:S110. [Medline].\nEugster EA, Francis G. Position statement: Continuous subcutaneous insulin infusion in very young children with type 1 diabetes. Pediatrics. 2006 Oct. 118(4):e1244-9. [Medline].\nGrunberger G, Bailey TS, Cohen AJ, et al. Statement by the American Association of Clinical Endocrinologists Consensus Panel on insulin pump management. Endocr Pract. 2010 Sep-Oct. 16(5):746-62. [Medline].\nAberle I, Scholz U, Bach-Kliegel B, Fischer C, Gorny M, Langer K, et al. Psychological aspects in continuous subcutaneous insulin infusion: a retrospective study. J Psychol. 2009 Mar. 143(2):147-60. [Medline].\nThe effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993 Sep 30. 329(14):977-86. [Medline].\nHoogma RP, Hammond PJ, Gomis R, et al. Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial. Diabet Med. 2006 Feb. 23(2):141-7. [Medline].\nHanaire-Broutin H, Melki V, Bessières-Lacombe S, Tauber JP. Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens using insulin lispro in type 1 diabetic patients on intensified treatment: a randomized study. The Study Group for the Development of Pump Therapy in Diabetes. Diabetes Care. 2000 Sep. 23(9):1232-5. [Medline].\nDeVries JH, Snoek FJ, Kostense PJ, Masurel N, Heine RJ. A randomized trial of continuous subcutaneous insulin infusion and intensive injection therapy in type 1 diabetes for patients with long-standing poor glycemic control. Diabetes Care. 2002 Nov. 25(11):2074-80. [Medline].\nWeintrob N, Benzaquen H, Galatzer A, Shalitin S, Lazar L, Fayman G, et al. Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens in children with type 1 diabetes: a randomized open crossover trial. Pediatrics. 2003 Sep. 112(3 Pt 1):559-64. [Medline].\nJeitler K, Horvath K, Berghold A, Gratzer TW, Neeser K, Pieber TR, et al. Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis. Diabetologia. 2008 Jun. 51(6):941-51. [Medline].\nMisso ML, Egberts KJ, Page M, O'Connor D, Shaw J. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2010 Jan 20. CD005103. [Medline].\nDoyle EA, Weinzimer SA, Steffen AT, Ahern JA, Vincent M, Tamborlane WV. A randomized, prospective trial comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine. Diabetes Care. 2004 Jul. 27(7):1554-8. [Medline].\nSchiaffini R, Patera PI, Bizzarri C, Ciampalini P, Cappa M. Basal insulin supplementation in Type 1 diabetic children: a long-term comparative observational study between continuous subcutaneous insulin infusion and glargine insulin. J Endocrinol Invest. 2007 Jul-Aug. 30(7):572-7. [Medline].\nGarg SK, Walker AJ, Hoff HK, D'Souza AO, Gottlieb PA, Chase HP. Glycemic parameters with multiple daily injections using insulin glargine versus insulin pump. Diabetes Technol Ther. 2004 Feb. 6(1):9-15. [Medline].\nLepore G, Dodesini AR, Nosari I, Trevisan R. Both continuous subcutaneous insulin infusion and a multiple daily insulin injection regimen with glargine as basal insulin are equally better than traditional multiple daily insulin injection treatment. Diabetes Care. 2003 Apr. 26(4):1321-2. [Medline].\nMüller-Godeffroy E, Treichel S, Wagner VM. Investigation of quality of life and family burden issues during insulin pump therapy in children with Type 1 diabetes mellitus--a large-scale multicentre pilot study. Diabet Med. 2009 May. 26(5):493-501. [Medline].\nKnight S, Northam E, Donath S, Gardner A, Harkin N, Taplin C, et al. Improvements in cognition, mood and behaviour following commencement of continuous subcutaneous insulin infusion therapy in children with type 1 diabetes mellitus: a pilot study. Diabetologia. 2009 Feb. 52(2):193-8. [Medline].\nRaskin P, Bode BW, Marks JB, et al. Continuous subcutaneous insulin infusion and multiple daily injection therapy are equally effective in type 2 diabetes: a randomized, parallel-group, 24-week study. Diabetes Care. 2003 Sep. 26(9):2598-603. [Medline].\nHerman WH, Ilag LL, Johnson SL, et al. A clinical trial of continuous subcutaneous insulin infusion versus multiple daily injections in older adults with type 2 diabetes. Diabetes Care. 2005 Jul. 28(7):1568-73. [Medline].\nBerthe E, Lireux B, Coffin C, Goulet-Salmon B, Houlbert D, Boutreux S, et al. Effectiveness of intensive insulin therapy by multiple daily injections and continuous subcutaneous infusion: a comparison study in type 2 diabetes with conventional insulin regimen failure. Horm Metab Res. 2007 Mar. 39(3):224-9. [Medline].\nGonzález-Romero S, González-Molero I, Fernández-Abellán M, et al. Continuous subcutaneous insulin infusion versus multiple daily injections in pregnant women with type 1 diabetes. Diabetes Technol Ther. 2010 Apr. 12(4):263-9. [Medline].\nCyganek K, Hebda-Szydlo A, Katra B, et al. Glycemic control and selected pregnancy outcomes in type 1 diabetes women on continuous subcutaneous insulin infusion and multiple daily injections: the significance of pregnancy planning. Diabetes Technol Ther. 2010 Jan. 12(1):41-7. [Medline].\nFarrar D, Tuffnell DJ, West J. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. Cochrane Database Syst Rev. 2007 Jul 18. CD005542. [Medline].\nWollitzer AD, Zisser H, Jovanovic L. Insulin pumps and their use in pregnancy. Diabetes Technol Ther. 2010 Jun. 12 Suppl 1:S33-6. [Medline].\nKatz ML, Volkening LK, Anderson BJ, Laffel LM. Contemporary rates of severe hypoglycaemia in youth with Type 1 diabetes: variability by insulin regimen. Diabet Med. 2012 Jul. 29(7):926-32. [Medline].\nCohen D, Weintrob N, Benzaquen H, Galatzer A, Fayman G, Phillip M. Continuous subcutaneous insulin infusion versus multiple daily injections in adolescents with type I diabetes mellitus: a randomized open crossover trial. J Pediatr Endocrinol Metab. 2003 Sep. 16(7):1047-50. [Medline].\nHunger-Dathe W, Braun A, Müller UA, Schiel R, Femerling M, Risse A. Insulin pump therapy in patients with Type 1 diabetes mellitus: results of the Nationwide Quality Circle in Germany (ASD) 1999-2000. Exp Clin Endocrinol Diabetes. 2003 Oct. 111(7):428-34. [Medline].\nBruttomesso D, Pianta A, Crazzolara D, et al. Continuous subcutaneous insulin infusion (CSII) in the Veneto region: efficacy, acceptability and quality of life. Diabet Med. 2002 Aug. 19(8):628-34. [Medline].\nLinkeschova R, Raoul M, Bott U, Berger M, Spraul M. Less severe hypoglycaemia, better metabolic control, and improved quality of life in Type 1 diabetes mellitus with continuous subcutaneous insulin infusion (CSII) therapy; an observational study of 100 consecutive patients followed for a mean of 2 years. Diabet Med. 2002 Sep. 19(9):746-51. [Medline].\nMecklenburg RS, Benson EA, Benson JW Jr, Fredlund PN, Guinn T, Metz RJ, et al. Acute complications associated with insulin infusion pump therapy. Report of experience with 161 patients. JAMA. 1984 Dec 21. 252(23):3265-9. [Medline].\nHirsch IB, Bode BW, Garg S, et al. Continuous subcutaneous insulin infusion (CSII) of insulin aspart versus multiple daily injection of insulin aspart/insulin glargine in type 1 diabetic patients previously treated with CSII. Diabetes Care. 2005 Mar. 28(3):533-8. [Medline].\nBending JJ, Pickup JC, Keen H. Frequency of diabetic ketoacidosis and hypoglycemic coma during treatment with continuous subcutaneous insulin infusion. Audit of medical care. Am J Med. 1985 Dec. 79(6):685-91. [Medline].\nClausen TS, Kaastrup P, Stallknecht B. Effect of insulin catheter wear-time on subcutaneous adipose tissue blood flow and insulin absorption in humans. Diabetes Technol Ther. 2009 Sep. 11(9):575-80. [Medline].\nSchmid V, Hohberg C, Borchert M, Forst T, Pfützner A. Pilot study for assessment of optimal frequency for changing catheters in insulin pump therapy-trouble starts on day 3. J Diabetes Sci Technol. 2010 Jul 1. 4(4):976-82. [Medline]. [Full Text].\nKarges B, Schwandt A, Heidtmann B, Kordonouri O, Binder E, Schierloh U, et al. Association of Insulin Pump Therapy vs Insulin Injection Therapy With Severe Hypoglycemia, Ketoacidosis, and Glycemic Control Among Children, Adolescents, and Young Adults With Type 1 Diabetes. JAMA. 2017 Oct 10. 318 (14):1358-1366. [Medline].\nNowakowska M, Jarosz-Chobot P, Polanska J, Machnica L. Bacterial strains colonizing subcutaneous catheters of personal insulin pumps. Pol J Microbiol. 2007. 56(4):239-43. [Medline].\nGuinn TS, Bailey GJ, Mecklenburg RS. Factors related to discontinuation of continuous subcutaneous insulin-infusion therapy. Diabetes Care. 1988 Jan. 11(1):46-51. [Medline].\nWood JR, Moreland EC, Volkening LK, Svoren BM, Butler DA, Laffel LM. Durability of insulin pump use in pediatric patients with type 1 diabetes. Diabetes Care. 2006 Nov. 29(11):2355-60. [Medline].\nFloyd JC Jr, Cornell RG, Jacober SJ, Griffith LE, Funnell MM, Wolf LL, et al. A prospective study identifying risk factors for discontinuance of insulin pump therapy. Diabetes Care. 1993 Nov. 16(11):1470-8. [Medline].\nBell DS, Ackerson C, Cutter G, Clements RS Jr. Factors associated with discontinuation of continuous subcutaneous insulin infusion. Am J Med Sci. 1988 Jan. 295(1):23-8. [Medline].\n2012 Consumer Guide Chart, Insulin Pump. Available at http://forecast.diabetes.org/files/images/v65n01_Insulin_Pumps.pdf.\nGreene C, Brown D, Wallace JF, Pardo S, Pflug B. Comparative Accuracy of 3 Blood Glucose Monitoring Systems that Communicate with an Insulin Pump. Endocr Pract. 2014 Oct 1. 20(10):1016-21. [Medline].\nLy TT, Nicholas JA, Retterath A, Lim EM, Davis EA, Jones TW. Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: a randomized clinical trial. JAMA. 2013 Sep 25. 310(12):1240-7. [Medline].\nBergenstal RM, Klonoff DC, Garg SK, et al. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med. 2013 Jul 18. 369(3):224-32. [Medline].\nReznik Y, Cohen O, Aronson R, Conget I, Runzis S, Castaneda J, et al. Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial. Lancet. 2014 Oct 4. 384(9950):1265-72. [Medline].\nSchiavon M, Dalla Man C, Kudva YC, Basu A, Cobelli C. Quantitative estimation of insulin sensitivity in type 1 diabetic subjects wearing a sensor-augmented insulin pump. Diabetes Care. 2014 May. 37(5):1216-23. [Medline]. [Full Text].\nLittle SA, Leelarathna L, Walkinshaw E, Tan HK, Chapple O, Lubina-Solomon A, et al. Recovery of hypoglycemia awareness in long-standing type 1 diabetes: a multicenter 2 × 2 factorial randomized controlled trial comparing insulin pump with multiple daily injections and continuous with conventional glucose self-monitoring (HypoCOMPaSS). Diabetes Care. 2014 Aug. 37(8):2114-22. [Medline].\nRothacker KM, Kaye J. Insulin oedema and treatment-induced neuropathy occurring in a 20-year-old patient with Type 1 diabetes commenced on an insulin pump. Diabet Med. 2014 Jan. 31(1):e6-e10. [Medline].\nHolterhus PM, Bokelmann J, Riepe F, et al. Predicting the optimal basal insulin infusion pattern in children and adolescents on insulin pumps. Diabetes Care. 2013 Jun. 36(6):1507-11. [Medline]. [Full Text].\nRamotowska A, Golicki D, Dzygalo K, Szypowska A. The effect of using the insulin pump bolus calculator compared to standard insulin dosage calculations in patients with type 1 diabetes mellitus - systematic review. Exp Clin Endocrinol Diabetes. 2013 May. 121(5):248-54. [Medline].\nLansang MC, Modic MB, Sauvey R, Lock P, Ross D, Combs P, et al. Approach to the adult hospitalized patient on an insulin pump. J Hosp Med. 2013 Dec. 8(12):721-7. [Medline].\nSe Min Kim, MD Consulting Staff Physician, Department of Endocrinology, Cedars-Sinai Medical Center\nRobert H Becker, MD, MBA Resident Physician, Department of Internal Medicine, Albert Einstein Medical Center\nArthur Chernoff, MD Clinical Associate Professor of Medicine, University of Pennsylvania School of Medicine; Instructor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Division of Endocrinology and Metabolism, Senior Attending Physician, Albert Einstein Medical Center; Medical Director, Gutman Diabetes Institute; Associate Staff, Moss Rehabilitation Hospital\nArthur Chernoff, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Medical Association, Endocrine Society, Pennsylvania Medical Society, Philadelphia County Medical Society\nGeorge T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine\nGeorge T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society\nencoded search term (Insulin Pumps) and Insulin Pumps\nPediatric Type 1 Diabetes Mellitus\nFast Five Quiz: How Much Do You Know About Diabetic Neuropathy?\nFast Five Quiz: How Well Do You Know the Risk Factors and Treatment Indications for Type 2 Diabetes Mellitus?\nFast Five Quiz: Type 2 Diabetes Mellitus Presentation and Diagnosis\nDiabetes Mellitus Type 1 News & Perspectives\nPrevention of Heart Failure in Type 2 Diabetes Mellitus – The Importance of Lifestyle\nMeta-analysis Shows Efficacy of GLP-1 Agonists in Children with T2DM, Obesity\nRed, Hot, and Swollen Foot in Diabetes: Charcot or No?\nAccording to Endocrinologists\nBlood Glucose on Admission Predicts COVID-19 Severity in All\nFast Five Quiz: Metformin\nPilot Study Looks at Metformin in COVID-19\n'Thyroid Diet': What's the Evidence?\nTo Fast or Not? The New Dieting Dilemma\nHow Are Higher Insulin Prices Affecting Diabetes Care? 0.25 CME / CE / ABIM MOC Credits Clinical Review\nHow Are Higher Insulin Prices Affecting Diabetes Care?\nDiseases & Conditions Pediatric Type 1 Diabetes Mellitus\nDiseases & Conditions Type 1 Diabetes Mellitus"

ERROR: type should be string, got "https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvMzMyMzc4LXdvcmt1cA==\nDrugs & Diseases > Rheumatology\nTakayasu Arteritis Workup\nAuthor: Jefferson R Roberts, MD; Chief Editor: Herbert S Diamond, MD more...\nTakayasu Arteritis\nSections Takayasu Arteritis\nApproach Considerations\nAssessing Disease Activity\nTissue Biopsy\nSurgical Therapy\nAntineoplastics, Other\nDMARDs, TNF Inhibitors\nCalcium Channel Blockers\nAntiplatelet Agents, Hematologic\nAnticoagulants, Hematologic\nLaboratory test results in individuals with Takayasu arteritis tend to be nonspecific. The erythrocyte sedimentation rate may be high, generally greater than 50 mm/h, in early disease but normal later. Leukocyte count may be normal or slightly elevated. A moderate, normochromic anemia may be present in individuals with active disease. [17, 23]\nAutoantibodies observed in other connective tissue diseases, including rheumatoid factor, antinuclear antibodies, anticardiolipin antibodies, and antineutrophil cytoplasmic antibodies (ANCA), are as common as in the general population. Circulating antiendothelial antibodies may be present in high titers. This finding is considered nonspecific, because it is reported sporadically and may be present in other connective tissue diseases and in angiitis obliterans. Antiaorta antibodies may be present, but testing for them seldom is performed, if ever.\nSome researchers found that the levels of soluble vascular cell adhesion molecule–1 (VCAM-1) were significantly higher in patients with Takayasu arteritis compared with normal, healthy controls and that they were also significantly higher in older patients than in younger ones, suggesting that VCAM-1 may serve as a marker of disease activity and progression with age. Tripathy et al reported that cell adhesion molecule levels remain elevated in patients with inactive Takayasu arteritis. [33]\nHypoalbuminemia and increased levels of fibrinogen, alpha2-globulin, and gamma globulin are common. Urinalysis may be consistent with nephrotic syndrome.\nHLA typing is not a standard diagnostic procedure for North American patients. Presumably, a finding of HLA-B*52 in such patients reinforces the diagnosis; it is not a definite diagnostic tool.\nAlthough conventional angiography has historically been the standard for diagnosis and evaluation of the extent of disease, computed tomography and magnetic resonance techniques have gained favor for initial evaluation, as they are less invasive than standard angiography and allow diagnosis of Takayasu arteritis earlier in the disease course. [34, 35] Ultrasonography is useful for carotid assessment, while 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is useful for patients with no vascular signs or symptoms, fever of unknown origin, or an unexplained acute-phase response. (See the images below.) [36, 35, 34]\nTakayasu arteritis. MRI of thorax of 15-year-old girl with Takayasu arteritis. Note aneurysms of descending aorta. Image courtesy of Christine Hom, MD.\nTakayasu arteritis. Coronal MRI of abdomen of 15-year-old girl with Takayasu arteritis. Note thickening and tortuosity of abdominal aorta proximal to kidneys. Image courtesy of Christine Hom, MD.\nFor complete discussion, see Takayasu Arteritis Imaging\nIshikawa criteria\nThe Ishikawa criteria (1986) have been useful in defining Takayasu arteritis. One criterion is age younger than 40 years at diagnosis or at onset of characteristic signs and symptoms of 1-month duration.\nTwo major criteria involve lesions in the left and right midsubclavian artery, with the most severe stenosis or occlusion present in the mid portion of the artery from a 1 cm point proximal to the left and right, respectively, of the vertebral artery orifices to a 3-cm distal point to the orifice, as determined by angiography.\nThe minor criteria consist of annuloaortic ectasia or aortic regurgitation on angiography or echocardiography, and lesions of any of the following vessels:\nLeft mid ̶ common carotid artery\nDistal brachiocephalic trunk\nDescending aorta\nAbdominal aorta\nAmerican College of Rheumatology criteria\nThe American College of Rheumatology (ACR; 1990) put forward the following diagnostic criteria:\nAngiographic criteria must show narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities\nThese changes are not due to arteriosclerosis, fibromuscular dysplasia, or similar causes\nChanges are usually focal or segmental\nThese criteria probably allow greater flexibility to account for variability in actual clinical practice. In comparison to the Ishikawa criteria, which were established based on Japanese patients only, the ACR criteria may better reflect the North American population. The lesions can include stenosis, occlusion, or aneurysms.\nThe sensitivity and specificity of the American College of Rheumatology criteria are 90.5% and 97.9%, respectively.\nAssessing disease activity in patients with Takayasu arteritis is frequently challenging, since clinical, biologic, and radiologic information do not always correlate. Prospective study criteria established by Kerr et al (National Institutes of Health) are used to assess disease activity in patients with Takayasu arteritis. New onset or worsening of 2 or more of the following features indicates active disease [17] :\nSystemic features, such as fever and arthralgias (no identified cause)\nElevated erythrocyte sedimentation rate\nFeatures of vascular ischemia or inflammation, such as claudication, diminished or absent pulse, bruit, carotodynia, or asymmetrical blood pressure in either the upper or lower limbs (or both)\nTypical angiographic features\nPentraxin-3 (PTX3), a member of the superfamily of acute- phase proteins such as C-reactive protein (CRP) and serum amyloid P, has been suggested as a possible biomarker for identifying disease activity in patients with an established diagnosis of Takayasu arteritis. In a cross-sectional, noninterventional study, PTX3 plasma levels were shown to be more accurate than the erythrocyte sedimentation rate (ESR) and CRP level for differentiating active from inactive disease in 57 patients with previously diagnosed Takayasu arteritis. PTX3 levels greater than 1 ng/mL were more accurate than normal thresholds of CRP and ESR for defining disease activity. Patients with unknown or equivocal disease status were excluded from the study. [37]\nCertainly, PTX3 plasma levels may play a future role as a possible disease marker. However as pointed out by the authors of the study, PTX3 needs to be assessed in a broader spectrum of patients whose disease activity is unknown or equivocal before recommending using it clinically. [37]\nOther measures of disease activity in Takayasu arteritis include the Birmingham Vasculitis Activity Score (BVAS), Disease Extent Index for Takayasu's Arteritis (DEI.Tak), and Indian Takayasu's Arteritis Score (ITAS). The ITAS seems to have good correlation; however, none of those scores has been validated. [38, 39]\nImaging modalities for assessment of disease activity are limited by various factors, and no consensus has been reached on their sensitivity and specificity. Computed tomography angiography is limited by the amount of exposure to contrast. Magnetic resonance angiography is useful for providing information on vessel wall thickness, edema, and contrast enhancement; however, its ability to discriminate between acute versus inactive disease has been questioned.\n18-Fluorodeoxyglucose positron emission tomography (FDG-PET) is a promising imaging modality, given its noninvasiveness and ability to visualize regional distribution in the vascular tree. No consensus has been reached on its sensitivity and specificity in determining acute versus inactive disease. Increased vascular uptake may be visible on an18F-FDG scan performed years after the acute phase. [40]\nNovel ligands such as radioactive PK11195 that bind to peripheral benzodiazepine receptors on activated monocyte/macrophages are under investigation to improve specificity of PET for active disease. [38]\nAngiography, the criterion standard for the diagnosis and evaluation of Takayasu arteritis, is used to evaluate only the appearance of the lumen and cannot be used to differentiate between active and inactive lesions. (See the images below.) Takayasu arteritis can be divided into the following 6 types based on angiographic involvement: [4]\nType I - Branches of the aortic arch\nType IIa - Ascending aorta, aortic arch, and its branches\nType IIb - Type IIa region plus thoracic descending aorta\nType III - Thoracic descending aorta, abdominal aorta, renal arteries, or a combination\nType IV - Abdominal aorta, renal arteries, or both\nType V - Entire aorta and its branches\nTakayasu arteritis. Complete occlusion of the left common carotid artery in a 48-year-old woman with Takayasu disease. Also note narrowing of the origin of the right subclavian artery and a narrowed small vessel with subsequent aneurysmal dilatation on the right side. Image courtesy of Robert Cirillo, MD.\nTakayasu arteritis. Characteristic long, tapered narrowing of the distal aorta and iliac vessels. Image courtesy of Robert Cirillo, MD.\nTakayasu arteritis. Image obtained in the same patient as in Image 2 reveals narrowing of the proximal descending aorta and right brachiocephalic artery. Image courtesy of Robert Cirillo, MD.\nTakayasu arteritis. Aortogram of a 15-year-old girl with Takayasu arteritis. Note large aneurysms of descending aorta and dilatation of innominate artery. Image courtesy of Christine Hom, MD.\nColor Doppler ultrasonography provides details of the vascular wall, lumen, and flow and is a useful tool for screening and follow-up, particularly for carotid and subclavian arteries.\nCT helical scanning angiography is a sensitive and specific diagnostic tool. CT scanning or ultrasonography may be used to assess the thickness of the aorta. One study found that multi-slice CT scanning was useful in detecting lesions. [41]\nThe sensitivity of magnetic resonance angiography (MRA) is the same as or greater than that of angiography for revealing lesions in the aorta and its brachycephalic branches but is less sensitive for helping to detect smaller branch involvement. MRA that uses fast spin-echo sequences designed to enhance the detection of vessel wall edema shows promise in assessing disease activity before irreversible lesions develop.\nAdvances in technology have substantially improved the sensitivity and specificity of MRA, and the entire arterial vasculature can be displayed in less than 90 seconds. The risks are practically nonexistent. [42]\nPET scanning\nThe modality 18-F-FDG-PET has been shown to be useful in monitoring disease activity and response to treatment in preliminary studies. The presence or absence of FDG uptake correlates well with a patient’s clinical state and MRI findings. Its use in patients with Takayasu arteritis requires further investigation.\nSeveral studies have shown that whole-body PET scanning demonstrates anatomic changes consistent with the diagnosis of Takayasu arteritis. [36, 35, 34]\nOther imaging modalities\nSingle-photon emission computed tomography (SPECT) scanning has been used to assess cerebral blood flow and may be useful in patients who undergo bypass surgery.\nGallium scanning has been used to assess inflammatory involvement of the vessels.\nIn contrast to other vasculitides, tissue biopsy plays little to no role in the diagnosis of Takayasu arteritis, as histologic examination of the great vessels is usually possible only at the time of vascular procedures or postmortem. Biopsy of medium- to large-sized vessels may be diagnostic in early stages of the disease; however, in the chronic phase, diagnosis based on biopsy alone is inadequate. Whenever possible, the feasibility of submitting arterial tissue should be discussed with the attending surgeon prior to any surgical revascularization procedure.\nTakayasu arteritis is characterized by a special pattern of histopathologic changes. The early stage consists of a continuous or patchy granulomatous inflammatory reaction involving macrophages, lymphocytes, and multinucleated giant cells. Inflammation initially occurs in the vasa vasorum, with the artery wall becoming irregularly thickened and the lumen becoming narrowed. Takayasu arteritis progresses to a sclerotic stage, with intimal and adventitial fibrosis and scarring of the media. Lesions are initially inflammatory and later become occlusive.\nIn the early phase of Takayasu arteritis, histologic features include granulomatous changes in the media and adventitia of the aorta and its branches, followed by intimal hyperplasia, medial degeneration, and adventitial fibrosis of the sclerotic type. The duration is variable. Inflammatory cells—predominantly CD4 and CD8 lymphocytes, macrophages, plasma cells, histiocytes, and giant cells—invade the adventitia and media but not the intima.\nIn the vasoocclusive stage, the lesions are characterized by occlusion and signs of ischemia. The adventitia and media are replaced by fibrous scarring, the vasa vasorum are obliterated, and the intima undergoes irregular thickening. Medial degeneration, disruption of the elastic lamellae, and thrombosis can occur. Aneurysms can form, but no aneurysms attributed to Takayasu arteritis have been identified in the intracranial circulation. The literature reports a few cases of intracranial aneurysms that are considered to be incidental.\nThe ground substance in the intima is increased markedly, histochemically showing a basophilic acid mucopolysaccharide in a state of gelatinous swelling.\nAn increase in CD4 and decrease in CD8 lymphocytes, along with reduced B lymphocytes, have suggested a defect in T-cell regulation (cell-mediated immunity). Biopsy samples exhibit infiltrates of lymphocytes and monocytes in both the vessel walls and a peripheral nerve vasculitis. Lymphocytes and monocytes are attracted to the vessel wall either by an infectious agent or an autoimmune response, modulated by intercellular adhesion molecules (ICAMs).\nTombetti E, Mason JC. Takayasu arteritis: advanced understanding is leading to new horizons. Rheumatology (Oxford). 2018 Apr 4. [Medline].\nTrinidad B, Surmachevska N, Lala V. Takayasu Arteritis. 2020 Jan. [Medline]. 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Successful Antiviral Treatment of Giant Cell Arteritis and Takayasu Arteritis. JAMA Neurol. 2015 Aug. 72 (8):943-6. [Medline].\nKatz-Agranov N, Tanay A, Bachar DJ, Zandman-Goddard G. What to do when the Diagnosis of Giant Cell Arteritis and Takayasu's Arteritis Overlap. Isr Med Assoc J. 2015 Feb. 17 (2):123-5. [Medline]. [Full Text].\nTripathy NK, Chandran V, Garg NK, Sinha N, Nityanand S. Soluble endothelial cell adhesion molecules and their relationship to disease activity in Takayasu's arteritis. J Rheumatol. 2008 Sep. 35 (9):1842-5. [Medline].\nEspígol-Frigolé G, Prieto-González S, Alba MA, Tavera-Bahillo I, García-Martínez A, Gilabert R, et al. Advances in the diagnosis of large vessel vasculitis. Rheum Dis Clin North Am. 2015. 41 (1):125-40, ix. [Medline].\nDireskeneli H. Clinical assessment in Takayasu's arteritis: major challenges and controversies. Clin Exp Rheumatol. 2017 Mar-Apr. 35 Suppl 103 (1):189-193. [Medline].\nSchmidt WA, Blockmans D. 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Clinical utility of magnetic resonance angiography (MRA) in the diagnosis and treatment of Takayasu's arteritis. Clin Rheumatol. 2007 Aug. 26(8):1393-5. [Medline].\nNakaoka Y, Isobe M, Takei S, Tanaka Y, Ishii T, Yokota S, et al. Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study). Ann Rheum Dis. 2018 Mar. 77 (3):348-354. [Medline]. [Full Text].\nMekinian A, et al; French Takayasu network. Efficacy of tocilizumab in Takayasu arteritis: Multicenter retrospective study of 46 patients. J Autoimmun. 2018 Jul. 91:55-60. [Medline].\nDecker P, Olivier P, Risse J, Zuily S, Wahl D. Tocilizumab and refractory Takayasu disease: Four case reports and systematic review. Autoimmun Rev. 2018 Apr. 17 (4):353-360. [Medline].\nUnizony S, Stone JH, Stone JR. New treatment strategies in large-vessel vasculitis. Curr Opin Rheumatol. 2013 Jan. 25(1):3-9. 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[Medline].\nJefferson R Roberts, MD Chief of Rheumatology Service, Tripler Army Medical Center; Assistant Clinical Professor of Medicine, Uniformed Services University of the Health Sciences\nJefferson R Roberts, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Society for Simulation in Healthcare\nLuke A Monteagudo, MD Resident Physician, Department of Internal Medicine, Tripler Army Medical Center\nLuke A Monteagudo, MD is a member of the following medical societies: American College of Physicians\nPhalgoon A Shah, MD Resident Physician, Department of Medicine, Tripler Army Medical Center\nPhalgoon A Shah, MD is a member of the following medical societies: American College of Physicians\nRodger Stitt, MD Department of Internal Medicine, Tripler Army Medical Center, Honolulu\nRodger Stitt, MD is a member of the following medical societies: American College of Physicians\nHerbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital\nHerbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa\nGabriel Bucurescu, MD, MS Attending Neurologist, Neurology Service, Corporal Michael J Crescenz Veterans Affairs Medical Center\nGabriel Bucurescu, MD, MS is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society\nRobert E Wolf, MD, PhD Professor Emeritus, Department of Medicine, Louisiana State University School of Medicine in Shreveport; Chief, Rheumatology Section, Medical Service, Overton Brooks Veterans Affairs Medical Center\nRobert E Wolf, MD, PhD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation, Society for Leukocyte Biology\nMohammed Mubashir Ahmed, MD Associate Professor, Department of Medicine, Division of Rheumatology, University of Toledo College of Medicine\nMohammed Mubashir Ahmed, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, American Federation for Medical Research\nElliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine\nElliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology\nB Mark Keegan, MD, FRCPC Assistant Professor of Neurology, College of Medicine, Mayo Clinic; Master's Faculty, Mayo Graduate School; Consultant, Department of Neurology, Mayo Clinic, Rochester\nB Mark Keegan, MD, FRCPC is a member of the following medical societies: American Academy of Neurology, American Medical Association, and Minnesota Medical Association\nDisclosure: Novartis Consulting fee Consulting\nSydney Louis, MBBCh, MD Emeritus Professor, Department of Neurology, The Warren Alpert Medical School of Brown University\nSydney Louis, MBBCh, MD is a member of the following medical societies: American Academy of Neurology\nMichael G Rossman, MD, LTC, MC, FS Fellow, Department of Rheumatology, Walter Reed Army Medical Center\nMichael G Rossman, MD, LTC, MC, FS is a member of the following medical societies: American College of Physicians, American College of Rheumatology, American Medical Association, and Society of US Army Flight Surgeons\nFrancisco Talavera, PharmD, PhD Senior Pharmacy Editor, eMedicine\nDisclosure: eMedicine Salary Employment\nFlorian P Thomas, MD, MA, PhD, Drmed Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Director, Neuropathy Association Center of Excellence, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University School of Medicine\nFlorian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Paraplegia Society, Consortium of Multiple Sclerosis Centers, and National Multiple Sclerosis Society\nencoded search term (Takayasu Arteritis) and Takayasu Arteritis\nVasculitis and Thrombophlebitis\nLeukocytoclastic Vasculitis\nHypersensitivity Vasculitis\nUrticarial Vasculitis\nPrimary Angiitis of the CNS\nErythema Induratum (Nodular Vasculitis)\nPrimary CNS Vasculitis of Childhood\nExpert Offers Clinical Pearls on Leg Ulcer Therapy\nRange of COVID-19 Neurological Complications Seen in Kids\nRheumatoid Arthritis: In and Out of the Joint\nAccording to Rheumatologists\nProposed RA Guidelines: Maximize Methotrexate Before Switching\nGout Clinical Practice Guidelines (ACR, 2020)\nA Man With Stooped Posture and Mysterious Back and Neck Pain\nHow Sjogren Syndrome Intersects With COVID-19\nDenosumab Favored Over Alendronate for BMD Protection in Glucocorticoid-Induced Osteoporosis\n2002 1008239-overview Diseases & Conditions\nDiseases & Conditions Vasculitis and Thrombophlebitis\nManifestations of ANCA-Associated Vasculitis: Leveraging Novel Pathways 0.5 CME Credits\n0.5 CME\nManifestations of ANCA-Associated Vasculitis: Leveraging Novel Pathways\nDiseases & Conditions Hypersensitivity Vasculitis\nDiseases & Conditions Urticarial Vasculitis"